Breast Conserving Treatment for Breast Cancer: Dosimetric Comparison of Sequential versus Simultaneous Integrated Photon Boost

PubMed Central

Reynders, Truus; Heuninckx, Karina; Verellen, Dirk; Storme, Guy; De Ridder, Mark

2014-01-01

Background. Breast conserving surgery followed by whole breast irradiation is widely accepted as standard of care for early breast cancer. Addition of a boost dose to the initial tumor area further reduces local recurrences. We investigated the dosimetric benefits of a simultaneously integrated boost (SIB) compared to a sequential boost to hypofractionate the boost volume, while maintaining normofractionation on the breast. Methods. For 10 patients 4 treatment plans were deployed, 1 with a sequential photon boost, and 3 with different SIB techniques: on a conventional linear accelerator, helical TomoTherapy, and static TomoDirect. Dosimetric comparison was performed. Results. PTV-coverage was good in all techniques. Conformity was better with all SIB techniques compared to sequential boost (P = 0.0001). There was less dose spilling to the ipsilateral breast outside the PTVboost (P = 0.04). The dose to the organs at risk (OAR) was not influenced by SIB compared to sequential boost. Helical TomoTherapy showed a higher mean dose to the contralateral breast, but less than 5 Gy for each patient. Conclusions. SIB showed less dose spilling within the breast and equal dose to OAR compared to sequential boost. Both helical TomoTherapy and the conventional technique delivered acceptable dosimetry. SIB seems a safe alternative and can be implemented in clinical routine. PMID:25162031

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

Chang, David W., E-mail: David.Chang@petermac.org; Marvelde, Luc te; Chua, Boon H.

Purpose: To report the local recurrence rate and late toxicity of intraoperative radiation therapy (IORT) boost to the tumor bed using the Intrabeam System followed by external-beam whole-breast irradiation (WBI) in women with early-stage breast cancer in a prospective single-institution study. Methods and Materials: Women with breast cancer ≤3 cm were recruited between February 2003 and May 2005. After breast-conserving surgery, a single dose of 5 Gy IORT boost was delivered using 50-kV x-rays to a depth of 10 mm from the applicator surface. This was followed by WBI to a total dose of 50 Gy in 25 fractions. Patientsmore » were reviewed at regular, predefined intervals. Late toxicities were recorded using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring systems. Results: Fifty-five patients completed both IORT boost and external-beam WBI. Median follow-up was 3.3 years (range, 1.4-4.1 years). There was no reported locoregional recurrence or death. One patient developed distant metastases. Grade 2 and 3 subcutaneous fibrosis was detected in 29 (53%) and 8 patients (15%), respectively. Conclusions: The use of IORT as a tumor bed boost using kV x-rays in breast-conserving therapy was associated with good local control but a clinically significant rate of grade 2 and 3 subcutaneous fibrosis.« less

Short-Course Hypofractionated Radiation Therapy With Boost in Women With Stages 0 to IIIa Breast Cancer: A Phase 2 Trial.

PubMed

Ahlawat, Stuti; Haffty, Bruce G; Goyal, Sharad; Kearney, Thomas; Kirstein, Laurie; Chen, Chunxia; Moore, Dirk F; Khan, Atif J

2016-01-01

Conventionally fractionated whole-breast irradiation (WBI) with a boost takes approximately 6 to 7 weeks. We evaluated a short course of hypofractionated (HF), accelerated WBI in which therapy was completed in 3 weeks inclusive of a sequential boost. We delivered a whole-breast dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days, followed by a lumpectomy bed boost in 4 fractions of 3.33 Gy delivered once daily for a total of 15 treatment days. Acute toxicities were scored using Common Terminology Criteria for Adverse Events version 4. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Cosmesis was scored using the Harvard Cosmesis Scale. Our primary endpoint was freedom from locoregional failure; we incorporated early stopping criteria based on predefined toxicity thresholds. Cosmesis was examined as a secondary endpoint. We enrolled 83 women with stages 0 to IIIa breast cancer. After a median follow-up of 40 months, 2 cases of isolated ipsilateral breast tumor recurrence occurred (2 of 83; crude rate, 2.4%). Three-year estimated local recurrence-free survival was 95.9% (95% confidence interval [CI]: 87.8%-98.7%). The 3-year estimated distant recurrence-free survival was 97.3% (95% CI: 89.8%-99.3%). Three-year secondary malignancy-free survival was 94.3% (95% CI: 85.3%-97.8%). Twenty-nine patients (34%) had grade 2 acute toxicity, and 1 patient had a late grade 2 toxicity (fibrosis). One patient had acute grade 3 dermatitis, whereas 2 patients experienced grade 3 late skin toxicity. Ninety-four percent of evaluable patients had good or excellent cosmesis. Our phase 2 institutional study offers one of the shortest courses of HF therapy, delivered in 15 fractions inclusive of a sequential boost. We demonstrated expected low toxicity and high local control rates with good to excellent cosmetic outcomes. This fractionation scheme is feasible and well tolerated and offers women WBI in a highly convenient schedule. Copyright © 2016 Elsevier Inc. All rights reserved.

The clinical study of the optimalization of surgical treatment and the traditional Chinese medicine intervention on palmar hyperhidrosis.

PubMed

Yang, Yong; Yan, Zhikun; Fu, Xiaoqing; Dong, Liwen; Xu, Linhai; Wang, Jun; Cheng, Genmiao

2014-11-01

To analyze the efficacy of different surgical methods in treating palmar hyperhidrosis and the compensatory hyperhidrosis after surgery and to observe the efficacy of "Energy-boosting and Yin-nourishing anti-perspirant formula" on postsurgical hyperhidrosis patients. Two-hundred patients were randomly assigned to groups A (Chinese and Western medicine, T4 transection plus "Energy-boosting and Yin-nourishing anti-perspirant formula") and B (Western medicine, T4 transection). The surgical efficiency, recurrence rate, compensatory hyperhidrosis, and the long-term life quality were compared. Another 100 cases (group C, T2 transection) were analyzed as a control group. After surgery, the palmar hyperhidrosis and armpit sweating were relieved in all the three group patients and in 34 % of patients combined with plantar hyperhidrosis, the symptoms were relieved. Transient palmar hyperhidrosis was found in three cases at day 2 to day 5 postoperatively. One case of Horner's syndrome and one case recurrence were found in group C patients. The compensatory sweating of various degrees occurred in all the three groups. There were 25, 24, and 43 cases in groups A, B, and C, respectively. There is a significant difference between groups C, A, and B. The compensatory sweating in 13 cases of group A and four cases of group B had different degrees of improvement in the follow-up 6 months after surgery. There is a significant difference. Thoracoscopic bilateral T4 sympathetic chain and the Kuntz resection are the optimized surgical treatments for the palmar hyperhidrosis. "Energy-boosting and Yin-nourishing anti-perspirant formula" is effective in treating the postoperative compensatory sweating.

Patterns-of-failure guided biological target volume definition for head and neck cancer patients: FDG-PET and dosimetric analysis of dose escalation candidate subregions.

PubMed

Mohamed, Abdallah S R; Cardenas, Carlos E; Garden, Adam S; Awan, Musaddiq J; Rock, Crosby D; Westergaard, Sarah A; Brandon Gunn, G; Belal, Abdelaziz M; El-Gowily, Ahmed G; Lai, Stephen Y; Rosenthal, David I; Fuller, Clifton D; Aristophanous, Michalis

2017-08-01

To identify the radio-resistant subvolumes in pretreatment FDG-PET by mapping the spatial location of the origin of tumor recurrence after IMRT for head-and-neck squamous cell cancer to the pretreatment FDG-PET/CT. Patients with local/regional recurrence after IMRT with available FDG-PET/CT and post-failure CT were included. For each patient, both pre-therapy PET/CT and recurrence CT were co-registered with the planning CT (pCT). A 4-mm radius was added to the centroid of mapped recurrence growth target volumes (rGTV's) to create recurrence nidus-volumes (NVs). The overlap between boost-tumor-volumes (BTV) representing different SUV thresholds/margins combinations and NVs was measured. Forty-seven patients were eligible. Forty-two (89.4%) had type A central high dose failure. Twenty-six (48%) of type A rGTVs were at the primary site and 28 (52%) were at the nodal site. The mean dose of type A rGTVs was 71Gy. BTV consisting of 50% of the maximum SUV plus 10mm margin was the best subvolume for dose boosting due to high coverage of primary site NVs (92.3%), low average relative volume to CTV1 (41%), and least average percent voxels outside CTV1 (19%). The majority of loco-regional recurrences originate in the regions of central-high-dose. When correlated with pretreatment FDG-PET, the majority of recurrences originated in an area that would be covered by additional 10mm margin on the volume of 50% of the maximum FDG uptake. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Tinkle, Christopher L.; Weinberg, Vivian; Chen, Lee-May

Purpose: Evaluate the efficacy and toxicity of image guided brachytherapy using inverse planning simulated annealing (IPSA) high-dose-rate brachytherapy (HDRB) boost for locoregionally advanced cervical cancer. Methods and Materials: From December 2003 through September 2009, 111 patients with primary cervical cancer were treated definitively with IPSA-planned HDRB boost (28 Gy in 4 fractions) after external radiation at our institution. We performed a retrospective review of our experience using image guided brachytherapy. Of the patients, 70% had a tumor size >4 cm, 38% had regional nodal disease, and 15% had clinically evident distant metastasis, including nonregional nodal disease, at the time of diagnosis. Surgicalmore » staging involving pelvic lymph node dissection was performed in 15% of patients, and 93% received concurrent cisplatin-based chemotherapy. Toxicities are reported according to the Common Terminology Criteria for Adverse Events version 4.0 guidelines. Results: With a median follow-up time of 42 months (range, 3-84 months), no acute or late toxicities of grade 4 or higher were observed, and grade 3 toxicities (both acute and late) developed in 8 patients (1 constitutional, 1 hematologic, 2 genitourinary, 4 gastrointestinal). The 4-year Kaplan-Meier estimate of late grade 3 toxicity was 8%. Local recurrence developed in 5 patients (4 to 9 months after HDRB), regional recurrence in 3 (6, 16, and 72 months after HDRB), and locoregional recurrence in 1 (4 months after HDR boost). The 4-year estimates of local, locoregional, and distant control of disease were 94.0%, 91.9%, and 69.1%, respectively. The overall and disease-free survival rates at 4 years were 64.3% (95% confidence interval [CI] of 54%-73%) and 61.0% (95% CI, 51%-70%), respectively. Conclusions: Definitive radiation by use of inverse planned HDRB boost for locoregionally advanced cervical cancer is well tolerated and achieves excellent local control of disease. However, overall survival continues to be limited by the high rates of distant metastasis.« less

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for malignant glioma

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

Tsao, May N.; Mehta, Minesh P.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery or stereotactic fractionated radiation therapy in adult patients with malignant glioma. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncologymore » (1997-2004), ASTRO (1997-2004), and the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed malignant glioma, radiosurgery as boost therapy with conventional external beam radiation was examined in one randomized trial, five prospective cohort studies, and seven retrospective series. There is Level I evidence that the use of radiosurgery boost followed by external beam radiotherapy and carmustine (BCNU) does not confer benefit with respect to overall survival, quality of life, or patterns of failure as compared with external beam radiotherapy and BCNU. There is Level I-III evidence of toxicity associated with radiosurgery boost as compared with external beam radiotherapy alone. The results of the prospective and retrospective studies may be influenced by selection bias. Radiosurgery used as salvage for recurrent or progressive malignant glioma after conventional external beam radiotherapy failure was reported in zero randomized trials, three prospective cohort studies, and five retrospective series. The available data are sparse and insufficient to make absolute recommendations. Stereotactic fractionated radiation therapy has been reported as boost therapy with external beam radiotherapy for patients with newly diagnosed malignant glioma in only three prospective studies. As primary therapy alone without conventional external beam radiotherapy for newly diagnosed malignant glioma patients, stereotactic fractionated radiation therapy has been reported in only one prospective study. There were only three prospective series and two retrospective studies reported for patients with recurrent or progressive malignant glioma. Conclusions: For patients with malignant glioma, there is Level I-III evidence that the use of radiosurgery boost followed by external beam radiotherapy and BCNU does not confer benefit in terms of overall survival, local brain control, or quality of life as compared with external beam radiotherapy and BCNU. The use of radiosurgery boost is associated with increased toxicity. For patients with malignant glioma, there is insufficient evidence regarding the benefits/harms of using radiosurgery at the time progression or recurrence. There is also insufficient evidence regarding the benefits/harms in the use of stereotactic fractionated radiation therapy for patients with newly diagnosed or progressive/recurrent malignant glioma.« less

Training the Recurrent neural network by the Fuzzy Min-Max algorithm for fault prediction

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

Zemouri, Ryad; Racoceanu, Daniel; Zerhouni, Noureddine

2009-03-05

In this paper, we present a training technique of a Recurrent Radial Basis Function neural network for fault prediction. We use the Fuzzy Min-Max technique to initialize the k-center of the RRBF neural network. The k-means algorithm is then applied to calculate the centers that minimize the mean square error of the prediction task. The performances of the k-means algorithm are then boosted by the Fuzzy Min-Max technique.

Estimate variable importance for recurrent event outcomes with an application to identify hypoglycemia risk factors.

PubMed

Duan, Ran; Fu, Haoda

2015-08-30

Recurrent event data are an important data type for medical research. In particular, many safety endpoints are recurrent outcomes, such as hypoglycemic events. For such a situation, it is important to identify the factors causing these events and rank these factors by their importance. Traditional model selection methods are not able to provide variable importance in this context. Methods that are able to evaluate the variable importance, such as gradient boosting and random forest algorithms, cannot directly be applied to recurrent events data. In this paper, we propose a two-step method that enables us to evaluate the variable importance for recurrent events data. We evaluated the performance of our proposed method by simulations and applied it to a data set from a diabetes study. Copyright © 2015 John Wiley & Sons, Ltd.

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

Ahlawat, Stuti; Haffty, Bruce G.; Goyal, Sharad

Purpose: Conventionally fractionated whole-breast irradiation (WBI) with a boost takes approximately 6 to 7 weeks. We evaluated a short course of hypofractionated (HF), accelerated WBI in which therapy was completed in 3 weeks inclusive of a sequential boost. Methods and Materials: We delivered a whole-breast dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days, followed by a lumpectomy bed boost in 4 fractions of 3.33 Gy delivered once daily for a total of 15 treatment days. Acute toxicities were scored using Common Terminology Criteria for Adverse Events version 4. Late toxicities were scored using the Radiation Therapy Oncology Group/European Organization for Researchmore » and Treatment of Cancer scale. Cosmesis was scored using the Harvard Cosmesis Scale. Our primary endpoint was freedom from locoregional failure; we incorporated early stopping criteria based on predefined toxicity thresholds. Cosmesis was examined as a secondary endpoint. Results: We enrolled 83 women with stages 0 to IIIa breast cancer. After a median follow-up of 40 months, 2 cases of isolated ipsilateral breast tumor recurrence occurred (2 of 83; crude rate, 2.4%). Three-year estimated local recurrence-free survival was 95.9% (95% confidence interval [CI]: 87.8%-98.7%). The 3-year estimated distant recurrence-free survival was 97.3% (95% CI: 89.8%-99.3%). Three-year secondary malignancy-free survival was 94.3% (95% CI: 85.3%-97.8%). Twenty-nine patients (34%) had grade 2 acute toxicity, and 1 patient had a late grade 2 toxicity (fibrosis). One patient had acute grade 3 dermatitis, whereas 2 patients experienced grade 3 late skin toxicity. Ninety-four percent of evaluable patients had good or excellent cosmesis. Conclusions: Our phase 2 institutional study offers one of the shortest courses of HF therapy, delivered in 15 fractions inclusive of a sequential boost. We demonstrated expected low toxicity and high local control rates with good to excellent cosmetic outcomes. This fractionation scheme is feasible and well tolerated and offers women WBI in a highly convenient schedule.« less

A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong

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

Teo, P.; Tsao, S.Y.; Shiu, W.

Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximalmore » diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.« less

The Role of Concomitant Radiation Boost in Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

PubMed

Badakhshi, Harun; Ismail, Mahmoud; Boskos, Christos; Zhao, Kuaile; Kaul, David

2017-06-01

This study analyzed the impact of concomitant boost on long-term clinical outcomes in locally advanced rectal cancer. A total of 141 patients (median age=61 years) were treated with neoadjuvant chemoradiotherapy. Median total dose was 50.4 Gy. Forty-three patients received a concomitant boost. Concurrent chemotherapy consisted of 5-fluorouracil (5-FU), given as a 24-h continuous infusion. Mean follow-up was 83.7 months. The 3, 5-, and 10-year overall survival (OS) rates were 91.9%, 84.6%, and 52.9%, respectively. Recurrence-free survival (RFS) rates at 3, 5, and 10 years were 91.4%, 88.9%, and 79.3%, respectively. Metastasis-free survival (MFS) rates at 3, 5, and 10 years were 84.6%, 75.4%, and 49.9%, respectively. Overall, 9.9% of all patients achieved pathological complete response. Down-staging of T- or N-stage was achieved in 55.1% and 41.5% of patients. Multivariate analysis revealed that female sex (p=0.011), concomitant boost-radiotherapy (p=0.014), and the presence of fewer than five positive lymph nodes (p<0.001) were positive predictors of OS. Fewer than five positive lymph nodes was also a positive predictor for RFS (p=0.019). Female gender (p=0.018) and fewer than five positive lymph nodes (p<0.001) were significant predictors for MFS. Our data support the efficacy of preoperative treatment for rectal cancer in terms of local outcomes. Intensified radiotherapy using a concomitant boost has a positive effect on OS. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Retroperitoneal sarcoma (RPS) high risk gross tumor volume boost (HR GTV boost) contour delineation agreement among NRG sarcoma radiation and surgical oncologists.

PubMed

Baldini, Elizabeth H; Bosch, Walter; Kane, John M; Abrams, Ross A; Salerno, Kilian E; Deville, Curtiland; Raut, Chandrajit P; Petersen, Ivy A; Chen, Yen-Lin; Mullen, John T; Millikan, Keith W; Karakousis, Giorgos; Kendrick, Michael L; DeLaney, Thomas F; Wang, Dian

2015-09-01

Curative intent management of retroperitoneal sarcoma (RPS) requires gross total resection. Preoperative radiotherapy (RT) often is used as an adjuvant to surgery, but recurrence rates remain high. To enhance RT efficacy with acceptable tolerance, there is interest in delivering "boost doses" of RT to high-risk areas of gross tumor volume (HR GTV) judged to be at risk for positive resection margins. We sought to evaluate variability in HR GTV boost target volume delineation among collaborating sarcoma radiation and surgical oncologist teams. Radiation planning CT scans for three cases of RPS were distributed to seven paired radiation and surgical oncologist teams at six institutions. Teams contoured HR GTV boost volumes for each case. Analysis of contour agreement was performed using the simultaneous truth and performance level estimation (STAPLE) algorithm and kappa statistics. HRGTV boost volume contour agreement between the seven teams was "substantial" or "moderate" for all cases. Agreement was best on the torso wall posteriorly (abutting posterior chest abdominal wall) and medially (abutting ipsilateral para-vertebral space and great vessels). Contours varied more significantly abutting visceral organs due to differing surgical opinions regarding planned partial organ resection. Agreement of RPS HRGTV boost volumes between sarcoma radiation and surgical oncologist teams was substantial to moderate. Differences were most striking in regions abutting visceral organs, highlighting the importance of collaboration between the radiation and surgical oncologist for "individualized" target delineation on the basis of areas deemed at risk and planned resection.

940 nm diode laser therapy in management of recurrent apthous ulcer

PubMed Central

Misra, Neeta; Maiti, Debasmita; Misra, Pradyumna; Singh, Ashish Kumar

2013-01-01

Recurrent apthous stomatitis (RAS) is one of the most common oral inflammatory diseases characterised by painful recurrent ulcerations of the orofacial region. The ulcers occur in three clinical forms: minor, major and herpetiform. Several therapies have been advocated to manage these lesions such as topical corticosteroids (triamcinolone acetonide, hydrocortisone acetate and clobetasol propionate), chlorhexidine mouth rinses, tetracycline oral rinses, thalidomide, fluocinonide, colchicines and the immune boosting agent levamosile, vitamin therapy and topical interferon α-2a. Laser therapy is used as an alternative method in treatment of RAS. In this paper one patient with RAS was treated using a 940 nm diode laser for symptomatic relief of pain and burning sensation and healing of ulcer. PMID:23598930

Adjuvant Vaginal Brachytherapy for Early Stage Endometrial Cancer: A Comprehensive Review

PubMed Central

Harkenrider, Matthew M; Block, Alec M; Alektiar, Kaled M; Gaffney, David K; Jones, Ellen; Klopp, Ann; Viswanathan, Akila N; Small, William

2017-01-01

This article aims to review the risk stratification of endometrial cancer, treatment rationale, outcomes, treatment planning, and treatment recommendations of vaginal brachytherapy (VBT) in the post-operative management of endometrial cancer patients. The authors performed a thorough review of the literature and reference pertinent articles pertaining to the aims of this review. Adjuvant VBT for early stage endometrial cancer patients results in very low rates of vaginal recurrence (0–3.1%) with low rates of late toxicity which are primarily vaginal in nature. PORTEC-2 supports that VBT results in non-inferior rates of vaginal recurrence compared to external beam radiotherapy (EBRT) for the treatment of high-intermediate risk patients. VBT as a boost following EBRT, in combination with chemotherapy, and for high-risk histologies have shown excellent results as well though randomized data do not exist supporting VBT boost. There are many different applicators, dose-fractionation schedules, and treatment planning techniques which all result in favorable clinical outcomes and low rates of toxicity. Recommendations have been published by the American Brachytherapy Society and the American Society of Radiation Oncology to help guide practitioners in the use of VBT. Data support that patients and physicians both prefer joint decision-making regarding the use of VBT, and patients often desire additional treatment for a marginal benefit in risk of recurrence. Discussions regarding adjuvant therapy for endometrial cancer are best performed in a multi-disciplinary setting and patients should be counseled properly regarding the risks and benefits of adjuvant therapy. PMID:27260082

High-Dose Split-Course Radiation Therapy for Anal Cancer: Outcome Analysis Regarding the Boost Strategy (CORS-03 Study)

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

Hannoun-Levi, Jean-Michel, E-mail: jean-michel.hannoun-levi@nice.fnclcc.fr; Cercle des Oncologues Radiotherapeutes du Sud; Ortholan, Cecile

2011-07-01

Purpose: To retrospectively assess the clinical outcome in anal cancer patients treated with split-course radiation therapy and boosted through external-beam radiation therapy (EBRT) or brachytherapy (BCT). Methods and Materials: From January 2000 to December 2004, a selected group (162 patients) with invasive nonmetastatic anal squamous cell carcinoma was studied. Tumor staging reported was T1 = 31 patients (19%), T2 = 77 patients (48%), T3 = 42 patients (26%), and T4= 12 patients (7%). Lymph node status was N0-1 (86%) and N2-3 (14%). Patients underwent a first course of EBRT: mean dose 45.1 Gy (range, 39.5-50) followed by a boost: meanmore » dose 17.9 Gy (range, 8-25) using EBRT (76 patients, 47%) or BCT (86 patients, 53%). All characteristics of patients and tumors were well balanced between the BCT and EBRT groups. Results: The mean overall treatment time (OTT) was 82 days (range, 45-143) and 67 days (range, 37-128) for the EBRT and BCT groups, respectively (p < 0.001). The median follow-up was 62 months (range, 2-108). The 5-year cumulative rate of local recurrence (CRLR) was 21%. In the univariate analysis, the prognostic factors for CRLR were as follows: T stage (T1-2 = 15% vs. T3-4 = 36%, p = 0.03), boost technique (BCT = 12% vs. EBRT = 33%, p = 0.002) and OTT (OTT <80 days = 14%, OTT {>=}80 days = 34%, p = 0.005). In the multivariate analysis, BCT boost was the unique prognostic factor (hazard ratio = 0.62 (0.41-0.92). In the subgroup of patients with OTT <80 days, the 5-year CRLR was significantly increased with the BCT boost (BC = 9% vs. EBRT = 28%, p = 0.03). In the case of OTT {>=}80 days, the 5-year CRLR was not affected by the boost technique (BCT = 29% vs. EBRT = 38%, p = 0.21). Conclusion: In anal cancer, when OTT is <80 days, BCT boost is superior to EBRT boost for CRLR. These results suggest investigating the benefit of BCT boost in prospective trials.« less

Memory replay in balanced recurrent networks

PubMed Central

Chenkov, Nikolay; Sprekeler, Henning; Kempter, Richard

2017-01-01

Complex patterns of neural activity appear during up-states in the neocortex and sharp waves in the hippocampus, including sequences that resemble those during prior behavioral experience. The mechanisms underlying this replay are not well understood. How can small synaptic footprints engraved by experience control large-scale network activity during memory retrieval and consolidation? We hypothesize that sparse and weak synaptic connectivity between Hebbian assemblies are boosted by pre-existing recurrent connectivity within them. To investigate this idea, we connect sequences of assemblies in randomly connected spiking neuronal networks with a balance of excitation and inhibition. Simulations and analytical calculations show that recurrent connections within assemblies allow for a fast amplification of signals that indeed reduces the required number of inter-assembly connections. Replay can be evoked by small sensory-like cues or emerge spontaneously by activity fluctuations. Global—potentially neuromodulatory—alterations of neuronal excitability can switch between network states that favor retrieval and consolidation. PMID:28135266

Intraoperative radiotherapy given as a boost for early breast cancer: Long-term clinical and cosmetic results

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

Lemanski, Claire; Azria, David; Thezenas, Simon

2006-04-01

Purpose: The standard radiotherapy (RT) of breast cancer consists of 50 Gy external beam RT (EBRT) to the whole breast followed by an electron boost of 10-16 Gy to the tumor bed, but this has several cosmetic disadvantages. Intraoperative radiotherapy (IORT) could be an alternative to overcome these. Methods and Materials: We evaluated 50 women with early breast cancer operated on in a dedicated IORT facility. Median dose of 10 Gy was delivered using 9-MeV electron beams. All patients received postoperative EBRT (50 Gy in 2 Gy fractions). Late toxicity and cosmetic results were assessed independently by two physicians accordingmore » to the Common Terminology Criteria for Adverse Event v3.0 grading system and the European Organization for Research and Treatment of Cancer questionnaires. Results: After a median follow-up of 9.1 years (range, 5-15 years), two local recurrences were observed within the primary tumor bed. At the time of analysis, 45 patients are alive with (n = 1) or without disease. Among the 42 disease-free remaining patients, 6 experienced Grade 2 late subcutaneous fibrosis within the boost area. Overall, the scores indicated a very good quality of life and cosmesis was good to excellent in the evaluated patients. Conclusion: Our results confirm that IORT given as a boost after breast-conserving surgery is a reliable alternative to conventional postoperative fractionated boost radiation.« less

Recurrent urinary tract infections in women: How promising is the use of probiotics?

PubMed

Gupta, Varsha; Nag, Deepika; Garg, Pratibha

2017-01-01

Urinary tract infections (UTIs) currently rank amongst the most prevalent bacterial infections, representing a major health hazard. UTIs in females usually start as vaginal infections and ascend to the urethra and bladder. Recurrent UTIs (rUTIs) can be defined as at least three episodes of UTI in 1 year or two episodes in 6 months. Various antibiotics have been the mainstay of therapy in ameliorating the incidence of UTIs, but recurrent infections continue to afflict many women. It necessitates the exploitation of alternative antimicrobial therapy. Probiotics have been shown to be effective in varied clinical trials for long-term preventions of rUTI. Because Escherichia coli is the primary pathogen involved in UTIs which spreads from the rectum to vagina and then ascends up the sterile urinary tract, improving the gut or vaginal flora will thus impact the urinary tract. Since a healthy vaginal microbiota is mainly dominated by Lactobacillus species, in this context, exogenously administered probiotics containing Lactobacilli play a pivotal role in reducing the risk of rUTI. The concept of artificially boosting the Lactobacilli numbers through probiotic administration has long been conceived but has been recently shown to be possible. Lactobacilli may especially be useful for women with a history of recurrent, complicated UTIs or on prolonged antibiotic use. Probiotics do not cause antibiotic resistance and may offer other health benefits due to vaginal re-colonisation with Lactobacilli. However, more comprehensive research is still needed, to recommend for probiotics as an alternative to antibiotics.

FIVE-YEAR RESULTS OF ADJUVANT RADIOTHER

PubMed Central

Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Kerimian, Maria Fenton; Goldberg, Judith D.; Formenti, Silvia C.

2015-01-01

Purpose/Objective A technique of prone breast radiotherapy delivered by a regimen of accelerated intensity modulated radiation therapy (IMRT) with a concurrent boost to the tumor bed, was developed at our institution. We report the five year results of this approach. Methods and Materials Between 2003–2006, 404 patients with Stage I–II breast cancer were prospectively enrolled into two consecutive protocols, institutional trials 03–30 and 05–181, that used the same regimen of 40.5Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5Gy (total dose=48Gy). All patients were treated after segmental mastectomy, had negative margins, and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine set-up attempted, and chosen if found to better spare these organs. Results 92% of patients were treated prone, 8% supine. 72% had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 –228.27cc, mean: 19.65cc. In-field heart volume for left breast cancer patients ranged from 0–21.24cc, mean: 1.59cc. There was no heart in the field for right breast cancer patients. At a median follow-up of five years, the five-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI: 0.65–1.04). The five-year cumulative incidence of regional recurrence was 0.53% (95% CI:0.41–0.69) and the five-year overall cumulative death rate was 1.28% (95% CI: 0.48–3.38). 82% (95% CI: 77–85) of patients judged their final cosmetic result as excellent/good. Conclusions Prone accelerated IMRT with a concomitant boost results in excellent local control, optimal sparing of heart and lung, with good cosmesis. RTOG 10–05, a phase III, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard six weeks radiotherapy with a sequential boost. PMID:24867535

Dopamine-Modulated Recurrent Corticoefferent Feedback in Primary Sensory Cortex Promotes Detection of Behaviorally Relevant Stimuli

PubMed Central

Handschuh, Juliane

2014-01-01

Dopaminergic neurotransmission in primary auditory cortex (AI) has been shown to be involved in learning and memory functions. Moreover, dopaminergic projections and D1/D5 receptor distributions display a layer-dependent organization, suggesting specific functions in the cortical circuitry. However, the circuit effects of dopaminergic neurotransmission in sensory cortex and their possible roles in perception, learning, and memory are largely unknown. Here, we investigated layer-specific circuit effects of dopaminergic neuromodulation using current source density (CSD) analysis in AI of Mongolian gerbils. Pharmacological stimulation of D1/D5 receptors increased auditory-evoked synaptic currents in infragranular layers, prolonging local thalamocortical input via positive feedback between infragranular output and granular input. Subsequently, dopamine promoted sustained cortical activation by prolonged recruitment of long-range corticocortical networks. A detailed circuit analysis combining layer-specific intracortical microstimulation (ICMS), CSD analysis, and pharmacological cortical silencing revealed that cross-laminar feedback enhanced by dopamine relied on a positive, fast-acting recurrent corticoefferent loop, most likely relayed via local thalamic circuits. Behavioral signal detection analysis further showed that activation of corticoefferent output by infragranular ICMS, which mimicked auditory activation under dopaminergic influence, was most effective in eliciting a behaviorally detectable signal. Our results show that D1/D5-mediated dopaminergic modulation in sensory cortex regulates positive recurrent corticoefferent feedback, which enhances states of high, persistent activity in sensory cortex evoked by behaviorally relevant stimuli. In boosting horizontal network interactions, this potentially promotes the readout of task-related information from cortical synapses and improves behavioral stimulus detection. PMID:24453315

High-dose-rate interstitial brachytherapy for the treatment of high-volume locally recurrent endometrial carcinoma.

PubMed

Huang, Kitty; D'Souza, David; Patil, Nikhilesh; Velker, Vikram; Leung, Eric; Stitt, Larry; Whiston, Frances; Sugimoto, Akira; McGee, Jacob; Prefontaine, Michel

2016-01-01

Limited therapeutic options are available for the treatment of locally recurrent endometrial carcinoma. Our objective was to report an institutional experience using interstitial brachytherapy (IBT) to treat significant recurrent endometrial carcinoma, including previously irradiated disease. Between December 2004 and September 2012, 40 patients with high-volume locally recurrent endometrial cancer were treated by high-dose-rate IBT (± external beam radiation therapy EBRT). Sixteen patients had prior radiotherapy: EBRT alone (n = 5), intracavitary brachytherapy alone (n = 3), or EBRT with intracavitary brachytherapy boost (n = 8). Actuarial outcome rates were calculated using the Kaplan-Meier method and compared using the log-rank test. Median followup interval was 18 months. Median disease-free interval was 61 months. Actuarial local control, progression-free survival (PFS), and overall survival were 74% and 60%, 70% and 51%, and 83% and 72% at 12 and 24 months, respectively. p-Values for local control, progression-free survival, and overall survival between patient who had prior RT (n = 16) to no prior RT (n = 24) were p = 0.38, 0.32, and 0.90, respectively. Acute toxicities include Grade 1-2 pain (5%), genitourinary (7%), gastrointestinal (12%), soft tissue (5%), and dermatologic (12%). Four patients observed late Grade 3-4 toxicities, including rectal bleeding/fistula and soft tissue necrosis. High-dose-rate IBT is an effective treatment for locally recurrent endometrial carcinoma with an acceptable toxicity profile. Outcomes are similar between previously irradiated and nonirradiated patients. In women who have received prior radiotherapy and are often considered for palliative treatment, interstitial brachytherapy is a potentially curative option. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Image-Guided Hypofractionated Radiation Therapy With Stereotactic Body Radiation Therapy Boost and Combination Chemotherapy in Treating Patients With Stage II-III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

ClinicalTrials.gov

2017-06-12

Adenocarcinoma of the Lung; Adenosquamous Cell Lung Cancer; Large Cell Lung Cancer; Recurrent Non-small Cell Lung Cancer; Squamous Cell Lung Cancer; Stage IIA Non-small Cell Lung Cancer; Stage IIB Non-small Cell Lung Cancer; Stage IIIA Non-small Cell Lung Cancer; Stage IIIB Non-small Cell Lung Cancer

Clinical trial aims to improve outcomes for children and young adults with primary brain tumors | Center for Cancer Research

Cancer.gov

Central nervous system (CNS) tumors are the most common solid tumors among children and account for up to 25 percent of all childhood cancer cases. With few treatment options available at the time of recurrence or progression, this multicenter study will test the safety and efficacy of a drug that boosts the function of the immune system to fight tumors. Read more…

Preoperative radiotherapy and local excision of rectal cancer: Long-term results of a randomised study.

PubMed

Wawok, Przemysław; Polkowski, Wojciech; Richter, Piotr; Szczepkowski, Marek; Olędzki, Janusz; Wierzbicki, Ryszard; Gach, Tomasz; Rutkowski, Andrzej; Dziki, Adam; Kołodziejski, Leszek; Sopyło, Rafał; Pietrzak, Lucyna; Kryński, Jacek; Wiśniowska, Katarzyna; Spałek, Mateusz; Pawlewicz, Konrad; Polkowski, Marcin; Kowalska, Teresa; Paprota, Krzysztof; Jankiewicz, Małgorzata; Radkowski, Andrzej; Chalubińska-Fendler, Justyna; Michalski, Wojciech; Bujko, Krzysztof

2018-06-01

It is uncertain whether local control is acceptable after preoperative radiotherapy and local excision (LE). An optimal preoperative dose/fractionation schedule has not yet been established. In a phase III study, patients with cT1-2N0M0 or borderline cT2/T3N0M0 < 4 cm rectal adenocarcinomas were randomised to receive either 5 × 5 Gy plus 1 × 4 Gy boost or chemoradiation: 50.4 Gy in 28 fractions plus 3 × 1.8 Gy boost and 5-fluorouracil with leucovorin bolus. LE was performed 6-8 weeks later. Patients with ypT0-1R0 disease were observed. Completion total mesorectal excision (CTME) was recommended for poor responders, i.e. ypT1R1/ypT2-3. Of 61 randomised patients, 10 were excluded leaving 51 for analysis; 29 in the short-course group and 22 in the chemoradiation group. YpT0-1R0 was observed in 66% of patients in the short-course group and in 86% in the chemoradiation group, p = 0.11. CTME was performed only in 46% of patients with ypT1R1/ypT2-3. The median follow-up was 8.7 years. Local recurrence incidences and overall survival at 10 years were respectively for the short-course group vs. the chemoradiation group 35% vs. 5%, p = 0.036 and 47% vs. 86%, p = 0.009. In total, local recurrence at 10 years was 79% for ypT1R1/T2-3 without CTME. This trial suggests that in the LE setting, both local recurrence and survival are worse after short-course radiotherapy than after chemoradiation. Because of the risk of bias, a confirmatory study is desirable. Lack of CTME is associated with an unacceptably high local recurrence rate. Copyright © 2018 Elsevier B.V. All rights reserved.

Patterns of failure after radical prostatectomy in prostate cancer - implications for radiation therapy planning after 68Ga-PSMA-PET imaging.

PubMed

Schiller, Kilian; Sauter, K; Dewes, S; Eiber, M; Maurer, T; Gschwend, J; Combs, S E; Habl, G

2017-09-01

Salvage radiotherapy (SRT) after radical prostatectomy (RPE) and lymphadenectomy (LAE) is the appropriate radiotherapy option for patients with persistent/ recurrent prostate cancer (PC). 68 Ga-PSMA-PET imaging has been shown to accurately detect PC lesions in a primary setting as well as for local recurrence or for lymph node (LN) metastases. In this study we evaluated the patterns of recurrence after RPE in patients with PC, putting a highlight on the differentiation between sites that would have been covered by a standard radiation therapy (RT) field in consensus after the RTOG consensus and others that would have not. Thirty-one out of 83 patients (37%) with high-risk PC were the subject of our study. Information from 68 Ga-PSMA-PET imaging was used to individualize treatment plans to include suspicious lesions as well as possibly boost sites with tracer uptake in LN or the prostate bed. For evaluation, 68 Ga-PSMA-PET-positive LN were contoured in a patient dataset with a standard lymph drainage (RTOG consensus on CTV definition of pelvic lymph nodes) radiation field depicting color-coded nodes that would have been infield or outfield of that standard lymph drainage field and thereby visualizing typical patterns of failure of a "blind" radiation therapy after RPE and LAE. Compared to negative conventional imaging (CT/MRI), lesions suspicious for PC were detected in 27/31 cases (87.1%) by 68 Ga-PSMA-PET imaging, which resulted in changes to the radiation concept. There were 16/31 patients (51.6%) that received a simultaneous integrated boost (SIB) to a subarea of the prostate bed (in only three cases this dose escalation would have been planned without the additional knowledge of 68 Ga-PSMA-PET imaging) and 18/31 (58.1%) to uncommon (namely presacral, paravesical, pararectal, preacetabular and obturatoric) LN sites. Furthermore, 14 patients (45.2%) had a changed TNM staging result by means of 68 Ga-PSMA-PET imaging. Compared to conventional CT or MRI staging, 68 Ga-PSMA-PET imaging detects more PC lesions and, thus, significantly influences radiation planning in recurrent prostate cancer patients enabling individually tailored treatment.

Concurrent Chemoradiation with Concomitant Boost in Locally Advanced Rectal Cancer: A Phase II Study.

PubMed

Picardi, Vincenzo; Deodato, Francesco; Guido, Alessandra; Giaccherini, Lucia; Macchia, Gabriella; Gambacorta, Maria A; Arcelli, Alessandra; Farioli, Andrea; Cellini, Francesco; Cuicchi, Dajana; DI Fabio, Francesca; Poggioli, Gilberto; Ardizzoni, Andrea; Frezza, Giovanni; Cilla, Savino; Caravatta, Luciana; Valentini, Vincenzo; Fuccio, Lorenzo; Morganti, Alessio G

2016-08-01

The aim of this study was to evaluate the pathological response of locally advanced rectal cancer after preoperative concurrent two-drug chemotherapy and intensified radiation therapy (RT) with concomitant boost. Patients with T4 tumor or local recurrence were included. A trial based on two-stage Simon's design was planned. RT was performed with 3D-conformal technique. The dose to the mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered to Gross Tumor Volume (GTV) 2 cm margin to a total dose of 55 Gy (2.2 Gy/fraction). The following concurrent chemotherapy was administered: Raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) on days 1, 17, and 35 of RT. Pathological response was evaluated according to the Mandard classification. Toxicities were scored according to the Common Terminology Criteria for Adverse Events v3.0 scale. Eighteen patients (median age=64.5 years) were enrolled. The median follow-up was 22 months (range=2-36 months). After chemoradiation treatment, 16 patients underwent surgical resection (seven anterior resections and nine abdominal-perineal amputation); two patients did not undergo surgery due to early metastatic progression or refusal. R0 resection was achieved in all patients who underwent surgery. Five patients had pathological complete response [27.7%; 95% confidence interval (CI)=9.7-53.5%] and two patients showed only microscopic residual disease (11.1%; 95% CI=0.1-34.7%). Mandard grades 1 and 2 were detected in seven patients (38.9%; 95% CI=17.3-64.3%). Acute grade 3 or more toxicity was found in eight patients (44.4%; 95% CI=21.5-69.2%): one leucopenia-neutropenia, one liver, one skin and five cases of gastrointestinal toxicities. No patient had local tumor recurrence. One-, 2- and 3-year cumulative disease-free survival were 93.8%. One-, 2- and 3-year cumulative overall survival were 92.3%. Concurrent chemoradiation with concomitant boost in patients with advanced rectal cancer allows complete or near-complete pathological response in more than 38% of patients. However, severe acute toxicity was reported in more than one-third of patients. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy.

PubMed

Haefner, Matthias F; Lang, Kristin; Krug, David; Koerber, Stefan A; Uhlmann, Lorenz; Kieser, Meinhard; Debus, Juergen; Sterzing, Florian

2015-07-01

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients recieved either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Chaotic genetic algorithm and Adaboost ensemble metamodeling approach for optimum resource planning in emergency departments.

PubMed

Yousefi, Milad; Yousefi, Moslem; Ferreira, Ricardo Poley Martins; Kim, Joong Hoon; Fogliatto, Flavio S

2018-01-01

Long length of stay and overcrowding in emergency departments (EDs) are two common problems in the healthcare industry. To decrease the average length of stay (ALOS) and tackle overcrowding, numerous resources, including the number of doctors, nurses and receptionists need to be adjusted, while a number of constraints are to be considered at the same time. In this study, an efficient method based on agent-based simulation, machine learning and the genetic algorithm (GA) is presented to determine optimum resource allocation in emergency departments. GA can effectively explore the entire domain of all 19 variables and identify the optimum resource allocation through evolution and mimicking the survival of the fittest concept. A chaotic mutation operator is used in this study to boost GA performance. A model of the system needs to be run several thousand times through the GA evolution process to evaluate each solution, hence the process is computationally expensive. To overcome this drawback, a robust metamodel is initially constructed based on an agent-based system simulation. The simulation exhibits ED performance with various resource allocations and trains the metamodel. The metamodel is created with an ensemble of the adaptive neuro-fuzzy inference system (ANFIS), feedforward neural network (FFNN) and recurrent neural network (RNN) using the adaptive boosting (AdaBoost) ensemble algorithm. The proposed GA-based optimization approach is tested in a public ED, and it is shown to decrease the ALOS in this ED case study by 14%. Additionally, the proposed metamodel shows a 26.6% improvement compared to the average results of ANFIS, FFNN and RNN in terms of mean absolute percentage error (MAPE). Copyright © 2017 Elsevier B.V. All rights reserved.

The treatment of recurrent brain metastases with stereotactic radiosurgery.

PubMed

Loeffler, J S; Kooy, H M; Wen, P Y; Fine, H A; Cheng, C W; Mannarino, E G; Tsai, J S; Alexander, E

1990-04-01

Between May 1986 and August 1989, we treated 18 patients with 21 recurrent or persistent brain metastases with stereotactic radiosurgery using a modified linear accelerator. To be eligible for radiosurgery, patients had to have a performance status of greater than or equal to 70% and have no evidence of (or stable) systemic disease. All but one patient had received prior radiotherapy, and were treated with stereotactic radiosurgery at the time of recurrence. Polar lesions were treated only if the patient had undergone and failed previous complete surgical resection (10 patients). Single doses of radiation (900 to 2,500 cGy) were delivered to limited volumes (less than 27 cm3) using a modified 6MV linear accelerator. The most common histology of the metastatic lesion was carcinoma of the lung (seven patients), followed by carcinoma of the breast (four patients), and melanoma (four patients). With median follow-up of 9 months (range, 1 to 39), all tumors have been controlled in the radiosurgery field. Two patients failed in the immediate margin of the treated volume and were subsequently treated with surgery and implantation of 125I to control the disease. Radiographic response was dramatic and rapid in the patients with adenocarcinoma, while slight reduction and stabilization occurred in those patients with melanoma, renal cell carcinoma, and sarcoma. The majority of patients improved neurologically following treatment, and were able to be withdrawn from corticosteroid therapy. Complications were limited and transient in nature and no cases of symptomatic radiation necrosis occurred in any patient despite previous exposure to radiotherapy. Stereotactic radiosurgery is an effective and relatively safe treatment for recurrent solitary metastases and is an appealing technique for the initial management of deep-seated lesions as a boost to whole brain radiotherapy.

Outcome and toxicity of intensity modulated radiotherapy with simultaneous integrated boost in locally advanced non-small cell lung cancer patients.

PubMed

Fondevilla Soler, A; López-Guerra, J L; Dzugashvili, M; Sempere Rincón, P; Sautbaet, A; Castañeda, P; Díaz, J M; Praena-Fernandez, J M; Rivin Del Campo, E; Azinovic, I

2017-12-01

The aim of this study was to assess the feasibility and treatment outcome of intensity modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) in locally advanced non-small cell lung cancer (NSCLC) patients. A total of 64 NSCLC patients with stage IIB (3%), IIIA (36%), and IIIB (61%) were treated with concomitant (N = 47; 73%) or sequential (N = 9; 14%) chemotherapy between February 2009 and January 2014. Eight patients (13%) received RT alone. All patients received the same irradiation scheme using IMRT: prophylactic dose for mediastinum was 56 Gy at 1.65 Gy/fraction and SIB to macroscopic disease up to 68 Gy at 2 Gy/fraction. The median follow-up was 16 months (range, 1-70 months). The overall survival rate for all patients was 79% after 1 year and 46% after 2 years. Disease-free survival (DFS) was 81 and 45% after 1 and 2 years, respectively, resulting in a median DFS of 16 months. Multivariate analysis showed a statistically significant association between stage IIIB patients and a higher risk of mortality (HR 2.11; P = 0.019). In addition, T4 stage associated with higher risk of recurrence (HR 2.23; P = 0.024) while concomitant chemoradiation was associated with lower risk of any recurrence (HR 0.34; P = 0.004) No patient experienced grade ≥3 esophagitis and only 6 cases (9%) had grade 3 pneumonitis. Only having a higher lung volume was associated with higher risk of pneumonitis in the multivariate analysis (HR 16.21; P = 0.022). This study in advanced NSCLC patients shows that SIB-IMRT is an effective technique with acceptable toxicity, also when combined with chemotherapy.

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

Milne boost from Galilean gauge theory

NASA Astrophysics Data System (ADS)

Banerjee, Rabin; Mukherjee, Pradip

2018-03-01

Physical origin of Milne boost invariance of the Newton Cartan spacetime is traced to the effect of local Galilean boosts in its metric structure, using Galilean gauge theory. Specifically, we do not require any gauge field to understand Milne boost invariance.

Intensity-modulated salvage radiotherapy with simultaneous integrated boost for local recurrence of prostate carcinoma: a pilot study on the place of PET-choline for guiding target volume delineation.

PubMed

Wahart, Aurélien; Guy, Jean-Baptiste; Vallard, Alexis; Geissler, Benjamin; Ben Mrad, Majed; Falk, Alexander T; Prevot, Nathalie; de Laroche, Guy; Rancoule, Chloé; Chargari, Cyrus; Magné, Nicolas

2016-01-01

The aim of this study was to report the first cases of salvage radiotherapy (RT) using the intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) targeted on choline positron emission tomography (PET) uptake in a local recurrent prostate cancer, after a radical prostatectomy. Four patients received salvage irradiation for biochemical relapse that occurred after the initial radical prostatectomy. The relapse occurred from 10 months to 6 years with PSA levels ranging from 2.35 to 4.86 ng ml(-1). For each patient, an (18)F-choline PET-CT showed a focal choline uptake in prostatic fossa, with standardized uptake value calculated on the basis of predicted lean body mass (SUL) max of 3.3-6.8. No involved lymph node or distant metastases were diagnosed. IMRT doses were of 62.7 Gy (1.9 Gy/fraction, 33 fractions), with a SIB of 69.3 Gy (2.1 Gy/fraction, 33 fractions) to a PET-guided target volume. Acute toxicities were limited. We observed no gastrointestinal toxicity ≥grade 2 and only one grade 2 genitourinary toxicity. At 1-month follow-up evaluation, no complication and a decrease in PSA level (6.8-43.8% of the pre-therapeutic level) were reported. After 4 months, a decrease in PSA level was obtained for all the patients, ranging from 30% to 70%. At a median follow-up of 15 months, PSA level was controlled for all the patients, but one of them experienced a distant lymph node recurrence. Salvage irradiation to the prostate bed with SIB guided by PET-CT is feasible, with biological efficacy and no major acute toxicity. IMRT with PET-oriented SIB for salvage treatment of prostate cancer is possible, without major acute toxicity.

SU-E-J-124: 18F-FDG PET Imaging to Improve RT Treatment Outcome for Locally Advanced Lung Cancer

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

Shusharina, N; Khan, F; Sharp, G

2015-06-15

Purpose: To investigate spatial correlation between high uptake regions of pre- and 10-days-post therapy{sup 1} {sup 8}F-FDG PET in recurrent lung cancer and to evaluate the feasibility of dose escalation boosting only regions with high FDG uptake identified on baseline PET. Methods: Nineteen patients with stages II– IV inoperable lung cancer were selected. Volumes of interest (VOI) on pre-therapy FDG-PET were defined using an isocontour at ≥50% of SUVmax. VOI of pre- and post-therapy PET images were correlated for the extent of overlap. A highly optimized IMRT plan to 60 Gy prescribed to PTV defined on the planning CT wasmore » designed using clinical dose constraints for the organs at risk. A boost of 18 Gy was prescribed to the VOI defined on baseline PET. A composite plan of the total 78 Gy was compared with the base 60 Gy plan. Increases in dose to the lungs, spinal cord and heart were evaluated. IMRT boost plan was compared with proton RT and SBRT boost plans. Results: Overlap fraction of baseline PET VOI with the VOI on 10 days-post therapy PET was 0.8 (95% CI: 0.7 – 0.9). Using baseline VOI as a boosting volume, dose could be escalated to 78 Gy for 15 patients without compromising the dose constraints. For 4 patients, the dose limiting factors were V20Gy and Dmean for the total lung, and Dmax for the spinal cord. An increase of the dose to OARs correlated significantly with the relative size of the boost volume. Conclusion: VOI defined on baseline 18F-FDG PET by the SUVmax-≥50% isocontour may be a biological target volume for escalated radiation dose. Dose escalation to this volume may provide improved tumor control without breaching predefined dose constraints for OARs. The best treatment outcome may be achieved with proton RT for large targets and with SBRT for small targets.« less

Potential roles of hyperbaric oxygenation in the treatments of brain tumors.

PubMed

Kohshi, Kiyotaka; Beppu, Takaaki; Tanaka, Katsuyuki; Ogawa, Kazuhiko; Inoue, Osamu; Kukita, Ichiro; Clarke, Richard E

2013-01-01

Over the past 50 years hyperbaric oxygen (HBO2) therapy has been used in a wide variety of medical conditions, and one of them is cancer. Many clinical studies have been conducted to evaluate potential therapeutic effects of HBO2 as a part of cancer treatment. This review briefly summaries the potential role of HBO2 therapy in the treatment of malignant tumors and radiation injury of the brain. HBO2 therapy is used for the enhancement of radiosensitivity in the treatment of some cancers, including malignant brain tumors. Radiotherapy within 15 minutes following HBO2 exposure, a relatively new treatment regimen, has been studied at several institutes and has demonstrated promising clinical results for malignant gliomas of the brain. HBO2 therapy also increases sensitivity to some antineoplastic agents; non-randomized clinical trials using carboplatin-based chemotherapy combined with HBO2 show a significant advantage in survival for recurrent malignant gliomas. The possibilities of combining HBO2 therapy with radiotherapy and/or chemotherapy to overcome newly diagnosed and recurrent malignant gliomas deserve extensive clinical trials. HBO2 therapy also shows promising potential for the treatment and/or prevention of radiation injury of the brain after stereotactic radiosurgery for brain lesions. The possibilities with HBO2 to enhance the therapeutic effect of irradiation per se, and to even increase the radiation dose if there are ways to combat the side effects, should boost new scientific interest into the whole field of oncology looking for new armamentaria to fight cancer.

Boosted one dimensional fermionic superfluids on a lattice

NASA Astrophysics Data System (ADS)

Ray, Sayonee; Mukerjee, Subroto; Shenoy, Vijay B.

2017-09-01

We study the effect of a boost (Fermi sea displaced by a finite momentum) on one dimensional systems of lattice fermions with short-ranged interactions. In the absence of a boost such systems with attractive interactions possess algebraic superconducting order. Motivated by physics in higher dimensions, one might naively expect a boost to weaken and ultimately destroy superconductivity. However, we show that for one dimensional systems the effect of the boost can be to strengthen the algebraic superconducting order by making correlation functions fall off more slowly with distance. This phenomenon can manifest in interesting ways, for example, a boost can produce a Luther-Emery phase in a system with both charge and spin gaps by engendering the destruction of the former.

Intranasal boosting with an adenovirus-vectored vaccine markedly enhances protection by parenteral Mycobacterium bovis BCG immunization against pulmonary tuberculosis.

PubMed

Santosuosso, Michael; McCormick, Sarah; Zhang, Xizhong; Zganiacz, Anna; Xing, Zhou

2006-08-01

Parenterally administered Mycobacterium bovis BCG vaccine confers only limited immune protection from pulmonary tuberculosis in humans. There is a need for developing effective boosting vaccination strategies. We examined a heterologous prime-boost regimen utilizing BCG as a prime vaccine and our recently described adenoviral vector expressing Ag85A (AdAg85A) as a boost vaccine. Since we recently demonstrated that a single intranasal but not intramuscular immunization with AdAg85A was able to induce potent protection from pulmonary Mycobacterium tuberculosis challenge in a mouse model, we compared the protective effects of parenteral and mucosal booster immunizations following subcutaneous BCG priming. Protection by BCG prime immunization was not effectively boosted by subcutaneous BCG or intramuscular AdAg85A. In contrast, protection by BCG priming was remarkably boosted by intranasal AdAg85A. Such enhanced protection by intranasal AdAg85A was correlated to the numbers of gamma interferon-positive CD4 and CD8 T cells residing in the airway lumen of the lung. Our study demonstrates that intranasal administration of AdAg85A represents an effective way to boost immune protection by parenteral BCG vaccination.

Ten-year results of accelerated hypofractionated adjuvant whole-breast radiation with concomitant boost to the lumpectomy cavity after conserving surgery for early breast cancer.

PubMed

Cante, Domenico; Petrucci, Edoardo; Sciacero, Piera; Piva, Cristina; Ferrario, Silvia; Bagnera, Silvia; Patania, Sebastiano; Mondini, Guido; Pasquino, Massimo; Casanova Borca, Valeria; Vellani, Giorgio; La Porta, Maria Rosa; Franco, Pierfrancesco

2017-09-01

Accelerated hypofractionated whole-breast radiotherapy (WBRT) is considered a standard therapeutic option for early breast cancer (EBC) in the postoperative setting after breast conservation (BCS). A boost to the lumpectomy cavity may further increase local control. We herein report on the 10-year results of a series of EBC patients treated after BCS with hypofractionated WBRT with a concomitant photon boost to the surgical bed over 4 weeks. Between 2005 and 2007, 178 EBC patients were treated with a basic course of radiotherapy consisting of 45 Gy to the whole breast in 20 fractions (2.25 Gy daily) with an additional boost dose of 0.25 Gy delivered concomitantly to the lumpectomy cavity, for an additional dose of 5 Gy. Median follow-up period was 117 months. At 10-year, overall, cancer-specific, disease-free survival and local control were 92.2% (95% CI 88.7-93.4%), 99.2% (95% CI 96.7-99.7%), 95.5% (95% CI 91.2-97.2%) and 97.3% (95% CI 94.5-98.9%), respectively. Only eight patients recurred. Four in-breast recurrences, two axillary node relapses and two metastatic localizations were observed. Fourteen patients died during the observation period due to other causes while breast cancer-related deaths were eight. At last follow-up, ≥G2 fibrosis and telangiectasia were seen in 7% and 5% of patients. No major lung and heart toxicities were observed. Cosmetic results were excellent/good in 87.8% of patients and fair/poor in 12.2%. Hypofractionated WBRT with concomitant boost to the lumpectomy cavity after BCS in EBC led to consistent clinical results at 10 years. Hence, it can be considered a valid treatment option in this setting.

Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

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

Freedman, Gary M., E-mail: Gary.Freedman@uphs.upenn.edu; Anderson, Penny R.; Bleicher, Richard J.

Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged {>=}18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and themore » tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.« less

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis.

PubMed

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M; Lucas, Megan; Spencer, John S; Amara, Rama Rao; Plikaytis, Bonnie B; Posey, James E; Sable, Suraj B

2016-05-13

Heterologous prime-boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32-52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime-Apa-subunit-boost strategy compared to Apa-subunit-prime-BCG-boost approach. However, parenteral BCG-prime-Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime-boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime-boost regimens against tuberculosis in humans.

Postponed Is Not Canceled: Role of Craniospinal Radiation Therapy in the Management of Recurrent Infant Medulloblastoma—An Experience From the HIT-REZ 1997 and 2005 Studies

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

Müller, Klaus, E-mail: Klaus.Mueller@medizin.uni-leipzig.de; Mynarek, Martin; Zwiener, Isabella

2014-04-01

Purpose: To evaluate the efficacy of craniospinal irradiation (CSI) in the management of recurrent infant medulloblastoma after surgery and chemotherapy alone. Methods and Materials: Seventeen pediatric medulloblastoma patients registered in the HIT-REZ 1997 and 2005 studies underwent CSI as salvage treatment at first recurrence. All patients had achieved complete remission after first-line treatment consisting of surgery and chemotherapy. Eleven patients showed metastatic disease at relapse. Five patients underwent surgery prior to radiation therapy, which resulted in complete resection in 1 case. In 1 patient, complete resection of the residual tumor was performed after CSI. Eleven patients received chemotherapy prior, 6 patientsmore » during and 8 patients after CSI. All patients received CSI with a median total dose of 35.2 Gy, and all but 1 received a boost to the posterior fossa (median total dose, 55.0 Gy). Metastases were boosted with an individual radiation dose, depending on their location and extent. Results: During a median follow-up time of 6.2 years since recurrence, 11 patients showed progressive disease and died. Median progression-free (overall) survival was 2.9 ± 1.1 (3.8 ± 0.8) years. Progression-free survival (PFS) rates at 1, 3, and 5 years were 88% ± 8%, 46% ± 12%, and 40% ± 12%, respectively. Overall survival (OS) rates at 1, 3, and 5 years were 94% ± 6%, 58% ± 12%, and 39% ± 12%, respectively. For 11 patients with classic medulloblastoma, 3-year (and 5-year) PFS and OS were 62% ± 15% and 72% ± 14% (52% ± 16% and 51% ± 16%), respectively. On univariate analysis, metastatic disease was not associated with poorer progression-free and overall survival. Conclusions: Our results suggest that salvage treatment of relapsed medulloblastomas consisting of CSI and chemotherapy offers a second chance for cure, even for patients with classic histological findings. Metastatic disease at relapse did not have an impact on survival. However, this may be explained by the small number of patients.« less

Ten-year results of treatment of ductal carcinoma in situ (DCIS) of the breast with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Arcicasa, M; Coghetto, F; Valdagni, R; Maluta, S; Di Marco, A

1997-09-01

The optimal treatment of ductal carcinoma in situ (DCIS) of the breast has not yet been established. The effectiveness of adjuvant postoperative radiotherapy after conservative surgery is debated. Few data are available in Italy on the combined treatment. A collaborative multi-institutional study on this issue in 10 radiation oncology departments of the north-east of Italy was conducted. One hundred and thirty nine women with DCIS of the breast were treated between 1980 and 1990. Age ranged between 28 and 88 years (median 50 years). Surgical procedures were: quadrantectomy in 108, lumpectomy in 22 and wide excision in 9 cases. The axilla was surgically staged in 97 cases: all the patients were node-negative. Radiation therapy was delivered with 60Co units (78%) or 6 MV linear accelerators (22%) for a median total dose to the entire breast of 50 Gy (mean 49.48 Gy; range 45-60 Gy). The tumour bed was boosted in 109 cases (78%) at a dose of 4-30 Gy (median 10 Gy) for a minimum tumour dose of 58 Gy. Median follow-up was 81 months. Thirteen local recurrences were recorded, 7 intraductal and 6 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease. Actuarial overall, cause-specific and recurrence-free survival at 10 years are of 93%, 100% and 86%, respectively. The results of this retrospective multicentric study substantiate the favourable data reported in the literature and confirm the efficacy of the breast-conserving treatment of DCIS employing conservative surgery and adjuvant radiation therapy.

Meta-Analysis of Cell-based CaRdiac stUdiEs (ACCRUE) in patients with acute myocardial infarction based on individual patient data.

PubMed

Gyöngyösi, Mariann; Wojakowski, Wojciech; Lemarchand, Patricia; Lunde, Ketil; Tendera, Michal; Bartunek, Jozef; Marban, Eduardo; Assmus, Birgit; Henry, Timothy D; Traverse, Jay H; Moyé, Lemuel A; Sürder, Daniel; Corti, Roberto; Huikuri, Heikki; Miettinen, Johanna; Wöhrle, Jochen; Obradovic, Slobodan; Roncalli, Jérome; Malliaras, Konstantinos; Pokushalov, Evgeny; Romanov, Alexander; Kastrup, Jens; Bergmann, Martin W; Atsma, Douwe E; Diederichsen, Axel; Edes, Istvan; Benedek, Imre; Benedek, Theodora; Pejkov, Hristo; Nyolczas, Noemi; Pavo, Noemi; Bergler-Klein, Jutta; Pavo, Imre J; Sylven, Christer; Berti, Sergio; Navarese, Eliano P; Maurer, Gerald

2015-04-10

The meta-Analysis of Cell-based CaRdiac study is the first prospectively declared collaborative multinational database, including individual data of patients with ischemic heart disease treated with cell therapy. We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI), including individual patient data from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). The primary end point was freedom from combined major adverse cardiac and cerebrovascular events (including all-cause death, AMI recurrance, stroke, and target vessel revascularization). The secondary end point was freedom from hard clinical end points (death, AMI recurrence, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy end points included changes in end-diastolic volume, end-systolic volume, and ejection fraction, analyzed with random-effects meta-analyses and ANCOVA. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on major adverse cardiac and cerebrovascular events (14.0% versus 16.3%; hazard ratio, 0.86; 95% confidence interval, 0.63-1.18) or death (1.4% versus 2.1%) or death/AMI recurrence/stroke (2.9% versus 4.7%) was identified in comparison with controls. No changes in ejection fraction (mean difference: 0.96%; 95% confidence interval, -0.2 to 2.1), end-diastolic volume, or systolic volume were observed compared with controls. These results were not influenced by anterior AMI location, reduced baseline ejection fraction, or the use of MRI for assessing left ventricular parameters. This meta-analysis of individual patient data from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01098591. © 2015 American Heart Association, Inc.

A core/satellite multifunctional nanotheranostic for in vivo imaging and tumor eradication by radiation/photothermal synergistic therapy.

PubMed

Xiao, Qingfeng; Zheng, Xiangpeng; Bu, Wenbo; Ge, Weiqiang; Zhang, Shengjian; Chen, Feng; Xing, Huaiyong; Ren, Qingguo; Fan, Wenpei; Zhao, Kuaile; Hua, Yanqing; Shi, Jianlin

2013-09-04

To integrate photothermal ablation (PTA) with radiotherapy (RT) for improved cancer therapy, we constructed a novel multifunctional core/satellite nanotheranostic (CSNT) by decorating ultrasmall CuS nanoparticles onto the surface of a silica-coated rare earth upconversion nanoparticle. These CSNTs could not only convert near-infrared light into heat for effective thermal ablation but also induce a highly localized radiation dose boost to trigger substantially enhanced radiation damage both in vitro and in vivo. With the synergistic interaction between PTA and the enhanced RT, the tumor could be eradicated without visible recurrence in 120 days. Notably, hematological analysis and histological examination unambiguously revealed their negligible toxicity to the mice within a month. Moreover, the novel CSNTs facilitate excellent upconversion luminescence/magnetic resonance/computer tomography trimodal imagings. This multifunctional nanocomposite is believed to be capable of playing a vital role in future oncotherapy by the synergistic effects between enhanced RT and PTA under the potential trimodal imaging guidance.

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

Recombinant BCG prime and PPE protein boost provides potent protection against acute Mycobacterium tuberculosis infection in mice.

PubMed

Yang, Enzhuo; Gu, Jin; Wang, Feifei; Wang, Honghai; Shen, Hongbo; Chen, Zheng W

2016-04-01

Since BCG, the only vaccine widely used against tuberculosis (TB) in the world, provides varied protective efficacy and may not be effective for inducing long-term cellular immunity, it is in an urgent need to develop more effective vaccines and more potent immune strategies against TB. Prime-boost is proven to be a good strategy by inducing long-term protection. In this study, we tested the protective effect against Mycobacterium tuberculosis (Mtb) challenge of prime-boost strategy by recombinant BCG (rBCG) expressing PPE protein Rv3425 fused with Ag85B and Rv3425. Results showed that the prime-boost strategy could significantly increase the protective efficiency against Mtb infection, characterized by reduction of bacterial load in lung and spleen, attenuation of tuberculosis lesions in lung tissues. Importantly, we found that Rv3425 boost, superior to Ag85B boost, provided better protection against Mtb infection. Further research proved that rBCG prime-Rv3425 boost could obviously increase the expansion of lymphocytes, significantly induce IL-2 production by lymphocytes upon PPD stimulation, and inhibit IL-6 production at an early stage. It implied that rBCG prime-Rv3425 boost opted to induce Th1 immune response and provided a long-term protection against TB. These results implicated that rBCG prime-Rv3425 boost is a potent and promising strategy to prevent acute Mtb infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Boosting BCG-primed responses with a subunit Apa vaccine during the waning phase improves immunity and imparts protection against Mycobacterium tuberculosis

PubMed Central

Nandakumar, Subhadra; Kannanganat, Sunil; Dobos, Karen M.; Lucas, Megan; Spencer, John S.; Amara, Rama Rao; Plikaytis, Bonnie B.; Posey, James E.; Sable, Suraj B.

2016-01-01

Heterologous prime–boosting has emerged as a powerful vaccination approach against tuberculosis. However, optimal timing to boost BCG-immunity using subunit vaccines remains unclear in clinical trials. Here, we followed the adhesin Apa-specific T-cell responses in BCG-primed mice and investigated its BCG-booster potential. The Apa-specific T-cell response peaked 32–52 weeks after parenteral or mucosal BCG-priming but waned significantly by 78 weeks. A subunit-Apa-boost during the contraction-phase of BCG-response had a greater effect on the magnitude and functional quality of specific cellular and humoral responses compared to a boost at the peak of BCG-response. The cellular response increased following mucosal BCG-prime–Apa-subunit-boost strategy compared to Apa-subunit-prime–BCG-boost approach. However, parenteral BCG-prime–Apa-subunit-boost by a homologous route was the most effective strategy in-terms of enhancing specific T-cell responses during waning in the lung and spleen. Two Apa-boosters markedly improved waning BCG-immunity and significantly reduced Mycobacterium tuberculosis burdens post-challenge. Our results highlight the challenges of optimization of prime–boost regimens in mice where BCG drives persistent immune-activation and suggest that boosting with a heterologous vaccine may be ideal once the specific persisting effector responses are contracted. Our results have important implications for design of prime–boost regimens against tuberculosis in humans. PMID:27173443

Pulsed reduced dose-rate radiotherapy as re-irradiation for brain metastasis in a patient with lung squamous-celled carcinoma.

PubMed

Li, Guang-Hui; Liu, Yong; Tang, Jin-Liang; Zhang, Dong; Zhou, Pu; Yang, Ding-Qiang; Ma, Chuan-Kun

2012-09-01

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.

Future of an “Asymptomatic” T-cell Epitope-Based Therapeutic Herpes Simplex Vaccine

PubMed Central

Dervillez, Xavier; Gottimukkala, Chetan; Kabbara, Khaled W.; Nguyen, Chelsea; Badakhshan, Tina; Kim, Sarah M.; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

2012-01-01

Summary Considering the limited success of the recent herpes clinical vaccine trial [1], new vaccine strategies are needed. Infections with herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) in the majority of men and women are usually asymptomatic and results in lifelong viral latency in neurons of sensory ganglia (SG). However, in a minority of men and women HSV spontaneous reactivation can cause recurrent disease (i.e., symptomatic individuals). Our recent findings show that T cells from symptomatic and asymptomatic men and women (i.e. those with and without recurrences, respectively) recognize different herpes epitopes. This finding breaks new ground and opens new doors to assess a new vaccine strategy: mucosal immunization with HSV-1 & HSV-2 epitopes that induce strong in vitro CD4 and CD8 T cell responses from PBMC derived from asymptomatic men and women (designated here as “asymptomatic” protective epitopes”) could boost local and systemic “natural” protective immunity, induced by wild-type infection. Here we highlight the rationale and the future of our emerging “asymptomatic” T cell epitope-based mucosal vaccine strategy to decrease recurrent herpetic disease. PMID:22701511

Probiotics to prevent urinary tract infections: the rationale and evidence.

PubMed

Reid, Gregor; Bruce, Andrew W

2006-02-01

For over 30 years, urologists have recognized in females, that urinary pathogens almost always infect the host through ascension from the rectum, vagina to the urethra and bladder. Likewise, the Lactobacillus organisms that predominate in the vagina of healthy women, spread from the rectum and perineum and form a barrier in the vagina to bladder entry by uropathogens. The concept of artificially boosting the lactobacilli numbers through probiotic instillation has long been conceived, but only in recent years shown to be possible. Not all lactobacilli are effective, and to date clinical efficacy only exists for Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri B-54 and RC-14. These strains are only commercially available in Austria, and therefore for most urologists, while some probiotic organisms may reduce the recurrences of bladder cancer or oxaluria, no probiotics can be recommended widely to prevent UTI at present.

Conservative treatment for breast cancer. Complications requiring reconstructive surgery

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

Bostwick, J. 3d.; Paletta, C.; Hartrampf, C.R.

Women who select conservative treatment for carcinoma of the breast (tumor excision followed by supervoltage radiation therapy) place a premium on breast preservation and aesthetics. When local control fails and they require a mastectomy, or when the aesthetic appearance is unacceptable, they may request breast reconstruction. The goal of this study is to evaluate a series of 10 patients who required reconstructive breast surgery after complications of conservative treatment. Patient classification: I. Breast or chest wall necrosis (3). II. Breast fibrosis and gross asymmetry (3). III. Local recurrence of breast cancer (5). IV. Positive margins after the initial lumpectomy (1).more » The mean age was 34 years. Radiation dosage average was 5252 rads with two patients receiving iridium-192 implant boosts. The reconstructive management was complex and usually required a major musculocutaneous flap because of the radiation effects.« less

Effect of pole zero location on system dynamics of boost converter for micro grid

NASA Astrophysics Data System (ADS)

Lavanya, A.; Vijayakumar, K.; Navamani, J. D.; Jayaseelan, N.

2018-04-01

Green clean energy like photo voltaic, wind energy, fuel cell can be brought together by microgrid.For low voltage sources like photovoltaic cell boost converter is very much essential. This paper explores the dynamic analysis of boost converter in a continuous conduction mode (CCM). The transient performance and stability analysis is carried out in this paper using time domain analysis and frequency domain analysis techniques. Boost converter is simulated using both PSIM and MATLAB software. Furthermore, state space model obtained and the transfer function is derived. The converter behaviour when a step input is applied is analyzed and stability of the converter is analyzed from bode plot frequency for open loop. Effect of the locations of poles and zeros in the transfer function of boost converter and how the performance parameters are affected is discussed in this paper. Closed loop performance with PI controller is also analyzed for boost converter.

Modeling the effect of boost timing in murine irradiated sporozoite prime-boost vaccines

PubMed Central

Zhang, Min; Herrero, Miguel A.; Acosta, Francisco J.; Tsuji, Moriya

2018-01-01

Vaccination with radiation-attenuated sporozoites has been shown to induce CD8+ T cell-mediated protection against pre-erythrocytic stages of malaria. Empirical evidence suggests that successive inoculations often improve the efficacy of this type of vaccines. An initial dose (prime) triggers a specific cellular response, and subsequent inoculations (boost) amplify this response to create a robust CD8+ T cell memory. In this work we propose a model to analyze the effect of T cell dynamics on the performance of prime-boost vaccines. This model suggests that boost doses and timings should be selected according to the T cell response elicited by priming. Specifically, boosting during late stages of clonal contraction would maximize T cell memory production for vaccines using lower doses of irradiated sporozoites. In contrast, single-dose inoculations would be indicated for higher vaccine doses. Experimental data have been obtained that support theoretical predictions of the model. PMID:29329308

Black String and Velocity Frame Dragging

NASA Astrophysics Data System (ADS)

Lee, Jungjai; Kim, Hyeong-Chan

We investigate velocity frame dragging with the boosted Schwarzschild black string solution and the boosted Kaluza-Klein bubble solution, in which a translational symmetry along the boosted z-coordinate is implemented. The velocity frame dragging effect can be nullified by the motion of an observer using the boost symmetry along the z-coordinate if it is not compact. However, in spacetime with the compact z-coordinate, we show that the effect cannot be removed since the compactification breaks the global Lorentz boost symmetry. As a result, the comoving velocity depends on r and the momentum parameter along the z-coordinate becomes an observer independent characteristic quantity of the black string and bubble solutions. The dragging induces a spherical ergo-region around the black string.

Cytokines in immunogenic cell death: Applications for cancer immunotherapy.

PubMed

Showalter, Anne; Limaye, Arati; Oyer, Jeremiah L; Igarashi, Robert; Kittipatarin, Christina; Copik, Alicja J; Khaled, Annette R

2017-09-01

Despite advances in treatments like chemotherapy and radiotherapy, metastatic cancer remains a leading cause of death for cancer patients. While many chemotherapeutic agents can efficiently eliminate cancer cells, long-term protection against cancer is not achieved and many patients experience cancer recurrence. Mobilizing and stimulating the immune system against tumor cells is one of the most effective ways to protect against cancers that recur and/or metastasize. Activated tumor specific cytotoxic T lymphocytes (CTLs) can seek out and destroy metastatic tumor cells and reduce tumor lesions. Natural Killer (NK) cells are a front-line defense against drug-resistant tumors and can provide tumoricidal activity to enhance tumor immune surveillance. Cytokines like IFN-γ or TNF play a crucial role in creating an immunogenic microenvironment and therefore are key players in the fight against metastatic cancer. To this end, a group of anthracyclines or treatments like photodynamic therapy (PDT) exert their effects on cancer cells in a manner that activates the immune system. This process, known as immunogenic cell death (ICD), is characterized by the release of membrane-bound and soluble factors that boost the function of immune cells. This review will explore different types of ICD inducers, some in clinical trials, to demonstrate that optimizing the cytokine response brought about by treatments with ICD-inducing agents is central to promoting anti-cancer immunity that provides long-lasting protection against disease recurrence and metastasis. Copyright © 2017. Published by Elsevier Ltd.

Radiotherapy of Ductal Carcinoma In Situ

PubMed Central

Krug, David; Souchon, Rainer

2015-01-01

Summary Ductal carcinoma in situ (DCIS) is a heterogeneous disease in both its biology and clinical course. In the past, recurrence rates after breast-conserving surgery have been as high as 30% after 10 years. The introduction of mammography screening and advances in imaging have led to an increase in the detection of DCIS. The focus of this review is on the role of radiotherapy in the multidisciplinary treatment, including current developments in hypofractionation and boost delivery, and attempts to define low-risk subsets of DCIS for which the need for adjuvant radiation is repeatedly questioned. PMID:26600762

TU-F-CAMPUS-T-05: Dose Escalation to Biological Tumor Volumes of Prostate Cancer Patients Using Gold Nanoparticles

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

Jermoumi, M; Ngwa, W; Department of Radiation Oncology, Dana Farber Cancer Insitute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA

2015-06-15

Purpose: Studies have shown that radiation boosting could help reduce prostate cancer (PCa) recurrence. Biological tumor volumes (BTV) are a high priority for such radiation boosting. The purpose of this study is to investigate the potential of radiation boosting of real patient BTVs using gold nanoparticles (GNP) released from gold-loaded brachytherapy spacers (GBS) during brachytherapy. Methods: The BTVs of 12 patients having prostate adenocarcinoma identified with positron emission tomography (PET) and CT scanner using C-11 labeled tracer [11C]acetate were investigated. The initial GNP concentration and time to achieve a dose enhancement effect (DEF) of 2 was simulated using the freelymore » downloadable software RAID APP. The investigations were carried out for low dose rate (LDR) brachytherapy sources (BTS) described in AAPM Task Group report 43: Cs-131, I-125, and Pd-103. In first case, we used 7 mg/g and 18 mg/g of GNP initial concentrations to estimate the time needed for released GNP to achieve a DEF of 2 for the different BTS, and compare with clinically relevant treatment times. In second case, we calculated the initial concentration of GNPs needed to achieve a DEF of 2 during the time the BTS would typically deliver 50%, 70% and 90% of the total dose. Results: For an initial concentration of 18 mg/g, when using Cs-131, and Pd-103, a DEF of 2 could only be achieved for BTV of 3.3 cm3 and 1 cm3 respectively. Meanwhile a DEF of 2 could be achieved for all 12 BTVs when using I-125. To achieve a DEF of 2 for all patients using Cs-131 and Pd-103, much higher initial concentrations would have to be used than have been typically employed in pre-clinical studies. Conclusion: The I-125 is the most viable BTS that can be employed with GBS to guide dose painting treatment planning for localized PCa.« less

CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.

PubMed

Cai, Gang; Zhu, Ji; Palmer, Joshua D; Xu, Ye; Hu, Weigang; Gu, Weilie; Cai, Sanjun; Zhang, Zhen

2015-02-28

This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.

Boosted Schwarzschild metrics from a Kerr–Schild perspective

NASA Astrophysics Data System (ADS)

Mädler, Thomas; Winicour, Jeffrey

2018-02-01

The Kerr–Schild version of the Schwarzschild metric contains a Minkowski background which provides a definition of a boosted black hole. There are two Kerr–Schild versions corresponding to ingoing or outgoing principle null directions. We show that the two corresponding Minkowski backgrounds and their associated boosts have an unexpected difference. We analyze this difference and discuss the implications in the nonlinear regime for the gravitational memory effect resulting from the ejection of massive particles from an isolated system. We show that the nonlinear effect agrees with the linearized result based upon the retarded Green function only if the velocity of the ejected particle corresponds to a boost symmetry of the ingoing Minkowski background. A boost with respect to the outgoing Minkowski background is inconsistent with the absence of ingoing radiation from past null infinity.

Radiotherapy Breast Boost With Reduced Whole-Breast Dose Is Associated With Improved Cosmesis: The Results of a Comprehensive Assessment From the St. George and Wollongong Randomized Breast Boost Trial

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

Hau, Eric, E-mail: helloerico@yahoo.com; Browne, Lois H.; Khanna, Sam

Purpose: To evaluate comprehensively the effect of a radiotherapy boost on breast cosmetic outcomes after 5 years in patients treated with breast-conserving surgery. Methods: The St. George and Wollongong trial (NCT00138814) randomized 688 patients with histologically proven Tis-2, N 0-1, M0 carcinoma to the control arm of 50 Gy in 25 fractions (342 patients) and the boost arm of 45 Gy in 25 fractions to the whole breast followed by a 16 Gy in 8 fraction electron boost (346 patients). Five-year cosmetic outcomes were assessed by a panel subjectively in 385 patients and objectively using pBRA (relative breast retraction assessment).more » A subset of patients also had absolute BRA measurements. Clinician assessment and patient self-assessment of overall cosmetic and specific items as well as computer BCCT.core analysis were also performed. Results: The boost arm had improved cosmetic overall outcomes as scored by the panel and BCCT.core software with 79% (p = 0.016) and 81% (p = 0.004) excellent/good cosmesis respectively compared with 68% in no-boost arm. The boost arm also had lower pBRA and BRA values with a mean difference of 0.60 and 1.82 mm, respectively, but was not statistically significant. There was a very high proportion of overall excellent/good cosmetic outcome in 95% and 93% in the boost and no-boost arms using patient self-assessment. However, no difference in overall and specific items scored by clinician assessment and patient self-assessment was found. Conclusion: The results show the negative cosmetic effect of a 16-Gy boost is offset by a lower whole-breast dose of 45 Gy.« less

Redefining diabetes and the concept of self-management from a patient's perspective: implications for disease risk factor management.

PubMed

Masupe, T K; Ndayi, K; Tsolekile, L; Delobelle, P; Puoane, T

2018-02-01

The colliding epidemics of non-communicable diseases including diabetes with chronic infectious diseases in Sub-Saharan Africa requires contextualized innovative disease management strategies. This qualitative study conducted in a peri-urban township near Cape Town, South Africa aimed to identify and gain in-depth understanding of contextual and environmental issues pertinent to the patient that could influence Type 2-diabetes mellitus (T2DM) care and self-management. Participants included purposively sampled diabetics or pre-diabetics from the community, PURE study database, facility health club and health care providers. Data collection employed in-depth interviews, focus group discussions (FGDs) using structured interviews and FGD topic guides. Thematic data analysis was done to identify recurrent themes. Themes identified: knowledge and awareness about T2DM; health-seeking behaviour; weight perceptions; healthy lifestyles; self-management; health education needs and health care provider experiences. Patients defined T2DM as a physically and emotionally dangerous disease caused by socio-cultural factors, influenced by the sufferers' food and socio-cultural environment with significance placed on physical, social and emotional effects of T2DM diagnosis. Patient-centred definition of T2DM is key to enhancing T2DM self-management. Patients suggested that personally rewarding benefits of physical activity and healthy diet such as anti-ageing, brain boosting, energy boosting which are commonly harnessed by food, tobacco and beauty industry should be considered in T2DM self-management strategies.

Distribution of Health Effects and Cost-effectiveness of Varicella Vaccination are Shaped by the Impact on Herpes Zoster.

PubMed

van Lier, Alies; Lugnér, Anna; Opstelten, Wim; Jochemsen, Petra; Wallinga, Jacco; Schellevis, François; Sanders, Elisabeth; de Melker, Hester; van Boven, Michiel

2015-10-01

Varicella zoster virus (VZV) is the etiological agent of varicella and herpes zoster (HZ). It has been hypothesised that immune boosting of latently infected persons by contact with varicella reduces the probability of HZ. If true, universal varicella vaccination may increase HZ incidence due to reduced VZV circulation. To inform decision-making, we conduct cost-effectiveness analyses of varicella vaccination, including effects on HZ. Effects of varicella vaccination are simulated with a dynamic transmission model, parameterised with Dutch VZV seroprevalence and HZ incidence data, and linked to an economic model. We consider vaccination scenarios that differ by whether or not they include immune boosting, and reactivation of vaccine virus. Varicella incidence decreases after introduction of vaccination, while HZ incidence may increase or decrease depending on whether or not immune boosting is present. Without immune boosting, vaccination is expected to be cost-effective or even cost-saving. With immune boosting, vaccination at 95% coverage is not expected to be cost-effective, and may even cause net health losses. Cost-effectiveness of varicella vaccination depends strongly on the impact on HZ and the economic time horizon. Our findings reveal ethical dilemmas as varicella vaccination may result in unequal distribution of health effects between generations.

Relationship of environmental tobacco smoke to otitis media (OM) in children.

PubMed

Csákányi, Zsuzsanna; Czinner, Antal; Spangler, John; Rogers, Todd; Katona, Gábor

2012-07-01

Many, but not all, studies have found a correlation between environmental tobacco smoke (ETS) and acute otitis media (AOM) and other adverse otologic outcomes. Given its high personal and societal costs and the divergent findings of the effect of ETS on middle ear disease, the aim of the current study was to assess the impact and possible determinant factors of ETS on recurrent (two or more) episodes of AOM. The study was performed at Heim Pal Children's Hospital, Ear, Nose and Throat (ENT) Department, Budapest, Hungary. Caregivers of a convenience sample of 412 children attending the ENT outpatient clinic were surveyed via a 22-item questionnaire regarding demographics, socioeconomics, and smoking behaviours of the child's family; as well as care-givers' self report of the number of AOM episodes of the child. Of the 412 participants, 155 (38%) children's parents smoked. In bivariate analysis, two or more episodes of AOM correlated with reported hearing problems, day care enrolment, parental employment and increased age of the child. In multivariate logistic regression, parental smoking more than doubled a child's risk for recurrent AOM while increased maternal employment (e.g. part-time or full-time versus unemployed) boosted risk up to fourfold. Among children whose parents smoked, half-packs of cigarettes smoked per day and day care attendance doubled or nearly tripled, respectively, the risk of recurrent AOM episodes. Childhood exposure to ETS is high among an ENT clinic population of Hungarian children. Such exposure correlates with AOM episodes, ENT operations and conductive hearing loss. Data such as these argue for strict laws smoke-free laws not only in Hungary, but also in Europe and around the world. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Hypofractionated Radiation Therapy for Breast Ductal Carcinoma In Situ

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

Hathout, Lara; Hijal, Tarek; Théberge, Valérie

2013-12-01

Purpose: Conventional radiation therapy (RT) administered in 25 fractions after breast-conserving surgery (BCS) is the standard treatment for ductal carcinoma in situ (DCIS) of the breast. Although accelerated hypofractionated regimens in 16 fractions have been shown to be equivalent to conventional RT for invasive breast cancer, few studies have reported results of using hypofractionated RT in DCIS. Methods and Materials: In this multicenter collaborative effort, we retrospectively reviewed the records of all women with DCIS at 3 institutions treated with BCS followed by hypofractionated whole-breast RT (WBRT) delivered in 16 fractions. Results: Between 2003 and 2010, 440 patients with DCISmore » underwent BCS followed by hypofractionated WBRT in 16 fractions for a total dose of 42.5 Gy (2.66 Gy per fraction). Boost RT to the surgical bed was given to 125 patients (28%) at a median dose of 10 Gy in 4 fractions (2.5 Gy per fraction). After a median follow-up time of 4.4 years, 14 patients had an ipsilateral local relapse, resulting in a local recurrence-free survival of 97% at 5 years. Positive surgical margins, high nuclear grade, age less than 50 years, and a premenopausal status were all statistically associated with an increased occurrence of local recurrence. Tumor hormone receptor status, use of adjuvant hormonal therapy, and administration of additional boost RT did not have an impact on local control in our cohort. On multivariate analysis, positive margins, premenopausal status, and nuclear grade 3 tumors had a statistically significant worse local control rate. Conclusions: Hypofractionated RT using 42.5 Gy in 16 fractions provides excellent local control for patients with DCIS undergoing BCS.« less

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

Johnson, D.W.; Safai, C.; Goffinet, D.R.

Eleven patients with obstructive jaundice from unresectable cholangiocarcinoma, metastatic porta hepatis adenopathy, or direct compression from a pancreatic malignancy were treated at the Stanford University Medical Center from 1978-1983 with an external drainage procedure followed by high-dose external-beam radiotherapy and by an intracavitary boost to the site of obstruction with Iridium/sup 192/ (Ir/sup 192/). A median dose of 5000 cGy was delivered with 4-6 Mv photons to the tumor bed and regional lymphatics in 9 patients, 1 patient received 2100 cGy to the liver in accelerated fractions because of extensive intrahepatic disease, and 1 patient received 7000 equivalent cGy tomore » his pancreatic tumor bed and regional lymphatics with neon heavy particles. An Ir/sup 192/ wire source later delivered a 3100-10,647 cGy boost to the site of biliary obstruction in each patient, for a mean combined dose of 10,202 cGy to a point 5 mm from the line source. Few acute complications were noted, but 3/11 patients (27%) subsequently developed upper gastrointestinal bleeding from duodenitis or frank duodenal ulceration 4 weeks, 4 months, and 7.5 months following treatment. Eight patients died - 5 with local recurrence +/- distant metastasis, 2 with sepsis, and 1 with widespread systemic metastasis. Autopsies revealed no evidence of biliary tree obstruction in 3/3 patients. Evolution of radiation treatment technqiues for biliary obstruction in the literature is reviewed. High-dose external-beam therapy followed by high-dose Ir/sup 192/ intracavitary boost is well tolerated and provides significant palliation.« less

An efficient ensemble learning method for gene microarray classification.

PubMed

Osareh, Alireza; Shadgar, Bita

2013-01-01

The gene microarray analysis and classification have demonstrated an effective way for the effective diagnosis of diseases and cancers. However, it has been also revealed that the basic classification techniques have intrinsic drawbacks in achieving accurate gene classification and cancer diagnosis. On the other hand, classifier ensembles have received increasing attention in various applications. Here, we address the gene classification issue using RotBoost ensemble methodology. This method is a combination of Rotation Forest and AdaBoost techniques which in turn preserve both desirable features of an ensemble architecture, that is, accuracy and diversity. To select a concise subset of informative genes, 5 different feature selection algorithms are considered. To assess the efficiency of the RotBoost, other nonensemble/ensemble techniques including Decision Trees, Support Vector Machines, Rotation Forest, AdaBoost, and Bagging are also deployed. Experimental results have revealed that the combination of the fast correlation-based feature selection method with ICA-based RotBoost ensemble is highly effective for gene classification. In fact, the proposed method can create ensemble classifiers which outperform not only the classifiers produced by the conventional machine learning but also the classifiers generated by two widely used conventional ensemble learning methods, that is, Bagging and AdaBoost.

Scaling Trends and Tradeoffs between Short Channel Effect and Channel Boosting Characteristics in Sub-20 nm Bulk/Silicon-on-Insulator NAND Flash Memory

NASA Astrophysics Data System (ADS)

Miyaji, Kousuke; Hung, Chinglin; Takeuchi, Ken

2012-04-01

The scaling trends and limitation in sub-20 nm a bulk and silicon-on-insulator (SOI) NAND flash memory is studied by the three-dimensional (3D) device simulation focusing on short channel effects (SCE), channel boost leakage and channel voltage boosting characteristics during the program-inhibit operation. Although increasing punch-through stopper doping concentration is effective for suppressing SCE in bulk NAND cells, the generation of junction leakage becomes serious. On the other hand, SCE can be suppressed by thinning the buried oxide (BOX) in SOI NAND cells. However, the boosted channel voltage decreases by the higher BOX capacitance. It is concluded that the scaling limitation is dominated by the junction leakage and channel boosting capability for bulk and SOI NAND flash cells, respectively, and the scaling limit is decreased to 9 nm using SOI NAND flash memory cells from 13 nm in bulk NAND flash memory cells.

Clinically Significant Prostate Cancer Local Recurrence After Radiation Therapy Occurs at the Site of Primary Tumor: Magnetic Resonance Imaging and Step-Section Pathology Evidence

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

Pucar, Darko; Hricak, Hedvig; Shukla-Dave, Amita

2007-09-01

Purpose: To determine whether prostate cancer local recurrence after radiation therapy (RT) occurs at the site of primary tumor by retrospectively comparing the tumor location on pre-RT and post-RT magnetic resonance imaging (MRI) and using step-section pathology after salvage radical prostatectomy (SRP) as the reference standard. Methods and Materials: Nine patients with localized prostate cancer were treated with intensity modulated RT (69-86.4 Gy), and had pre-RT and post-RT prostate MRI, biopsy-proven local recurrence, and SRP. The location and volume of lesions on pre-RT and post-RT MRI were correlated with step-section pathology findings. Tumor foci >0.2 cm{sup 3} and/or resulting inmore » extraprostatic disease on pathology were considered clinically significant. Results: All nine significant tumor foci (one in each patient; volume range, 0.22-8.63 cm{sup 3}) were detected both on pre-RT and post-RT MRI and displayed strikingly similar appearances on pre-RT and post-RT MRI and step-section pathology. Two clinically insignificant tumor foci ({<=}0.06 cm{sup 3}) were not detected on imaging. The ratios between tumor volumes on pathology and on post-RT MRI ranged from 0.52 to 2.80. Conclusions: Our study provides a direct visual confirmation that clinically significant post-RT local recurrence occurs at the site of primary tumor. Our results are in agreement with reported clinical and pathologic results and support the current practice of boosting the radiation dose within the primary tumor using imaging guidance. They also suggest that monitoring of primary tumor with pre-RT and post-RT MRI could lead to early detection of local recurrence amenable to salvage treatment.« less

HIV-1 gp120 and Modified Vaccinia Virus Ankara (MVA) gp140 Boost Immunogens Increase Immunogenicity of a DNA/MVA HIV-1 Vaccine.

PubMed

Shen, Xiaoying; Basu, Rahul; Sawant, Sheetal; Beaumont, David; Kwa, Sue Fen; LaBranche, Celia; Seaton, Kelly E; Yates, Nicole L; Montefiori, David C; Ferrari, Guido; Wyatt, Linda S; Moss, Bernard; Alam, S Munir; Haynes, Barton F; Tomaras, Georgia D; Robinson, Harriet L

2017-12-15

An important goal of human immunodeficiency virus (HIV) vaccine design is identification of strategies that elicit effective antiviral humoral immunity. One novel approach comprises priming with DNA and boosting with modified vaccinia virus Ankara (MVA) expressing HIV-1 Env on virus-like particles. In this study, we evaluated whether the addition of a gp120 protein in alum or MVA-expressed secreted gp140 (MVAgp140) could improve immunogenicity of a DNA prime-MVA boost vaccine. Five rhesus macaques per group received two DNA primes at weeks 0 and 8 followed by three MVA boosts (with or without additional protein or MVAgp140) at weeks 18, 26, and 40. Both boost immunogens enhanced the breadth of HIV-1 gp120 and V1V2 responses, antibody-dependent cellular cytotoxicity (ADCC), and low-titer tier 1B and tier 2 neutralizing antibody responses. However, there were differences in antibody kinetics, linear epitope specificity, and CD4 T cell responses between the groups. The gp120 protein boost elicited earlier and higher peak responses, whereas the MVAgp140 boost resulted in improved antibody durability and comparable peak responses after the final immunization. Linear V3 specific IgG responses were particularly enhanced by the gp120 boost, whereas the MVAgp140 boost also enhanced responses to linear C5 and C2.2 epitopes. Interestingly, gp120, but not the MVAgp140 boost, increased peak CD4 + T cell responses. Thus, both gp120 and MVAgp140 can augment potential protection of a DNA/MVA vaccine by enhancing gp120 and V1/V2 antibody responses, whereas potential protection by gp120, but not MVAgp140 boosts, may be further impacted by increased CD4 + T cell responses. IMPORTANCE Prior immune correlate analyses with humans and nonhuman primates revealed the importance of antibody responses in preventing HIV-1 infection. A DNA prime-modified vaccinia virus Ankara (MVA) boost vaccine has proven to be potent in eliciting antibody responses. Here we explore the ability of boosts with recombinant gp120 protein or MVA-expressed gp140 to enhance antibody responses elicited by the GOVX-B11 DNA prime-MVA boost vaccine. We found that both types of immunogen boosts enhanced potentially protective antibody responses, whereas the gp120 protein boosts also increased CD4 + T cell responses. Our data provide important information for HIV vaccine designs that aim for effective and balanced humoral and T cell responses. Copyright © 2017 Shen et al.

An Update on Statistical Boosting in Biomedicine.

PubMed

Mayr, Andreas; Hofner, Benjamin; Waldmann, Elisabeth; Hepp, Tobias; Meyer, Sebastian; Gefeller, Olaf

2017-01-01

Statistical boosting algorithms have triggered a lot of research during the last decade. They combine a powerful machine learning approach with classical statistical modelling, offering various practical advantages like automated variable selection and implicit regularization of effect estimates. They are extremely flexible, as the underlying base-learners (regression functions defining the type of effect for the explanatory variables) can be combined with any kind of loss function (target function to be optimized, defining the type of regression setting). In this review article, we highlight the most recent methodological developments on statistical boosting regarding variable selection, functional regression, and advanced time-to-event modelling. Additionally, we provide a short overview on relevant applications of statistical boosting in biomedicine.

Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio

PubMed Central

Henriques-Alves, Aron M.; Queiroz, Claudio M.

2016-01-01

In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress. PMID:26869895

Ethological Evaluation of the Effects of Social Defeat Stress in Mice: Beyond the Social Interaction Ratio.

PubMed

Henriques-Alves, Aron M; Queiroz, Claudio M

2015-01-01

In rodents, repeated exposure to unavoidable aggression followed by sustained sensory treat can lead to prolonged social aversion. The chronic social defeat stress model explores that phenomenon and it has been used as an animal model for human depression. However, some authors have questioned whether confounding effects may arise as the model also boosts anxiety-related behaviors. Despite its wide acceptance, most studies extract limited information from the behavior of the defeated animal. Often, the normalized occupancy around the social stimulus, the interaction zone, is taken as an index of depression. We hypothesized that this parameter is insufficient to fully characterize the behavioral consequences of this form of stress. Using an ethological approach, we showed that repeated social defeat delayed the expression of social investigation in long (10 min) sessions of social interaction. Also, the incidence of defensive behaviors, including stretched-attend posture and high speed retreats, was significantly higher in defeated mice in comparison to controls. Interestingly, a subpopulation of defeated mice showed recurrent and non-habituating stretched-attend posture and persistent flights during the entire session. Two indexes were created based on defensive behaviors to show that only recurrent flights correlates with sucrose intake. Together, the present study corroborates the idea that this model of social stress can precipitate a myriad of behaviors not readily disentangled. We propose that long sessions (>150 s) and detailed ethological evaluation during social interaction tests are necessary to provide enough information to correctly classify defeated animals in terms of resilience and susceptibility to social defeat stress.

Cell-line-specific stimulation of tumor cell aggressiveness by wound healing factors - a central role for STAT3.

PubMed

Ekblad, Lars; Lindgren, Gustaf; Persson, Emma; Kjellén, Elisabeth; Wennerberg, Johan

2013-01-25

Local recurrence is a major factor affecting survival after treatment for head and neck squamous cell carcinoma (HNSCC). It is possible that the normal processes involved in wound healing after surgical removal of a primary tumor can boost the regrowth of residual cancer cells, thereby contributing to the recurrent growth. In this work, we collected human wound fluids and used them to investigate the effect of wound healing factors on HNSCC cell lines in vitro. Wound fluids were collected from thyroidectomized patients diagnosed with benign disease and were included in assays of cell proliferation, migration, cell scattering, and invasion. The involvement of intracellular signaling pathways and membrane receptors were investigated by western blotting and the inclusion of specific inhibitors. One out of four cell lines was greatly stimulated in proliferation, migration, cell scattering, and invasion by the addition of wound fluid as compared with addition of fetal bovine or human serum. These effects were accompanied by a sharp increase in activation of signal transducer and activator of transcription 3 (STAT3). Inhibition of STAT3 activation abolished the wound fluid response, showing that STAT3 plays an important role in the wound healing response. Several of the observed phenotypic changes were epithelial-to-mesenchymal transition (EMT)-like, but the appropriate changes were not seen in any of the EMT markers investigated. The involvement of c-Met or epidermal growth factor receptor family members was excluded, while the interleukin-6 receptor was found to be partly responsible for the activation of STAT3. In conclusion, we found cell-line-specific effects of wound healing factors on HNSCC, setting the stage for therapy development and predictive opportunities.

Reducing late effects of radiotherapy in average risk medulloblastoma.

PubMed

Ibrahim, Noha Yehia; Abdel Aal, Hisham H; Abdel Kader, Mohamed S; Makaar, Wael S; Shaaban, Ahmed H

2014-03-01

To assess the efficacy and safety in average-risk pediatric medulloblastoma (MB) receiving tumor bed boost irradiation compared to a posterior fossa (PF) boost. Thirty patients were enrolled in the study and divided evenly into two treatment arms of 15. Both arms received 23.4 Gy craniospinal irradiation (CS) and a 32.4 Gy boost. Patients in arm 1 were given PF boosts, and those in arm 2 were given boosts to the gross target volume (GTV). Weekly oncovin was given throughout all radiotherapy (RT). Eight cycles of adjuvant chemotherapy of CCNU, oncovin and platinol were given to all patients after RT. MRI, pure tone audiogram (PTA) and intelligence quotient (IQ) tests were performed before and after RT and every three months thereafter. There were significant differences in the sparing dose to the cochlea and brain stem as well as the volume of the normal brain receiving a 100% dose. There was a significant initial improvement of hearing function in patients given the target volume boost after RT, which was lost after chemotherapy. With a median follow up of 23 months, there was no difference in progression free survival or overall survival between the two arms. Irradiation of the tumor bed after 23.4 Gy craniospinal irradiation for average-risk MB results in similar disease control as a PF boost. Dosimetric sparing for the cochleae and normal tissue is evident in patients receiving tumor bed boosts. The hearing improvement and cognitive function preservation effects of the treatment need more follow up.

Boosting multi-state models.

PubMed

Reulen, Holger; Kneib, Thomas

2016-04-01

One important goal in multi-state modelling is to explore information about conditional transition-type-specific hazard rate functions by estimating influencing effects of explanatory variables. This may be performed using single transition-type-specific models if these covariate effects are assumed to be different across transition-types. To investigate whether this assumption holds or whether one of the effects is equal across several transition-types (cross-transition-type effect), a combined model has to be applied, for instance with the use of a stratified partial likelihood formulation. Here, prior knowledge about the underlying covariate effect mechanisms is often sparse, especially about ineffectivenesses of transition-type-specific or cross-transition-type effects. As a consequence, data-driven variable selection is an important task: a large number of estimable effects has to be taken into account if joint modelling of all transition-types is performed. A related but subsequent task is model choice: is an effect satisfactory estimated assuming linearity, or is the true underlying nature strongly deviating from linearity? This article introduces component-wise Functional Gradient Descent Boosting (short boosting) for multi-state models, an approach performing unsupervised variable selection and model choice simultaneously within a single estimation run. We demonstrate that features and advantages in the application of boosting introduced and illustrated in classical regression scenarios remain present in the transfer to multi-state models. As a consequence, boosting provides an effective means to answer questions about ineffectiveness and non-linearity of single transition-type-specific or cross-transition-type effects.

How the Brain Converts Negative Evaluation into Performance Facilitation.

PubMed

Prévost, Charlotte; Lau, Hakwan; Mobbs, Dean

2018-02-01

Surpassing negative evaluation is a recurrent theme of success stories. Yet, there is little evidence supporting the counterintuitive idea that negative evaluation might not only motivate people, but also enhance performance. To address this question, we designed a task that required participants to decide whether taking up a risky challenge after receiving positive or negative evaluations from independent judges. Participants believed that these evaluations were based on their prior performance on a related task. Results showed that negative evaluation caused a facilitation in performance. Concurrent functional magnetic resonance imaging revealed that the motivating effect of negative evaluation was represented in the insula and striatum, while the performance boost was associated with functional positive connectivity between the insula and a set of brain regions involved in goal-directed behavior and the orienting of attention. These findings provide new insight into the neural representation of negative evaluation-induced facilitation. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antibody responses to prime-boost vaccination with an HIV-1 gp145 envelope protein and chimpanzee adenovirus vectors expressing HIV-1 gp140.

PubMed

Emmer, Kristel L; Wieczorek, Lindsay; Tuyishime, Steven; Molnar, Sebastian; Polonis, Victoria R; Ertl, Hildegund C J

2016-10-23

Over 2 million individuals are infected with HIV type 1 (HIV-1) each year, yet an effective vaccine remains elusive. The most successful HIV-1 vaccine to date demonstrated 31% efficacy. Immune correlate analyses associated HIV-1 envelope (Env)-specific antibodies with protection, thus providing a path toward a more effective vaccine. We sought to test the antibody response from novel prime-boost vaccination with a chimpanzee-derived adenovirus (AdC) vector expressing a subtype C Env glycoprotein (gp)140 combined with either a serologically distinct AdC vector expressing gp140 of a different subtype C isolate or an alum-adjuvanted, partially trimeric gp145 from yet another subtype C isolate. Three different prime-boost regimens were tested in mice: AdC prime-protein boost, protein prime-AdC boost, and AdC prime-AdC boost. Each regimen was tested at two different doses of AdC vector in a total of six experimental groups. Sera were collected at various time points and evaluated by ELISA for Env-specific antibody binding, isotype, and avidity. Antibody functionality was assessed by pseudovirus neutralization assay. Priming with AdC followed by a protein boost or sequential immunizations with two AdC vectors induced HIV-1 Env-specific binding antibodies, including those to the variable region 2, whereas priming with protein followed by an AdC boost was relatively ineffective. Antibodies that cross-neutralized tier 1 HIV-1 from different subtypes were elicited with vaccine regimens that included immunizations with protein. Our study warrants further investigation of AdC vector and gp145 protein prime-boost vaccines and their ability to protect against acquisition in animal challenge studies.

A nebulized gelatin nanoparticle-based CpG formulation is effective in immunotherapy of allergic horses.

PubMed

Klier, John; Fuchs, Sebastian; May, Anna; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Coester, Conrad; Gehlen, Heidrun

2012-06-01

In the recent years, nanotechnology has boosted the development of potential drug delivery systems and material engineering on nanoscale basis in order to increase drug specificity and reduce side effects. A potential delivery system for immunostimulating agents such as cytosine-phosphate-guanine-oligodeoxynucleotides (CpG-ODN) needs to be developed to maximize the efficacy of immunotherapy against hypersensitivity. In this study, an aerosol formulation of biodegradable, biocompatible and nontoxic gelatin nanoparticle-bound CpG-ODN 2216 was used to treat equine recurrent airway obstruction in a clinical study. Bronchoalveolar lavage fluid was obtained from healthy and allergic horses to quantify Th1/Th2 cytokine levels before and after inhalation regimen. Full clinical examinations were performed to evaluate the therapeutic potential of this nebulized gelatin nanoparticle-based CpG formulation. Most remarkable was that regulatory anti-inflammatory and anti-allergic cytokine IL-10 expression was significantly triggered by five consecutive inhalations. Thorough assessment of clinical parameters following nanoparticle treatment indicated a partial remission of the allergic condition. Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans.

Repeat exposure to group A streptococcal M protein exacerbates cardiac damage in a rat model of rheumatic heart disease.

PubMed

Gorton, Davina; Sikder, Suchandan; Williams, Natasha L; Chilton, Lisa; Rush, Catherine M; Govan, Brenda L; Cunningham, Madeleine W; Ketheesan, Natkunam

2016-12-01

Rheumatic fever and rheumatic heart disease (RF/RHD) develop following repeated infection with group A streptococci (GAS). We used the Rat Autoimmune Valvulitis (RAV) model of RF/RHD to demonstrate that repetitive booster immunization with GAS-derived recombinant M protein (rM5) resulted in an enhanced anti-cardiac myosin antibody response that may contribute to the breaking of immune tolerance leading to RF/RHD and increased infiltration of heart valves by mononuclear cells. With each boost, more inflammatory cells were observed infiltrating heart tissue which could lead to severe cardiac damage. We also found evidence that both complement and anti-M protein antibodies in serum from rM5-immunized rats have the potential to contribute to inflammation in heart valves by activating cardiac endothelium. More importantly, we have demonstrated by electrocardiography for the first time in the RAV model that elongation of P-R interval follows repetitive boost with rM5. Our observations provide experimental evidence for cardiac alterations following repeated exposure to GAS M protein with immunological and electrophysiological features resembling that seen in humans following recurrent GAS infection.

Technology Insight: Combined external-beam radiation therapy and brachytherapy in the management of prostate cancer.

PubMed

Hurwitz, Mark D

2008-11-01

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.

Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

PubMed Central

Brown, Scott A.; Surman, Sherri L.; Sealy, Robert; Jones, Bart G.; Slobod, Karen S.; Branum, Kristen; Lockey, Timothy D.; Howlett, Nanna; Freiden, Pamela; Flynn, Patricia; Hurwitz, Julia L.

2010-01-01

Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans. PMID:20407589

Cheese powder as an ingredient in emulsion sausages: Effect on sensory properties and volatile compounds.

PubMed

Xiang, Chen; Ruiz-Carrascal, Jorge; Petersen, Mikael A; Karlsson, Anders H

2017-08-01

Different types of cheese powder were added to meat emulsion sausages in order to address its influence on chemical composition, volatile compounds profile and sensory properties, and its potential to reduce salt content through boosting saltiness. Addition of cheese powder to emulsion sausages modified their profile of volatile compounds. Blue cheese increased some ketones, alcohols, and esters, while brown cheese brought typical Maillard reaction compounds. Overall, addition of cheese powders to sausages enhanced the intensity of flavour traits. A mixture of hard and blue cheese powder showed the highest effect on boosting saltiness, while brown cheese powder showed the strongest umami and meat flavour boosting effect, and sausages with added blue cheese powder showed a more intense aftertaste. Hardness significantly increased due to the addition of blue cheese powder. Addition of cheese powder to emulsion sausages might be an interesting tool to boost flavour and reduce salt content in cooked sausages with no negative effect on saltiness or overall flavour. Copyright © 2017 Elsevier Ltd. All rights reserved.

Standard and Nonstandard Craniospinal Radiotherapy Using Helical TomoTherapy

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

Parker, William, E-mail: william@medphys.mcgill.c; Brodeur, Marylene; Roberge, David

2010-07-01

Purpose: To show the advantages of planning and delivering craniospinal radiotherapy with helical TomoTherapy (TomoTherapy Inc., Madison, WI) by presenting 4 cases treated at our institution. Methods and Materials: We first present a standard case of craniospinal irradiation in a patient with recurrent myxopapillary ependymoma (MPE) and follow this with 2 cases requiring differential dosing to multiple target volumes. One of these, a patient with recurrent medulloblastoma, required a lower dose to be delivered to the posterior fossa because the patient had been previously irradiated to the full dose, and the other required concurrent boosts to leptomeningeal metastases as partmore » of his treatment for newly diagnosed MPE. The final case presented is a patient with pronounced scoliosis who required spinal irradiation for recurrent MPE. Results: The four cases presented were planned and treated successfully with Helical Tomotherapy. Conclusions: Helical TomoTherapy delivers continuous arc-based intensity-modulated radiotherapy that gives high conformality and excellent dose homogeneity for the target volumes. Increased healthy tissue sparing is achieved at higher doses albeit at the expense of larger volumes of tissue receiving lower doses. Helical TomoTherapy allows for differential dosing of multiple targets, resulting in very elegant dose distributions. Daily megavoltage computed tomography imaging allows for precision of patient positioning, permitting a reduction in planning margins and increased healthy tissue sparing in comparison with standard techniques.« less

The Attentional Boost Effect with Verbal Materials

ERIC Educational Resources Information Center

Mulligan, Neil W.; Spataro, Pietro; Picklesimer, Milton

2014-01-01

Study stimuli presented at the same time as unrelated targets in a detection task are better remembered than stimuli presented with distractors. This attentional boost effect (ABE) has been found with pictorial (Swallow & Jiang, 2010) and more recently verbal materials (Spataro, Mulligan, & Rossi-Arnaud, 2013). The present experiments…

Surgery for Locally Recurrent Rectal Cancer: Tips, Tricks, and Pitfalls.

PubMed

Warrier, Satish K; Heriot, Alexander G; Lynch, Andrew Craig

2016-06-01

Rectal cancer can recur locally in up to 10% of the patients who undergo definitive resection for their primary cancer. Surgical salvage is considered appropriate in the curative setting as well as select cases with palliative intent. Disease-free survival following salvage resection is dependent upon achieving an R0 resection margin. A clear understanding of applied surgical anatomy, appropriate preoperative planning, and a multidisciplinary approach to aggressive soft tissue, bony, and vascular resection with appropriate reconstruction is necessary. Technical tips, tricks, and pitfalls that may assist in managing these cancers are discussed and the roles of additional boost radiation and intraoperative radiation therapy in the management of such cancers are also discussed.

The Attentional Boost Effect and Context Memory

ERIC Educational Resources Information Center

Mulligan, Neil W.; Smith, S. Adam; Spataro, Pietro

2016-01-01

Stimuli co-occurring with targets in a detection task are better remembered than stimuli co-occurring with distractors--the attentional boost effect (ABE). The ABE is of interest because it is an exception to the usual finding that divided attention during encoding impairs memory. The effect has been demonstrated in tests of item memory but it is…

Toxicity and efficacy of salvage carbon 11-choline positron emission tomography/computed tomography-guided radiation therapy in patients with lymph node recurrence of prostate cancer.

PubMed

Fodor, Andrei; Berardi, Genoveffa; Fiorino, Claudio; Picchio, Maria; Busnardo, Elena; Kirienko, Margarita; Incerti, Elena; Dell'Oca, Italo; Cozzarini, Cesare; Mangili, Paola; Pasetti, Marcella; Calandrino, Riccardo; Gianolli, Luigi; Di Muzio, Nadia G

2017-03-01

To report the 3-year toxicity and outcomes of carbon 11 (11C)-choline-positron emission tomography (PET)/computed tomography (CT)-guided radiotherapy (RT), delivered via helical tomotherapy (HTT; Tomotherapy ® Hi-Art II ® Treatment System, Accuray Inc., Sunnyvale, CA, USA) after lymph node (LN) relapses in patients with prostate cancer. From January 2005 to March 2013, 81 patients with biochemical recurrence after surgery, with or without adjuvant/salvage RT or radical RT, and with evidence of LN 11C-choline-PET/CT pathological uptake, underwent HTT (median [range] prostate-specific antigen level 2.59 [0.61-187] ng/mL). Of the 81 patients, 72 were treated at the pelvic and/or lumbar-aortic LN chain with HTT at 51.8 Gy/28 fr and with simultaneous integrated boost to a median dose of 65.5 Gy on the pathological uptake sites detected by 11C-choline-PET/CT. Nine patients were treated without simultaneous integrated boost (50-65.5 Gy, 25-30 fr). With a median (range) follow-up of 36 (9-116) months, 91.4% of the patients had a PSA reduction 3 months after HTT. The 3-year overall, local relapse-free and clinical relapse-free survival rates were 80.0, 89.8 and 61.8%, respectively. The 3-year actuarial incidences of ≥grade 2 rectal and ≥grade 2 genitourinary toxicity were 6.6% (±2.9%) and 26.3% (±5.5%), respectively. A PSA nadir of ≥0.26 ng/mL (hazard ratio [HR] 3.6, 95% confidence interval [CI] 1.7-7.7; P = 0.001), extrapelvic 11C-choline-PET/CT-positive LN location (HR 2.4, 95% CI 0.9-6.4; P = 0.07), RT previous to HTT (HR 2.7; 95% CI 1.07-6.9, P = 0.04) and number of positive LNs (HR 1.13, 95% CI 1.04-1.22; P = 0.003) were the main predictors of clinical relapse after HTT. 11C-choline-PET/CT-guided HTT is safe and effective in the treatment of LN relapses of prostate cancer in previously treated patients. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Global Dirac bispinor entanglement under Lorentz boosts

NASA Astrophysics Data System (ADS)

Bittencourt, Victor A. S. V.; Bernardini, Alex E.; Blasone, Massimo

2018-03-01

The effects of Lorentz boosts on the quantum entanglement encoded by a pair of massive spin-1/2 particles are described according to the Lorentz covariant structure described by Dirac bispinors. The quantum system considered incorporates four degrees of freedom: two of them related to the bispinor intrinsic parity and the other two related to the bispinor spin projection, i.e., the Dirac particle helicity. Because of the natural multipartite structure involved, the Meyer-Wallach global measure of entanglement is preliminarily used for computing global quantum correlations, while the entanglement separately encoded by spin degrees of freedom is measured through the negativity of the reduced two-particle spin-spin state. A general framework to compute the changes on quantum entanglement induced by a boost is developed and then specialized to describe three particular antisymmetric two-particle states. According to the results obtained, two-particle spin-spin entanglement cannot be created by the action of a Lorentz boost in a spin-spin separable antisymmetric state. On the other hand, the maximal spin-spin entanglement encoded by antisymmetric superpositions is degraded by Lorentz boosts driven by high-speed frame transformations. Finally, the effects of boosts on chiral states are shown to exhibit interesting invariance properties, which can only be obtained through such a Lorentz covariant formulation of the problem.

Syntactic Priming and the Lexical Boost Effect during Sentence Production and Sentence Comprehension: An fMRI Study

ERIC Educational Resources Information Center

Segaert, Katrien; Kempen, Gerard; Petersson, Karl Magnus; Hagoort, Peter

2013-01-01

Behavioral syntactic priming effects during sentence comprehension are typically observed only if both the syntactic structure and lexical head are repeated. In contrast, during production syntactic priming occurs with structure repetition alone, but the effect is boosted by repetition of the lexical head. We used fMRI to investigate the neuronal…

Monitoring tool usage in surgery videos using boosted convolutional and recurrent neural networks.

PubMed

Al Hajj, Hassan; Lamard, Mathieu; Conze, Pierre-Henri; Cochener, Béatrice; Quellec, Gwenolé

2018-05-09

This paper investigates the automatic monitoring of tool usage during a surgery, with potential applications in report generation, surgical training and real-time decision support. Two surgeries are considered: cataract surgery, the most common surgical procedure, and cholecystectomy, one of the most common digestive surgeries. Tool usage is monitored in videos recorded either through a microscope (cataract surgery) or an endoscope (cholecystectomy). Following state-of-the-art video analysis solutions, each frame of the video is analyzed by convolutional neural networks (CNNs) whose outputs are fed to recurrent neural networks (RNNs) in order to take temporal relationships between events into account. Novelty lies in the way those CNNs and RNNs are trained. Computational complexity prevents the end-to-end training of "CNN+RNN" systems. Therefore, CNNs are usually trained first, independently from the RNNs. This approach is clearly suboptimal for surgical tool analysis: many tools are very similar to one another, but they can generally be differentiated based on past events. CNNs should be trained to extract the most useful visual features in combination with the temporal context. A novel boosting strategy is proposed to achieve this goal: the CNN and RNN parts of the system are simultaneously enriched by progressively adding weak classifiers (either CNNs or RNNs) trained to improve the overall classification accuracy. Experiments were performed in a dataset of 50 cataract surgery videos, where the usage of 21 surgical tools was manually annotated, and a dataset of 80 cholecystectomy videos, where the usage of 7 tools was manually annotated. Very good classification performance are achieved in both datasets: tool usage could be labeled with an average area under the ROC curve of A z =0.9961 and A z =0.9939, respectively, in offline mode (using past, present and future information), and A z =0.9957 and A z =0.9936, respectively, in online mode (using past and present information only). Copyright © 2018 Elsevier B.V. All rights reserved.

Quality Assurance of Multifractionated Pelvic Interstitial Brachytherapy for Postoperative Recurrences of Cervical Cancers: A Prospective Study

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

Shukla, Pragya; Chopra, Supriya, E-mail: schopra@actrec.gov.in; Engineer, Reena

2012-03-15

Purpose: To evaluate three-dimensional needle displacements during multifractionated interstitial brachytherapy (BT) for cervical cancers. Methods and Materials: Patients scheduled to undergo pelvic interstitial BT for postoperative and or postradiation vault recurrences were included from November 2009 to December 2010. All procedures were performed under spinal anesthesia. Postprocedure BT planning CT scans were obtained with patients in supine position with arms on the chest (interslice thickness of 3 mm). Thereafter, verification CT was repeated at every alternate fraction. Needle displacements were measured in reference to a relocatable bony point. The mean cranial, caudal, anteroposterior, and mediolateral displacements were recorded. Statistical significancemore » of mean interfraction displacements was evaluated with Wilcoxon Test. Results: Twenty patients were included. Seventeen received boost BT (20 Gy/5 fractions/3 days) after external radiation, three received radical BT alone (36 Gy/9 fractions/5-8 days). An average of three scans (range, 2-3) were available per patient, and 357 needle displacements were analyzed. For the entire study cohort, the average of mean needle displacement was 2.5 mm (range, 0-7.4), 17.4 mm (range, 0-27.9), 1.7 mm (range, 0-6.7), 2.1 mm (range, 0-9.5), 1.7 mm (range, 0-9.3), and 0.6 mm (range, 0-7.8) in cranial, caudal, anterior, posterior, right, and left directions, respectively. The mean displacement in the caudal direction was higher between Days 1 and 2 than that between Days 2 and 3 (13.4 mm vs. 3.8 mm; p = 0.01). The average caudal displacements were no different between reirradiation and boost cohort (15.2 vs. 17.8 mm). Conclusions: Clinically significant caudal displacements occur during multifractionated pelvic brachytherapy. Optimal margins need to be incorporated while preplanning brachytherapy to account for interfraction displacements.« less

Phase I/II Trial of Hyperfractionated Concomitant Boost Proton Radiotherapy for Supratentorial Glioblastoma Multiforme

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

Mizumoto, Masashi; Tsuboi, Koji, E-mail: tsuboi@pmrc.tsukuba.ac.j; Department of Neurosurgery, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki

2010-05-01

Purpose: To evaluate the safety and efficacy of postoperative hyperfractionated concomitant boost proton radiotherapy with nimustine hydrochloride for supratentorial glioblastoma multiforme (GBM). Methods and Materials: Twenty patients with histologically confirmed supratentorial GBM met the following criteria: (1) a Karnofsky performance status of >=60; (2) the diameter of the enhanced area before radiotherapy was <=40 cm; and (3) the enhanced area did not extend to the brain stem, hypothalamus, or thalamus. Magnetic resonance imaging (MRI) T{sub 2}-weighted high area (clinical tumor volume 3 [CTV3]) was treated by x-ray radiotherapy in the morning (50.4 Gy in 28 fractions). More than 6 hoursmore » later, 250 MeV proton beams were delivered to the enhanced area plus a 10-mm margin (CTV2) in the first half of the protocol (23.1 GyE in 14 fractions) and to the enhanced volume (CTV1) in the latter half (23.1 GyE in 14 fraction). The total dose to the CTV1 was 96.6 GyE. Nimustine hydrochloride (80 mg/m2) was administered during the first and fourth weeks. Results: Acute toxicity was mainly hematologic and was controllable. Late radiation necrosis and leukoencephalopathy were each seen in one patient. The overall survival rates after 1 and 2 years were 71.1% and 45.3%, respectively. The median survival period was 21.6 months. The 1- and 2-year progression-free survival rates were 45.0% and 15.5%, respectively. The median MRI change-free survival was 11.2 months. Conclusions: Hyperfractionated concomitant boost proton radiotherapy (96.6 GyE in 56 fractions) for GBM was tolerable and beneficial if the target size was well considered. Further studies are warranted to pursue the possibility of controlling border region recurrences.« less

Of Mice and not Humans: How Reliable are Animal Models for Evaluation of Herpes CD8+-T cell-Epitopes-Based Immunotherapeutic Vaccine Candidates?

PubMed Central

Dasgupta, Gargi; BenMohamed, Lbachir

2011-01-01

Herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) -specific CD8+ T cells that reside in sensory ganglia, appears to control recurrent herpetic disease by aborting or reducing spontaneous and sporadic reactivations of latent virus. A reliable animal model is the ultimate key factor to test the efficacy of therapeutic vaccines that boost the level and the quality of sensory ganglia-resident CD8+ T cells against spontaneous herpes reactivation from sensory neurons, yet its relevance has been often overlooked. Herpes vaccinologists are hesitant about using mouse as a model in pre-clinical development of therapeutic vaccines because they do not adequately mimic spontaneous viral shedding or recurrent symptomatic diseases, as occurs in human. Alternatives to mouse models are rabbits and guinea pigs in which reactivation arise spontaneously with clinical features relevant to human disease. However, while rabbits and guinea pigs develop spontaneous HSV reactivation and recurrent ocular and genital disease none of them can mount CD8+ T cell responses specific to Human Leukocyte Antigen- (HLA-) restricted epitopes. In this review, we discuss the advantages and limitations of these animal models and describe a novel “humanized” HLA transgenic rabbit, which shows spontaneous HSV-1 reactivation, recurrent ocular disease and mounts CD8+ T cell responses to HLA-restricted epitopes. Adequate investments are needed to develop reliable preclinical animal models, such as HLA class I and class II double transgenic rabbits and guinea pigs to balance the ethical and financial concerns associated with the rising number of unsuccessful clinical trials for therapeutic vaccine formulations tested in unreliable mouse models. PMID:21718746

An empirical comparison of several recent epistatic interaction detection methods.

PubMed

Wang, Yue; Liu, Guimei; Feng, Mengling; Wong, Limsoon

2011-11-01

Many new methods have recently been proposed for detecting epistatic interactions in GWAS data. There is, however, no in-depth independent comparison of these methods yet. Five recent methods-TEAM, BOOST, SNPHarvester, SNPRuler and Screen and Clean (SC)-are evaluated here in terms of power, type-1 error rate, scalability and completeness. In terms of power, TEAM performs best on data with main effect and BOOST performs best on data without main effect. In terms of type-1 error rate, TEAM and BOOST have higher type-1 error rates than SNPRuler and SNPHarvester. SC does not control type-1 error rate well. In terms of scalability, we tested the five methods using a dataset with 100 000 SNPs on a 64 bit Ubuntu system, with Intel (R) Xeon(R) CPU 2.66 GHz, 16 GB memory. TEAM takes ~36 days to finish and SNPRuler reports heap allocation problems. BOOST scales up to 100 000 SNPs and the cost is much lower than that of TEAM. SC and SNPHarvester are the most scalable. In terms of completeness, we study how frequently the pruning techniques employed by these methods incorrectly prune away the most significant epistatic interactions. We find that, on average, 20% of datasets without main effect and 60% of datasets with main effect are pruned incorrectly by BOOST, SNPRuler and SNPHarvester. The software for the five methods tested are available from the URLs below. TEAM: http://csbio.unc.edu/epistasis/download.php BOOST: http://ihome.ust.hk/~eeyang/papers.html. SNPHarvester: http://bioinformatics.ust.hk/SNPHarvester.html. SNPRuler: http://bioinformatics.ust.hk/SNPRuler.zip. Screen and Clean: http://wpicr.wpic.pitt.edu/WPICCompGen/. wangyue@nus.edu.sg.

The Reduced Effectiveness of EGR to Mitigate Knock at High Loads in Boosted SI Engines

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

Szybist, James P.; Wagnon, Scott W.; Splitter, Derek A.

Numerous studies have demonstrated that exhaust gas recirculation (EGR) can attenuate knock propensity in spark ignition (SI) engines at naturally aspirated or lightly boosted conditions. In this paper, we investigate the role of cooled EGR under higher load conditions with multiple fuel compositions, where highly retarded combustion phasing typical of modern SI engines was used. It was found that under these conditions, EGR attenuation of knock is greatly reduced, where EGR doesn’t allow significant combustion phasing advance as it does under lighter load conditions. Detailed combustion analysis shows that when EGR is added, the polytropic coefficient increases causing the compressivemore » pressure and temperature to increase. At sufficiently highly boosted conditions, the increase in polytropic coefficient and additional trapped mass from EGR can sufficiently reduce fuel ignition delay to overcome knock attenuation effects. Kinetic modeling demonstrates that the effectiveness of EGR to mitigate knock is highly dependent on the pressure-temperature condition. Experiments at 2000 rpm have confirmed reduced fuel ignition delay under highly boosted conditions relevant to modern downsized boosted SI engines, where in-cylinder pressure is higher and the temperature is cooler. Finally, at these conditions, charge reactivity increases compared to naturally aspirated conditions, and attenuation of knock by EGR is reduced.« less

The Reduced Effectiveness of EGR to Mitigate Knock at High Loads in Boosted SI Engines

DOE PAGES

Szybist, James P.; Wagnon, Scott W.; Splitter, Derek A.; ...

2017-09-04

Numerous studies have demonstrated that exhaust gas recirculation (EGR) can attenuate knock propensity in spark ignition (SI) engines at naturally aspirated or lightly boosted conditions. In this paper, we investigate the role of cooled EGR under higher load conditions with multiple fuel compositions, where highly retarded combustion phasing typical of modern SI engines was used. It was found that under these conditions, EGR attenuation of knock is greatly reduced, where EGR doesn’t allow significant combustion phasing advance as it does under lighter load conditions. Detailed combustion analysis shows that when EGR is added, the polytropic coefficient increases causing the compressivemore » pressure and temperature to increase. At sufficiently highly boosted conditions, the increase in polytropic coefficient and additional trapped mass from EGR can sufficiently reduce fuel ignition delay to overcome knock attenuation effects. Kinetic modeling demonstrates that the effectiveness of EGR to mitigate knock is highly dependent on the pressure-temperature condition. Experiments at 2000 rpm have confirmed reduced fuel ignition delay under highly boosted conditions relevant to modern downsized boosted SI engines, where in-cylinder pressure is higher and the temperature is cooler. Finally, at these conditions, charge reactivity increases compared to naturally aspirated conditions, and attenuation of knock by EGR is reduced.« less

[18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine

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

Cheney, Matthew D., E-mail: mcheney@lroc.harvard.edu; Chen, Yen-Lin; Lim, Ruth

2014-12-01

Purpose: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. Methods and Materials: A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared betweenmore » patients with and without HSVs. Results: The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm{sup 3}) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm{sup 3} vs 63.4 cm{sup 3}; P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Conclusions: Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.« less

Boost breaking in the EFT of inflation

DOE PAGES

Delacrétaz, Luca V.; Noumi, Toshifumi; Senatore, Leonardo

2017-02-17

If time-translations are spontaneously broken, so are boosts. This symmetry breaking pattern can be non-linearly realized by either just the Goldstone boson of time translations, or by four Goldstone bosons associated with time translations and boosts. Here in this paper we extend the Effective Field Theory of Multifield Inflation to consider the case in which the additional Goldstone bosons associated with boosts are light and coupled to the Goldstone boson of time translations. The symmetry breaking pattern forces a coupling to curvature so that the mass of the additional Goldstone bosons is predicted to be equal to √2H in themore » vast majority of the parameter space where they are light. This pattern therefore offers a natural way of generating self-interacting particles with Hubble mass during inflation. After constructing the general effective Lagrangian, we study how these particles mix and interact with the curvature fluctuations, generating potentially detectable non-Gaussian signals.« less

HFE genotype affects exosome phenotype in cancer.

PubMed

Mrowczynski, Oliver D; Madhankumar, A B; Slagle-Webb, Becky; Lee, Sang Y; Zacharia, Brad E; Connor, James R

2017-08-01

Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells. Copyright © 2017. Published by Elsevier B.V.

Menthol smokers: metabolomic profiling and smoking behavior

PubMed Central

Hsu, Ping-Ching; Lan, Renny S.; Brasky, Theodore M.; Marian, Catalin; Cheema, Amrita K.; Ressom, Habtom W.; Loffredo, Christopher A.; Pickworth, Wallace B.; Shields, Peter G.

2016-01-01

Background The use of menthol in cigarettes and marketing is under consideration for regulation by the FDA. However, the effects of menthol on smoking behavior and carcinogen exposure have been inconclusive. We previously reported metabolomic profiling for cigarette smokers, and novelly identified a menthol-glucuronide (MG) as the most significant metabolite directly related to smoking. Here, MG is studied in relation to smoking behavior and metabolomic profiles. Methods A cross-sectional study of 105 smokers who smoked two cigarettes in the laboratory one hour apart. Blood nicotine, MG and exhaled carbon monoxide (CO) boosts were determined (the difference before and after smoking). Spearman's correlation, Chi-Square and ANCOVA adjusted for gender, race and cotinine levels for menthol smokers assessed the relationship of MG boost, smoking behavior, and metabolic profiles. Multivariate metabolite characterization using supervised Partial Least Squares-Discriminant Analysis (PLS-DA) was carried out for the classification of metabolomics profiles. Results MG boost was positively correlated with CO boost, nicotine boost, average puff volume, puff duration, and total smoke exposure. Classification using PLS-DA, MG was the top metabolite discriminating metabolome of menthol vs. non-menthol smokers. Among menthol smokers, forty-two metabolites were significantly correlated with MG boost, which linked to cellular functions such as of cell death, survival, and movement. Conclusion Plasma MG boost is a new smoking behavior biomarker that may provides novel information over self-reported use of menthol cigarettes by integrating different smoking measures for understanding smoking behavior and harm of menthol cigarettes. Impacts These results provide insight into the biological effect of menthol smoking. PMID:27628308

Supplement to This School Works for Me: Creating Choices to Boost Achievement. A Guide for Data Analysts

ERIC Educational Resources Information Center

Bill & Melinda Gates Foundation, 2010

2010-01-01

This paper serves as a supplement to the "This School Works for Me: Creating Choices to Boost Achievement. A Guide for Data Analysts" report. This paper contains the following sections: (1) Initial Steps; (2) Developing Baseline District Facts; (3) Identifying Effective Options; (4) Identifying Effective Options: Preventative; and (5) Identifying…

Clinical Response of Pelvic and Para-aortic Lymphadenopathy to a Radiation Boost in the Definitive Management of Locally Advanced Cervical Cancer

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

Rash, Dominique L.; Lee, Yongsook C.; Kashefi, Amir

Purpose: Optimal treatment with radiation for metastatic lymphadenopathy in locally advanced cervical cancer remains controversial. We investigated the clinical dose response threshold for pelvic and para-aortic lymph node boost using radiographic imaging and clinical outcomes. Methods and Materials: Between 2007 and 2011, 68 patients were treated for locally advanced cervical cancer; 40 patients had clinically involved pelvic and/or para-aortic lymph nodes. Computed tomography (CT) or 18F-labeled fluorodeoxyglucose-positron emission tomography scans obtained pre- and postchemoradiation for 18 patients were reviewed to assess therapeutic radiographic response of individual lymph nodes. External beam boost doses to involved nodes were compared to treatment response,more » assessed by change in size of lymph nodes by short axis and change in standard uptake value (SUV). Patterns of failure, time to recurrence, overall survival (OS), and disease-free survival (DFS) were determined. Results: Sixty-four lymph nodes suspicious for metastatic involvement were identified. Radiation boost doses ranged from 0 to 15 Gy, with a mean total dose of 52.3 Gy. Pelvic lymph nodes were treated with a slightly higher dose than para-aortic lymph nodes: mean 55.3 Gy versus 51.7 Gy, respectively. There was no correlation between dose delivered and change in size of lymph nodes along the short axis. All lymph nodes underwent a decrease in SUV with a complete resolution of abnormal uptake observed in 68%. Decrease in SUV was significantly greater for lymph nodes treated with ≥54 Gy compared to those treated with <54 Gy (P=.006). Median follow-up was 18.7 months. At 2 years, OS and DFS for the entire cohort were 78% and 50%, respectively. Locoregional control at 2 years was 84%. Conclusions: A biologic response, as measured by the change in SUV for metastatic lymph nodes, was observed at a dose threshold of 54 Gy. We recommend that involved lymph nodes be treated to this minimum dose.« less

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

Yan, S; Broussard, G; De, K

Purpose: Recurrent chordomas are difficult to control locally. This dosimetric study investigates the feasibility of dose escalation to hypoxic regions, visualized on FMISO-PET, while respecting the dose constraints to the neighboring normal tissues/organs. We propose to deliver a higher dose to the areas of hypoxia (84.5Gy) using IMPT with the goal of improving local control. Methods: We currently have four patients with hypoxic subvolumes (HSV) greater than 10cc from the FMISO-PET image. The HSV was delineated based on the standardized uptake values of greater than 1.4 times of the muscle mean. Gross tumor volume (GTV) was delineated using planning CTmore » with the assistance of MRI fusion. The dose scheme is 50.4Gy RBE to CTV in 1.8Gy fractions, followed by an integrated boost of 27.0Gy RBE to GTV in 1.8Gy fractions and 34.5Gy RBE to HSV in 2.3Gy fractions. IMPT integrated boost plans were optimized with multi-criteria optimization (MCO). Posterior-anterior beam angles were used for these plans. We also propose using two posterior oblique fields to boost HSV to spare the skin folding. A medium spot size with 8mm to 15 mm (σ) in air at isocenter with energies from 220 MeV down to 90 MeV was used. Aperture was used for the medium spot size. A small spot size of 2.5 mm to 4.5 mm (σ) in air at isocenter with energies from 240 MeV down to 70 MeV was also proposed. Target coverage and dose to OARs were evaluated. Results: For the sacral chordoma patient that has been planned, the target homogeneity index is 3.2% for HSV, 55.9% for CTV and 11.9% for GTV. The max dose is 77GyRBE to rectum, 86.2GyRBE to sacral nerves and 73.9GyRBE to cauda equina. Conclusion: IMPT with integrated high dose boost to HSV determined from FMISO PET image is feasible. OAR dose constraints were met.« less

Is breast conservative surgery a reasonable option in multifocal or multicentric tumors?

PubMed Central

Houvenaeghel, Gilles; Tallet, Agnès; Jalaguier-Coudray, Aurélie; Cohen, Monique; Bannier, Marie; Jauffret-Fara, Camille; Lambaudie, Eric

2016-01-01

The incidence of multifocal (MF) and multicentric (MC) carcinomas varies widely among clinical studies, depending on definitions and methods for pathological sampling. Magnetic resonance imaging is increasingly used because it can help identify additional and conventionally occult tumors with high sensitivity. However, false positive lesions might incorrectly influence treatment decisions. Therefore, preoperative biopsies must be performed to avoid unnecessary surgery. Most studies have shown higher lymph node involvement rates in MF/MC tumors than in unifocal tumors. However, the rate of local recurrences is usually low after breast conservative treatment (BCT) of MC/MF tumors. It has been suggested that BCT is a reasonable option for MC/MF tumors in women aged 50-69 years, with small tumors and absence of extensive ductal carcinoma in situ. A meta-analysis showed an apparent decreased overall survival in MC/MF tumors but data are controversial. Surgery should achieve both acceptable cosmetic results and negative margins, which requires thorough preoperative radiological workup and localization of lesions. Boost radiotherapy techniques must be evaluated since double boosts might result in increased toxicity, namely fibrosis. In conclusion, BCT is feasible in selected patients with MC/MF but the choice of surgery must be discussed in a multidisciplinary team comprising at least radiologists, surgeons and radiotherapists. PMID:27081646

"Mind the gap"--the impact of variations in the duration of the treatment gap and overall treatment time in the first UK Anal Cancer Trial (ACT I).

PubMed

Glynne-Jones, Rob; Sebag-Montefiore, David; Adams, Richard; McDonald, Alec; Gollins, Simon; James, Roger; Northover, John M A; Meadows, Helen M; Jitlal, Mark

2011-12-01

The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone or CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p=0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p=0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p=0.51). OTT was longer by 6.1 days for EBRT (p=0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p=0.03). These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control. Copyright © 2011 Elsevier Inc. All rights reserved.

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

Glynne-Jones, Rob, E-mail: rob.glynnejones@nhs.net; Sebag-Montefiore, David; Adams, Richard

Purpose: The United Kingdom Coordinating Committee on Cancer Research anal cancer trial demonstrated the benefit of combined modality treatment (CMT) using radiotherapy (RT), infusional 5-fluorouracil, and mitomycin C over RT alone. The present study retrospectively examines the impact of the recommended 6-week treatment gap and local RT boost on long-term outcome. Methods and Materials: A total of 577 patients were randomly assigned RT alone or CMT. After a 6-week gap responders received a boost using either additional external beam radiotherapy (EBRT) (15 Gy) or iridium-192 implant (25 Gy). The effect of boost, the gap between initial treatment (RT alone ormore » CMT) and boost (Tgap), and overall treatment time (OTT) were examined for their impact on outcome. Results: Among the 490 good responders, 436 (89%) patients received a boost after initial treatment. For boosted patients, the risk of anal cancer death decreased by 38% (hazard ratio [HR]: 0.62, 99% CI 0.35-1.12; p = 0.04), but there was no evidence this was mediated via a reduction in locoregional failure (LRF) (HR: 0.90, 99% CI 0.48-1.68; p = 0.66). The difference in Tgap was only 1.4 days longer for EBRT boost, compared with implant (p = 0.51). OTT was longer by 6.1 days for EBRT (p = 0.006). Tgap and OTT were not associated with LRF. Radionecrosis was reported in 8% of boosted, compared with 0% in unboosted patients (p = 0.03). Conclusions: These results question the benefit of a radiotherapy boost after a 6-week gap. The higher doses of a boost may contribute more to an increased risk of late morbidity, rather than local control.« less

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

PubMed

Bacorro, Warren; Dumas, Isabelle; Escande, Alexandre; Gouy, Sebastien; Bentivegna, Enrica; Morice, Philippe; Haie-Meder, Christine; Chargari, Cyrus

2018-03-01

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated. Patients with node-positive cervical cancer treated curatively with external beam radiotherapy (EBRT) and image-guided brachytherapy (IGABT) were identified. Nodal doses during EBRT, IGABT and boost were converted to 2-Gy equivalent (α/β = 10 Gy) and summed. Pathologic nodes were followed individually from diagnosis to relapse. Statistical analyses comprised log-rank tests (univariate analyses), Cox proportional model (factors with p ≤ 0.1 in univariate) and Probit analyses. A total of 108 patients with 254 unresected pathological nodes were identified. The mean nodal volume at diagnosis was 3.4 ± 5.8 cm 3 . The mean total nodal EQD2 doses were 55.3 ± 5.6 Gy. Concurrent chemotherapy was given in 96%. With a median follow-up of 33.5 months, 20 patients (18.5%) experienced relapse in nodes considered pathologic at diagnosis. Overall nodal recurrence rate was 9.1% (23/254). On univariate analyses, nodal volume (threshold: 3 cm 3 , p < .0001) and lymph node dose (≥57.5 Gy α/β10 , p = .039) were significant for nodal control. The use of simultaneous boost was borderline for significance (p = .07). On multivariate analysis, volume (HR = 8.2, 4.0-16.6, p < .0001) and dose (HR = 2, 1.05-3.9, p = .034) remained independent factors. Probit analysis combining dose and volume showed significant relationships with NCP, with increasing gap between the curves with higher nodal volumes. A nodal dose-volume effect on NCP is demonstrated for the first time, with increasing NCP benefit of additional doses to higher-volume nodes. Copyright © 2018 Elsevier Inc. All rights reserved.

Boosting structured additive quantile regression for longitudinal childhood obesity data.

PubMed

Fenske, Nora; Fahrmeir, Ludwig; Hothorn, Torsten; Rzehak, Peter; Höhle, Michael

2013-07-25

Childhood obesity and the investigation of its risk factors has become an important public health issue. Our work is based on and motivated by a German longitudinal study including 2,226 children with up to ten measurements on their body mass index (BMI) and risk factors from birth to the age of 10 years. We introduce boosting of structured additive quantile regression as a novel distribution-free approach for longitudinal quantile regression. The quantile-specific predictors of our model include conventional linear population effects, smooth nonlinear functional effects, varying-coefficient terms, and individual-specific effects, such as intercepts and slopes. Estimation is based on boosting, a computer intensive inference method for highly complex models. We propose a component-wise functional gradient descent boosting algorithm that allows for penalized estimation of the large variety of different effects, particularly leading to individual-specific effects shrunken toward zero. This concept allows us to flexibly estimate the nonlinear age curves of upper quantiles of the BMI distribution, both on population and on individual-specific level, adjusted for further risk factors and to detect age-varying effects of categorical risk factors. Our model approach can be regarded as the quantile regression analog of Gaussian additive mixed models (or structured additive mean regression models), and we compare both model classes with respect to our obesity data.

Influence of FDG-PET on primary nodal target volume definition for head and neck carcinomas.

PubMed

van Egmond, Sylvia L; Piscaer, Vera; Janssen, Luuk M; Stegeman, Inge; Hobbelink, Monique G; Grolman, Wilko; Terhaard, Chris H

The role of 2-[ 18 F]-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computed tomography (CT) in routine diagnostic staging remains controversial. In case of discordance between FDG-PET and CT, a compromise has to be made between the risk of false positive FDG-PET and the risk of delaying appropriate salvage intervention. Second, with intensity modulated radiation therapy (IMRT), smaller radiation fields allow tissue sparing, but could also lead to more marginal failures. We retrospectively studied 283 patients with head and neck carcinoma scheduled for radiotherapy between 2002 and 2010. We analyzed the influence of FDG-PET/CT versus CT alone on defining nodal target volume definition and evaluated its long-term clinical results. Second, the location of nodal recurrences was related to the radiation regional dose distribution. In 92 patients, CT and FDG-PET, performed in mold, showed discordant results. In 33%, nodal staging was altered by FDG-PET. In 24%, FDG-PET also led to an alteration in nodal treatment, including a nodal upstage of 18% and downstage of 6%. In eight of these 92 patients, a regional recurrence occurred. Only two patients had a recurrence in the discordant node on FDG-PET and CT and both received a boost (high dose radiation). These results support the complementary value of FDG-PET/CT compared to CT alone in defining nodal target volume definition for radiotherapy of head and neck cancer.

HIV-DNA priming alters T-cell responses to HIV-adenovirus vaccine even when responses to DNA are undetectable1

PubMed Central

De Rosa, Stephen C.; Thomas, Evan P.; Bui, John; Huang, Yunda; deCamp, Allan; Morgan, Cecilia; Kalams, Spyros; Tomaras, Georgia D.; Akondy, Rama; Ahmed, Rafi; Lau, Chuen-Yen; Graham, Barney S.; Nabel, Gary J.; McElrath, M. Juliana

2011-01-01

Many candidate HIV vaccines are designed to primarily elicit T-cell responses. Although repeated immunization with the same vaccine boosts antibody responses, the benefit for T-cell responses is ill-defined. We compared two immunization regimens that include the same recombinant adenoviral serotype 5 (rAd5) boost. Repeated homologous rAd5 immunization fails to increase T-cell responses, but increases gp140 antibody responses ten-fold. DNA prime, as compared with rAd5 prime, directs long-term memory CD8+ T cells toward a terminally differentiated effector memory phenotype with cytotoxic potential. Based on the kinetics of activated cells measured directly ex vivo, the DNA vaccination primes for both CD4+ and CD8+ T cells, despite the lack of detection of the latter until after the boost. These results suggest that heterologous prime-boost combinations have distinct immunological advantages over homologous prime-boosts, and suggest that the effect of DNA on subsequent boosting may not be easily detectable directly after the DNA vaccination. PMID:21844392

Fever: Views in Anthroposophic Medicine and Their Scientific Validity

PubMed Central

2016-01-01

Objective. To conduct a scoping review to characterize how fever is viewed in anthroposophic medicine (AM) and discuss the scientific validity of these views. Methods. Systematic searches were run in Medline, Embase, CAMbase, and Google Scholar. Material from anthroposophic medical textbooks and articles was also used. Data was extracted and interpreted. Results. Most of the anthroposophic literature on this subject is in the German language. Anthroposophic physicians hold a beneficial view on fever, rarely suppress fever with antipyretics, and often use complementary means of alleviating discomfort. In AM, fever is considered to have the following potential benefits: promoting more complete recovery; preventing infection recurrences and atopic diseases; providing a unique opportunity for caregivers to provide loving care; facilitating individual development and resilience; protecting against cancer and boosting the anticancer effects of mistletoe products. These views are discussed with regard to the available scientific data. Conclusion. AM postulates that fever can be of short-term and long-term benefit in several ways; many of these opinions have become evidence-based (though still often not practiced) while others still need empirical studies to be validated, refuted, or modified. PMID:27999605

Divided Attention Can Enhance Early-Phase Memory Encoding: The Attentional Boost Effect and Study Trial Duration

ERIC Educational Resources Information Center

Mulligan, Neil W.; Spataro, Pietro

2015-01-01

Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better…

Effects of gasoline reactivity and ethanol content on boosted premixed and partially stratified low-temperature gasoline combustion (LTGC)

DOE PAGES

Dec, John E.; Yang, Yi; Ji, Chunsheng; ...

2015-04-14

Low-temperature gasoline combustion (LTGC), based on the compression ignition of a premixed or partially premixed dilute charge, can provide thermal efficiencies (TE) and maximum loads comparable to those of turbo-charged diesel engines, and ultra-low NOx and particulate emissions. Intake boosting is key to achieving high loads with dilute combustion, and it also enhances the fuel's autoignition reactivity, reducing the required intake heating or hot residuals. These effects have the advantages of increasing TE and charge density, allowing greater timing retard with good stability, and making the fuel Φ- sensitive so that partial fuel stratification (PFS) can be applied for highermore » loads and further TE improvements. However, at high boost the autoignition reactivity enhancement can become excessive, and substantial amounts of EGR are required to prevent overly advanced combustion. Accordingly, an experimental investigation has been conducted to determine how the tradeoff between the effects of intake boost varies with fuel-type and its impact on load range and TE. Five fuels are investigated: a conventional AKI=87 petroleum-based gasoline (E0), and blends of 10 and 20% ethanol with this gasoline to reduce its reactivity enhancement with boost (E10 and E20). Furthermore, a second zero-ethanol gasoline with AKI=93 (matching that of E20) was also investigated (CF-E0), and some neat ethanol data are also reported.« less

Stereotactic Body Radiotherapy: A Promising Treatment Option for the Boost of Oropharyngeal Cancers Not Suitable for Brachytherapy: A Single-Institutional Experience

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

Al-Mamgani, Abrahim, E-mail: a.al-mamgani@erasmusmc.nl; Tans, Lisa; Teguh, David N.

2012-03-15

Purpose: To prospectively assess the outcome and toxicity of frameless stereotactic body radiotherapy (SBRT) as a treatment option for boosting primary oropharyngeal cancers (OPC) in patients who not suitable for the standard brachytherapy boost (BTB). Methods and Materials: Between 2005 and 2010, 51 patients with Stage I to IV biopsy-proven OPC who were not suitable for BTB received boosts by means of SBRT (3 times 5.5 Gy, prescribed to the 80% isodose line), after 46 Gy of IMRT to the primary tumor and neck (when indicated). Endpoints of the study were local control (LC), disease-free survival (DFS), overall survival (OS),more » and acute and late toxicity. Results: After a median follow-up of 18 months (range, 6-65 months), the 2-year actuarial rates of LC, DFS, and OS were 86%, 80%, and 82%, respectively, and the 3-year rates were 70%, 66%, and 54%, respectively. The treatment was well tolerated, as there were no treatment breaks and no Grade 4 or 5 toxicity reported, either acute or chronic. The overall 2-year cumulative incidence of Grade {>=}2 late toxicity was 28%. Of the patients with 2 years with no evidence of disease (n = 20), only 1 patient was still feeding tube dependent and 2 patients had Grade 3 xerostomia. Conclusions: According to our knowledge, this study is the first report of patients with primary OPC who received boosts by means of SBRT. Patients with OPC who are not suitable for the standard BTB can safely and effectively receive boosts by SBRT. With this radiation technique, an excellent outcome was achieved. Furthermore, the SBRT boost did not have a negative impact regarding acute and late side effects.« less

AveBoost2: Boosting for Noisy Data

NASA Technical Reports Server (NTRS)

Oza, Nikunj C.

2004-01-01

AdaBoost is a well-known ensemble learning algorithm that constructs its constituent or base models in sequence. A key step in AdaBoost is constructing a distribution over the training examples to create each base model. This distribution, represented as a vector, is constructed to be orthogonal to the vector of mistakes made by the pre- vious base model in the sequence. The idea is to make the next base model's errors uncorrelated with those of the previous model. In previous work, we developed an algorithm, AveBoost, that constructed distributions orthogonal to the mistake vectors of all the previous models, and then averaged them to create the next base model s distribution. Our experiments demonstrated the superior accuracy of our approach. In this paper, we slightly revise our algorithm to allow us to obtain non-trivial theoretical results: bounds on the training error and generalization error (difference between training and test error). Our averaging process has a regularizing effect which, as expected, leads us to a worse training error bound for our algorithm than for AdaBoost but a superior generalization error bound. For this paper, we experimented with the data that we used in both as originally supplied and with added label noise-a small fraction of the data has its original label changed. Noisy data are notoriously difficult for AdaBoost to learn. Our algorithm's performance improvement over AdaBoost is even greater on the noisy data than the original data.

Radical radiotherapy incorporating a brachytherapy boost for the treatment of carcinoma of the thoracic oesophagus: results from a cohort of patients and review of the literature.

PubMed

Churn, M; Jones, B; Myint, A Sun

2002-04-01

The optimal treatment for potentially curable carcinoma of the oesophagus unsuitable for surgical resection is unresolved. An intraluminal brachytherapy boost (ILBT) can be used following external beam radiotherapy (EBRT) with or without concurrent chemotherapy (CRT). ILBT increases the dose to the tumour volume substantially while reducing the lung dose but the corresponding high dose to the oesophageal wall may cause increased complications. We report the outcomes of 32 consecutive patients treated with radical radiotherapy. A dose of 45-55 Gy in 20-25 fractions with external beam radiotherapy (EBRT) followed by an ILBT boost. Earlier in the series a low dose rate (LDR) brachytherapy technique using 125Iodine seeds delivering a dose of 20-22 Gy at 25-40 cGy/h was used. This was later superseded by high dose rate (HDR) treatments delivering 8.5-10 Gy in one fraction at 1 cm from the catheter. Patients of age below 76 years, of good performance status and with no other medical contraindication were considered for concurrent chemotherapy (CRT) using a planned regime of cisplatin (80 mg/m2 day 1) and 5-flurouracil (1 g/m2 days 1 to 4) in the first and last weeks of radiotherapy (13 patients). The EBRT and ILBT were well tolerated but 8/13 (62%) patients had dose modifications of chemotherapy in one or both cycles due to advanced age, co-morbidity or toxicity. The median follow-up period of surviving patients was 37 months (range 35-39) and the median overall survival for the whole group was 9 months. The overall survival at 1 year was 34.4% (17.6-51.2%), 15.6% (2.8-28.4%) at 2 and 3 years. Local recurrence-free survival at 1 year was 35.3% (15.9-54.7%) and 24.5% (8.3-44.6%) at 2 and 3 years (Fig. 2). Though symptom relief was good there were six cases of ulceration, six of stricture and two fistulae. Biological equivalent for tumour response (BED Gy,10) and late radiation effects (BED Gy3) were calculated for the different radiotherapy regimens using equations derived from the linear quadratic model. In this series no advantage was found in terms of local control or survival for patients receiving radiotherapy doses resulting in a BED Gy10 greater than 75% of the maximum. Similarly, no significant increase in complications was noted in those patients receiving doses resulting in a BED Gy3 > 75% of the maximum. The merits and hazards of the ILBT boost used in radical radiotherapy are discussed and the relevant literature reviewed.

Potentiating Effects of MPL on DSPC Bearing Cationic Liposomes Promote Recombinant GP63 Vaccine Efficacy: High Immunogenicity and Protection

PubMed Central

Mazumder, Saumyabrata; Maji, Mithun; Ali, Nahid

2011-01-01

Background Vaccines that activate strong specific Th1-predominant immune responses are critically needed for many intracellular pathogens, including Leishmania. The requirement for sustained and efficient vaccination against leishmaniasis is to formulate the best combination of immunopotentiating adjuvant with the stable antigen (Ag) delivery system. The aim of the present study is to evaluate the effectiveness of an immunomodulator on liposomal Ag through subcutaneous (s.c.) route of immunization, and its usefulness during prime/boost against visceral leishmaniasis (VL) in BALB/c mice. Methodology/Principal Findings Towards this goal, we formulated recombinant GP63 (rGP63)-based vaccines either with monophosphoryl lipid A-trehalose dicorynomycolate (MPL-TDM) or entrapped within cationic liposomes or both. Combinatorial administration of liposomes with MPL-TDM during prime confers activation of dendritic cells, and induces an early robust T cell response. To investigate whether the combined formulation is required for optimum immune response during boost as well, we chose to evaluate the vaccine efficacy in mice primed with combined adjuvant system followed by boosting with either rGP63 alone, in association with MPL-TDM, liposomes or both. We provide evidences that the presence of either liposomal rGP63 or combined formulations during boost is necessary for effective Th1 immune responses (IFN-γ, IL-12, NO) before challenge infection. However, boosting with MPL-TDM in conjugation with liposomal rGP63 resulted in a greater number of IFN-γ producing effector T cells, significantly higher levels of splenocyte proliferation, and Th1 responses compared to mice boosted with liposomal rGP63, after virulent Leishmania donovani (L. donovani) challenge. Moreover, combined formulations offered superior protection against intracellular amastigote replication in macrophages in vitro, and hepatic and splenic parasite load in vivo. Conclusion Our results define the immunopotentiating effect of MPL-TDM on protein Ag encapsulated in a controlled release system against experimental VL. PMID:22206029

Effect of priming/booster immunisation protocols on immune response to canine parvovirus peptide induced by vaccination with a chimaeric plant virus construct.

PubMed

Nicholas, B L; Brennan, F R; Hamilton, W D O; Wakelin, D

2003-06-02

Expression of a 17-mer peptide sequence from canine parvovirus expressed on cowpea mosaic virus (CPMV) to form chimaeric virus particles (CVPs) creates vaccine antigens that elicit strong anti-peptide immune responses in mice. Systemic (subcutaneous, s.c.) immunisation and boosting with such CVP constructs produces IgG(2a) serum antibody responses, while mucosal (intranasal, i.n.) immunisation and boosting elicits intestinal IgA responses. Combinations of systemic and mucosal routes for priming and boosting immunisations were used to examine their influence on the level, type and location of immune response generated to one of these constructs (CVP-1). In all cases, s.c. administration, whether for immunisation or boosting, generated a Th1-biased response, reflected in a predominantly IgG(2a) serum antibody isotype and secretion of IFN-gamma from in vitro-stimulated lymphocytes. Serum antibody responses were greatest in animals primed and boosted subcutaneously, and least in mucosally vaccinated mice. The i.n. exposure also led to IFN-gamma release from in vitro-stimulated cells, but serum IgG(2a) was significantly elevated only in mice primed intranasally and boosted subcutaneously. Peptide- and wild-type CPMV-specific IgA responses in gut lavage fluid were greatest in animals exposed mucosally and least in those primed and boosted subcutaneously or primed subcutaneously and boosted orally. Lymphocytes from immunised mice proliferated in response to in vitro stimulation with CPMV but not with peptide. The predominant secretion of IFN-gamma from all immunising/boosting combinations indicates that the route of vaccination and challenge does not alter the Th1 bias of the response to CVP constructs. However, optimal serum and intestinal antibody responses were achieved by combining s.c. and i.n. administration.

Attentional load and attentional boost: a review of data and theory.

PubMed

Swallow, Khena M; Jiang, Yuhong V

2013-01-01

Both perceptual and cognitive processes are limited in capacity. As a result, attention is selective, prioritizing items and tasks that are important for adaptive behavior. However, a number of recent behavioral and neuroimaging studies suggest that, at least under some circumstances, increasing attention to one task can enhance performance in a second task (e.g., the attentional boost effect). Here we review these findings and suggest a new theoretical framework, the dual-task interaction model, that integrates these findings with current views of attentional selection. To reconcile the attentional boost effect with the effects of attentional load, we suggest that temporal selection results in a temporally specific enhancement across modalities, tasks, and spatial locations. Moreover, the effects of temporal selection may be best observed when the attentional system is optimally tuned to the temporal dynamics of incoming stimuli. Several avenues of research motivated by the dual-task interaction model are then discussed.

Attentional Load and Attentional Boost: A Review of Data and Theory

PubMed Central

Swallow, Khena M.; Jiang, Yuhong V.

2013-01-01

Both perceptual and cognitive processes are limited in capacity. As a result, attention is selective, prioritizing items and tasks that are important for adaptive behavior. However, a number of recent behavioral and neuroimaging studies suggest that, at least under some circumstances, increasing attention to one task can enhance performance in a second task (e.g., the attentional boost effect). Here we review these findings and suggest a new theoretical framework, the dual-task interaction model, that integrates these findings with current views of attentional selection. To reconcile the attentional boost effect with the effects of attentional load, we suggest that temporal selection results in a temporally specific enhancement across modalities, tasks, and spatial locations. Moreover, the effects of temporal selection may be best observed when the attentional system is optimally tuned to the temporal dynamics of incoming stimuli. Several avenues of research motivated by the dual-task interaction model are then discussed. PMID:23730294

Applying additive modeling and gradient boosting to assess the effects of watershed and reach characteristics on riverine assemblages

USGS Publications Warehouse

Maloney, Kelly O.; Schmid, Matthias; Weller, Donald E.

2012-01-01

Issues with ecological data (e.g. non-normality of errors, nonlinear relationships and autocorrelation of variables) and modelling (e.g. overfitting, variable selection and prediction) complicate regression analyses in ecology. Flexible models, such as generalized additive models (GAMs), can address data issues, and machine learning techniques (e.g. gradient boosting) can help resolve modelling issues. Gradient boosted GAMs do both. Here, we illustrate the advantages of this technique using data on benthic macroinvertebrates and fish from 1573 small streams in Maryland, USA.

Prime-boost immunization using a DNA vaccine delivered by attenuated Salmonella enterica serovar typhimurium and a killed vaccine completely protects chickens from H5N1 highly pathogenic avian influenza virus.

PubMed

Pan, Zhiming; Zhang, Xiaoming; Geng, Shizhong; Fang, Qiang; You, Meng; Zhang, Lei; Jiao, Xinan; Liu, Xiufan

2010-04-01

H5N1 highly pathogenic avian influenza virus (HPAIV) has posed a great threat not only for the poultry industry but also for human health. However, an effective vaccine to provide a full spectrum of protection is lacking in the poultry field. In the current study, a novel prime-boost vaccination strategy against H5N1 HPAIV was developed: chickens were first orally immunized with a hemagglutinin (HA) DNA vaccine delivered by attenuated Salmonella enterica serovar Typhimurium, and boosting with a killed vaccine followed. Chickens in the combined vaccination group but not in single vaccination and control groups were completely protected against disease following H5N1 HPAIV intranasal challenge, with no clinical signs and virus shedding. Chickens in the prime-boost group also generated significantly higher serum hemagglutination inhibition (HI) titers and intestinal mucosal IgA titers against avian influenza virus (AIV) and higher host immune cellular responses than those from other groups before challenge. These results demonstrated that the prime-boost vaccination strategy provides an effective way to prevent and control H5N1 highly pathogenic avian influenza virus.

Application of Boosting Regression Trees to Preliminary Cost Estimation in Building Construction Projects

PubMed Central

2015-01-01

Among the recent data mining techniques available, the boosting approach has attracted a great deal of attention because of its effective learning algorithm and strong boundaries in terms of its generalization performance. However, the boosting approach has yet to be used in regression problems within the construction domain, including cost estimations, but has been actively utilized in other domains. Therefore, a boosting regression tree (BRT) is applied to cost estimations at the early stage of a construction project to examine the applicability of the boosting approach to a regression problem within the construction domain. To evaluate the performance of the BRT model, its performance was compared with that of a neural network (NN) model, which has been proven to have a high performance in cost estimation domains. The BRT model has shown results similar to those of NN model using 234 actual cost datasets of a building construction project. In addition, the BRT model can provide additional information such as the importance plot and structure model, which can support estimators in comprehending the decision making process. Consequently, the boosting approach has potential applicability in preliminary cost estimations in a building construction project. PMID:26339227

Application of Boosting Regression Trees to Preliminary Cost Estimation in Building Construction Projects.

PubMed

Shin, Yoonseok

2015-01-01

Among the recent data mining techniques available, the boosting approach has attracted a great deal of attention because of its effective learning algorithm and strong boundaries in terms of its generalization performance. However, the boosting approach has yet to be used in regression problems within the construction domain, including cost estimations, but has been actively utilized in other domains. Therefore, a boosting regression tree (BRT) is applied to cost estimations at the early stage of a construction project to examine the applicability of the boosting approach to a regression problem within the construction domain. To evaluate the performance of the BRT model, its performance was compared with that of a neural network (NN) model, which has been proven to have a high performance in cost estimation domains. The BRT model has shown results similar to those of NN model using 234 actual cost datasets of a building construction project. In addition, the BRT model can provide additional information such as the importance plot and structure model, which can support estimators in comprehending the decision making process. Consequently, the boosting approach has potential applicability in preliminary cost estimations in a building construction project.

The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster

PubMed Central

Marangi, Luigi; Mirinaviciute, Grazina; Flem, Elmira; Scalia Tomba, Gianpaolo; Guzzetta, Giorgio; Freiesleben de Blasio, Birgitte; Manfredi, Piero

2017-01-01

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3–5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation. PMID:28545047

Copper-boosting compounds: a novel concept for antimycobacterial drug discovery.

PubMed

Speer, Alexander; Shrestha, Tej B; Bossmann, Stefan H; Basaraba, Randall J; Harber, Gregory J; Michalek, Suzanne M; Niederweis, Michael; Kutsch, Olaf; Wolschendorf, Frank

2013-02-01

We and others recently identified copper resistance as important for virulence of Mycobacterium tuberculosis. Here, we introduce a high-throughput screening assay for agents that induce a copper hypersensitivity phenotype in M. tuberculosis and demonstrate that such copper-boosting compounds are effective against replicating and nonreplicating M. tuberculosis strains.

Explaining Charter School Effectiveness. NBER Working Paper No. 17332

ERIC Educational Resources Information Center

Angrist, Joshua D.; Pathak, Parag A.; Walters, Christopher R.

2011-01-01

Estimates using admissions lotteries suggest that urban charter schools boost student achievement, while charter schools in other settings do not. We explore student-level and school-level explanations for these differences using a large sample of Massachusetts charter schools. Our results show that urban charter schools boost achievement well…

Evolvability of flower geometry: Convergence in pollinator-driven morphological evolution of flowers.

PubMed

Woźniak, Natalia Joanna; Sicard, Adrien

2018-07-01

Flowers represent a key innovation during plant evolution. Driven by reproductive optimization, evolution of flower morphology has been central in boosting species diversification. In most cases, this has happened through specialized interactions with animal pollinators and subsequent reduction of gene flow between specialized morphs. While radiation has led to an enormous variability in flower forms and sizes, recurrent evolutionary patterns can be observed. Here, we discuss the targets of selection involved in major trends of pollinator-driven flower evolution. We review recent findings on their adaptive values, developmental grounds and genetic bases, in an attempt to better understand the repeated nature of pollinator-driven flower evolution. This analysis highlights how structural innovation can provide flexibility in phenotypic evolution, adaptation and speciation. Copyright © 2017 Elsevier Ltd. All rights reserved.

TRMM On-Orbit Performance Re-Accessed After Control Change

NASA Technical Reports Server (NTRS)

Bilanow, Steve

2006-01-01

The Tropical Rainfall Measuring Mission (TRMM) spacecraft, a joint mission between the U.S. and Japan, launched onboard an HI1 rocket on November 27,1997 and transitioned in August, 2001 from an average operating altitude of 350 kilometers to 402.5 kilometers. Due to problems using the Earth Sensor Assembly (ESA) at the higher altitude, TRMM switched to a backup attitude control mode. Prior to the orbit boost TRMM controlled pitch and roll to the local vertical using ESA measurements while using gyro data to propagate yaw attitude between yaw updates from the Sun sensors. After the orbit boost, a Kalman filter used 3-axis gyro data with Sun sensor and magnetometers to estimate onboard attitude. While originally intended to meet a degraded attitude accuracy of 0.7 degrees, the new control mode met the original 0.2 degree attitude accuracy requirement after improving onboard ephemeris prediction and adjusting the magnetometer calibration onboard. Independent roll attitude checks using a science instrument, the Precipitation Radar (PR) which was built in Japan, provided a novel insight into the pointing performance. The PR data helped identify the pointing errors after the orbit boost, track the performance improvements, and show subtle effects from ephemeris errors and gyro bias errors. It also helped identify average bias trends throughout the mission. Roll errors tracked by the PR from sample orbits pre-boost and post-boost are shown in Figure 1. Prior to the orbit boost the largest attitude errors were due to occasional interference in the ESA. These errors were sometime larger than 0.2 degrees in pitch and roll, but usually less, as estimated from a comprehensive review of the attitude excursions using gyro data. Sudden jumps in the onboard roll show up as spikes in the reported attitude since the control responds within tens of seconds to null the pointing error. The PR estimated roll tracks well with an estimate of the roll history propagated using gyro data. After the orbit boost, the attitude errors shown by the PR roll have a smooth sine-wave type signal because of the way that attitude errors propagate with the use of gyro data. Yaw errors couple at orbit period to roll with '/4 orbit lag. By tracking the amplitude, phase, and bias of the sinusoidal PR roll error signal, it was shown that the average pitch rotation axis tends to be offset from orbit normal in a direction perpendicular to the Sun direction, as shown in Figure 2 for a 200 day period following the orbit boost. This is a result of the higher accuracy and stability of the Sun sensor measurements relative to the magnetometer measurements used in the Kalman filter. In November, 2001 a magnetometer calibration adjustment was uploaded which improved the pointing performance, keeping the roll and yaw amplitudes within about 0.1 degrees. After the boost, onboard ephemeris errors had a direct effect on the pitch pointing, being used to compute the Earth pointing reference frame. Improvements after the orbit boost have kept the the onboard ephemeris errors generally below 20 kilometers. Ephemeris errors have secondary effects on roll and yaw, especially during high beta angle when pitch effects can couple into roll and yaw. This is illustrated in figure 3. The onboard roll bias trends as measured by PR data show correlations with the Kalman filter's gyro bias error. This particularly shows up after yaw turns (every 2 to 4 weeks) as shown in Figure 3, when a slight roll bias is observed while the onboard computed gyro biases settle to new values. As for longer term trends, the PR data shows that the roll bias was influenced by Earth horizon radiance effects prior to the boost, changing values at yaw turns, and indicated a long term drift as shown in Figure 4. After the boost, the bias variations were smaller and showed some possible correlation with solar beta angle, probably due to sun sensor misalignment effects.

Co-occurrence frequency evaluated with large language corpora boosts semantic priming effects.

PubMed

Brunellière, Angèle; Perre, Laetitia; Tran, ThiMai; Bonnotte, Isabelle

2017-09-01

In recent decades, many computational techniques have been developed to analyse the contextual usage of words in large language corpora. The present study examined whether the co-occurrence frequency obtained from large language corpora might boost purely semantic priming effects. Two experiments were conducted: one with conscious semantic priming, the other with subliminal semantic priming. Both experiments contrasted three semantic priming contexts: an unrelated priming context and two related priming contexts with word pairs that are semantically related and that co-occur either frequently or infrequently. In the conscious priming presentation (166-ms stimulus-onset asynchrony, SOA), a semantic priming effect was recorded in both related priming contexts, which was greater with higher co-occurrence frequency. In the subliminal priming presentation (66-ms SOA), no significant priming effect was shown, regardless of the related priming context. These results show that co-occurrence frequency boosts pure semantic priming effects and are discussed with reference to models of semantic network.

Optimization of heterologous DNA-prime, protein boost regimens and site of vaccination to enhance therapeutic immunity against human papillomavirus-associated disease.

PubMed

Peng, Shiwen; Qiu, Jin; Yang, Andrew; Yang, Benjamin; Jeang, Jessica; Wang, Joshua W; Chang, Yung-Nien; Brayton, Cory; Roden, Richard B S; Hung, Chien-Fu; Wu, T-C

2016-01-01

Human papillomavirus (HPV) has been identified as the primary etiologic factor of cervical cancer as well as subsets of anogenital and oropharyngeal cancers. The two HPV viral oncoproteins, E6 and E7, are uniquely and consistently expressed in all HPV infected cells and are therefore promising targets for therapeutic vaccination. Both recombinant naked DNA and protein-based HPV vaccines have been demonstrated to elicit HPV-specific CD8+ T cell responses that provide therapeutic effects against HPV-associated tumor models. Here we examine the immunogenicity in a preclinical model of priming with HPV DNA vaccine followed by boosting with filterable aggregates of HPV 16 L2E6E7 fusion protein (TA-CIN). We observed that priming twice with an HPV DNA vaccine followed by a single TA-CIN booster immunization generated the strongest antigen-specific CD8+ T cell response compared to other prime-boost combinations tested in C57BL/6 mice, whether naïve or bearing the HPV16 E6/E7 transformed syngeneic tumor model, TC-1. We showed that the magnitude of antigen-specific CD8+ T cell response generated by the DNA vaccine prime, TA-CIN protein vaccine boost combinatorial strategy is dependent on the dose of TA-CIN protein vaccine. In addition, we found that a single booster immunization comprising intradermal or intramuscular administration of TA-CIN after priming twice with an HPV DNA vaccine generated a comparable boost to E7-specific CD8+ T cell responses. We also demonstrated that the immune responses elicited by the DNA vaccine prime, TA-CIN protein vaccine boost strategy translate into potent prophylactic and therapeutic antitumor effects. Finally, as seen for repeat TA-CIN protein vaccination, we showed that the heterologous DNA prime and protein boost vaccination strategy is well tolerated by mice. Our results provide rationale for future clinical testing of HPV DNA vaccine prime, TA-CIN protein vaccine boost immunization regimen for the control of HPV-associated diseases.

Adjuvant radiotherapy with brachytherapy boost in soft tissue sarcomas

PubMed Central

Cortesi, Annalisa; Galuppi, Andrea; Arcelli, Alessandra; Romani, Fabrizio; Mattiucci, Gian Carlo; Bianchi, Giuseppe; Ferrari, Stefano; Ferraro, Andrea; Farioli, Andrea; Gambarotti, Marco; Righi, Alberto; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Buwenge, Milly; Valentini, Vincenzo; Morganti, Alessio Giuseppe; Donati, Davide; Cammelli, Silvia

2017-01-01

Purpose The standard primary treatment for soft tissue sarcoma (STS) is a wide surgical resection, preceded or followed by radiotherapy. Purpose of this retrospective study was to assess the efficacy of perioperative brachytherapy (BRT) plus postoperative external beam radiation therapy (EBRT) in patients with intermediate-high risk STS. Material and methods BRT delivered dose was 20 Gy. External beam radiation therapy was delivered with 3D-technique using multiple beams. The prescribed dose was 46 Gy to the PTV. Neoadjuvant and adjuvant chemotherapy (CHT) was used in patients with potentially chemosensitive histological subtypes. The primary aim of the study was to analyze overall survival (OS) and local control (LC) in a large patient population treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Secondary objective was to identify prognostic factors for patients outcome in terms of LC, disease-free survival (DFS), and OS. Results From 2000 to 2011, 107 patients presenting 2-3 grade (FNLCC) primary or recurrent STS were treated with surgery, perioperative BRT, and adjuvant EBRT ± CHT. Five-year LC and OS were 80.9% and 87.4%, respectively. At univariate analysis, a higher LC was recorded in primary vs. recurrent tumors (p = 0.015), and in lower limb tumors vs. other sites (p = 0.027). An improved DFS was recorded in patients with lower limb tumors vs. other sites (p = 0.034). Conclusions The combination of BRT and EBRT was able to achieve satisfactory results even in a patients population with intermediate-high risk STS. Patients with recurrent or other than lower limb sited tumors show a worse LC. PMID:28725250

A trivalent subunit antigen glycoprotein vaccine as immunotherapy for genital herpes in the guinea pig genital infection model.

PubMed

Awasthi, Sita; Hook, Lauren M; Shaw, Carolyn E; Friedman, Harvey M

2017-12-02

An estimated 417 million people worldwide ages 15 to 49 are infected with herpes simplex virus type 2 (HSV-2), the most common cause of genital ulcer disease. Some individuals experience frequent recurrences of genital lesions, while others only have subclinical infection, yet all risk transmitting infection to their intimate partners. A vaccine was developed that prevents shingles, which is a recurrent infection caused by varicella-zoster virus (VZV), a closely related member of the Herpesviridae family. The success of the VZV vaccine has stimulated renewed interest in a therapeutic vaccine for genital herpes. We have been evaluating a trivalent subunit antigen vaccine for prevention of genital herpes. Here, we assess the trivalent vaccine as immunotherapy in guinea pigs that were previously infected intravaginally with HSV-2. The trivalent vaccine contains HSV-2 glycoproteins C, D, and E (gC2, gD2, gE2) subunit antigens administered with CpG and alum as adjuvants. We previously demonstrated that antibodies to gD2 neutralize the virus while antibodies to gC2 and gE2 block their immune evasion activities, including evading complement attack and inhibiting activities mediated by the IgG Fc domain, respectively. Here, we demonstrate that the trivalent vaccine significantly boosts ELISA titers and neutralizing antibody titers. The trivalent vaccine reduces the frequency of recurrent genital lesions and vaginal shedding of HSV-2 DNA by approximately 50% and almost totally eliminates vaginal shedding of replication-competent virus, suggesting that the trivalent vaccine is a worthy candidate for immunotherapy of genital herpes.

Long-term prognostic significance of rising PSA levels following radiotherapy for localized prostate cancer - focus on overall survival.

PubMed

Freiberger, Carla; Berneking, Vanessa; Vögeli, Thomas-Alexander; Kirschner-Hermanns, Ruth; Eble, Michael J; Pinkawa, Michael

2017-06-14

The aim of this study was to evaluate the long-term prognostic significance of rising PSA levels, particularly focussing on overall survival. Two hundred ninety-five patients with localized prostate cancer were either treated with low-dose-rate (LDR) brachytherapy with I-125 seeds as monotherapy (n = 94; 145Gy), high-dose-rate (HDR) brachytherapy with Ir-192 as a boost to external beam RT (n = 66; 50.4Gy in 1.8Gy fractions EBRT + 18Gy in 9Gy fractions HDR) or EBRT alone (70.2Gy in 1.8Gy fractions; n = 135). "PSA bounce" was defined as an increase of at least 0.2 ng/ml followed by spontaneous return to pre-bounce level or lower, biochemical failure was defined according to the Phoenix definition. Median follow-up after the end of radiotherapy was 108 months. A PSA bounce showed to be a significant factor for biochemical control (BC) and overall survival (OS) after ten years (BC10 of 83% with bounce vs. 34% without, p < 0.01; OS10 of 82% with bounce vs. 59% without bounce, p < 0.01). The occurrence of a bounce, a high nadir and the therapy modality (LDR-BT vs. EBRT and HDR-BT + EBRT vs. EBRT) proved to be independent factors for PSA recurrence in multivariate Cox regression analysis. A bounce was detected significantly earlier than a PSA recurrence (median 20 months vs. 32 months after RT; p < 0.01; median PSA doubling time 5.5 vs. 5.0 months, not significant). PSA doubling time was prognostically significant in case of PSA recurrence (OS10 of 72% vs. 36% with PSA doubling time ˃ 5 months vs. ≤ 5 months; p < 0.01). Rising PSA levels within the first two years can usually be classified as a benign PSA bounce, with favourable recurrence-free and overall survival rates. PSA doubling time is an important predictor for overall survival following the diagnosis of a recurrence.

The American Society for Therapeutic Radiology and Oncology (ASTRO) evidence-based review of the role of radiosurgery for brain metastases

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

Mehta, Minesh P.; Tsao, May N.; Whelan, Timothy J.

2005-09-01

Purpose: To systematically review the evidence for the use of stereotactic radiosurgery in adult patients with brain metastases. Methods: Key clinical questions to be addressed in this evidence-based review were identified. Outcomes considered were overall survival, quality of life or symptom control, brain tumor control or response and toxicity. MEDLINE (1990-2004 June Week 2), CANCERLIT (1990-2003), CINAHL (1990-2004 June Week 2), EMBASE (1990-2004 Week 25), and the Cochrane library (2004 issue 2) databases were searched using OVID. In addition, the Physician Data Query clinical trials database, the proceedings of the American Society of Clinical Oncology (ASCO) (1997-2004), ASTRO (1997-2004), andmore » the European Society of Therapeutic Radiology and Oncology (ESTRO) (1997-2003) were searched. Data from the literature search were reviewed and tabulated. This process included an assessment of the level of evidence. Results: For patients with newly diagnosed brain metastases, managed with whole-brain radiotherapy alone vs. whole-brain radiotherapy and radiosurgery boost, there were three randomized controlled trials, zero prospective studies, and seven retrospective series (which satisfied inclusion criteria). For patients with up to three (<4 cm) newly diagnosed brain metastases (and in one study up to four brain metastases), radiosurgery boost with whole-brain radiotherapy significantly improves local brain control rates as compared with whole-brain radiotherapy alone (Level I-III evidence). In one large randomized trial, survival benefit with whole-brain radiotherapy was observed in patients with single brain metastasis. In this trial, an overall increased ability to taper down on steroid dose and an improvement in Karnofsky performance status was seen in patients who were treated with radiosurgery boost as compared with patients treated with whole-brain radiotherapy alone. However, Level I evidence regarding overall quality of life outcomes using a validated instrument has not been reported. All randomized trials showed improved local control with the addition of radiosurgery to whole-brain radiotherapy. For patients with multiple brain metastases, there is no overall survival benefit with the use of radiosurgery boost to whole-brain radiotherapy (Level I-III evidence). Radiosurgery boost is associated with a small risk of early or late toxicity. In patients treated with radiosurgery alone (withholding whole-brain radiotherapy) as initial treatment, there were 2 randomized trials, 2 prospective cohort studies, and 16 retrospective series. There is Level I to Level III evidence that the use of radiosurgery alone does not alter survival as compared to the use of whole-brain radiotherapy. However, there is Level I to Level III evidence that omission of whole-brain radiotherapy results in poorer intracranial disease control, both local and distant (defined as remaining brain, outside the radiosurgery field). Quality of life outcomes have not been adequately reported. Radiosurgery is associated with a small risk of early or late toxicity. Radiosurgery as salvage for patients with brain metastases was reported in zero randomized trials, one prospective study, and seven retrospective series. Conclusions: Based on Level I-III evidence, for selected patients with small (up to 4 cm) brain metastases (up to three in number and four in one randomized trial), the addition of radiosurgery boost to whole-brain radiotherapy improves brain control as compared with whole-brain radiotherapy alone. In patients with a single brain metastasis, radiosurgery boost with whole-brain radiotherapy improves survival. There is a small risk of toxicity associated with radiosurgery boost as compared with whole-brain radiotherapy alone. In selected patients treated with radiosurgery alone for newly diagnosed brain metastases, overall survival is not altered. However, local and distant brain control is significantly poorer with omission of upfront whole-brain radiotherapy (Level I-III evidence). Whether neurocognition or quality of life outcomes are different between initial radiosurgery alone vs. whole-brain radiotherapy (with or without radiosurgery boost) is unknown, because this has not been adequately tested. There was no statistically significant difference in overall toxicity between those treated with radiosurgery alone vs. whole-brain radiotherapy and radiosurgery boost based on an interim report from one randomized study. There is insufficient evidence as to the clinical benefit/risks radiosurgery used in the setting of recurrent or progressive brain metastases, although radiographic responses are well-documented.« less

Characterizing boosted dijet resonances with energy correlation functions

NASA Astrophysics Data System (ADS)

Chivukula, R. Sekhar; Mohan, Kirtimaan A.; Sengupta, Dipan; Simmons, Elizabeth H.

2018-03-01

Jet Energy Correlation Variables are powerful tools to study jet physics at LHC. We show that a class of such variables, known as Energy Correlation Functions can be used effectively to discover and distinguish a wide variety of boosted light dijet resonances at the LHC through sensitivity to their transverse momentum and color structures.

Intranasal mucosal boosting with an adenovirus-vectored vaccine markedly enhances the protection of BCG-primed guinea pigs against pulmonary tuberculosis.

PubMed

Xing, Zhou; McFarland, Christine T; Sallenave, Jean-Michel; Izzo, Angelo; Wang, Jun; McMurray, David N

2009-06-10

Recombinant adenovirus-vectored (Ad) tuberculosis (TB) vaccine platform has demonstrated great potential to be used either as a stand-alone or a boost vaccine in murine models. However, Ad TB vaccine remains to be evaluated in a more relevant and sensitive guinea pig model of pulmonary TB. Many vaccine candidates shown to be effective in murine models have subsequently failed to pass the test in guinea pig models. Specific pathogen-free guinea pigs were immunized with BCG, AdAg85A intranasally (i.n), AdAg85A intramuscularly (i.m), BCG boosted with AdAg85A i.n, BCG boosted with AdAg85A i.m, or treated only with saline. The animals were then infected by a low-dose aerosol of M. tuberculosis (M.tb). At the specified times, the animals were sacrificed and the levels of infection in the lung and spleen were assessed. In separate studies, the long-term disease outcome of infected animals was monitored until the termination of this study. Immunization with Ad vaccine alone had minimal beneficial effects. Immunization with BCG alone and BCG prime-Ad vaccine boost regimens significantly reduced the level of M.tb infection in the tissues to a similar extent. However, while BCG alone prolonged the survival of infected guinea pigs, the majority of BCG-immunized animals succumbed by 53 weeks post-M.tb challenge. In contrast, intranasal or intramuscular Ad vaccine boosting of BCG-primed animals markedly improved the survival rate with 60% of BCG/Ad i.n- and 40% of BCG/Ad i.m-immunized guinea pigs still surviving by 74 weeks post-aerosol challenge. Boosting, particularly via the intranasal mucosal route, with AdAg85A vaccine is able to significantly enhance the long-term survival of BCG-primed guinea pigs following pulmonary M.tb challenge. Our results thus support further evaluation of this viral-vectored TB vaccine in clinical trials.

Three-Year Durability of Immune Responses Induced by HIV-DNA and HIV-Modified Vaccinia Virus Ankara and Effect of a Late HIV-Modified Vaccinia Virus Ankara Boost in Tanzanian Volunteers.

PubMed

Joachim, Agricola; Munseri, Patricia J; Nilsson, Charlotta; Bakari, Muhammad; Aboud, Said; Lyamuya, Eligius F; Tecleab, Teghesti; Liakina, Valentina; Scarlatti, Gabriella; Robb, Merlin L; Earl, Patricia L; Moss, Bernard; Wahren, Britta; Mhalu, Fred; Ferrari, Guido; Sandstrom, Eric; Biberfeld, Gunnel

2017-08-01

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)-mediating antibodies, 70% against CRF01_AE virus-infected cells (median titer 239) and 84% against CRF01_AE gp120-coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p < .0001 and p < .05, respectively. The frequency of IFN-γ ELISpot responses increased to 95% against Gag or Env and 90% to both Gag and Env, p = .064 and p = .002, respectively. In conclusion, the HIV-DNA prime/HIV-MVA boost regimen elicited potent antibody and cellular immune responses with remarkable durability, and a third HIV-MVA immunization significantly boosted both antibody and cellular immune responses relative to the levels detected at the time of the third HIV-MVA, but not to higher levels than after the second HIV-MVA.

Chaos minimization in DC-DC boost converter using circuit parameter optimization

NASA Astrophysics Data System (ADS)

Sudhakar, N.; Natarajan, Rajasekar; Gourav, Kumar; Padmavathi, P.

2017-11-01

DC-DC converters are prone to several types of nonlinear phenomena including bifurcation, quasi periodicity, intermittency and chaos. These undesirable effects must be controlled for periodic operation of the converter to ensure the stability. In this paper an effective solution to control of chaos in solar fed DC-DC boost converter is proposed. Controlling of chaos is significantly achieved using optimal circuit parameters obtained through Bacterial Foraging Optimization Algorithm. The optimization renders the suitable parameters in minimum computational time. The obtained results are compared with the operation of traditional boost converter. Further the obtained results with BFA optimized parameter ensures the operations of the converter are within the controllable region. To elaborate the study of bifurcation analysis with optimized and unoptimized parameters are also presented.

Serum Cytokine Profiles Associated with Specific Adjuvants Used in a DNA Prime-Protein Boost Vaccination Strategy

PubMed Central

Buglione-Corbett, Rachel; Pouliot, Kimberly; Marty-Roix, Robyn; West, Kim; Wang, Shixia; Lien, Egil; Lu, Shan

2013-01-01

In recent years, heterologous prime-boost vaccines have been demonstrated to be an effective strategy for generating protective immunity, consisting of both humoral and cell-mediated immune responses against a variety of pathogens including HIV-1. Previous reports of preclinical and clinical studies have shown the enhanced immunogenicity of viral vector or DNA vaccination followed by heterologous protein boost, compared to using either prime or boost components alone. With such approaches, the selection of an adjuvant for inclusion in the protein boost component is expected to impact the immunogenicity and safety of a vaccine. In this study, we examined in a mouse model the serum cytokine and chemokine profiles for several candidate adjuvants: QS-21, Al(OH)3, monophosphoryl lipid A (MPLA) and ISCOMATRIX™ adjuvant, in the context of a previously tested pentavalent HIV-1 Env DNA prime-protein boost formulation, DP6-001. Our data revealed that the candidate adjuvants in the context of the DP6-001 formulation are characterized by unique serum cytokine and chemokine profiles. Such information will provide valuable guidance in the selection of an adjuvant for future AIDS vaccine development, with the ultimate goal of enhancing immunogenicity while minimizing reactogenicity associated with the use of an adjuvant. More significantly, results reported here will add to the knowledge on how to include an adjuvant in the context of a heterologous prime-protein boost vaccination strategy in general. PMID:24019983

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies

PubMed Central

Manitz, Juliane; Burger, Patricia; Amos, Christopher I.; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility. PMID:28785300

Pathway-Based Kernel Boosting for the Analysis of Genome-Wide Association Studies.

PubMed

Friedrichs, Stefanie; Manitz, Juliane; Burger, Patricia; Amos, Christopher I; Risch, Angela; Chang-Claude, Jenny; Wichmann, Heinz-Erich; Kneib, Thomas; Bickeböller, Heike; Hofner, Benjamin

2017-01-01

The analysis of genome-wide association studies (GWAS) benefits from the investigation of biologically meaningful gene sets, such as gene-interaction networks (pathways). We propose an extension to a successful kernel-based pathway analysis approach by integrating kernel functions into a powerful algorithmic framework for variable selection, to enable investigation of multiple pathways simultaneously. We employ genetic similarity kernels from the logistic kernel machine test (LKMT) as base-learners in a boosting algorithm. A model to explain case-control status is created iteratively by selecting pathways that improve its prediction ability. We evaluated our method in simulation studies adopting 50 pathways for different sample sizes and genetic effect strengths. Additionally, we included an exemplary application of kernel boosting to a rheumatoid arthritis and a lung cancer dataset. Simulations indicate that kernel boosting outperforms the LKMT in certain genetic scenarios. Applications to GWAS data on rheumatoid arthritis and lung cancer resulted in sparse models which were based on pathways interpretable in a clinical sense. Kernel boosting is highly flexible in terms of considered variables and overcomes the problem of multiple testing. Additionally, it enables the prediction of clinical outcomes. Thus, kernel boosting constitutes a new, powerful tool in the analysis of GWAS data and towards the understanding of biological processes involved in disease susceptibility.

DNA prime–protein boost increased the titer, avidity and persistence of anti-Aβ antibodies in wild-type mice

PubMed Central

Davtyan, H; Mkrtichyan, M; Movsesyan, N; Petrushina, I; Mamikonyan, G; Cribbs, DH; Agadjanyan, MG; Ghochikyan, A

2010-01-01

Recently, we reported that a DNA vaccine, composed of three copies of a self B cell epitope of amyloid-β (Aβ42) and the foreign T-cell epitope, Pan DR epitope (PADRE), generated strong anti-Aβ immune responses in wild-type and amyloid precursor protein transgenic animals. Although DNA vaccines have several advantages over peptide–protein vaccines, they induce lower immune responses in large animals and humans compared with those in mice. The focus of this study was to further enhance anti-Aβ11 immune responses by developing an improved DNA vaccination protocol of the prime–boost regimen, in which the priming step would use DNA and the boosting step would use recombinant protein. Accordingly, we generated DNA and recombinant protein-based epitope vaccines and showed that priming with DNA followed by boosting with a homologous recombinant protein vaccine significantly increases the anti-Aβ antibody responses and do not change the immunoglobulin G1 (IgG1) profile of humoral immune responses. Furthermore, the antibodies generated by this prime–boost regimen were long-lasting and possessed a higher avidity for binding with an Aβ42 peptide. Thus, we showed that a heterologous prime–boost regimen could be an effective protocol for developing a potent Alzheimer’s disease (AD) vaccine. PMID:19865176

Proton beam therapy for invasive bladder cancer: A prospective study of bladder-preserving therapy with combined radiotherapy and intra-arterial chemotherapy

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

Hata, Masaharu; Miyanaga, Naoto; Tokuuye, Koichi

Purpose: To present outcomes of bladder-preserving therapy with proton beam irradiation in patients with invasive bladder cancer. Methods and Materials: Twenty-five patients with transitional cell carcinoma of the urinary bladder, cT2-3N0M0, underwent transurethral resection of bladder tumor(s), followed by pelvic X-ray irradiation combined with intra-arterial chemotherapy with methotrexate and cisplatin. Upon completion of these treatments, patients were evaluated by transurethral resection biopsy. Patients with no residual tumor received proton irradiation boost to the primary sites, whereas patients demonstrating residual tumors underwent radical cystectomy. Results: Of 25 patients, 23 (92%) were free of residual tumor at the time of re-evaluation; consequently,more » proton beam therapy was applied. The remaining 2 patients presenting with residual tumors underwent radical cystectomy. Of the 23 patients treated with proton beam therapy, 9 experienced recurrence at the median follow-up time of 4.8 years: local recurrences and distant metastases in 6 and 2 patients, respectively, and both situations in 1. The 5-year overall, disease-free, and cause-specific survival rates were 60%, 50%, and 80%, respectively. The 5-year local control and bladder-preservation rates were 73% and 96%, respectively, in the patients treated with proton beam therapy. Therapy-related toxicities of Grade 3-4 were observed in 9 patients: hematologic toxicities in 6, pulmonary thrombosis in 1, and hemorrhagic cystitis in 2. Conclusions: The present bladder-preserving regimen for invasive bladder cancer was feasible and effective. Proton beam therapy might improve local control and facilitate bladder preservation.« less

Effectiveness of the BOOST-A™ online transition planning program for adolescents on the autism spectrum: a quasi-randomized controlled trial.

PubMed

Hatfield, Megan; Falkmer, Marita; Falkmer, Torbjorn; Ciccarelli, Marina

2017-01-01

The majority of existing transition planning programs are focused on people with a disability in general and may not meet the specific need of adolescents on the autism spectrum. In addition, these interventions focus on specific skills (e.g. job readiness or self-determination) rather than the overall transition planning process and there are methodological limitations to many of the studies determining their effectiveness. The Better OutcOmes & Successful Transitions for Autism (BOOST-A™) is an online program that supports adolescents on the autism spectrum to prepare for leaving school. This study aimed to determine the effectiveness of the BOOST-A™ in enhancing self-determination. A quasi-randomized controlled trial was conducted with adolescents on the autism spectrum enrolled in years 8 to 11 in Australian schools (N = 94). Participants had to have basic computer skills and the ability to write at a year 5 reading level. Participants were allocated to a control (n = 45) or intervention (n = 49) group and participants were blinded to the trial hypothesis. The intervention group used the BOOST-A™ for 12 months, while the control group participated in regular practice. Outcomes included self-determination, career planning and exploration, quality of life, environmental support and domain specific self-determination. Data were collected from parents and adolescents. There were no significant differences in overall self-determination between groups. Results indicated significant differences in favor of the intervention group in three areas: opportunity for self-determination at home as reported by parents; career exploration as reported by parents and adolescents; and transition-specific self-determination as reported by parents. Results provide preliminary evidence that the BOOST-A™ can enhance some career-readiness outcomes. Lack of significant outcomes related to self-determination at school and career planning may be due to the lack of face-to-face training and parents being the primary contacts in the study. Further research is needed to determine effectiveness of the BOOST-A™ related to post-secondary education and employment. Trial registration #ACTRN12615000119594.

Reirradiation of Prostate Cancer Local Failures After Previous Curative Radiation Therapy: Long-Term Outcome and Tolerance

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

Zilli, Thomas, E-mail: Thomas.Zilli@hcuge.ch; Faculty of Medicine, Geneva University, Geneva; Benz, Eileen

2016-10-01

Purpose: To evaluate the safety, feasibility, side-effect profile, and proof of concept of external beam radiation therapy (EBRT) with or without a brachytherapy (BT) boost for salvage of exclusive local failure after primary EBRT for prostate cancer. Methods and Materials: Fourteen patients with presumed exclusive local recurrence after primary EBRT with or without BT were considered eligible for reirradiation. The median normalized total dose in 2-Gy fractions (NTD{sub 2Gy}, α/β ratio = 1.5 Gy) was 74 Gy (range, 66-98.4 Gy) at first irradiation. Median time between the first irradiation and the reirradiation was 6.1 years (range, 4.7-10.2 years). Results: Between 2003 and 2008 salvage treatment was deliveredmore » with a median NTD{sub 2Gy} of 85.1 Gy (range, 70-93.4) to the prostate with EBRT with (n=10) or without (n=4) BT. Androgen deprivation was given to 12 patients (median time of 12 months). No grade ≥3 toxicity was observed during and within 6 weeks after RT. After a median follow-up of 94 months (range, 48-172 months) after salvage RT, 5-year grade ≥3 genitourinary and gastrointestinal toxicity-free survival figures were 77.9% ± 11.3% and 57.1% ± 13.2%, respectively. Four patients presented with combined grade 4 genitourinary/gastrointestinal toxicity. The 5-year biochemical relapse-free, local relapse-free, distant metastasis-free, and cancer-specific survival rates were 35.7% ± 12.8%, 50.0% ± 13.4%, 85.7% ± 9.4%, and 100%, respectively. Conclusion: Salvage whole-gland reirradiation for patients with a suspicion of exclusive local recurrence after initial RT may be associated with a high rate of severe radiation-induced side effects and poor long-term biochemical and local control.« less

Analysis and design of a high power, digitally-controlled spacecraft power system

NASA Technical Reports Server (NTRS)

Lee, F. C.; Cho, B. H.

1990-01-01

The progress to date on the analysis and design of a high power, digitally controlled spacecraft power system is described. Several battery discharger topologies were compared for use in the space platform application. Updated information has been provided on the battery voltage specification. Initially it was thought to be in the 30 to 40 V range. It is now specified to be 53 V to 84 V. This eliminated the tapped-boost and the current-fed auto-transformer converters from consideration. After consultations with NASA, it was decided to trade-off the following topologies: (1) boost converter; (2) multi-module, multi-phase boost converter; and (3) voltage-fed push-pull with auto-transformer. A non-linear design optimization software tool was employed to facilitate an objective comparison. Non-linear design optimization insures that the best design of each topology is compared. The results indicate that a four-module, boost converter with each module operating 90 degrees out of phase is the optimum converter for the space platform. Large-signal and small-signal models were generated for the shunt, charger, discharger, battery, and the mode controller. The models were first tested individually according to the space platform power system specifications supplied by NASA. The effect of battery voltage imbalance on parallel dischargers was investigated with respect to dc and small-signal responses. Similarly, the effects of paralleling dischargers and chargers were also investigated. A solar array and shunt model was included in these simulations. A model for the bus mode controller (power control unit) was also developed to interface the Orbital replacement Unit (ORU) model to the platform power system. Small signal models were used to generate the bus impedance plots in the various operating modes. The large signal models were integrated into a system model, and time domain simulations were performed to verify bus regulation during mode transitions. Some changes have subsequently been incorporated into the models. The changes include the use of a four module boost discharger, and a new model for the mode controller, which includes the effects of saturation. The new simulations for the boost discharger show the improvement in bus ripple that can be achieved by phase-shifted operation of each of the boost modules.

Radiotherapy boost dose-escalation for invasive breast cancer after breast-conserving surgery: 2093 patients treated with a prospective margin-directed policy.

PubMed

Livi, Lorenzo; Meattini, Icro; Franceschini, Davide; Saieva, Calogero; Meacci, Fiammetta; Marrazzo, Livia; Gerlain, Elena; Desideri, Isacco; Scotti, Vieri; Nori, Jacopo; Sanchez, Luis Jose; Orzalesi, Lorenzo; Bonomo, Pierluigi; Greto, Daniela; Bianchi, Simonetta; Biti, Giampaolo

2013-08-01

To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS). A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive. After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence. Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Cost-effectiveness of competing strategies for management of recurrent Clostridium difficile infection: a decision analysis.

PubMed

Konijeti, Gauree G; Sauk, Jenny; Shrime, Mark G; Gupta, Meera; Ananthakrishnan, Ashwin N

2014-06-01

Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI.

CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8+ TEM and CD8+ TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease.

PubMed

Srivastava, Ruchi; Khan, Arif A; Chilukuri, Sravya; Syed, Sabrina A; Tran, Tien T; Furness, Julie; Bahraoui, Elmostafa; BenMohamed, Lbachir

2017-07-15

Herpes simplex virus 1 (HSV-1) establishes latency within the sensory neurons of the trigeminal ganglia (TG). HSV-specific memory CD8 + T cells play a critical role in preventing HSV-1 reactivation from TG and subsequent virus shedding in tears that trigger recurrent corneal herpetic disease. The CXC chemokine ligand 10 (CXCL10)/CXC chemokine receptor 3 (CXCR3) chemokine pathway promotes T cell immunity to many viral pathogens, but its importance in CD8 + T cell immunity to recurrent herpes has been poorly elucidated. In this study, we determined how the CXCL10/CXCR3 pathway affects TG- and cornea-resident CD8 + T cell responses to recurrent ocular herpesvirus infection and disease using a well-established murine model in which HSV-1 reactivation was induced from latently infected TG by UV-B light. Following UV-B-induced HSV-1 reactivation, a significant increase in both the number and function of HSV-specific CXCR3 + CD8 + T cells was detected in TG and corneas of protected C57BL/6 (B6) mice, but not in TG and corneas of nonprotected CXCL10 -/- or CXCR3 -/- deficient mice. This increase was associated with a significant reduction in both virus shedding and recurrent corneal herpetic disease. Furthermore, delivery of exogenous CXCL10 chemokine in TG of CXCL10 -/- mice, using the neurotropic adeno-associated virus type 8 (AAV8) vector, boosted the number and function of effector memory CD8 + T cells (T EM ) and tissue-resident memory CD8 + T cells (T RM ), but not of central memory CD8 + T cells (T CM ), locally within TG, and improved protection against recurrent herpesvirus infection and disease in CXCL10 -/- deficient mice. These findings demonstrate that the CXCL10/CXCR3 chemokine pathway is critical in shaping CD8 + T cell immunity, locally within latently infected tissues, which protects against recurrent herpesvirus infection and disease. IMPORTANCE We determined how the CXCL10/CXCR3 pathway affects CD8 + T cell responses to recurrent ocular herpesvirus infection and disease. Using a well-established murine model, in which HSV-1 reactivation in latently infected trigeminal ganglia was induced by UV-B light, we demonstrated that lack of either CXCL10 chemokine or its CXCR3 receptor compromised the mobilization of functional CD8 + T EM and CD8 + T RM cells within latently infected trigeminal ganglia following virus reactivation. This lack of T cell mobilization was associated with an increase in recurrent ocular herpesvirus infection and disease. Inversely, augmenting the amount of CXCL10 in trigeminal ganglia of latently infected CXCL10-deficient mice significantly restored the number of local antiviral CD8 + T EM and CD8 + T RM cells associated with protection against recurrent ocular herpes. Based on these findings, a novel "prime/pull" therapeutic ocular herpes vaccine strategy is proposed and discussed. Copyright © 2017 American Society for Microbiology.

A single dose of a DNA vaccine encoding apa coencapsulated with 6,6'-trehalose dimycolate in microspheres confers long-term protection against tuberculosis in Mycobacterium bovis BCG-primed mice.

PubMed

Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C C; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon; Horn, Cynthia

2013-08-01

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6'-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice

PubMed Central

Carlétti, Dyego; Morais da Fonseca, Denise; Gembre, Ana Flávia; Masson, Ana Paula; Weijenborg Campos, Lívia; Leite, Luciana C. C.; Rodrigues Pires, Andréa; Lannes-Vieira, Joseli; Lopes Silva, Célio; Bonato, Vânia Luiza Deperon

2013-01-01

Mycobacterium bovis BCG prime DNA (Mycobacterium tuberculosis genes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted by M. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratracheal M. tuberculosis challenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carrying apa and 6,6′-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB. PMID:23740922

SemiBoost: boosting for semi-supervised learning.

PubMed

Mallapragada, Pavan Kumar; Jin, Rong; Jain, Anil K; Liu, Yi

2009-11-01

Semi-supervised learning has attracted a significant amount of attention in pattern recognition and machine learning. Most previous studies have focused on designing special algorithms to effectively exploit the unlabeled data in conjunction with labeled data. Our goal is to improve the classification accuracy of any given supervised learning algorithm by using the available unlabeled examples. We call this as the Semi-supervised improvement problem, to distinguish the proposed approach from the existing approaches. We design a metasemi-supervised learning algorithm that wraps around the underlying supervised algorithm and improves its performance using unlabeled data. This problem is particularly important when we need to train a supervised learning algorithm with a limited number of labeled examples and a multitude of unlabeled examples. We present a boosting framework for semi-supervised learning, termed as SemiBoost. The key advantages of the proposed semi-supervised learning approach are: 1) performance improvement of any supervised learning algorithm with a multitude of unlabeled data, 2) efficient computation by the iterative boosting algorithm, and 3) exploiting both manifold and cluster assumption in training classification models. An empirical study on 16 different data sets and text categorization demonstrates that the proposed framework improves the performance of several commonly used supervised learning algorithms, given a large number of unlabeled examples. We also show that the performance of the proposed algorithm, SemiBoost, is comparable to the state-of-the-art semi-supervised learning algorithms.

Boosted nutritional quality of food by CO2 enrichment fails to offset energy demand of herbivores under ocean warming, causing energy depletion and mortality.

PubMed

Leung, Jonathan Y S; Nagelkerken, Ivan; Russell, Bayden D; Ferreira, Camilo M; Connell, Sean D

2018-05-20

The CO 2 -boosted trophic transfer from primary producers to herbivores has been increasingly discovered at natural CO 2 vents and in laboratory experiments. Despite the emerging knowledge of this boosting effect, we do not know the extent to which it may be enhanced or dampened by ocean warming. We investigated whether ocean acidification and warming enhance the nutritional quality (C:N ratio) and energy content of turf algae, which is speculated to drive higher feeding rate, greater energy budget and eventually faster growth of herbivores. This proposal was tested by observing the physiological (feeding rate, respiration rate and energy budget) and demographic responses (growth and survival) of a common grazing gastropod (Phasianella australis) to ocean acidification and warming in a 6-month mesocosm experiment. Whilst we observed the boosting effect of ocean acidification and warming in isolation on the energy budget of herbivores by either increasing feeding rate on the more nutritious algae or increasing energy gain per feeding effort, their growth and survival were reduced by the sublethal thermal stress under ocean warming, especially when both climate change stressors were combined. This reduced growth and survival occurred as a consequence of depleted energy reserves, suggesting that the boosting effect via trophic transfer might not sufficiently compensate for the increased energy demand imposed by ocean warming. In circumstances where ocean acidification and warming create an energy demand on herbivores that outweighs the energy enhancement of their food (i.e. primary producers), the performance of herbivores to control their blooming resources likely deteriorates and thus runaway primary production ensues. Copyright © 2018 Elsevier B.V. All rights reserved.

Process Evaluation of the Boost-A™ Transition Planning Program for Adolescents on the Autism Spectrum: A Strengths-Based Approach

ERIC Educational Resources Information Center

Hatfield, Megan; Falkmer, Marita; Falkmer, Torbjörn; Ciccarelli, Marina

2018-01-01

A process evaluation was conducted to determine the effectiveness, usability, and barriers and facilitators related to the Better OutcOmes & Successful Transitions for Autism (BOOST-A™), an online transition planning program. Adolescents on the autism spectrum (n = 33) and their parents (n = 39) provided feedback via an online questionnaire.…

Energy Management of Manned Boost-Glide Vehicles: A Historical Perspective

NASA Technical Reports Server (NTRS)

Day, Richard E.

2004-01-01

As flight progressed from propellers to jets to rockets, the propulsive energy grew exponentially. With the development of rocket-only boosted vehicles, energy management of these boost-gliders became a distinct requirement for the unpowered return to base, alternate landing site, or water-parachute landing, starting with the X-series rocket aircraft and terminating with the present-day Shuttle. The problem presented here consists of: speed (kinetic energy) - altitude (potential energy) - steep glide angles created by low lift-to-drag ratios (L/D) - distance to landing site - and the bothersome effects of the atmospheric characteristics varying with altitude. The primary discussion regards post-boost, stabilized glides; however, the effects of centrifugal and geopotential acceleration are discussed as well. The aircraft and spacecraft discussed here are the X-1, X-2, X-15, and the Shuttle; and to a lesser, comparative extent, Mercury, Gemini, Apollo, and lifting bodies. The footprints, landfalls, and methods developed for energy management are also described. The essential tools required for energy management - simulator planning, instrumentation, radar, telemetry, extended land or water range, Mission Control Center (with specialist controllers), and emergency alternate landing sites - were first established through development of early concepts and were then validated by research flight tests.

Bayesian Mapping Reveals That Attention Boosts Neural Responses to Predicted and Unpredicted Stimuli.

PubMed

Garrido, Marta I; Rowe, Elise G; Halász, Veronika; Mattingley, Jason B

2018-05-01

Predictive coding posits that the human brain continually monitors the environment for regularities and detects inconsistencies. It is unclear, however, what effect attention has on expectation processes, as there have been relatively few studies and the results of these have yielded contradictory findings. Here, we employed Bayesian model comparison to adjudicate between 2 alternative computational models. The "Opposition" model states that attention boosts neural responses equally to predicted and unpredicted stimuli, whereas the "Interaction" model assumes that attentional boosting of neural signals depends on the level of predictability. We designed a novel, audiospatial attention task that orthogonally manipulated attention and prediction by playing oddball sequences in either the attended or unattended ear. We observed sensory prediction error responses, with electroencephalography, across all attentional manipulations. Crucially, posterior probability maps revealed that, overall, the Opposition model better explained scalp and source data, suggesting that attention boosts responses to predicted and unpredicted stimuli equally. Furthermore, Dynamic Causal Modeling showed that these Opposition effects were expressed in plastic changes within the mismatch negativity network. Our findings provide empirical evidence for a computational model of the opposing interplay of attention and expectation in the brain.

Evaluation of the effect of chickenpox vaccination on shingles epidemiology using agent-based modeling.

PubMed

Rafferty, Ellen; McDonald, Wade; Qian, Weicheng; Osgood, Nathaniel D; Doroshenko, Alexander

2018-01-01

Biological interactions between varicella (chickenpox) and herpes zoster (shingles), two diseases caused by the varicella zoster virus (VZV), continue to be debated including the potential effect on shingles cases following the introduction of universal childhood chickenpox vaccination programs. We investigated how chickenpox vaccination in Alberta impacts the incidence and age-distribution of shingles over 75 years post-vaccination, taking into consideration a variety of plausible theories of waning and boosting of immunity. We developed an agent-based model representing VZV disease, transmission, vaccination states and coverage, waning and boosting of immunity in a stylized geographic area, utilizing a distance-based network. We derived parameters from literature, including modeling, epidemiological, and immunology studies. We calibrated our model to the age-specific incidence of shingles and chickenpox prior to vaccination to derive optimal combinations of duration of boosting (DoB) and waning of immunity. We conducted paired simulations with and without implementing chickenpox vaccination. We computed the count and cumulative incidence rate of shingles cases at 10, 25, 50, and 75 years intervals, following introduction of vaccination, and compared the difference between runs with vaccination and without vaccination using the Mann-Whitney U-test to determine statistical significance. We carried out sensitivity analyses by increasing and lowering vaccination coverage and removing biological effect of boosting. Chickenpox vaccination led to a decrease in chickenpox cases. The cumulative incidence of chickenpox had dropped from 1,254 cases per 100,000 person-years pre chickenpox vaccination to 193 cases per 100,000 person-years 10 years after the vaccine implementation. We observed an increase in the all-ages shingles cumulative incidence at 10 and 25 years post chickenpox vaccination and mixed cumulative incidence change at 50 and 75 years post-vaccination. The magnitude of change was sensitive to DoB and ranged from an increase of 22-100 per 100,000 person-years at 10 years post-vaccination for two and seven years of boosting respectively ( p < 0.001). At 75 years post-vaccination, cumulative incidence ranged from a decline of 70 to an increase of 71 per 100,000 person-years for two and seven years of boosting respectively ( p < 0.001). Sensitivity analyses had a minimal impact on our inferences except for removing the effect of boosting. Our model demonstrates that over the longer time period, there will be a reduction in shingles incidence driven by the depletion of the source of shingles reactivation; however in the short to medium term some age cohorts may experience an increase in shingles incidence. Our model offers a platform to further explore the relationship between chickenpox and shingles, including analyzing the impact of different chickenpox vaccination schedules and cost-effectiveness studies.

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

Carvalho, P.A.; Garada, B.M.; Loeffler, J.S.

To verify the utility of a volumetric estimation of Tl-201 uptake in the context of possible astrocytoma recurrence after surgery, radiotherapy plus stereotactic boost (radiosurgery/brachitherapy), we analyzed sequential Tl-201/Tc99m-HMPAO brain SPECT studies of 28 patients (18 m/10 f). These were categorized as having tumor mass recurrence (TM), infiltrating tumor cells but no definite tumor mass (IT), or radiation changes and necrosis (RCN) after stereotactic biopsy and/or craniotomy. SPECT studies were obtained with a high-resolution dedicated gamma camera (CERASPECT, Digital Scinitgraphics, Inc.) and image acquisition was performed after intravenous Tl-201 (18.5 MBq) and Tc-99m HMPAO (740 MBq). In order to includemore » relevant information about tumor burden, a volumetric index of Tl-201 uptake was expressed in cm{sup 3} related to voxel size (4.6 x 10{sup -3} cc) within an elliptical ROI that included the tumor area. Only voxels with a threshold {ge} 2 in relation to the average scalp Tl-201 uptake were included and this total number of voxels expressed in cc was compared to previously established maximal tumor/scalp Tl-201 uptake ratios (T/S) and histopathology. Results are presented as the median (min-max) and differences were considered significant for p<0.05. Differences were significant between all groups for both ratios and volume indices and correlation between the two variables was 0.90. In conclusion, the volumetric index of Tl-201 is similar to the maximal Tl-201 T/S ratios in discriminating tumor recurrence and radiation necrosis, suggesting a future role for the volumetric index estimation in the evaluation of treatment efficacy and patient follow-up.« less

A trivalent subunit antigen glycoprotein vaccine as immunotherapy for genital herpes in the guinea pig genital infection model

PubMed Central

Awasthi, Sita; Hook, Lauren M.; Shaw, Carolyn E.; Friedman, Harvey M.

2017-01-01

ABSTRACT An estimated 417 million people worldwide ages 15 to 49 are infected with herpes simplex virus type 2 (HSV-2), the most common cause of genital ulcer disease. Some individuals experience frequent recurrences of genital lesions, while others only have subclinical infection, yet all risk transmitting infection to their intimate partners. A vaccine was developed that prevents shingles, which is a recurrent infection caused by varicella-zoster virus (VZV), a closely related member of the Herpesviridae family. The success of the VZV vaccine has stimulated renewed interest in a therapeutic vaccine for genital herpes. We have been evaluating a trivalent subunit antigen vaccine for prevention of genital herpes. Here, we assess the trivalent vaccine as immunotherapy in guinea pigs that were previously infected intravaginally with HSV-2. The trivalent vaccine contains HSV-2 glycoproteins C, D, and E (gC2, gD2, gE2) subunit antigens administered with CpG and alum as adjuvants. We previously demonstrated that antibodies to gD2 neutralize the virus while antibodies to gC2 and gE2 block their immune evasion activities, including evading complement attack and inhibiting activities mediated by the IgG Fc domain, respectively. Here, we demonstrate that the trivalent vaccine significantly boosts ELISA titers and neutralizing antibody titers. The trivalent vaccine reduces the frequency of recurrent genital lesions and vaginal shedding of HSV-2 DNA by approximately 50% and almost totally eliminates vaginal shedding of replication-competent virus, suggesting that the trivalent vaccine is a worthy candidate for immunotherapy of genital herpes. PMID:28481687

PHASE II STUDY OF HIGH DOSE PHOTON/PROTON RADIOTHERAPY IN THE MANAGEMENT OF SPINE SARCOMAS

PubMed Central

DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.; Adams, Judith; Dean, Susan; Yeap, Beow Y.; McManus, Patricia; Rosenberg, Andrew E.; Nielsen, G. Petur; Harmon, David C.; Spiro, Ira J.; Raskin, Kevin A.; Suit, Herman D.; Yoon, Sam S.; Hornicek, Francis J.

2009-01-01

Purpose Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of ≥ 66 Gy are recommended. A Phase II clinical trial evaluated high dose photon/proton XRT for spine sarcomas. Materials/Methods Eligible patients had non-metastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or post-op photon/proton XRT +/- radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (GyRBE) to subclinical disease, 70.2 GyRBE to microscopic disease in the tumor bed, and 77.4 GyRBE to gross disease at 1.8 GyRBE q.d. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 GyRBE to surface/center. Intra-operative boost doses of 7.5-10 Gy could be given by dural plaque. Results 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n=25) or subtotal (n=12) resection or biopsy (n=13). With 48 month median follow-up, five-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence, p<0.001. Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared following 77.12-77.4 GyRBE. Conclusions Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 GyRBE are at risk for late toxicity. PMID:19095372

Streamlining the Design-to-Build Transition with Build-Optimization Software Tools.

PubMed

Oberortner, Ernst; Cheng, Jan-Fang; Hillson, Nathan J; Deutsch, Samuel

2017-03-17

Scaling-up capabilities for the design, build, and test of synthetic biology constructs holds great promise for the development of new applications in fuels, chemical production, or cellular-behavior engineering. Construct design is an essential component in this process; however, not every designed DNA sequence can be readily manufactured, even using state-of-the-art DNA synthesis methods. Current biological computer-aided design and manufacture tools (bioCAD/CAM) do not adequately consider the limitations of DNA synthesis technologies when generating their outputs. Designed sequences that violate DNA synthesis constraints may require substantial sequence redesign or lead to price-premiums and temporal delays, which adversely impact the efficiency of the DNA manufacturing process. We have developed a suite of build-optimization software tools (BOOST) to streamline the design-build transition in synthetic biology engineering workflows. BOOST incorporates knowledge of DNA synthesis success determinants into the design process to output ready-to-build sequences, preempting the need for sequence redesign. The BOOST web application is available at https://boost.jgi.doe.gov and its Application Program Interfaces (API) enable integration into automated, customized DNA design processes. The herein presented results highlight the effectiveness of BOOST in reducing DNA synthesis costs and timelines.

Nudging and Boosting: Steering or Empowering Good Decisions.

PubMed

Hertwig, Ralph; Grüne-Yanoff, Till

2017-11-01

In recent years, policy makers worldwide have begun to acknowledge the potential value of insights from psychology and behavioral economics into how people make decisions. These insights can inform the design of nonregulatory and nonmonetary policy interventions-as well as more traditional fiscal and coercive measures. To date, much of the discussion of behaviorally informed approaches has emphasized "nudges," that is, interventions designed to steer people in a particular direction while preserving their freedom of choice. Yet behavioral science also provides support for a distinct kind of nonfiscal and noncoercive intervention, namely, "boosts." The objective of boosts is to foster people's competence to make their own choices-that is, to exercise their own agency. Building on this distinction, we further elaborate on how boosts are conceptually distinct from nudges: The two kinds of interventions differ with respect to (a) their immediate intervention targets, (b) their roots in different research programs, (c) the causal pathways through which they affect behavior, (d) their assumptions about human cognitive architecture, (e) the reversibility of their effects, (f) their programmatic ambitions, and (g) their normative implications. We discuss each of these dimensions, provide an initial taxonomy of boosts, and address some possible misconceptions.

Priming-boosting vaccination with recombinant Mycobacterium bovis bacillus Calmette-Guérin and a nonreplicating vaccinia virus recombinant leads to long-lasting and effective immunity.

PubMed

Ami, Yasushi; Izumi, Yasuyuki; Matsuo, Kazuhiro; Someya, Kenji; Kanekiyo, Masaru; Horibata, Shigeo; Yoshino, Naoto; Sakai, Koji; Shinohara, Katsuaki; Matsumoto, Sohkichi; Yamada, Takeshi; Yamazaki, Shudo; Yamamoto, Naoki; Honda, Mitsuo

2005-10-01

Virus-specific T-cell responses can limit immunodeficiency virus type 1 (HIV-1) transmission and prevent disease progression and so could serve as the basis for an affordable, safe, and effective vaccine in humans. To assess their potential for a vaccine, we used Mycobacterium bovis bacillus Calmette-Guérin (BCG)-Tokyo and a replication-deficient vaccinia virus strain (DIs) as vectors to express full-length gag from simian immunodeficiency viruses (SIVs) (rBCG-SIVgag and rDIsSIVgag). Cynomolgus macaques were vaccinated with either rBCG-SIVgag dermally as a single modality or in combination with rDIsSIVgag intravenously. When cynomologus macaques were primed with rBCG-SIVgag and then boosted with rDIsSIVgag, high levels of gamma interferon (IFN-gamma) spot-forming cells specific for SIV Gag were induced. This combination regimen elicited effective protective immunity against mucosal challenge with pathogenic simian-human immunodeficiency virus for the 1 year the macaques were under observation. Antigen-specific intracellular IFN-gamma activity was similarly induced in each of the macaques with the priming-boosting regimen. Other groups receiving the opposite combination or the single-modality vaccines were not effectively protected. These results suggest that a recombinant M. bovis BCG-based vector may have potential as an HIV/AIDS vaccine when administered in combination with a replication-deficient vaccinia virus DIs vector in a priming-boosting strategy.

Cost-effectiveness of Competing Strategies for Management of Recurrent Clostridium difficile Infection: A Decision Analysis

PubMed Central

Konijeti, Gauree G.; Sauk, Jenny; Shrime, Mark G.; Gupta, Meera; Ananthakrishnan, Ashwin N.

2014-01-01

Background. Clostridium difficile infection (CDI) is an important cause of morbidity and healthcare costs, and is characterized by high rates of disease recurrence. The cost-effectiveness of newer treatments for recurrent CDI has not been examined, yet would be important to inform clinical practice. The aim of this study was to analyze the cost effectiveness of competing strategies for recurrent CDI. Methods. We constructed a decision-analytic model comparing 4 treatment strategies for first-line treatment of recurrent CDI in a population with a median age of 65 years: metronidazole, vancomycin, fidaxomicin, and fecal microbiota transplant (FMT). We modeled up to 2 additional recurrences following the initial recurrence. We assumed FMT delivery via colonoscopy as our base case, but conducted sensitivity analyses based on different modes of delivery. Willingness-to-pay threshold was set at $50 000 per quality-adjusted life-year. Results. At our base case estimates, initial treatment of recurrent CDI using FMT colonoscopy was the most cost-effective strategy, with an incremental cost-effectiveness ratio of $17 016 relative to oral vancomycin. Fidaxomicin and metronidazole were both dominated by FMT colonoscopy. On sensitivity analysis, FMT colonoscopy remained the most cost-effective strategy at cure rates >88.4% and CDI recurrence rates <14.9%. Fidaxomicin required a cost <$1359 to meet our cost-effectiveness threshold. In clinical settings where FMT is not available or applicable, the preferred strategy appears to be initial treatment with oral vancomycin. Conclusions. In this decision analysis examining treatment strategies for recurrent CDI, we demonstrate that FMT colonoscopy is the most cost-effective initial strategy for management of recurrent CDI. PMID:24692533

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

Delacrétaz, Luca V.; Senatore, Leonardo; Noumi, Toshifumi, E-mail: lvd@stanford.edu, E-mail: tnoumi@phys.sci.kobe-u.ac.jp, E-mail: senatore@stanford.edu

If time-translations are spontaneously broken, so are boosts. This symmetry breaking pattern can be non-linearly realized by either just the Goldstone boson of time translations, or by four Goldstone bosons associated with time translations and boosts. In this paper we extend the Effective Field Theory of Multifield Inflation to consider the case in which the additional Goldstone bosons associated with boosts are light and coupled to the Goldstone boson of time translations. The symmetry breaking pattern forces a coupling to curvature so that the mass of the additional Goldstone bosons is predicted to be equal to √2 H in themore » vast majority of the parameter space where they are light. This pattern therefore offers a natural way of generating self-interacting particles with Hubble mass during inflation. After constructing the general effective Lagrangian, we study how these particles mix and interact with the curvature fluctuations, generating potentially detectable non-Gaussian signals.« less

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

Delacrétaz, Luca V.; Noumi, Toshifumi; Senatore, Leonardo

If time-translations are spontaneously broken, so are boosts. This symmetry breaking pattern can be non-linearly realized by either just the Goldstone boson of time translations, or by four Goldstone bosons associated with time translations and boosts. Here in this paper we extend the Effective Field Theory of Multifield Inflation to consider the case in which the additional Goldstone bosons associated with boosts are light and coupled to the Goldstone boson of time translations. The symmetry breaking pattern forces a coupling to curvature so that the mass of the additional Goldstone bosons is predicted to be equal to √2H in themore » vast majority of the parameter space where they are light. This pattern therefore offers a natural way of generating self-interacting particles with Hubble mass during inflation. After constructing the general effective Lagrangian, we study how these particles mix and interact with the curvature fluctuations, generating potentially detectable non-Gaussian signals.« less

Symmetry boost of the fidelity of Shor factoring

NASA Astrophysics Data System (ADS)

Nam, Y. S.; Blümel, R.

2018-05-01

In Shor's algorithm quantum subroutines occur with the structure F U F-1 , where F is a unitary transform and U is performing a quantum computation. Examples are quantum adders and subunits of quantum modulo adders. In this paper we show, both analytically and numerically, that if, in analogy to spin echoes, F and F-1 can be implemented symmetrically when executing Shor's algorithm on actual, imperfect quantum hardware, such that F and F-1 have the same hardware errors, a symmetry boost in the fidelity of the combined F U F-1 quantum operation results when compared to the case in which the errors in F and F-1 are independently random. Running the complete gate-by-gate implemented Shor algorithm, we show that the symmetry-induced fidelity boost can be as large as a factor 4. While most of our analytical and numerical results concern the case of over- and under-rotation of controlled rotation gates, in the numerically accessible case of Shor's algorithm with a small number of qubits, we show explicitly that the symmetry boost is robust with respect to more general types of errors. While, expectedly, additional error types reduce the symmetry boost, we show explicitly, by implementing general off-diagonal SU (N ) errors (N =2 ,4 ,8 ), that the boost factor scales like a Lorentzian in δ /σ , where σ and δ are the error strengths of the diagonal over- and underrotation errors and the off-diagonal SU (N ) errors, respectively. The Lorentzian shape also shows that, while the boost factor may become small with increasing δ , it declines slowly (essentially like a power law) and is never completely erased. We also investigate the effect of diagonal nonunitary errors, which, in analogy to unitary errors, reduce but never erase the symmetry boost. Going beyond the case of small quantum processors, we present analytical scaling results that show that the symmetry boost persists in the practically interesting case of a large number of qubits. We illustrate this result explicitly for the case of Shor factoring of the semiprime RSA-1024, where, analytically, focusing on over- and underrotation errors, we obtain a boost factor of about 10. In addition, we provide a proof of the fidelity product formula, including its range of applicability.

An implementation of discrete electron transport models for gold in the Geant4 simulation toolkit

NASA Astrophysics Data System (ADS)

Sakata, D.; Incerti, S.; Bordage, M. C.; Lampe, N.; Okada, S.; Emfietzoglou, D.; Kyriakou, I.; Murakami, K.; Sasaki, T.; Tran, H.; Guatelli, S.; Ivantchenko, V. N.

2016-12-01

Gold nanoparticle (GNP) boosted radiation therapy can enhance the biological effectiveness of radiation treatments by increasing the quantity of direct and indirect radiation-induced cellular damage. As the physical effects of GNP boosted radiotherapy occur across energy scales that descend down to 10 eV, Monte Carlo simulations require discrete physics models down to these very low energies in order to avoid underestimating the absorbed dose and secondary particle generation. Discrete physics models for electron transportation down to 10 eV have been implemented within the Geant4-DNA low energy extension of Geant4. Such models allow the investigation of GNP effects at the nanoscale. At low energies, the new models have better agreement with experimental data on the backscattering coefficient, and they show similar performance for transmission coefficient data as the Livermore and Penelope models already implemented in Geant4. These new models are applicable in simulations focussed towards estimating the relative biological effectiveness of radiation in GNP boosted radiotherapy applications with photon and electron radiation sources.

Finding structure in data using multivariate tree boosting

PubMed Central

Miller, Patrick J.; Lubke, Gitta H.; McArtor, Daniel B.; Bergeman, C. S.

2016-01-01

Technology and collaboration enable dramatic increases in the size of psychological and psychiatric data collections, but finding structure in these large data sets with many collected variables is challenging. Decision tree ensembles such as random forests (Strobl, Malley, & Tutz, 2009) are a useful tool for finding structure, but are difficult to interpret with multiple outcome variables which are often of interest in psychology. To find and interpret structure in data sets with multiple outcomes and many predictors (possibly exceeding the sample size), we introduce a multivariate extension to a decision tree ensemble method called gradient boosted regression trees (Friedman, 2001). Our extension, multivariate tree boosting, is a method for nonparametric regression that is useful for identifying important predictors, detecting predictors with nonlinear effects and interactions without specification of such effects, and for identifying predictors that cause two or more outcome variables to covary. We provide the R package ‘mvtboost’ to estimate, tune, and interpret the resulting model, which extends the implementation of univariate boosting in the R package ‘gbm’ (Ridgeway et al., 2015) to continuous, multivariate outcomes. To illustrate the approach, we analyze predictors of psychological well-being (Ryff & Keyes, 1995). Simulations verify that our approach identifies predictors with nonlinear effects and achieves high prediction accuracy, exceeding or matching the performance of (penalized) multivariate multiple regression and multivariate decision trees over a wide range of conditions. PMID:27918183

Dosimetric evaluation of simultaneous integrated boost during stereotactic body radiation therapy for pancreatic cancer

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

Yang, Wensha, E-mail: wensha.yang@cshs.org; Reznik, Robert; Fraass, Benedick A.

Stereotactic body radiation therapy (SBRT) provides a promising way to treat locally advanced pancreatic cancer and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage otherwise likely positive surgical margins. Despite the potential benefit of using SIB-SBRT, the ability to boost is limited by the local geometry of the organs at risk (OARs), such as stomach, duodenum, and bowel (SDB), relative to tumor. In this study, we have retrospectively replanned 20 patients with 25 Gy prescribed to the planning target volume (PTV) and 33~80 Gymore » to the boost target volume (BTV) using an SIB technique for all patients. The number of plans and patients able to satisfy a set of clinically established constraints is analyzed. The ability to boost vessels (within the gross target volume [GTV]) is shown to correlate with the overlap volume (OLV), defined to be the overlap between the GTV + a 1(OLV1)- or 2(OLV2)-cm margin with the union of SDB. Integral dose, boost dose contrast (BDC), biologically effective BDC, tumor control probability for BTV, and normal tissue complication probabilities are used to analyze the dosimetric results. More than 65% of the cases can deliver a boost to 40 Gy while satisfying all OAR constraints. An OLV2 of 100 cm{sup 3} is identified as the cutoff volume: for cases with OLV2 larger than 100 cm{sup 3}, it is very unlikely the case could achieve 25 Gy to the PTV while successfully meeting all the OAR constraints.« less

Dosimetric evaluation of simultaneous integrated boost during stereotactic body radiation therapy for pancreatic cancer.

PubMed

Yang, Wensha; Reznik, Robert; Fraass, Benedick A; Nissen, Nicholas; Hendifar, Andrew; Wachsman, Ashley; Sandler, Howard; Tuli, Richard

2015-01-01

Stereotactic body radiation therapy (SBRT) provides a promising way to treat locally advanced pancreatic cancer and borderline resectable pancreatic cancer. A simultaneous integrated boost (SIB) to the region of vessel abutment or encasement during SBRT has the potential to downstage otherwise likely positive surgical margins. Despite the potential benefit of using SIB-SBRT, the ability to boost is limited by the local geometry of the organs at risk (OARs), such as stomach, duodenum, and bowel (SDB), relative to tumor. In this study, we have retrospectively replanned 20 patients with 25Gy prescribed to the planning target volume (PTV) and 33~80Gy to the boost target volume (BTV) using an SIB technique for all patients. The number of plans and patients able to satisfy a set of clinically established constraints is analyzed. The ability to boost vessels (within the gross target volume [GTV]) is shown to correlate with the overlap volume (OLV), defined to be the overlap between the GTV + a 1(OLV1)- or 2(OLV2)-cm margin with the union of SDB. Integral dose, boost dose contrast (BDC), biologically effective BDC, tumor control probability for BTV, and normal tissue complication probabilities are used to analyze the dosimetric results. More than 65% of the cases can deliver a boost to 40Gy while satisfying all OAR constraints. An OLV2 of 100cm(3) is identified as the cutoff volume: for cases with OLV2 larger than 100cm(3), it is very unlikely the case could achieve 25Gy to the PTV while successfully meeting all the OAR constraints. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Computer simulations of optimum boost and buck-boost converters

NASA Technical Reports Server (NTRS)

Rahman, S.

1982-01-01

The development of mathematicl models suitable for minimum weight boost and buck-boost converter designs are presented. The facility of an augumented Lagrangian (ALAG) multiplier-based nonlinear programming technique is demonstrated for minimum weight design optimizations of boost and buck-boost power converters. ALAG-based computer simulation results for those two minimum weight designs are discussed. Certain important features of ALAG are presented in the framework of a comprehensive design example for boost and buck-boost power converter design optimization. The study provides refreshing design insight of power converters and presents such information as weight annd loss profiles of various semiconductor components and magnetics as a function of the switching frequency.

A prime-boost vaccination strategy using attenuated Salmonella typhimurium and a replication-deficient recombinant adenovirus vector elicits protective immunity against human respiratory syncytial virus.

PubMed

Fu, Yuan-Hui; He, Jin-Sheng; Wang, Xiao-Bo; Zheng, Xian-Xian; Wu, Qiang; Xie, Can; Zhang, Mei; Wei, Wei; Tang, Qian; Song, Jing-Dong; Qu, Jian-Guo; Hong, Tao

2010-04-23

Human respiratory syncytial virus (RSV), for which no clinically approved vaccine is available yet, is globally a serious pediatric pathogen of the lower respiratory tract. Several approaches have been used to develop vaccines against RSV, but none of these have been approved for use in humans. An efficient vaccine-enhancing strategy for RSV is still urgently needed. We found previously that oral SL7207/pcDNA3.1/F and intranasal FGAd/F were able to induce an effective protective immune response against RSV. The heterologous prime-boost immunization regime has been reported recently to be an efficient vaccine-enhancing strategy. Therefore, we investigated the ability of an oral SL7207/pcDNA3.1/F prime and intranasal (i.n.) FGAd/F boost regimen to generate immune responses to RSV. The SL7207/pcDNA3.1/F prime-FGAd/F boost regimen generated stronger RSV-specific humoral and mucosal immune responses in BALB/c mice than the oral SL7207/pcDNA3.1/F regimen alone, and stronger specific cellular immune responses than the i.n. FGAd/F regimen alone. Histopathological analysis showed an increased efficacy against RSV challenge by the heterologous prime-boost regimen. These results suggest that such a heterologous prime-boost strategy can enhance the efficacy of either the SL7207 or the FGAd vector regimen in generating immune responses in BALB/c mice. 2010 Elsevier Inc. All rights reserved.

Improved semi-supervised online boosting for object tracking

NASA Astrophysics Data System (ADS)

Li, Yicui; Qi, Lin; Tan, Shukun

2016-10-01

The advantage of an online semi-supervised boosting method which takes object tracking problem as a classification problem, is training a binary classifier from labeled and unlabeled examples. Appropriate object features are selected based on real time changes in the object. However, the online semi-supervised boosting method faces one key problem: The traditional self-training using the classification results to update the classifier itself, often leads to drifting or tracking failure, due to the accumulated error during each update of the tracker. To overcome the disadvantages of semi-supervised online boosting based on object tracking methods, the contribution of this paper is an improved online semi-supervised boosting method, in which the learning process is guided by positive (P) and negative (N) constraints, termed P-N constraints, which restrict the labeling of the unlabeled samples. First, we train the classification by an online semi-supervised boosting. Then, this classification is used to process the next frame. Finally, the classification is analyzed by the P-N constraints, which are used to verify if the labels of unlabeled data assigned by the classifier are in line with the assumptions made about positive and negative samples. The proposed algorithm can effectively improve the discriminative ability of the classifier and significantly alleviate the drifting problem in tracking applications. In the experiments, we demonstrate real-time tracking of our tracker on several challenging test sequences where our tracker outperforms other related on-line tracking methods and achieves promising tracking performance.

Clinical results of conformal versus intensity-modulated radiotherapy using a focal simultaneous boost for muscle-invasive bladder cancer in elderly or medically unfit patients.

PubMed

Lutkenhaus, Lotte J; van Os, Rob M; Bel, Arjan; Hulshof, Maarten C C M

2016-03-18

For elderly or medically unfit patients with muscle-invasive bladder cancer, cystectomy or chemotherapy are contraindicated. This leaves radical radiotherapy as the only treatment option. It was the aim of this study to retrospectively analyze the treatment outcome and associated toxicity of conformal versus intensity-modulated radiotherapy (IMRT) using a focal simultaneous tumor boost for muscle-invasive bladder cancer in patients not suitable for cystectomy. One hundred eighteen patients with T2-4 N0-1 M0 bladder cancer were analyzed retrospectively. Median age was 80 years. Treatment consisted of either a conformal box technique or IMRT and included a simultaneous boost to the tumor. To enable an accurate boost delivery, fiducial markers were placed around the tumor. Patients were treated with 40 Gy in 20 fractions to the elective treatment volumes, and a daily tumor boost up to 55-60 Gy. Clinical complete response was seen in 87 % of patients. Three-year overall survival was 44 %, with a locoregional control rate of 73 % at 3 years. Toxicity was low, with late urinary and intestinal toxicity rates grade ≥ 2 of 14 and 5 %, respectively. The use of IMRT reduced late intestinal toxicity, whereas fiducial markers reduced acute urinary toxicity. Radical radiotherapy using a focal boost is feasible and effective for elderly or unfit patients, with a 3-year locoregional control of 73 %. Toxicity rates were low, and were reduced by the use of IMRT and fiducial markers.

Online boosting for vehicle detection.

PubMed

Chang, Wen-Chung; Cho, Chih-Wei

2010-06-01

This paper presents a real-time vision-based vehicle detection system employing an online boosting algorithm. It is an online AdaBoost approach for a cascade of strong classifiers instead of a single strong classifier. Most existing cascades of classifiers must be trained offline and cannot effectively be updated when online tuning is required. The idea is to develop a cascade of strong classifiers for vehicle detection that is capable of being online trained in response to changing traffic environments. To make the online algorithm tractable, the proposed system must efficiently tune parameters based on incoming images and up-to-date performance of each weak classifier. The proposed online boosting method can improve system adaptability and accuracy to deal with novel types of vehicles and unfamiliar environments, whereas existing offline methods rely much more on extensive training processes to reach comparable results and cannot further be updated online. Our approach has been successfully validated in real traffic environments by performing experiments with an onboard charge-coupled-device camera in a roadway vehicle.

Notch-Boosted Domain Wall Propagation in Magnetic Nanowires

NASA Astrophysics Data System (ADS)

Wang, Xiang Rong; Yuan, Hauiyang

Magnetic domain wall (DW) motion along a nanowire underpins many proposals of spintronic devices. High DW propagation velocity is obviously important because it determines the device speed. Thus it is interesting to search for effective control knobs of DW dynamics. We report a counter-intuitive finding that notches in an otherwise homogeneous magnetic nanowire can boost current-induced domain wall (DW) propagation. DW motion in notch-modulated wires can be classified into three phases: 1) A DW is pinned around a notch when the current density is below the depinning current density. 2) DW propagation velocity above the depinning current density is boosted by notches when non-adiabatic spin-transfer torque strength is smaller than the Gilbert damping constant. The boost can be many-fold. 3) DW propagation velocity is hindered when non-adiabatic spin-transfer torque strength is larger than the Gilbert damping constant. This work was supported by Hong Kong GRF Grants (Nos. 163011151 and 605413) and the Grant from NNSF of China (No. 11374249).

Boosted performance of a compression-ignition engine with a displaced piston

NASA Technical Reports Server (NTRS)

Moore, Charles S; Foster, Hampton H

1936-01-01

Performance tests were made using a rectangular displacer arranged so that the combustion air was forced through equal passages at either end of the displacer into the vertical-disk combustion chamber of a single-cylinder, four-stroke-cycle compression-ignition test engine. After making tests to determine optimum displacer height, shape, and fuel-spray arrangement, engine-performance tests were made at 1,500 and 2,000 r.p.m. for a range of boost pressures from 0 to 20 inches of mercury and for maximum cylinder pressures up to 1,150 pounds per square inch. The engine operation for boosted conditions was very smooth, there being no combustion shock even at the highest maximum cylinder pressures. Indicated mean effective pressures of 240 pounds per square inch for fuel consumptions of 0.39 pound per horsepower-hour have been readily reproduced during routine testing at 2,000 r.p.m. at a boost pressure of 20 inches of mercury.

Simulation comparison of proportional integral derivative and fuzzy logic in controlling AC-DC buck boost converter

NASA Astrophysics Data System (ADS)

Faisal, A.; Hasan, S.; Suherman

2018-03-01

AC-DC converter is widely used in the commercial industry even for daily purposes. The AC-DC converter is used to convert AC voltage into DC. In order to obtain the desired output voltage, the converter usually has a controllable regulator. This paper discusses buck boost regulator with a power MOSFET as switching component which is adjusted based on the duty cycle of pulse width modulation (PWM). The main problems of the buck boost converter at start up are the high overshoot, the long peak time and rise time. This paper compares the effectiveness of two control techniques: proportional integral derivative (PID) and fuzzy logic control in controlling the buck boost converter through simulations. The results show that the PID is more sensitive to voltage change than fuzzy logic. However, PID generates higher overshoot, long peak time and rise time. On the other hand, fuzzy logic generates no overshoot and shorter rise time.

Prime-boost bacillus Calmette-Guérin vaccination with lentivirus-vectored and DNA-based vaccines expressing antigens Ag85B and Rv3425 improves protective efficacy against Mycobacterium tuberculosis in mice.

PubMed

Xu, Ying; Yang, Enzhuo; Wang, Jianguang; Li, Rui; Li, Guanghua; Liu, Guoyuan; Song, Na; Huang, Qi; Kong, Cong; Wang, Honghai

2014-10-01

To prevent the global spread of tuberculosis (TB), more effective vaccines and vaccination strategies are urgently needed. As a result of the success of bacillus Calmette-Guérin (BCG) in protecting children against miliary and meningeal TB, the majority of individuals will have been vaccinated with BCG; hence, boosting BCG-primed immunity will probably be a key component of future vaccine strategies. In this study, we compared the ability of DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 to boost the effects of BCG in the context of immunity and protection against Mycobacterium tuberculosis in C57BL/6 mice. Our results demonstrated that prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including T helper type 1 and CD8(+) cytotoxic T lymphocyte responses, compared with DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis, as indicated by a lack of weight loss and significantly reduced bacterial loads and histological damage in the lung. Our study suggests that the use of lentiviral or DNA vaccines containing the antigens Ag85B and Rv3425 to boost BCG is a good choice for the rational design of an efficient vaccination strategy against TB. © 2014 John Wiley & Sons Ltd.

A peptide prime-DNA boost immunization protocol provides significant benefits as a new generation Aβ42 DNA vaccine for Alzheimer disease.

PubMed

Lambracht-Washington, Doris; Qu, Bao-xi; Fu, Min; Anderson, Larry D; Eagar, Todd N; Stüve, Olaf; Rosenberg, Roger N

2013-01-15

Immunotherapy has the potential to provide a possible treatment therapy to prevent or delay Alzheimer disease. In a clinical trial (AN1792) in which patients received this immunotherapy and received active Aβ1-42 peptide immunizations, treatment was stopped when 6% of patients showed signs of meningoencephalitis. Follow up on these patients led to the conclusion that the antibody response was beneficial in removing Aβ1-42 from brain but an accompanying inflammatory Th1 T cell response was harmful. As a safe alternative treatment targeting the same self protein, Aβ1-42, in brain, we and others are working on a DNA Aβ1-42 immunization protocol as the immune response to DNA immunizations differs in many aspects from immunizations with peptide antigens. Because the immune response to DNA vaccination has different kinetics and has a significantly lower antibody production, we evaluated two different prime boost regimens, Aβ1-42 DNA prime/Aβ1-42 peptide boost and Aβ1-42 peptide prime/Aβ1-42 DNA boost for their effectiveness in antibody production and possible side effects due to inflammatory T cell responses. While both boost regimes significantly enhanced the specific antibody production with comparable antibody concentrations, the absence of the Aβ1-42 T cell response (no proliferation and no cytokine production) is consistent with our previous findings using this DNA Aβ1-42 trimer immunization and greatly enhances the safety aspect for possible clinical use. Copyright © 2012 Elsevier B.V. All rights reserved.

Transcriptomics of the Vaccine Immune Response: Priming With Adjuvant Modulates Recall Innate Responses After Boosting.

PubMed

Santoro, Francesco; Pettini, Elena; Kazmin, Dmitri; Ciabattini, Annalisa; Fiorino, Fabio; Gilfillan, Gregor D; Evenroed, Ida M; Andersen, Peter; Pozzi, Gianni; Medaglini, Donata

2018-01-01

Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of Mycobacterium tuberculosis administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7 days after priming and after boosting. Gene expression analysis at day 2 after priming showed that the CAF01 adjuvanted vaccine induced a stronger upregulation of the innate immunity modules compared with the unadjuvanted formulation. The immunostimulant effect of the CAF01 adjuvant, used in the primary immunization, was clearly seen after a booster immunization with a low dose of antigen alone. One day after boost, we observed a strong upregulation of multiple genes in blood of mice primed with H56 + CAF01 compared with mice primed with the H56 alone. In particular, blood transcription modules related to innate immune response, such as monocyte and neutrophil recruitment, activation of antigen-presenting cells, and interferon response were activated. Seven days after boost, differential expression of innate response genes faded while a moderate differential expression of T cell activation modules was appreciable. Indeed, immunological analysis showed a higher frequency of H56-specific CD4+ T cells and germinal center B cells in draining lymph nodes, a strong H56-specific humoral response and a higher frequency of antibody-secreting cells in spleen of mice primed with H56 + CAF01. Taken together, these data indicate that the adjuvant used for priming strongly reprograms the immune response that, upon boosting, results in a stronger recall innate response essential for shaping the downstream adaptive response.

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

PubMed

Wilkowski, Ralf; Thoma, Martin; Weingandt, Helmut; Dühmke, Eckhart; Heinemann, Volker

2005-05-10

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Long-term Outcomes of Hypofractionation Versus Conventional Radiation Therapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ of the Breast

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

Lalani, Nafisha; Paszat, Lawrence; Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario

Purpose: Whole-breast radiation therapy (XRT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) may decrease the risk of local recurrence, but the optimal dose regimen remains unclear. Past studies administered 50 Gy in 25 fractions (conventional); however, treatment pattern studies report that hypofractionated (HF) regimens (42.4 Gy in 16 fractions) are frequently used. We report the impact of HF (vs conventional) on the risk of local recurrence after BCS for DCIS. Methods and Materials: All women with DCIS treated with BCS and XRT in Ontario, Canada from 1994 to 2003 were identified. Treatment and outcomes were assessed through administrative databasesmore » and validated by chart review. Survival analyses were performed. To account for systematic differences between women treated with alternate regimens, we used a propensity score adjustment approach. Results: We identified 1609 women, of whom 971 (60%) received conventional regimens and 638 (40%) received HF. A total of 489 patients (30%) received a boost dose, of whom 143 (15%) received conventional radiation therapy and 346 (54%) received HF. The median follow-up time was 9.2 years. The median age at diagnosis was 56 years (interquartile range [IQR], 49-65 years). On univariate analyses, the 10-year actuarial local recurrence–free survival was 86% for conventional radiation therapy and 89% for HF (P=.03). On multivariable analyses, age <45 years (hazard ratio [HR] = 2.4; 95% CI: 1.6-3.4; P<.0001), high (HR=2.9; 95% CI: 1.2-7.3; P=.02) or intermediate nuclear grade (HR=2.7; 95% CI: 1.1-6.6; P=.04), and positive resection margins (HR=1.4; 95% CI: 1.0-2.1; P=.05) were associated with an increased risk of local recurrence. HF was not significantly associated with an increased risk of local recurrence compared with conventional radiation therapy on multivariate analysis (HR=0.8; 95% CI: 0.5-1.2; P=.34). Conclusions: The risk of local recurrence among individuals treated with HF regimens after BCS for DCIS was similar to that among individuals treated with conventional radiation therapy.« less

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

Dec, John E.; Yang, Yi; Ji, Chunsheng

Low-temperature gasoline combustion (LTGC), based on the compression ignition of a premixed or partially premixed dilute charge, can provide thermal efficiencies (TE) and maximum loads comparable to those of turbo-charged diesel engines, and ultra-low NOx and particulate emissions. Intake boosting is key to achieving high loads with dilute combustion, and it also enhances the fuel's autoignition reactivity, reducing the required intake heating or hot residuals. These effects have the advantages of increasing TE and charge density, allowing greater timing retard with good stability, and making the fuel Φ- sensitive so that partial fuel stratification (PFS) can be applied for highermore » loads and further TE improvements. However, at high boost the autoignition reactivity enhancement can become excessive, and substantial amounts of EGR are required to prevent overly advanced combustion. Accordingly, an experimental investigation has been conducted to determine how the tradeoff between the effects of intake boost varies with fuel-type and its impact on load range and TE. Five fuels are investigated: a conventional AKI=87 petroleum-based gasoline (E0), and blends of 10 and 20% ethanol with this gasoline to reduce its reactivity enhancement with boost (E10 and E20). Furthermore, a second zero-ethanol gasoline with AKI=93 (matching that of E20) was also investigated (CF-E0), and some neat ethanol data are also reported.« less

Update on Clostridium difficile infections.

PubMed

Le Monnier, A; Zahar, J-R; Barbut, F

2014-08-01

Clostridium difficile infections (CDI) occur primarily in hospitalized patients with risk factors such as concomitant or recent use of antibiotics. CDI related additional costs are important for the global population and health-care facilities. CDI epidemiology has changed since 2003: they became more frequent boosted by large outbreaks, more severe, more resistant to antibiotic treatment, and spread to new groups of population without any risk factor. This is partly due to the emergence and worldwide dissemination of new and more virulent C. difficile strains such as the epidemic clone 027/NAP1/BI. The host immune response plays a central role in the pathogenesis of CDI and could also be involved in the occurrence of recurrent or severe forms. New guidelines including new molecular tests (NAAT) have recently clarified and simplified the diagnostic strategies for the microbiological diagnosis of CDI. The CDI incidence was proven to be related to the level of clinical suspicion and the frequency of microbiological screening for C. difficile. The current recommendations for the treatment of CDI mention oral metronidazole as the first line treatment for mild to moderate diarrhea. Oral vancomycin use should be restricted to severe cases. In the absence of consensus, the treatment of multiple recurrences remains a major concern. New and more targeted antibiotics and innovative therapeutic strategies (fecal transplantation, monoclonal antibodies, and vaccination) have emerged as new therapies for CDI. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

PET imaging in adaptive radiotherapy of prostate tumors.

PubMed

Beuthien-Baumann, Bettina; Koerber, Stefan A

2018-06-04

The integration of data from positron-emission-tomography, combined with computed tomography as PET/CT or combined with magnet resonance imaging as PET/MRI, into radiation treatment planning of prostate cancer is gaining higher impact with the development of more sensitive and specific radioligands. The classic PET-tracer for prostate cancer imaging are [11C]choline and [11C]acetate, which are currently outperformed by ligands binding to the prostate-specific- membrane-antigen (PSMA). [68Ga]PSMA-11, which is the most frequently applied tracer, has shown to detect lymph node metastases, local recurrences, distant metastases and intraprostatic foci with high sensitivity, even at relatively low PSA levels. The results from PET-imaging may influence radiotherapeutic (RT) management at different stages of the disease i.e. during primary staging or biochemical recurrence, when the detection of distant metastases may alter the curative treatment concept into a palliative approach. On the other hand, the clinical target volume could be adapted by visualizing lymph node metastases at locations, which might not have been suspicious on morphologic imaging alone. The treatment plan might contain a boost to the dominant intraprostatic lesion, which could be delineated by a combination of PET-tracer uptake and multiparametric MRI. Therefore, PSMA-PET imaging is well suited for being integrated into prostate radiation planning. However, further prospective trials evaluating the impact on oncological outcome are indicated.

Childhood varicella-zoster virus vaccination in Belgium: cost-effective only in the long run or without exogenous boosting?

PubMed

Bilcke, Joke; van Hoek, Albert Jan; Beutels, Philippe

2013-04-01

To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y. An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.

Can you boost your metabolism?

MedlinePlus

Weight-loss boost metabolism; Obesity - boost metabolism; Overweight - boost metabolism ... Cowley MA, Brown WA, Considine RV. Obesity. In: Jameson JL, De Groot ... and Pediatric . 7th ed. Philadelphia, PA: Elsevier Saunders; ...

Long-term Recurrent Convolutional Networks for Visual Recognition and Description

DTIC Science & Technology

2014-11-17

deep???, are effective for tasks involving sequences, visual and otherwise. We develop a novel recurrent convolutional architecture suitable for large...models which are also recurrent, or “temporally deep”, are effective for tasks involving sequences, visual and otherwise. We develop a novel recurrent...limitation of simple RNN models which strictly integrate state information over time is known as the “vanishing gradient” effect : the ability to

Mucosal priming of newborn mice with S. Typhi Ty21a expressing anthrax protective antigen (PA) followed by parenteral PA-boost induces B and T cell-mediated immunity that protects against infection bypassing maternal antibodies

PubMed Central

Ramirez, Karina; Ditamo, Yanina; Galen, James E.; Baillie, Les W. J.; Pasetti, Marcela F.

2010-01-01

The currently licensed anthrax vaccine has several limitations and its efficacy has been proven only in adults. Effective immunization of newborns and infants requires adequate stimulation of their immune system, which is competent but not fully activated. We explored the use of the licensed live attenuated S. Typhi vaccine strain Ty21a expressing Bacillus anthracis protective antigen [Ty21a(PA)] followed PA-alum as a strategy for immunizing the pediatric population. Newborn mice primed with a single dose of Ty21a(PA) exhibited high frequencies of mucosal IgA-secreting B cells and IFN-γ-secreting T cells during the neonatal period, none of which was detected in newborns immunized with a single dose of PA-alum. Priming with Ty21a(PA) followed by PA-boost resulted in high levels of PA-specific IgG, toxin-neutralizing and opsonophagocytic antibodies and increased frequency of bone marrow IgG plasma cells and memory B cells compared with repeated immunization with PA-alum alone. Robust B and T cell responses developed even in the presence of maternal antibodies. The prime-boost protected against systemic and respiratory infection. Mucosal priming with a safe and effective S. Typhi-based anthrax vaccine followed by PA-boost could serve as a practical and effective prophylactic approach to prevent anthrax early in life. PMID:20619377

A Sensorless Predictive Current Controlled Boost Converter by Using an EKF with Load Variation Effect Elimination Function

PubMed Central

Tong, Qiaoling; Chen, Chen; Zhang, Qiao; Zou, Xuecheng

2015-01-01

To realize accurate current control for a boost converter, a precise measurement of the inductor current is required to achieve high resolution current regulating. Current sensors are widely used to measure the inductor current. However, the current sensors and their processing circuits significantly contribute extra hardware cost, delay and noise to the system. They can also harm the system reliability. Therefore, current sensorless control techniques can bring cost effective and reliable solutions for various boost converter applications. According to the derived accurate model, which contains a number of parasitics, the boost converter is a nonlinear system. An Extended Kalman Filter (EKF) is proposed for inductor current estimation and output voltage filtering. With this approach, the system can have the same advantages as sensored current control mode. To implement EKF, the load value is necessary. However, the load may vary from time to time. This can lead to errors of current estimation and filtered output voltage. To solve this issue, a load variation elimination effect elimination (LVEE) module is added. In addition, a predictive average current controller is used to regulate the current. Compared with conventional voltage controlled system, the transient response is greatly improved since it only takes two switching cycles for the current to reach its reference. Finally, experimental results are presented to verify the stable operation and output tracking capability for large-signal transients of the proposed algorithm. PMID:25928061

High-grade extremity soft tissue sarcomas: factors predictive of local recurrence and its effect on morbidity and mortality.

PubMed

Eilber, Fritz C; Rosen, Gerald; Nelson, Scott D; Selch, Michael; Dorey, Frederick; Eckardt, Jeffery; Eilber, Frederick R

2003-02-01

To identify patient characteristics associated with the development of local recurrence and the effect of local recurrence on subsequent morbidity and mortality in patients with intermediate- to high-grade extremity soft tissue sarcomas. Numerous studies on extremity soft tissue sarcomas have consistently shown that presentation with locally recurrent disease is associated with the development of subsequent local recurrences and that large tumor size and high histologic grade are significant factors associated with decreased survival. However, the effect of local recurrence on patient survival remains unclear. From 1975 to 1997, 753 patients with intermediate- to high-grade extremity soft tissue sarcomas were treated at UCLA. Treatment outcomes and patient characteristics were analyzed to identify factors associated with both local recurrence and survival. Patients with locally recurrent disease were at a significantly increased risk of developing a subsequent local recurrence. Local recurrence was a morbid event requiring amputation in 38% of the cases. The development of a local recurrence was the most significant factor associated with decreased survival. Once a patient developed a local recurrence, he or she was about three times more likely to die of disease compared to similar patients who had not developed a local recurrence. Local recurrence in patients with intermediate- to high-grade extremity soft tissue sarcomas is associated with the development of subsequent local recurrences, a morbid event decreasing functional outcomes and the most significant factor associated with decreased survival. Although 85% to 90% of patients with high-grade extremity soft tissue sarcomas are treatable with a limb salvage approach, patients who develop a local recurrence need aggressive treatment and should be considered for trials of adjuvant systemic therapy.

Patterns of Failure After Proton Therapy in Medulloblastoma; Linear Energy Transfer Distributions and Relative Biological Effectiveness Associations for Relapses

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

Sethi, Roshan V.; Giantsoudi, Drosoula; Raiford, Michael

2014-03-01

Purpose: The pattern of failure in medulloblastoma patients treated with proton radiation therapy is unknown. For this increasingly used modality, it is important to ensure that outcomes are comparable to those in modern photon series. It has been suggested this pattern may differ from photons because of variations in linear energy transfer (LET) and relative biological effectiveness (RBE). In addition, the use of matching fields for delivery of craniospinal irradiation (CSI) may influence patterns of relapse. Here we report the patterns of failure after the use of protons, compare it to that in the available photon literature, and determine themore » LET and RBE values in areas of recurrence. Methods and Materials: Retrospective review of patients with medulloblastoma treated with proton radiation therapy at Massachusetts General Hospital (MGH) between 2002 and 2011. We documented the locations of first relapse. Discrete failures were contoured on the original planning computed tomography scan. Monte Carlo calculation methods were used to estimate the proton LET distribution. Models were used to estimate RBE values based on the LET distributions. Results: A total of 109 patients were followed for a median of 38.8 months (range, 1.4-119.2 months). Of the patients, 16 experienced relapse. Relapse involved the supratentorial compartment (n=8), spinal compartment (n=11), and posterior fossa (n=5). Eleven failures were isolated to a single compartment; 6 failures in the spine, 4 failures in the supratentorium, and 1 failure in the posterior fossa. The remaining patients had multiple sites of disease. One isolated spinal failure occurred at the spinal junction of 2 fields. None of the 70 patients treated with an involved-field-only boost failed in the posterior fossa outside of the tumor bed. We found no correlation between Monte Carlo-calculated LET distribution and regions of recurrence. Conclusions: The most common site of failure in patients treated with protons for medulloblastoma was outside of the posterior fossa. The most common site for isolated local failure was the spine. We recommend consideration of spinal imaging in follow-up and careful attention to dose distribution in the spinal junction regions. Development of techniques that do not require field matching may be of benefit. We did not identify a direct correlation between lower LET values and recurrence in medulloblastoma patients treated with proton therapy. Patterns of failure do not appear to differ from those in patients treated with photon therapy.« less

Economic analysis of routine neuromonitoring of recurrent laryngeal nerve in total thyroidectomy.

PubMed

Sanabria, Álvaro; Ramírez, Adonis

2015-01-01

Thyroidectomy is a common surgery. Routine searching of the recurrent laryngeal nerve is the most important strategy to avoid palsy. Neuromonitoring has been recommended to decrease recurrent laryngeal nerve palsy. To assess if neuromonitoring of recurrent laryngeal nerve during thyroidectomy is cost-effective in a developing country. We designed a decision analysis to assess the cost-effectiveness of recurrent laryngeal nerve neuromonitoring. For probabilities, we used data from a meta-analysis. Utility was measured using preference values. We considered direct costs. We conducted a deterministic and a probabilistic analysis. We did not find differences in utility between arms. The frequency of recurrent laryngeal nerve injury was 1% in the neuromonitor group and 1.6% for the standard group. Thyroidectomy without monitoring was the less expensive alternative. The incremental cost-effectiveness ratio was COP$ 9,112,065. Routine neuromonitoring in total thyroidectomy with low risk of recurrent laryngeal nerve injury is neither cost-useful nor cost-effective in the Colombian health system.

Efficacy of N-methanocarbathymidine against genital herpes simplex virus type 2 shedding and infection in guinea pigs.

PubMed

Bernstein, David I; Bravo, Fernando J; Pullum, Derek A; Shen, Hui; Wang, Mei; Rahman, Aquilur; Glazer, Robert I; Cardin, Rhonda D

2015-02-01

Current approved nucleoside therapies for genital herpes simplex virus (HSV) infections are effective but improved therapies are needed for treatment of both acute and recurrent diseases. The effects of N-methanocarbathymidine were evaluated and compared to acyclovir using guinea pig models of acute and recurrent infection. For acute disease following intravaginal inoculation of 10(6 )pfu HSV-2 (MS strain), animals were treated intraperitoneally beginning 24 h post-infection, and the effects on disease severity, vaginal virus replication, subsequent recurrences, and latent virus loads were evaluated. For evaluation of recurrent infection, animals were treated for 21 days beginning 14 days after infection and disease recurrence and recurrent shedding were evaluated. Treatment of the acute disease with N-methanocarbathymidine significantly reduced the severity of acute disease and decreased acute vaginal virus shedding more effectively than acyclovir. Significantly, none of the animals developed visible disease in the high-dose N-methanocarbathymidine group and this was the only group in which the number of days with recurrent virus shedding was reduced. Treatment of recurrent disease was equivalent to acyclovir when acyclovir was continuously supplied in the drinking water. N-methanocarbathymidine was effective as therapy for acute and recurrent genital HSV-2 disease in the guinea pig models. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Voltage-Boosting Driver For Switching Regulator

NASA Technical Reports Server (NTRS)

Trump, Ronald C.

1990-01-01

Driver circuit assures availability of 10- to 15-V gate-to-source voltage needed to turn on n-channel metal oxide/semiconductor field-effect transistor (MOSFET) acting as switch in switching voltage regulator. Includes voltage-boosting circuit efficiently providing gate voltage 10 to 15 V above supply voltage. Contains no exotic parts and does not require additional power supply. Consists of NAND gate and dual voltage booster operating in conjunction with pulse-width modulator part of regulator.

A PIPO Boost Converter with Low Ripple and Medium Current Application

NASA Astrophysics Data System (ADS)

Bandri, S.; Sofian, A.; Ismail, F.

2018-04-01

This paper presents a Parallel Input Parallel Output (PIPO) boost converter is proposed to gain power ability of converter, and reduce current inductors. The proposed technique will distribute current for n-parallel inductor and switching component. Four parallel boost converters implement on input voltage 20.5Vdc to generate output voltage 28.8Vdc. The PIPO boost converter applied phase shift pulse width modulation which will compare with conventional PIPO boost converters by using a similar pulse for every switching component. The current ripple reduction shows an advantage PIPO boost converter then conventional boost converter. Varies loads and duty cycle will be simulated and analyzed to verify the performance of PIPO boost converter. Finally, the unbalance of current inductor is able to be verified on four area of duty cycle in less than 0.6.

Repopulation of interacting tumor cells during fractionated radiotherapy: stochastic modeling of the tumor control probability.

PubMed

Fakir, Hatim; Hlatky, Lynn; Li, Huamin; Sachs, Rainer

2013-12-01

Optimal treatment planning for fractionated external beam radiation therapy requires inputs from radiobiology based on recent thinking about the "five Rs" (repopulation, radiosensitivity, reoxygenation, redistribution, and repair). The need is especially acute for the newer, often individualized, protocols made feasible by progress in image guided radiation therapy and dose conformity. Current stochastic tumor control probability (TCP) models incorporating tumor repopulation effects consider "stem-like cancer cells" (SLCC) to be independent, but the authors here propose that SLCC-SLCC interactions may be significant. The authors present a new stochastic TCP model for repopulating SLCC interacting within microenvironmental niches. Our approach is meant mainly for comparing similar protocols. It aims at practical generalizations of previous mathematical models. The authors consider protocols with complete sublethal damage repair between fractions. The authors use customized open-source software and recent mathematical approaches from stochastic process theory for calculating the time-dependent SLCC number and thereby estimating SLCC eradication probabilities. As specific numerical examples, the authors consider predicted TCP results for a 2 Gy per fraction, 60 Gy protocol compared to 64 Gy protocols involving early or late boosts in a limited volume to some fractions. In sample calculations with linear quadratic parameters α = 0.3 per Gy, α∕β = 10 Gy, boosting is predicted to raise TCP from a dismal 14.5% observed in some older protocols for advanced NSCLC to above 70%. This prediction is robust as regards: (a) the assumed values of parameters other than α and (b) the choice of models for intraniche SLCC-SLCC interactions. However, α = 0.03 per Gy leads to a prediction of almost no improvement when boosting. The predicted efficacy of moderate boosts depends sensitively on α. Presumably, the larger values of α are the ones appropriate for individualized treatment protocols, with the smaller values relevant only to protocols for a heterogeneous patient population. On that assumption, boosting is predicted to be highly effective. Front boosting, apart from practical advantages and a possible advantage as regards iatrogenic second cancers, also probably gives a slightly higher TCP than back boosting. If the total number of SLCC at the start of treatment can be measured even roughly, it will provide a highly sensitive way of discriminating between various models and parameter choices. Updated mathematical methods for calculating repopulation allow credible generalizations of earlier results.

Effect of androgen deprivation therapy on intraprostatic tumour volume identified on 18F choline PET/CT for prostate dose painting radiotherapy.

PubMed

Chan, Joachim; Carver, Antony; Brunt, John N H; Vinjamuri, Sobhan; Syndikus, Isabel

2017-03-01

Prostate dose painting radiotherapy requires the accurate identification of dominant intraprostatic lesions (DILs) to be used as boost volumes; these can be identified on multiparametric MRI (mpMRI) or choline positron emission tomography (PET)/CT. Planning scans are usually performed after 2-3 months of androgen deprivation therapy (ADT). We examine the effect of ADT on choline tracer uptake and boost volumes identified on choline PET/CT. Fluoroethylcholine ( 18 F choline) PET/CT was performed for dose painting radiotherapy planning in patients with intermediate- to high-risk prostate cancer. Initially, they were performed at planning. Owing to low visual tracer uptake, PET/CT for subsequent patients was performed at staging. We compared these two approaches on intraprostatic lesions obtained on PET using both visual and automatic threshold methods [prostate maximum standardized uptake value (SUV max ) 60%] when compared with mpMRI. PET/CT was performed during ADT in 11 patients (median duration of 85 days) and before ADT in 29 patients. ADT significantly reduced overall prostate volume by 17%. During ADT, prostate SUV max was lower although it did not reach statistical significance (4.2 vs 6.6, p = 0.06); three patients had no visually identifiable PET DIL; and visually defined PET DILs were significantly smaller than corresponding mpMRI DILs (p = 0.03). However, all patients scanned before ADT had at least one visually identifiable PET DIL, with no significant size difference between MRI and visually defined PET DILs. In both groups, threshold PET produced larger DILs than visual PET. Both PET methods have moderate sensitivity (0.50-0.68) and high specificity (0.85-0.98) for identifying MRI-defined disease. For visual contouring of boost volumes in prostate dose painting radiotherapy, 18 F choline PET/CT should be performed before ADT. For threshold contouring of boost volumes using our PET/CT scanning protocol, threshold levels of above 60% prostate SUV max may be more suitable. Additional use of PET with MRI for radiotherapy planning can significantly change the overall boost volumes compared with using MRI alone. Advances in knowledge: For prostate dose painting radiotherapy, the additional use of 18 F choline PET with MRI can significantly change the overall boost volumes, and PET should be performed before hormone therapy, especially if boost volumes are visually identified.

Dose Escalation to the Dominant Intraprostatic Lesion Defined by Sextant Biopsy in a Permanent Prostate I-125 Implant: A Prospective Comparative Toxicity Analysis

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

Gaudet, Marc; Vigneault, Eric; Aubin, Sylviane

2010-05-01

Purpose: Using real-time intraoperative inverse-planned permanent seed prostate implant (RTIOP/PSI), multiple core biopsy maps, and three-dimensional ultrasound guidance, we planned a boost volume (BV) within the prostate to which hyperdosage was delivered selectively. The aim of this study was to investigate the potential negative effects of such a procedure. Methods and Materials: Patients treated with RTIOP/PSI for localized prostate cancer with topographic biopsy results received an intraprostatic boost (boost group [BG]). They were compared with patients treated with a standard plan (reference group [RG]). Plans were generated using a simulated annealing inverse planning algorithm. Prospectively recorded urinary, rectal, and sexualmore » toxicities and dosimetric parameters were compared between groups. Results: The study included 120 patients treated with boost technique who were compared with 70 patients treated with a standard plan. Boost technique did not significantly change the number of seeds (55.1/RG vs. 53.6/BG). The intraoperative prostate V150 was slightly higher in BG (75.2/RG vs. 77.2/BG, p = 0.039). Urethra V100, urethra D90, and rectal D50 were significantly lower in the BG. No significant differences were seen in acute or late urinary, rectal, or sexual toxicities. Conclusions: Because there were no differences between the groups in acute and late toxicities, we believe that BV can be planned and delivered to the dominant intraprostatic lesion without increasing toxicity. It is too soon to say whether a boost technique will ultimately increase local control.« less

Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer - A preliminary result.

PubMed

Lee, Hsin-Hua; Hou, Ming-Feng; Chuang, Hung-Yi; Huang, Ming-Yii; Tsuei, Le-Ping; Chen, Fang-Ming; Ou-Yang, Fu; Huang, Chih-Jen

2015-10-01

This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of pre-experimental knowledge on recognition memory.

PubMed

Bird, Chris M; Davies, Rachel A; Ward, Jamie; Burgess, Neil

2011-01-01

The influence of pre-experimental autobiographical knowledge on recognition memory was investigated using as memoranda faces that were either personally known or unknown to the participant. Under a dual process theory, such knowledge boosted both recollection- and familiarity-based recognition judgements. Under an unequal variance signal detection model, pre-experimental knowledge increased both the variance and the separation of the target and foil memory strength distributions, boosting hits and correct rejections. Thus, pre-experimental knowledge has profound effects on the multiple, interacting processes that subserve recognition memory, and likely in the neural systems that underpin them.

Chaos control in solar fed DC-DC boost converter by optimal parameters using nelder-mead algorithm powered enhanced BFOA

NASA Astrophysics Data System (ADS)

Sudhakar, N.; Rajasekar, N.; Akhil, Saya; Jyotheeswara Reddy, K.

2017-11-01

The boost converter is the most desirable DC-DC power converter for renewable energy applications for its favorable continuous input current characteristics. In other hand, these DC-DC converters known as practical nonlinear systems are prone to several types of nonlinear phenomena including bifurcation, quasiperiodicity, intermittency and chaos. These undesirable effects has to be controlled for maintaining normal periodic operation of the converter and to ensure the stability. This paper presents an effective solution to control the chaos in solar fed DC-DC boost converter since the converter experiences wide range of input power variation which leads to chaotic phenomena. Controlling of chaos is significantly achieved using optimal circuit parameters obtained through Nelder-Mead Enhanced Bacterial Foraging Optimization Algorithm. The optimization renders the suitable parameters in minimum computational time. The results are compared with the traditional methods. The obtained results of the proposed system ensures the operation of the converter within the controllable region.

Randomized Controlled Trial of Adding Telephone Follow-Up to an Occupational Rehabilitation Program to Increase Work Participation.

PubMed

Hara, Karen Walseth; Bjørngaard, Johan Håkon; Brage, Søren; Borchgrevink, Petter Christian; Halsteinli, Vidar; Stiles, Tore Charles; Johnsen, Roar; Woodhouse, Astrid

2018-06-01

Purpose Transfer from on-site rehabilitation to the participant's daily environment is considered a weak link in the rehabilitation chain. The main objective of this study is to see if adding boosted telephone follow-up directly after completing an occupational rehabilitation program effects work participation. Methods A randomized controlled study included participants with chronic pain, chronic fatigue or common mental disorders on long-term sick leave. After completing 3½ weeks of acceptance and commitment therapy based occupational rehabilitation, participants were randomized to boosted follow-up or a control group before returning to their daily environment. The intervention was delivered over 6 months by on-site RTW coordinators mainly via telephone. Primary outcome was RTW categorized as participation in competitive work ≥1 day per week on average over 8 weeks. Results There were 213 participants of mean age 42 years old. Main diagnoses of sick leave certification were mental disorders (38%) and musculoskeletal disorders (30%). One year after discharge the intervention group had 87% increased odds (OR 1.87, 95% confidence interval 1.06-3.31, p = 0.031), of (re)entry to competitive work ≥1 day per week compared with the controls, with similar positive results for sensitivity analysis of participation half time (≥2.5 days per week). The cost of boosted follow-up was 390.5 EUR per participant. Conclusion Participants receiving boosted RTW follow-up had higher (re)entry to competitive work ≥1 day per week at 1 year when compared to the control group. Adding low-cost boosted follow-up by telephone after completing an occupational rehabilitation program augmented the effect on return-to-work.

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

Kalaskar, Vickey B; Szybist, James P; Splitter, Derek A

In recent years a number of studies have demonstrated that boosted operation combined with external EGR is a path forward for expanding the high load limit of homogeneous charge compression ignition (HCCI) operation with the negative valve overlap (NVO) valve strategy. However, the effects of fuel composition with this strategy have not been fully explored. In this study boosted HCCI combustion is investigated in a single-cylinder research engine equipped with direct injection (DI) fueling, cooled external exhaust gas recirculation (EGR), laboratory pressurized intake air, and a fully-variable hydraulic valve actuation (HVA) valve train. Three fuels with significant compositional differences aremore » investigated: regular grade gasoline (RON = 90.2), 30% ethanol-gasoline blend (E30, RON = 100.3), and 24% iso-butanol-gasoline blend (IB24, RON = 96.6). Results include engine loads from 350 to 800 kPa IMEPg for all fuels at three engine speeds 1600, 2000, and 2500 rpm. All operating conditions achieved thermal efficiency (gross indicated efficiency) between 38 and 47%, low NOX emissions ( 0.1 g/kWh), and high combustion efficiency ( 96.5%). Detailed sweeps of intake manifold pressure (atmospheric to 250 kPaa), EGR (0 25% EGR), and injection timing are conducted to identify fuel-specific effects. The major finding of this study is that while significant fuel compositional differences exist, in boosted HCCI operation only minor changes in operational conditions are required to achieve comparable operation for all fuels. In boosted HCCI operation all fuels were able to achieve matched load-speed operation, whereas in conventional SI operation the fuel-specific knock differences resulted in significant differences in the operable load-speed space. Although all fuels were operable in boosted HCCI, the respective air handling requirements are also discussed, including an analysis of the demanded turbocharger efficiency.« less

Heterologous prime-boost immunization of Newcastle disease virus vectored vaccines protected broiler chickens against highly pathogenic avian influenza and Newcastle disease viruses.

PubMed

Kim, Shin-Hee; Samal, Siba K

2017-07-24

Avian Influenza virus (AIV) is an important pathogen for both human and animal health. There is a great need to develop a safe and effective vaccine for AI infections in the field. Live-attenuated Newcastle disease virus (NDV) vectored AI vaccines have shown to be effective, but preexisting antibodies to the vaccine vector can affect the protective efficacy of the vaccine in the field. To improve the efficacy of AI vaccine, we generated a novel vectored vaccine by using a chimeric NDV vector that is serologically distant from NDV. In this study, the protective efficacy of our vaccines was evaluated by using H5N1 highly pathogenic avian influenza virus (HPAIV) strain A/Vietnam/1203/2004, a prototype strain for vaccine development. The vaccine viruses were three chimeric NDVs expressing the hemagglutinin (HA) protein in combination with the neuraminidase (NA) protein, matrix 1 protein, or nonstructural 1 protein. Comparison of their protective efficacy between a single and prime-boost immunizations indicated that prime immunization of 1-day-old SPF chicks with our vaccine viruses followed by boosting with the conventional NDV vector strain LaSota expressing the HA protein provided complete protection of chickens against mortality, clinical signs and virus shedding. Further verification of our heterologous prime-boost immunization using commercial broiler chickens suggested that a sequential immunization of chickens with chimeric NDV vector expressing the HA and NA proteins following the boost with NDV vector expressing the HA protein can be a promising strategy for the field vaccination against HPAIVs and against highly virulent NDVs. Copyright © 2017 Elsevier Ltd. All rights reserved.

An in silico evaluation of treatment regimens for recurrent Clostridium difficile infection

PubMed Central

Blanco, Natalia; Foxman, Betsy; Malani, Anurag N.; Zhang, Min; Walk, Seth; Rickard, Alexander H.

2017-01-01

Background Clostridium difficile infection (CDI) is a significant nosocomial infection worldwide, that recurs in as many as 35% of infections. Risk of CDI recurrence varies by ribotype, which also vary in sporulation and germination rates. Whether sporulation/germination mediate risk of recurrence and effectiveness of treatment of recurring CDI remains unclear. We aim to assess the role of sporulation/germination patterns on risk of recurrence, and the relative effectiveness of the recommended tapered/pulsing regimens using an in silico model. Methods We created a compartmental in-host mathematical model of CDI, composed of vegetative cells, toxins, and spores, to explore whether sporulation and germination have an impact on recurrence rates. We also simulated the effectiveness of three tapered/pulsed vancomycin regimens by ribotype. Results Simulations underscored the importance of sporulation/germination patterns in determining pathogenicity and transmission. All recommended regimens for recurring CDI tested were effective in reducing risk of an additional recurrence. Most modified regimens were still effective even after reducing the duration or dosage of vancomycin. However, the effectiveness of treatment varied by ribotype. Conclusion Current CDI vancomycin regimen for treating recurrent cases should be studied further to better balance associated risks and benefits. PMID:28800598

Recurrent Clostridium difficile infections: The importance of the intestinal microbiota

PubMed Central

Zanella Terrier, Marie Céline; Simonet, Martine Louis; Bichard, Philippe; Frossard, Jean Louis

2014-01-01

Clostridium difficile infections (CDI) are a leading cause of antibiotic-associated and nosocomial diarrhea. Despite effective antibiotic treatments, recurrent infections are common. With the recent emergence of hypervirulent isolates of C. difficile, CDI is a growing epidemic with higher rates of recurrence, increasing severity and mortality. Fecal microbiota transplantation (FMT) is an alternative treatment for recurrent CDI. A better understanding of intestinal microbiota and its role in CDI has opened the door to this promising therapeutic approach. FMT is thought to resolve dysbiosis by restoring gut microbiota diversity thereby breaking the cycle of recurrent CDI. Since the first reported use of FMT for recurrent CDI in 1958, systematic reviews of case series and case report have shown its effectiveness with high resolution rates compared to standard antibiotic treatment. This article focuses on current guidelines for CDI treatment, the role of intestinal microbiota in CDI recurrence and current evidence about FMT efficacy, adverse effects and acceptability. PMID:24966611

Phase 2 Trial of Accelerated, Hypofractionated Whole-Breast Irradiation of 39 Gy in 13 Fractions Followed by a Tumor Bed Boost Sequentially Delivering 9 Gy in 3 Fractions in Early-Stage Breast Cancer

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

Kim, Ja Young; Jung, So-Youn; Lee, Seeyoun

Purpose: To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. Methods and Materials: Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks.more » Results: After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). Conclusions: AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery.« less

Phase 2 trial of accelerated, hypofractionated whole-breast irradiation of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions in early-stage breast cancer.

PubMed

Kim, Ja Young; Jung, So-Youn; Lee, Seeyoun; Kang, Han-Sung; Lee, Eun Sook; Park, In Hae; Lee, Keun Seok; Ro, Jungsil; Lee, Nam Kwon; Shin, Kyung Hwan

2013-12-01

To report a phase 2 trial of accelerated, hypofractionated whole-breast irradiation (AH-WBI) delivered as a daily dose of 3 Gy to the whole breast followed by a tumor bed boost. Two hundred seventy-six patients diagnosed with breast cancer (pT1-2 and pN0-1a) who had undergone breast-conserving surgery in which the operative margins were negative were treated with AH-WBI delivered as 39 Gy in 13 fractions of 3 Gy to the whole breast once daily over 5 consecutive working days, and 9 Gy in 3 sequential fractions of 3 Gy to a lumpectomy cavity, all within 3.2 weeks. After a median follow-up period of 57 months (range: 27-75 months), the rate of 5-year locoregional recurrence was 1.4% (n=4), whereas that of disease-free survival was 97.4%. No grade 3 skin toxicity was reported during the follow-up period. Qualitative physician cosmetic assessments of good or excellent were noted in 82% of the patients at 2 months after the completion of AH-WBI. The global cosmetic outcome did not worsen over time, and a good or excellent cosmetic outcome was reported in 82% of the patients at 3 years. The mean pretreatment percentage breast retraction assessment was 12.00 (95% confidence interval [CI]: 11.14-12.86). The mean value of percentage breast retraction assessment increased to 13.99 (95% CI: 12.17-15.96) after 1 year and decreased to 13.54 (95% CI: 11.84-15.46) after 3 years but was not significant (P>.05). AH-WBI consisting of 39 Gy in 13 fractions followed by a tumor bed boost sequentially delivering 9 Gy in 3 fractions can be delivered with excellent disease control and tolerable skin toxicity in patients with early-stage breast cancer after breast-conserving surgery. Copyright © 2013 Elsevier Inc. All rights reserved.

Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge.

PubMed

Morello, Christopher S; Kraynyak, Kimberly A; Levinson, Michael S; Chen, Zhijiang; Lee, Kuo-Fen; Spector, Deborah H

2012-10-12

Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

PubMed Central

Rao, Raghavendra

2015-01-01

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA) axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development. PMID:26343738

Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development.

PubMed

Rao, Raghavendra

2015-08-28

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA) axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development.

PDC-SGB: Prediction of effective drug combinations using a stochastic gradient boosting algorithm.

PubMed

Xu, Qian; Xiong, Yi; Dai, Hao; Kumari, Kotni Meena; Xu, Qin; Ou, Hong-Yu; Wei, Dong-Qing

2017-03-21

Combinatorial therapy is a promising strategy for combating complex diseases by improving the efficacy and reducing the side effects. To facilitate the identification of drug combinations in pharmacology, we proposed a new computational model, termed PDC-SGB, to predict effective drug combinations by integrating biological, chemical and pharmacological information based on a stochastic gradient boosting algorithm. To begin with, a set of 352 golden positive samples were collected from the public drug combination database. Then, a set of 732 dimensional feature vector involving biological, chemical and pharmaceutical information was constructed for each drug combination to describe its properties. To avoid overfitting, the maximum relevance & minimum redundancy (mRMR) method was performed to extract useful ones by removing redundant subsets. Based on the selected features, the three different type of classification algorithms were employed to build the drug combination prediction models. Our results demonstrated that the model based on the stochastic gradient boosting algorithm yield out the best performance. Furthermore, it is indicated that the feature patterns of therapy had powerful ability to discriminate effective drug combinations from non-effective ones. By analyzing various features, it is shown that the enriched features occurred frequently in golden positive samples can help predict novel drug combinations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Improving medical diagnosis reliability using Boosted C5.0 decision tree empowered by Particle Swarm Optimization.

PubMed

Pashaei, Elnaz; Ozen, Mustafa; Aydin, Nizamettin

2015-08-01

Improving accuracy of supervised classification algorithms in biomedical applications is one of active area of research. In this study, we improve the performance of Particle Swarm Optimization (PSO) combined with C4.5 decision tree (PSO+C4.5) classifier by applying Boosted C5.0 decision tree as the fitness function. To evaluate the effectiveness of our proposed method, it is implemented on 1 microarray dataset and 5 different medical data sets obtained from UCI machine learning databases. Moreover, the results of PSO + Boosted C5.0 implementation are compared to eight well-known benchmark classification methods (PSO+C4.5, support vector machine under the kernel of Radial Basis Function, Classification And Regression Tree (CART), C4.5 decision tree, C5.0 decision tree, Boosted C5.0 decision tree, Naive Bayes and Weighted K-Nearest neighbor). Repeated five-fold cross-validation method was used to justify the performance of classifiers. Experimental results show that our proposed method not only improve the performance of PSO+C4.5 but also obtains higher classification accuracy compared to the other classification methods.

Novel vehicle detection system based on stacked DoG kernel and AdaBoost

PubMed Central

Kang, Hyun Ho; Lee, Seo Won; You, Sung Hyun

2018-01-01

This paper proposes a novel vehicle detection system that can overcome some limitations of typical vehicle detection systems using AdaBoost-based methods. The performance of the AdaBoost-based vehicle detection system is dependent on its training data. Thus, its performance decreases when the shape of a target differs from its training data, or the pattern of a preceding vehicle is not visible in the image due to the light conditions. A stacked Difference of Gaussian (DoG)–based feature extraction algorithm is proposed to address this issue by recognizing common characteristics, such as the shadow and rear wheels beneath vehicles—of vehicles under various conditions. The common characteristics of vehicles are extracted by applying the stacked DoG shaped kernel obtained from the 3D plot of an image through a convolution method and investigating only certain regions that have a similar patterns. A new vehicle detection system is constructed by combining the novel stacked DoG feature extraction algorithm with the AdaBoost method. Experiments are provided to demonstrate the effectiveness of the proposed vehicle detection system under different conditions. PMID:29513727

Cost-effectiveness of the 21-gene recurrence score assay in the context of multifactorial decision making to guide chemotherapy for early-stage breast cancer.

PubMed

Reed, Shelby D; Dinan, Michaela A; Schulman, Kevin A; Lyman, Gary H

2013-03-01

New evidence is available regarding the utility of the 21-gene recurrence score assay in guiding chemotherapy use for node-negative, estrogen receptor-positive breast cancer. We applied this evidence in a decision-analytic model to re-evaluate the cost-effectiveness of the assay. We cross-classified patients by clinicopathologic characteristics from the Adjuvant! risk index and by recurrence score risk group. For non-recurrence score-guided treatment, we assumed patients receiving hormonal therapy alone had low-risk characteristics and patients receiving chemotherapy and hormonal therapy had higher-risk characteristics. For recurrence score-guided treatment, we assigned chemotherapy probabilities conditional on recurrence score risk group and clinicopathologic characteristics. An estimated 40.4% of patients in the recurrence score-guided strategy and 47.3% in the non-recurrence score-guided strategy were expected to receive chemotherapy. The incremental gain in quality-adjusted life-years was 0.16 (95% confidence interval, 0.08-0.28) with the recurrence score-guided strategy. Lifetime medical costs to the health system were $2,692 ($1,546-$3,821) higher with the recurrence score-guided strategy, for an incremental cost-effectiveness ratio of $16,677/quality-adjusted life-year ($7,613-$37,219). From a societal perspective, the incremental cost-effectiveness was $10,788/quality-adjusted life-year ($6,840-$30,265). The findings provide supportive evidence for the economic value of the 21-gene recurrence score assay in node-negative, estrogen receptor-positive breast cancer.

Thermal noise in a boost-invariant matter expansion in relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Chattopadhyay, Chandrodoy; Bhalerao, Rajeev S.; Pal, Subrata

2018-05-01

We formulate a general theory of thermal fluctuations within causal second-order viscous hydrodynamic evolution of matter formed in relativistic heavy-ion collisions. The fluctuation is treated perturbatively on top of a boost-invariant longitudinal expansion. Numerical simulation of thermal noise is performed for a lattice quantum chromodynamics equation of state and for various second-order dissipative evolution equations. Phenomenological effects of thermal fluctuations on the two-particle rapidity correlations are studied.

Robust boosting via convex optimization

NASA Astrophysics Data System (ADS)

Rätsch, Gunnar

2001-12-01

In this work we consider statistical learning problems. A learning machine aims to extract information from a set of training examples such that it is able to predict the associated label on unseen examples. We consider the case where the resulting classification or regression rule is a combination of simple rules - also called base hypotheses. The so-called boosting algorithms iteratively find a weighted linear combination of base hypotheses that predict well on unseen data. We address the following issues: o The statistical learning theory framework for analyzing boosting methods. We study learning theoretic guarantees on the prediction performance on unseen examples. Recently, large margin classification techniques emerged as a practical result of the theory of generalization, in particular Boosting and Support Vector Machines. A large margin implies a good generalization performance. Hence, we analyze how large the margins in boosting are and find an improved algorithm that is able to generate the maximum margin solution. o How can boosting methods be related to mathematical optimization techniques? To analyze the properties of the resulting classification or regression rule, it is of high importance to understand whether and under which conditions boosting converges. We show that boosting can be used to solve large scale constrained optimization problems, whose solutions are well characterizable. To show this, we relate boosting methods to methods known from mathematical optimization, and derive convergence guarantees for a quite general family of boosting algorithms. o How to make Boosting noise robust? One of the problems of current boosting techniques is that they are sensitive to noise in the training sample. In order to make boosting robust, we transfer the soft margin idea from support vector learning to boosting. We develop theoretically motivated regularized algorithms that exhibit a high noise robustness. o How to adapt boosting to regression problems? Boosting methods are originally designed for classification problems. To extend the boosting idea to regression problems, we use the previous convergence results and relations to semi-infinite programming to design boosting-like algorithms for regression problems. We show that these leveraging algorithms have desirable theoretical and practical properties. o Can boosting techniques be useful in practice? The presented theoretical results are guided by simulation results either to illustrate properties of the proposed algorithms or to show that they work well in practice. We report on successful applications in a non-intrusive power monitoring system, chaotic time series analysis and a drug discovery process. --- Anmerkung: Der Autor ist Träger des von der Mathematisch-Naturwissenschaftlichen Fakultät der Universität Potsdam vergebenen Michelson-Preises für die beste Promotion des Jahres 2001/2002. In dieser Arbeit werden statistische Lernprobleme betrachtet. Lernmaschinen extrahieren Informationen aus einer gegebenen Menge von Trainingsmustern, so daß sie in der Lage sind, Eigenschaften von bisher ungesehenen Mustern - z.B. eine Klassenzugehörigkeit - vorherzusagen. Wir betrachten den Fall, bei dem die resultierende Klassifikations- oder Regressionsregel aus einfachen Regeln - den Basishypothesen - zusammengesetzt ist. Die sogenannten Boosting Algorithmen erzeugen iterativ eine gewichtete Summe von Basishypothesen, die gut auf ungesehenen Mustern vorhersagen. Die Arbeit behandelt folgende Sachverhalte: o Die zur Analyse von Boosting-Methoden geeignete Statistische Lerntheorie. Wir studieren lerntheoretische Garantien zur Abschätzung der Vorhersagequalität auf ungesehenen Mustern. Kürzlich haben sich sogenannte Klassifikationstechniken mit großem Margin als ein praktisches Ergebnis dieser Theorie herausgestellt - insbesondere Boosting und Support-Vektor-Maschinen. Ein großer Margin impliziert eine hohe Vorhersagequalität der Entscheidungsregel. Deshalb wird analysiert, wie groß der Margin bei Boosting ist und ein verbesserter Algorithmus vorgeschlagen, der effizient Regeln mit maximalem Margin erzeugt. o Was ist der Zusammenhang von Boosting und Techniken der konvexen Optimierung? Um die Eigenschaften der entstehenden Klassifikations- oder Regressionsregeln zu analysieren, ist es sehr wichtig zu verstehen, ob und unter welchen Bedingungen iterative Algorithmen wie Boosting konvergieren. Wir zeigen, daß solche Algorithmen benutzt werden koennen, um sehr große Optimierungsprobleme mit Nebenbedingungen zu lösen, deren Lösung sich gut charakterisieren laesst. Dazu werden Verbindungen zum Wissenschaftsgebiet der konvexen Optimierung aufgezeigt und ausgenutzt, um Konvergenzgarantien für eine große Familie von Boosting-ähnlichen Algorithmen zu geben. o Kann man Boosting robust gegenüber Meßfehlern und Ausreissern in den Daten machen? Ein Problem bisheriger Boosting-Methoden ist die relativ hohe Sensitivität gegenüber Messungenauigkeiten und Meßfehlern in der Trainingsdatenmenge. Um dieses Problem zu beheben, wird die sogenannte 'Soft-Margin' Idee, die beim Support-Vector Lernen schon benutzt wird, auf Boosting übertragen. Das führt zu theoretisch gut motivierten, regularisierten Algorithmen, die ein hohes Maß an Robustheit aufweisen. o Wie kann man die Anwendbarkeit von Boosting auf Regressionsprobleme erweitern? Boosting-Methoden wurden ursprünglich für Klassifikationsprobleme entwickelt. Um die Anwendbarkeit auf Regressionsprobleme zu erweitern, werden die vorherigen Konvergenzresultate benutzt und neue Boosting-ähnliche Algorithmen zur Regression entwickelt. Wir zeigen, daß diese Algorithmen gute theoretische und praktische Eigenschaften haben. o Ist Boosting praktisch anwendbar? Die dargestellten theoretischen Ergebnisse werden begleitet von Simulationsergebnissen, entweder, um bestimmte Eigenschaften von Algorithmen zu illustrieren, oder um zu zeigen, daß sie in der Praxis tatsächlich gut funktionieren und direkt einsetzbar sind. Die praktische Relevanz der entwickelten Methoden wird in der Analyse chaotischer Zeitreihen und durch industrielle Anwendungen wie ein Stromverbrauch-Überwachungssystem und bei der Entwicklung neuer Medikamente illustriert.

Heterologous Prime-Boost Immunisation Regimens Against Infectious Diseases

DTIC Science & Technology

2006-08-01

of these cells by boosting. DNA vaccines are good priming agents since they are internalised by antigen presenting cells and can induce antigen...presentation via both MHC class I and class II, thereby inducing both cytotoxic T lymphocytes and type 1-helper T lymphocytes. Successful boosting agents ...assessing prime-boost vaccine combinations for protection against infectious agents . • In a number of prime - boost studies, the inclusion of growth

Cost-Effectiveness of Guided Self-Help Treatment for Recurrent Binge Eating

ERIC Educational Resources Information Center

Lynch, Frances L.; Striegel-Moore, Ruth H.; Dickerson, John F.; Perrin, Nancy; DeBar, Lynn; Wilson, G. Terence; Kraemer, Helena C.

2010-01-01

Objective: Adoption of effective treatments for recurrent binge-eating disorders depends on the balance of costs and benefits. Using data from a recent randomized controlled trial, we conducted an incremental cost-effectiveness analysis (CEA) of a cognitive-behavioral therapy guided self-help intervention (CBT-GSH) to treat recurrent binge eating…

Boosted ARTMAP: modifications to fuzzy ARTMAP motivated by boosting theory.

PubMed

Verzi, Stephen J; Heileman, Gregory L; Georgiopoulos, Michael

2006-05-01

In this paper, several modifications to the Fuzzy ARTMAP neural network architecture are proposed for conducting classification in complex, possibly noisy, environments. The goal of these modifications is to improve upon the generalization performance of Fuzzy ART-based neural networks, such as Fuzzy ARTMAP, in these situations. One of the major difficulties of employing Fuzzy ARTMAP on such learning problems involves over-fitting of the training data. Structural risk minimization is a machine-learning framework that addresses the issue of over-fitting by providing a backbone for analysis as well as an impetus for the design of better learning algorithms. The theory of structural risk minimization reveals a trade-off between training error and classifier complexity in reducing generalization error, which will be exploited in the learning algorithms proposed in this paper. Boosted ART extends Fuzzy ART by allowing the spatial extent of each cluster formed to be adjusted independently. Boosted ARTMAP generalizes upon Fuzzy ARTMAP by allowing non-zero training error in an effort to reduce the hypothesis complexity and hence improve overall generalization performance. Although Boosted ARTMAP is strictly speaking not a boosting algorithm, the changes it encompasses were motivated by the goals that one strives to achieve when employing boosting. Boosted ARTMAP is an on-line learner, it does not require excessive parameter tuning to operate, and it reduces precisely to Fuzzy ARTMAP for particular parameter values. Another architecture described in this paper is Structural Boosted ARTMAP, which uses both Boosted ART and Boosted ARTMAP to perform structural risk minimization learning. Structural Boosted ARTMAP will allow comparison of the capabilities of off-line versus on-line learning as well as empirical risk minimization versus structural risk minimization using Fuzzy ARTMAP-based neural network architectures. Both empirical and theoretical results are presented to enhance the understanding of these architectures.

TLR1/2 activation during heterologous prime-boost vaccination (DNA-MVA) enhances CD8+ T Cell responses providing protection against Leishmania (Viannia).

PubMed

Jayakumar, Asha; Castilho, Tiago M; Park, Esther; Goldsmith-Pestana, Karen; Blackwell, Jenefer M; McMahon-Pratt, Diane

2011-06-01

Leishmania (Viannia) parasites present particular challenges, as human and murine immune responses to infection are distinct from other Leishmania species, indicating a unique interaction with the host. Further, vaccination studies utilizing small animal models indicate that modalities and antigens that prevent infection by other Leishmania species are generally not protective. Using a newly developed mouse model of chronic L. (Viannia) panamensis infection and the heterologous DNA prime - modified vaccinia virus Ankara (MVA) boost vaccination modality, we examined whether the conserved vaccine candidate antigen tryparedoxin peroxidase (TRYP) could provide protection against infection/disease. Heterologous prime - boost (DNA/MVA) vaccination utilizing TRYP antigen can provide protection against disease caused by L. (V.) panamensis. However, protection is dependent on modulating the innate immune response using the TLR1/2 agonist Pam3CSK4 during DNA priming. Prime-boost vaccination using DNA alone fails to protect. Prior to infection protectively vaccinated mice exhibit augmented CD4 and CD8 IFNγ and memory responses as well as decreased IL-10 and IL-13 responses. IL-13 and IL-10 have been shown to be independently critical for disease in this model. CD8 T cells have an essential role in mediating host defense, as CD8 depletion reversed protection in the vaccinated mice; vaccinated mice depleted of CD4 T cells remained protected. Hence, vaccine-induced protection is dependent upon TLR1/2 activation instructing the generation of antigen specific CD8 cells and restricting IL-13 and IL-10 responses. Given the general effectiveness of prime-boost vaccination, the recalcitrance of Leishmania (Viannia) to vaccine approaches effective against other species of Leishmania is again evident. However, prime-boost vaccination modality can with modulation induce protective responses, indicating that the delivery system is critical. Moreover, these results suggest that CD8 T cells should be targeted for the development of a vaccine against infection caused by Leishmania (Viannia) parasites. Further, TLR1/2 modulation may be useful in vaccines where CD8 T cell responses are critical.

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect.

PubMed

Lin, Li-An; Luo, Sheng; Davis, Barry R

2018-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT).

Bayesian regression model for recurrent event data with event-varying covariate effects and event effect

PubMed Central

Lin, Li-An; Luo, Sheng; Davis, Barry R.

2017-01-01

In the course of hypertension, cardiovascular disease events (e.g., stroke, heart failure) occur frequently and recurrently. The scientific interest in such study may lie in the estimation of treatment effect while accounting for the correlation among event times. The correlation among recurrent event times come from two sources: subject-specific heterogeneity (e.g., varied lifestyles, genetic variations, and other unmeasurable effects) and event dependence (i.e., event incidences may change the risk of future recurrent events). Moreover, event incidences may change the disease progression so that there may exist event-varying covariate effects (the covariate effects may change after each event) and event effect (the effect of prior events on the future events). In this article, we propose a Bayesian regression model that not only accommodates correlation among recurrent events from both sources, but also explicitly characterizes the event-varying covariate effects and event effect. This model is especially useful in quantifying how the incidences of events change the effects of covariates and risk of future events. We compare the proposed model with several commonly used recurrent event models and apply our model to the motivating lipid-lowering trial (LLT) component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (ALLHAT-LLT). PMID:29755162

Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer

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

Donovan, E. M.; James, H.; Bonora, M.

2012-10-15

Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer.Method: Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB.more » Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCT imaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (<0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose. Conclusions: Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRTincreased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.« less

Percutaneous needle fasciotomy for recurrent Dupuytren disease.

PubMed

van Rijssen, Annet L; Werker, Paul M N

2012-09-01

Increasing options to treat Dupuytren disease include percutaneous needle fasciotomy (PNF), a minimally invasive technique that has proven to be effective for the treatment of primary disease. However, its effect on recurrent disease is not clear. We studied 30 patients with recurrent Dupuytren disease in 40 fingers, with a mean follow-up of 4.4 years. Primary outcome measures were total passive extension deficit reduction and interval to a second recurrence, defined as an increase of more than 30° compared with the result at the end of the previous treatment. We noted complications. Total passive extension reduction was 76%. Percutaneous needle fasciotomy was especially effective for the metacarpophalangeal joint, with an average reduction of 93%, whereas the average reduction in the proximal interphalangeal joint was 57%. A total of 50% of patients did not develop a secondary recurrence during follow-up. The other 50% did, and we treated recurrence within an average of 1.4 years after PNF. By means of PNF, we postponed tertiary treatment an average of 2.9 years starting from the initial treatment for Dupuytren disease. We successfully treated all secondary recurrences by limited fasciectomy, according to patients' wishes. We noted no major adverse effects. Percutaneous needle fasciotomy can be applied effectively for recurrent disease; 50% of patients remain free of recurrence for a mean of 4.4 years. If a secondary recurrence occurs, it does so relatively early after treatment. Patients must therefore be willing to accept this uncertainty in the context of the advantages of PNF, such as fast recovery, low complication rate, and minimal invasiveness. Copyright © 2012 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

Influence of Route of Administration on Immediate and Extended Protection in Rats Immunized with Escherichia coli Heat-Labile Enterotoxin

PubMed Central

Klipstein, Frederick A.; Engert, Richard F.

1980-01-01

The effect of route of administration, dosage, and number of boosts employed during immunization with the polymyxin-release form of Escherichia coli heat-labile (LT) enterotoxin on the degree and duration of protection afforded was evaluated in rats which were challenged by the ligated loop technique. Increasing the boosting dosage by fivefold from 50 to 250 μg resulted in a marked increase in protection against challenge with toxin in rats immunized either just by the parenteral route (i.p./i.p.) or by a parenteral prime, followed by peroral boosts (i.p./p.o.) in rats pretreated with cimetidine to ablate gastric secretions; such was not the case, however, even with a 50-fold increase in dosage in rats immunized just by the peroral route (p.o./p.o.). Four weekly peroral boosts were required to achieve the strongest degree of protection. Increasing the boosting dosage also increased the degree of protection against challenge with viable LT+/ST− and LT+/ST+ strains (ST indicates heat-stable enterotoxin) in rats immunized by the i.p./p.o., but not by the i.p./i.p., route; no protection was evident against an LT−/ST+ strain. Protection was lost within 3 weeks after immunization in rats immunized by the i.p./i.p. route. In contrast, protection was extended over the 3-month observation period in those immunized by the i.p./p.o. route; the degree of protection was enhanced in rats which received an additional boost at 2 months. These observations establish the fact that immunization with LT is similar to that with cholera toxin in that arousal of the local immune intestinal response by means of peroral immunization provides maximal extended protection. PMID:6987180

Comparison of the immunogenicity and protection against bovine tuberculosis following immunization by BCG-priming and boosting with adenovirus or protein based vaccines.

PubMed

Dean, G; Whelan, A; Clifford, D; Salguero, F J; Xing, Z; Gilbert, S; McShane, H; Hewinson, R G; Vordermeier, M; Villarreal-Ramos, B

2014-03-05

There is a requirement for vaccines or vaccination strategies that confer better protection against TB than the current live attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) vaccine for use in cattle. Boosting with recombinant viral vectors expressing mycobacterial proteins, such as Ag85A, has shown a degree of promise as a strategy for improving on the protection afforded by BCG. Experiments in small animal models have indicated that broadening the immune response to include mycobacterial antigens other than Ag85A, such as Rv0288, induced by boosting with Ad5 constructs has a direct effect on the protection afforded against TB. Here, we compared the immunogenicity and protection against challenge with M. bovis afforded by boosting BCG-vaccinated cattle with a human type 5 (Ad5)-based vaccine expressing the mycobacterial antigens Ag85A (Ad5-85A); or Ag85A, Rv0251, Rv0287 and Rv0288 (Ad5-TBF); or with protein TBF emulsified in adjuvant (Adj-TBF). Boosting with TBF broaden the immune response. The kinetics of Ad5-TBF and Adj-TBF were shown to be different, with effector T cell responses from the latter developing more slowly but being more durable than those induced by Ad5-TBF. No increase in protection compared to BCG alone was afforded by Ad5-TBF or Adj-TBF by gross pathology or bacteriology. Using histopathology, as a novel parameter of protection, we show that boosting BCG vaccinated cattle with Ad5-85A induced significantly better protection than BCG alone. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

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

Zheng, Y; Chang, A; Liu, Y

Purpose: Electron beams are commonly used for boost radiation following whole breast irradiation (WBI) to improve the in-breast local control. Proton beams have a finite range and a sharper distal dose falloff compared to electron beams, thus potentially sparing more heart and lung in breast treatment. The purpose of the study is to compare protons with electrons for boost breast treatment in terms of target coverage and normal tissue sparing. Methods: Six breast cancer patients were included in this study. All women received WBI to 45–50 Gy, followed by a 10–16.2 Gy boost with standard fractionation. If proton beams weremore » used for the boost treatment, an electron plan was retrospectively generated for comparison using the same CT set and structures, and vice versa if electron beams were used for treatment. Proton plans were generated using the treatment planning system (TPS) with two to three uniform scanning proton beams. Electron plans were generated using the Pinnacle TPS with one single en face beam. Dose-volume histograms (DVH) were calculated and compared between proton and electron boost plans. Results: Proton plans show a similar boost target coverage, similar skin dose, and much better heart and lung sparing. For an example patient, V95% for PTV was 99.98% and skin (5 mm shell) received a max dose close to the prescription dose for both protons and electrons; however, V2 and V5 for the ipsilateral lung and heart were 37.5%, 17.9% and 19.9%, 4.9% respectively for electrons, but were essentially 0 for protons. Conclusions: This dosimetric comparison demonstrates that while both proton therapy and electron therapy provided similar coverage and skin dose, proton therapy could largely reduce the dose to lung and heart, thus leading to potential less side effects.« less

Concurrent Cyclophosphamide, Methotrexate, and 5-Fluorouracil Chemotherapy and Radiotherapy for Early Breast Carcinoma

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

Livi, Lorenzo; Saieva, Calogero; Borghesi, Simona

2008-07-01

Purpose: The optimal sequencing of adjuvant chemotherapy (CT) and radiation therapy (RT) in patients with early-stage breast cancer remains unclear. Patients and Methods: We retrospectively compared 485 patients treated with conservative breast surgery and postoperative whole-breast RT and six courses of CMF (cyclophosphamide 600 mg/m{sup 2}, methotrexate 40 mg/m{sup 2}, and 5-fluorouracil 600 mg/m{sup 2}) with 300 patients who received postoperative CMF only and with 509 patients treated with postoperative whole-breast RT only. The mean radiation dose delivered was 50 Gy (range, 46-52 Gy) with standard fractionation. The boost dose was 6-16 Gy according to resection margins and at themore » discretion of the radiation oncologist. Acute and late RT toxicity were scored using respectively the Radiation Therapy Oncology Group and the Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scale. Results: A slightly higher Grade 2 acute skin toxicity was recorded in the concurrent group (21.2% vs. 11.2% of the RT only group, p < 0.0001). RT was interrupted more frequently in the CMF/RT group respective to the RT group (8.5% vs. 4.1%; p = 0.006). There was no difference in late toxicity between the two groups. All patients in the concurrent group successfully received the planned dose of RT and CT. Local recurrence rate was 7.6% in CT/RT group and 9.8% in RT group; this difference was not statistically significant at univariate analysis (log-rank test p = 0.98). However, at multivariate analysis adjusted also for pathological tumor, pathological nodes, and age, the CT/RT group showed a statistically lower rate of local recurrence (p = 0.04). Conclusions: Whole-breast RT and concurrent CMF are a safe adjuvant treatment in terms of toxicity.« less

Assessing the risk of recurrent venous thromboembolism--a practical approach.

PubMed

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice.

Dopaminergic Modulation of Decision Making and Subjective Well-Being.

PubMed

Rutledge, Robb B; Skandali, Nikolina; Dayan, Peter; Dolan, Raymond J

2015-07-08

The neuromodulator dopamine has a well established role in reporting appetitive prediction errors that are widely considered in terms of learning. However, across a wide variety of contexts, both phasic and tonic aspects of dopamine are likely to exert more immediate effects that have been less well characterized. Of particular interest is dopamine's influence on economic risk taking and on subjective well-being, a quantity known to be substantially affected by prediction errors resulting from the outcomes of risky choices. By boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness, we show here an effect on both choices and happiness. Boosting dopamine levels increased the number of risky options chosen in trials involving potential gains but not trials involving potential losses. This effect could be better captured as increased Pavlovian approach in an approach-avoidance decision model than as a change in risk preferences within an established prospect theory model. Boosting dopamine also increased happiness resulting from some rewards. Our findings thus identify specific novel influences of dopamine on decision making and emotion that are distinct from its established role in learning. Copyright © 2015 Rutledge et al.

Dopaminergic Modulation of Decision Making and Subjective Well-Being

PubMed Central

Skandali, Nikolina; Dayan, Peter; Dolan, Raymond J.

2015-01-01

The neuromodulator dopamine has a well established role in reporting appetitive prediction errors that are widely considered in terms of learning. However, across a wide variety of contexts, both phasic and tonic aspects of dopamine are likely to exert more immediate effects that have been less well characterized. Of particular interest is dopamine's influence on economic risk taking and on subjective well-being, a quantity known to be substantially affected by prediction errors resulting from the outcomes of risky choices. By boosting dopamine levels using levodopa (l-DOPA) as human subjects made economic decisions and repeatedly reported their momentary happiness, we show here an effect on both choices and happiness. Boosting dopamine levels increased the number of risky options chosen in trials involving potential gains but not trials involving potential losses. This effect could be better captured as increased Pavlovian approach in an approach–avoidance decision model than as a change in risk preferences within an established prospect theory model. Boosting dopamine also increased happiness resulting from some rewards. Our findings thus identify specific novel influences of dopamine on decision making and emotion that are distinct from its established role in learning. PMID:26156984

Recurrent urinary tract infection in women.

PubMed

Hooton, T M

2001-04-01

Recurrent urinary tract infections (UTI) are common among young healthy women even though they generally have anatomically and physiologically normal urinary tracts. Women with recurrent UTI have an increased susceptibility to vaginal colonization with uropathogens, which is due to a greater propensity for uropathogenic coliforms to adhere to uroepithelial cells. Risk factors for recurrent UTI include sexual intercourse, use of spermicidal products, having a first UTI at an early age, and having a maternal history of UTIs. Inherited factors may be important in some women with recurrent UTI. Many factors thought to predispose to recurrent UTI in women, such as pre- and post-coital voiding patterns, frequency of urination, wiping patterns, and douching have not been proven to be risk factors for UTI. In contrast to the predominantly behavioral risk factors for young women, mechanical and/or physiological factors that affect bladder emptying are most strongly associated with recurrent UTI in healthy postmenopausal women. The management of recurrent UTI is the same as that for sporadic UTI except that the likelihood of infection with an antibiotic resistant uropathogen is higher in women who have received recent antimicrobials. Strategies to prevent recurrent UTI in young women should include education about the association of recurrent UTI with frequency of sexual intercourse and the usage of spermicide-containing products. Continuous or post-coital prophylaxis with low-dose antimicrobials or intermittent self-treatment with antimicrobials have all been demonstrated to be effective in managing recurrent uncomplicated UTIs in women. Estrogen use is very effective in preventing recurrent UTI in post-menopausal women. Exciting new approaches to prevent recurrent UTI include the use of probiotics and vaccines. Further understanding of the pathogenesis of UTI will lead to more effective and safer methods to prevent these frequent infections.

Effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs on the incidence of recurrent colorectal adenomas: a systematic review with meta-analysis and trial sequential analysis of randomized clinical trials.

PubMed

Veettil, Sajesh K; Lim, Kean Ghee; Ching, Siew Mooi; Saokaew, Surasak; Phisalprapa, Pochamana; Chaiyakunapruk, Nathorn

2017-11-14

Beneficial effects of aspirin and non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) against recurrent colorectal adenomas have been documented in systematic reviews; however, the results have not been conclusive. Uncertainty remains about the appropriate dose of aspirin for adenoma prevention. The persistence of the protective effect of NSAIDs against recurrent adenomas after treatment cessation is yet to be established. Our objective was to update and systematically evaluate the evidence for aspirin and other NSAIDs on the incidence of recurrent colorectal adenomas taking into consideration the risks of random error and to appraise the quality of evidence using GRADE (The Grading of Recommendations, Assessment, Development and Evaluation) approach. Retrieved trials were evaluated using Cochrane risk of bias instrument. Meta-analytic estimates were calculated with random-effects model and random errors were evaluated with trial sequential analysis (TSA). In patients with a previous history of colorectal cancer or adenomas, low-dose aspirin (80-160 mg/day) compared to placebo taken for 2 to 4 years reduces the risk of recurrent colorectal adenomas (relative risk (RR), 0.80 [95% CI (confidence interval), 0.70-0.92]). TSA indicated a firm evidence for this beneficial effect. The evidence indicated moderate GRADE quality. Low-dose aspirin also reduces the recurrence of advanced adenomas (RR, 0.66 [95% CI, 0.44-0.99]); however, TSA indicated lack of firm evidence for a beneficial effect. High-dose aspirin (300-325 mg/day) did not statistically reduce the recurrent adenomas (RR, 0.90 [95% CI, 0.68-1.18]). Cyclooxygenase-2 (COX-2) inhibitors (e.g. celecoxib 400 mg/day) were associated with a significant decrease in the recurrence of both adenomas (RR, 0.66 [95% CI, 0.59-0.72]) and advanced adenomas (RR, 0.45 [95% CI, 0.33-0.57]); however, this association did not persist and there was a trend of an increased risk of recurrent adenomas observed 2 years after the withdrawal. Our findings confirm the beneficial effect of low-dose aspirin on recurrence of any adenomas; however, effect on advanced adenomas was inconclusive. COX-2 inhibitors seem to be more effective in preventing recurrence of adenomas; however, there was a trend of an increased risk of recurrence of adenomas observed after discontinuing regular use.

Understanding the Mechanisms Through Which an Influential Early Childhood Program Boosted Adult Outcomes

PubMed Central

Heckman, James; Pinto, Rodrigo

2013-01-01

A growing literature establishes that high quality early childhood interventions targeted toward disadvantaged children have substantial impacts on later life outcomes. Little is known about the mechanisms producing these impacts. This paper uses longitudinal data on cognitive and personality traits from an experimental evaluation of the influential Perry Preschool program to analyze the channels through which the program boosted both male and female participant outcomes. Experimentally induced changes in personality traits explain a sizable portion of adult treatment effects. PMID:24634518

Variable Thrust, Multiple Start Hybrid Motor Solutions for Missile and Space Applications

DTIC Science & Technology

2010-06-01

considered: I. Boost/Sustain/Boost. Simulating a tactical solid rocket motor profile with another boost at the end to demonstrate a "throttle up", this...of tactical solid rocket motors were tested with 75%, 50%, and lower sustain-to- boost chamber pressure ratios with rapid throttle-up achieved... solid rocket motors were tested with 75%, 50%, and lower sustain-to-boost chamber pressure ratios with rapid throttle-up achieved following the sustain

AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework.

PubMed

Zheng, Qi; Grice, Elizabeth A

2016-10-01

Accurate mapping of next-generation sequencing (NGS) reads to reference genomes is crucial for almost all NGS applications and downstream analyses. Various repetitive elements in human and other higher eukaryotic genomes contribute in large part to ambiguously (non-uniquely) mapped reads. Most available NGS aligners attempt to address this by either removing all non-uniquely mapping reads, or reporting one random or "best" hit based on simple heuristics. Accurate estimation of the mapping quality of NGS reads is therefore critical albeit completely lacking at present. Here we developed a generalized software toolkit "AlignerBoost", which utilizes a Bayesian-based framework to accurately estimate mapping quality of ambiguously mapped NGS reads. We tested AlignerBoost with both simulated and real DNA-seq and RNA-seq datasets at various thresholds. In most cases, but especially for reads falling within repetitive regions, AlignerBoost dramatically increases the mapping precision of modern NGS aligners without significantly compromising the sensitivity even without mapping quality filters. When using higher mapping quality cutoffs, AlignerBoost achieves a much lower false mapping rate while exhibiting comparable or higher sensitivity compared to the aligner default modes, therefore significantly boosting the detection power of NGS aligners even using extreme thresholds. AlignerBoost is also SNP-aware, and higher quality alignments can be achieved if provided with known SNPs. AlignerBoost's algorithm is computationally efficient, and can process one million alignments within 30 seconds on a typical desktop computer. AlignerBoost is implemented as a uniform Java application and is freely available at https://github.com/Grice-Lab/AlignerBoost.

Impact of the Educational Boost Your Brain and Memory Program Among Senior Living Residents.

PubMed

Nicholson, Roscoe; O'Brien, Catherine

2017-12-01

This random assignment waitlist control intervention study examined an implementation of the educational Boost Your Brain and Memory cognitive fitness intervention in 12 senior living organizations. Older adult participants ( n = 166) completed measures of brain health knowledge, use of memory techniques, physical and intellectual activity, and mindfulness, at baseline and after the intervention group's completion of the course. Changes in knowledge scores and in self-reported physical and intellectual activity increased significantly more for intervention participants than for waitlist controls at the conclusion of the course. There were no significant changes between the groups in mindfulness or use of memory techniques. This suggests that in senior living settings Boost Your Brain and Memory is effective in educating participants about brain healthy behaviors and in motivating behavioral change in the areas of physical and intellectual activity.

Increasing the Air Charge and Scavenging the Clearance Volume of a Compression-Ignition Engine

NASA Technical Reports Server (NTRS)

Spanogle, J A; Hicks, C W; Foster, H H

1934-01-01

The object of the investigation presented in this report was to determine the effects of increasing the air charge and scavenging the clearance volume of a 4-stroke-cycle compression-ignition engine having a vertical-disk form combustion chamber. Boosting the inlet-air pressure with normal valve timing increased the indicated engine power in proportion to the additional air inducted and resulted in smoother engine operation with less combustion shock. Scavenging the clearance volume by using a valve overlap of 145 degrees and an inlet-air boost pressure of approximately 2 1/2 inches of mercury produced a net increase in performance for clear exhaust operation of 33 percent over that obtained with normal valve timing and the same boost pressure. The improved combustion characteristics result in lower specific fuel consumption, and a clearer exhaust.

Observer-Pattern Modeling and Slow-Scale Bifurcation Analysis of Two-Stage Boost Inverters

NASA Astrophysics Data System (ADS)

Zhang, Hao; Wan, Xiaojin; Li, Weijie; Ding, Honghui; Yi, Chuanzhi

2017-06-01

This paper deals with modeling and bifurcation analysis of two-stage Boost inverters. Since the effect of the nonlinear interactions between source-stage converter and load-stage inverter causes the “hidden” second-harmonic current at the input of the downstream H-bridge inverter, an observer-pattern modeling method is proposed by removing time variance originating from both fundamental frequency and hidden second harmonics in the derived averaged equations. Based on the proposed observer-pattern model, the underlying mechanism of slow-scale instability behavior is uncovered with the help of eigenvalue analysis method. Then eigenvalue sensitivity analysis is used to select some key system parameters of two-stage Boost inverter, and some behavior boundaries are given to provide some design-oriented information for optimizing the circuit. Finally, these theoretical results are verified by numerical simulations and circuit experiment.

Dichroic subjettiness ratios to distinguish colour flows in boosted boson tagging

NASA Astrophysics Data System (ADS)

Salam, Gavin P.; Schunk, Lais; Soyez, Gregory

2017-03-01

N-subjettiness ratios are in wide use for tagging heavy boosted objects, in particular the ratio of 2-subjettiness to 1-subjettiness for tagging boosted electroweak bosons. In this article we introduce a new, dichroic ratio, which uses different regions of a jet to determine the two subjettiness measures, emphasising the hard substructure for the 1-subjettiness and the full colour radiation pattern for the 2-subjettiness. Relative to existing N -subjettiness ratios, the dichroic extension, combined with SoftDrop (pre-)grooming, makes it possible to increase the ultimate signal significance by about 25% (for 2 TeV jets), or to reduce non-perturbative effects by a factor of 2-3 at 50% signal efficiency while maintaining comparable background rejection. We motivate the dichroic approach through the study of Lund diagrams, supplemented with resummed analytical calculations.

14 CFR 27.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL CATEGORY ROTORCRAFT Design and Construction Control Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2013 CFR

2013-01-01

... TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: TRANSPORT CATEGORY ROTORCRAFT Design and Construction Control Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... 14 Aeronautics and Space 1 2013-01-01 2013-01-01 false Power boost and power-operated control...

Cortisol boosts risky decision-making behavior in men but not in women.

PubMed

Kluen, Lisa Marieke; Agorastos, Agorastos; Wiedemann, Klaus; Schwabe, Lars

2017-10-01

Acute stress may escalate risky decision-making in men, while there is no such effect in women. Although first evidence links these gender-specific effects of stress to stress-induced changes in cortisol, whether elevated cortisol is indeed sufficient to boost risk-taking, whether a potential cortisol effect depends on simultaneous noradrenergic activation, and whether cortisol and noradrenergic activation exert distinct effects on risk-taking in men and women is unknown. In this experiment, we therefore set out to elucidate the impact of cortisol and noradrenergic stimulation on risky decision-making in men and women. In a fully-crossed, placebo-controlled, double-blind design, male and female participants received orally either a placebo, hydrocortisone, yohimbine, an alpha-2-adrenoceptor-antagonist leading to increased noradrenergic stimulation, or both drugs before completing the balloon analogue risk task, a validated measure of risk-taking. Overall, participants' choice was risk-sensitive as reflected in reduced responding in high- compared to moderate- and low-risk conditions. Cortisol, however, led to a striking increase in risk-taking in men, whereas it had no effect on risk-taking behavior in women. Yohimbine had no such effect and the gender-specific effect of cortisol was not modulated by yohimbine. Our data show that cortisol boosts risk-taking behavior in men but not in women. This differential effect of cortisol on risk-taking may drive gender differences in risky decision-making under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nonlinear program based optimization of boost and buck-boost converter designs

NASA Astrophysics Data System (ADS)

Rahman, S.; Lee, F. C.

The facility of an Augmented Lagrangian (ALAG) multiplier based nonlinear programming technique is demonstrated for minimum-weight design optimizations of boost and buck-boost power converters. Certain important features of ALAG are presented in the framework of a comprehensive design example for buck-boost power converter design optimization. The study provides refreshing design insight of power converters and presents such information as weight and loss profiles of various semiconductor components and magnetics as a function of the switching frequency.

Risk factors for and causes and treatment of recurrence of inferior vena cava type of Budd-Chiari syndrome after stenting in China: A retrospective analysis of a large cohort.

PubMed

Li, Wen-Dong; Yu, Hui-Ying; Qian, Ai-Min; Rong, Jian-Jie; Zhang, Ye-Qing; Li, Xiao-Qiang

2017-03-01

To explore the risk factors for recurrence of inferior vena cava (IVC)-type Budd-Chiari syndrome (BCS) after stenting and evaluate the feasibility and primary outcomes of endovascular therapies for recurrent BCS. A retrospective analysis of 219 patients was performed to identify risk factors for recurrence. The images of the recurrent patients during follow-up duration and interventional surgery were also reviewed to find the possible reasons of recurrence. The outcome of endovascular therapies for recurrent BCS was evaluated by Kaplan-Meier analysis. Among the 219 patients, 172 patients with primary IVC-type BCS underwent stenting and 28 patients experienced recurrence. Multivariate analysis identified age, Child-Pugh score, MELD and total bilirubin as independent recurrent indicators. Possible causes of recurrence include thrombosis in the stent, re-obstruction in or above the stent, and stent-related hepatic vein obstruction. Twenty-five patients with recurrent BCS underwent endovascular therapies with a few complications and achieved a high level of short- and mid-term patency. Age, total bilirubin and severity of liver function are the main risk factors for BCS recurrence. These risks might contribute to thrombosis or subsequent fibrous obstruction. Endovascular therapies are effective and safe management options that yield positive outcomes for recurrent BCS. • Risk factors for recurrent Budd-Chiari syndrome were identified by multivariate analysis. • Causes of recurrent Budd-Chiari syndrome were investigated by assessing radiological images. • There is a correlation between risk factors and causes of recurrence. • Endovascular therapies for recurrent Budd-Chiari syndrome are effective and safe.

Assessing the risk of recurrent venous thromboembolism – a practical approach

PubMed Central

Fahrni, Jennifer; Husmann, Marc; Gretener, Silvia B; Keo, Hong H

2015-01-01

Recurrent venous thromboembolism (VTE) is associated with increased morbidity and mortality. This risk is lowered by anticoagulation, with a large effect in the initial phase following the venous thromboembolic event, and with a smaller effect in terms of secondary prevention of recurrence when extended anticoagulation is performed. On the other hand, extended anticoagulation is associated with an increased risk of major bleeding and thus leads to morbidity and mortality. Therefore, it is necessary to assess the risk of recurrence for VTE on an individual basis, and a recommendation for secondary prophylaxis should be specifically based on risk calculation of recurrence of VTE and bleeding. In this review, we provide a comprehensive summary of relevant risk factors for recurrent VTE and a practical approach for assessing the risk of recurrence in daily practice. PMID:26316770

Feasibility of combined modality therapy for localized high-grade soft tissue sarcomas in adults

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

Blum, R.H.; Greenberger, J.S.; Wilson, R.E.

1979-08-01

Seventeen consecutive patients with localized, high grade soft tissue sarcomas had resection of their primary tumor, radiation therapy and chemotherapy. The soft tissue sarcoma was primary in 14 patients and regionally recurrent in 3 patients. Chemotherapy consisted of cyclophosphamide 500 mg/M/sup 2/ day 1, Adriamycin (ADR) 60 mg/M/sup 2/ day 2, and DTIC 400 mg/M/sup 2/ days 1 and 2, given every 21 days to a maximum ADR dose of 450 mg/M/sup 2/. Cyclophosphamide and DTIC were then given to a total duration of 1 year. Radiation therapy consisted of 4000 to 5000 rad by megavoltage photons in 5 weeks,more » and in selected cases, an additional 1500 to 2000 rad by electron beam boost in the tumor bed delivered over 2 additional weeks. Following surgery, 12 patients were treated sequentially with an interval of chemotherapy, radiation therapy and then the completion of chemotherapy. The added morbidity of this sequential approach is minimal: one patient of 12 had delayed primary healing of her wound, 1 of 10 patients required a break in radiation therapy because of skin erythema. Four patients were treated with intensive pre-chemotherapy radiation therapy because of inadequate surgical margins. The median time on study was 18 months from onset of treatment (range, 8 to 41 months). Although there have been no local, regional or distant recurrences, the follow-up time is inadequate to assess the therapeutic benefit of this combined modality treatment.« less

Risk factors for pre-term birth in a Canadian cohort of HIV-positive women: role of ritonavir boosting?

PubMed Central

Kakkar, Fatima; Boucoiran, Isabelle; Lamarre, Valerie; Ducruet, Thierry; Amre, Devendra; Soudeyns, Hugo; Lapointe, Normand; Boucher, Marc

2015-01-01

Background The risk of pre-term birth (PTB) associated with the use of protease inhibitors (PIs) during pregnancy remains a subject of debate. Recent data suggest that ritonavir boosting of PIs may play a specific role in the initiation of PTB, through an effect on the maternal–fetal adrenal axis. The primary objective of this study is to compare the risk of PTB among women treated with boosted PI versus non-boosted PIs during pregnancy. Methods Between 1988 and 2011, 705 HIV-positive women were enrolled into the Centre Maternel et Infantile sur le SIDA mother–infant cohort at Centre Hospitalier Universitaire Sainte-Justine in Montreal, Canada. Inclusion criteria for the study were: 1) attendance at a minimum of two antenatal obstetric visits and 2) singleton live birth, at 24 weeks gestational or older. The association between PTB (defined as delivery at <37 weeks gestational age), antiretroviral drug exposure and maternal risk factors was assessed retrospectively using logistic regression. Results A total of 525 mother–infant pairs were included in the analysis. Among them, PI-based combination anti-retroviral therapy was used in 37.4%, boosted PI based in 24.4%, non-nucleoside reverse transcriptase inhibitor (NNRTI) or nucleoside reverse transcriptase inhibitor based in 28.1%, and no treatment was given in 10.0% of cases. Overall, 13.5% of women experienced PTB. Among women treated with antiretroviral therapy, the risk of PTB was significantly higher among women who received boosted versus non-boosted PI (OR 2.01, 95% CI 1.02–3.97). This remained significant after adjusting for maternal age, delivery CD4 count, hepatitis C co-infection, history of previous PTB, and parity (aOR 2.17, 95% CI 1.05–4.51). There was no increased risk of PTB with the use of unboosted PIs as compared to NNRTI- or NRTI-based regimens. Conclusion While previous studies on the association between PTB and PI use have generally considered all PIs the same, our results would indicate a possible role of ritonavir boosting as a risk factor for PTB. Further work is needed to understand the pathophysiologic mechanisms involved, and to identify the safest ARV regimens to be used in pregnancy. PMID:26051165

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

Heijst, T C F van; Hoekstra, N; Philippens, M E P

Purpose: The Utrecht MRI-linac (MRL) design enables new MR-guided radiotherapy (RT) approaches. This is a feasibility study for a single-fraction high dose (boost) to individual lymph nodes (LNs) in breast-cancer patients, after breast-conserving surgery (BCS) and hypofractionated whole-breast irradiation (WBI) with conventional axillary RT (AxRT). Methods: After written informed consent, 5 breast-cancer patients (cT1-3N0) were enrolled (NL500460.041.14 trial) and underwent 1.5T MRI in supine RT position, after BCS. Axillary levels, based on ESTRO guidelines, and organs-at-risk (OARs) – including lungs, chest wall, plexus and neurovascular bundle (NVB) – were delineated. Pseudo-CT scans (pCTs) were generated by HU bulk-assignment of water,more » lung, and air. With Monaco treatment-planning software (TPS Elekta), VMAT plans were generated for simultaneous WBI and AxRT, prescribing 16×2.66=42.56Gy (V95%>99% V107%<2cc). Two scenarios were considered: AxRT of levels I–II; AxRT of levels I–IV, depending on boost location. Per patient, 4 LNs with varying axillary locations were selected, delineated, and expanded to PTV with 2-mm margin. Using dedicated MRL TPS, accounting for magnetic-field effects, an IMRT 1×8.5Gy boost was simulated for each LN, to achieve a total target dose of 66Gy EQD2 (α/β=3.5Gy). WBI/ART doses and boost doses were added, and evaluated in EQD2. Results: For all scenarios, 1×8.5Gy boosts could be simulated within clinical constraints for a 66Gy total dose, in addition to WBI/AxRT. LN target coverage was excellent (V95%>95%, mean >8.5Gy). Additional dose to OARs was limited. Conclusion: Our study explored the concept of LN boosting using on-line MRI guidance. It is feasible to boost individual axillary LNs – with 2-mm margin – with an additional 1×8.5Gy, in all axillary levels, within clinical constraints. This may lead to more personalized RT approaches for patients with involved LNs and may reduce RT-induced toxicity, or the need for axillary surgery. Other LN boost strategies, including dose escalation, are under investigation.« less

Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial.

PubMed

Daar, Eric S; DeJesus, Edwin; Ruane, Peter; Crofoot, Gordon; Oguchi, Godson; Creticos, Catherine; Rockstroh, Jürgen K; Molina, Jean-Michel; Koenig, Ellen; Liu, Ya-Pei; Custodio, Joseph; Andreatta, Kristen; Graham, Hiba; Cheng, Andrew; Martin, Hal; Quirk, Erin

2018-06-15

Switching from therapy based on a boosted protease inhibitor to bictegravir, emtricitabine, and tenofovir alafenamide could avoid drug interactions and unwanted side-effects in virologically suppressed adults with HIV-1 infection, while maintaining a high barrier to resistance and providing a simplified once-daily, single-tablet regimen. Here, we report 48 week results of a phase 3 study investigating this switch. In this multicentre, randomised, open-label, active-controlled, non-inferiority, phase 3 trial, adults with HIV-1 infection were enrolled at 121 outpatient centres in ten countries. Eligible participants were aged 18 years or older, had an estimated glomerular filtration rate of 50 mL per min or higher, had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for 6 months or more before screening, and were on a regimen consisting of boosted atazanavir or darunavir plus either emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. We randomly assigned participants (1:1), using a computer-generated randomisation sequence, to switch to co-formulated once-daily bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg), herein known as the bictegravir group, or to remain on their baseline boosted protease inhibitor regimen, herein known as the boosted protease inhibitor group, for 48 weeks. Randomisation was stratified by use of tenofovir disoproxil fumarate or abacavir at screening. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or higher at week 48 (by US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 4%. Efficacy and safety analyses included all participants who received at least one dose of study drug. This study is ongoing but not actively recruiting patients and is registered with ClinicalTrials.gov, number NCT02603107. Between Dec 2, 2015, and July 15, 2016, 578 participants were randomly assigned and 577 were treated (290 in the bictegravir group and 287 in the boosted protease inhibitor group). At week 48, five participants (2%) in the bictegravir group and five (2%) in the boosted protease inhibitor group had plasma HIV-1 RNA of 50 copies per mL or higher (difference 0·0%, 95·002% CI -2·5 to 2·5), thus switching to the bictegravir regimen was non-inferior to continued boosted protease inhibitor therapy. The overall incidence and severity of adverse events was similar between groups, although headache occurred more frequently in the bictegravir group than in the boosted protease inhibitor group. 233 (80%) participants in the bictegravir group and 226 (79%) in the boosted protease inhibitor group had an adverse event. Only two (1%) participants in the bictegravir group and one (<1%) in the boosted protease inhibitor group discontinued treatment because of adverse events. 54 participants (19%) in the bictegravir group had drug-related adverse events compared with six (2%) in the protease inhibitor group. Fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide might be a safe and efficacious alternative to continued boosted protease inhibitor therapy in adults with HIV-1 infection. Gilead Sciences. Copyright © 2018 Elsevier Ltd. All rights reserved.

Energy Harvesting from Salinity Gradient

NASA Astrophysics Data System (ADS)

Muhthassim, B.; Thian, X. K.; Hasan, K. N. Md

2018-04-01

Abstract: Energy harvesting from salt water received attention started back in 1970s’, but due to varying interests in the field and the growing potentials of other more promising sources, more work was required to fully establish it. This paper aims at identifying existing techniques of energy harvesting and the methodology involved determining an effective technique for small scale applications of the method. Capacitive deionization technique which involves electrochemical reaction was chosen for further analysis. The experiment was conducted to analyze factors affecting its performance including the electrode and the electrolyte. Combination electrode of carbon/aluminium, copper/aluminium and carbon/copper were selected and tested with different concentration of salty water. From the experiment, copper and aluminum electrodes were found to be the most effective among the rest. A DC-DC boost converter was used to step-up the voltage. Physical implementation of the circuit was done and the circuit was tested in which an input voltage of 1.022 V was boosted to 1.255 V. The efficiency of the boost converter was 38.17 % based on input power and output power obtained.

Methods, systems and apparatus for controlling operation of two alternating current (AC) machines

DOEpatents

Gallegos-Lopez, Gabriel [Torrance, CA; Nagashima, James M [Cerritos, CA; Perisic, Milun [Torrance, CA; Hiti, Silva [Redondo Beach, CA

2012-02-14

A system is provided for controlling two AC machines. The system comprises a DC input voltage source that provides a DC input voltage, a voltage boost command control module (VBCCM), a five-phase PWM inverter module coupled to the two AC machines, and a boost converter coupled to the inverter module and the DC input voltage source. The boost converter is designed to supply a new DC input voltage to the inverter module having a value that is greater than or equal to a value of the DC input voltage. The VBCCM generates a boost command signal (BCS) based on modulation indexes from the two AC machines. The BCS controls the boost converter such that the boost converter generates the new DC input voltage in response to the BCS. When the two AC machines require additional voltage that exceeds the DC input voltage required to meet a combined target mechanical power required by the two AC machines, the BCS controls the boost converter to drive the new DC input voltage generated by the boost converter to a value greater than the DC input voltage.

Measure of the electroencephalographic effects of sevoflurane using recurrence dynamics.

PubMed

Li, Xiaoli; Sleigh, Jamie W; Voss, Logan J; Ouyang, Gaoxiang

2007-08-31

This paper proposes a novel method to interpret the effect of anesthetic agents (sevoflurane) on the neural activity, by using recurrence quantification analysis of EEG data. First, we reduce the artefacts in the scalp EEG using a novel filter that combines wavelet transforms and empirical mode decomposition. Then, the determinism in the recurrence plot is calculated. It is found that the determinism increases gradually with increasing the concentration of sevoflurane. Finally, a pharmacokinetic and pharmacodynamic (PKPD) model is built to describe the relationship between the concentration of sevoflurane and the processed EEG measure ('determinism' of the recurrence plot). A test sample of nine patients shows the recurrence in EEG data may track the effect of the sevoflurane on the brain.

Simulator platform motion requirements for recurrent airline pilot training and evaluation

DOT National Transportation Integrated Search

2004-09-30

This report presents the results of two studies that examined the effect of enhanced hexapod-simulator motion on recurrent evaluation in the simulator, on the course of recurrent training in the simulator, and on "quasi-transfer" of this recurrent tr...

Influence of Pulmonary Nodules on Chest Computed Tomography and Risk of Recurrence in Stage IV Wilms Tumor

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

Kirkland, Robert S.; Nanda, Ronica H., E-mail: rhazari@emory.edu; Alazraki, Adina

Purpose: Chest computed tomography (CT) is currently accepted as the main modality for initial disease staging and response assessment in Wilms tumor (WT). However, there is great variability in the number and size of lung metastases at the time of diagnosis and after induction chemotherapy. There is a lack of clinical evidence as to how this variability in tumor burden affects choice of therapy and disease outcome. This study sought to evaluate a previously proposed lung metastases risk stratification system based on CT findings and clinical outcomes in stage IV WT patients. Methods and Materials: Thirty-five pediatric patients with amore » diagnosis of stage IV WT with evaluable pre- and postdiagnosis CT scans between 1997 and 2012 were included in the analysis. Patients were divided into low-, intermediate-, and high-risk categories based on the size and number of pulmonary metastases before and after 6 weeks of chemotherapy. Association of the lung risk groups with lung recurrence-free survival and overall survival at each time point was analyzed with relevant covariates. Results: Risk group distribution both at diagnosis and after induction chemotherapy was not influenced by tumor histology. Initial risk grouping suggested an association with disease-free survival at 5 years (P=.074); however, the most significant correlation was with postinduction chemotherapy disease status (P=.027). In patients with an intermediate or high burden of disease after 6 weeks of chemotherapy, despite receiving whole-lung and boost irradiation, survival outcomes were poorer. Conclusions: Pulmonary tumor burden in stage IV WT on chest CT can predict disease outcome. Patients with intermediate- or low-risk disease, especially after induction therapy, have a higher risk for recurrence. After prospective validation, this method may become a valuable tool in adaptation of therapy to improve outcome.« less

Subclinical ductal carcinoma in situ of the breast: treatment with conservative surgery and radiotherapy.

PubMed

Amichetti, M; Caffo, O; Richetti, A; Zini, G; Rigon, A; Antonello, M; Roncadin, M; Coghetto, F; Valdagni, R; Fasan, S; Maluta, S; Di Marco, A; Neri, S; Vidali, C; Panizzoni, G; Aristei, C

1999-01-01

In spite of the fact that ductal carcinoma in situ (DCIS) of the breast is a frequently encountered clinical problem, there is no consensus about the optimal treatment of clinically occult (i.e., mammographic presentation only) DCIS. Interest in breast conservation therapy has recently increased. Few data are available in Italy on the conservative treatment with surgery and adjuvant postoperative radiotherapy. A retrospective multi-institutional study was performed in 15 Radiation Oncology Departments in northern Italy involving 112 women with subclinical DCIS of the breast treated between 1982 and 1993. Age of the patients ranged between 32 and 72 years (median, 50 years). All of them underwent conservative surgery: quadrantectomy in 89, tumorectomy in 11, and wide excision in 12 cases. The most common histologic subtype was comedocarcinoma (37%). The median pathologic size was 10 mm (range 1 to 55 mm). Axillary dissection was performed in 83 cases: all the patients were node negative. All the patients received adjunctive radiation therapy with 60Co units (77%) or 6 MV linear accelerators (23%) for a median total dose to the entire breast of 50 Gy (mean, 49.48 Gy; range, 45-60 Gy). Seventy-six cases (68%) received a boost to the tumor bed at a dose of 8-20 Gy (median 10 Gy) for a minimum tumor dose of 58 Gy. At a median follow-up of 66 months, 8 local recurrences were observed, 4 intraductal and 4 invasive. All recurrent patients had a salvage mastectomy and are alive and free of disease at this writing. The 10-year actuarial overall, cause-specific, and recurrence-free survival was of 98.8%, 100%, and 91%, respectively. The retrospective multicentric study, with a local control rate of more than 90% at 10 years with 100% cause-specific survival, showed that conservative surgery and adjuvant radiation therapy is a safe and efficacious treatment for patients with occult, non-palpable DCIS.

Phase II Study of High-Dose Photon/Proton Radiotherapy in the Management of Spine Sarcomas

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

DeLaney, Thomas F.; Liebsch, Norbert J.; Pedlow, Francis X.

Purpose: Radiotherapy (XRT) for spine sarcomas is constrained by spinal cord, nerve, and viscera tolerance. Negative surgical margins are uncommon; hence, doses of {>=}66 Gy are recommended. A Phase II clinical trial evaluated high-dose photon/proton XRT for spine sarcomas. Methods and Materials: Eligible patients had nonmetastatic, thoracic, lumbar, and/or sacral spine/paraspinal sarcomas. Treatment included pre- and/or postoperative photon/proton XRT with or without radical resection; patients with osteosarcoma and Ewing's sarcoma received chemotherapy. Shrinking fields delivered 50.4 cobalt Gray equivalent (Gy RBE) to subclinical disease, 70.2 Gy RBE to microscopic disease in the tumor bed, and 77.4 Gy RBE to grossmore » disease at 1.8 Gy RBE qd. Doses were reduced for radiosensitive histologies, concurrent chemoradiation, or when diabetes or autoimmune disease present. Spinal cord dose was limited to 63/54 Gy RBE to surface/center. Intraoperative boost doses of 7.5 to 10 Gy could be given by dural plaque. Results: A total of 50 patients (29 chordoma, 14 chondrosarcoma, 7 other) underwent gross total (n = 25) or subtotal (n = 12) resection or biopsy (n = 13). With 48 month median follow-up, 5-year actuarial local control, recurrence-free survival, and overall survival are: 78%, 63%, and 87% respectively. Two of 36 (5.6%) patients treated for primary versus 7/14 (50%) for recurrent tumor developed local recurrence (p < 0.001). Five patients developed late radiation-associated complications; no myelopathy developed but three sacral neuropathies appeared after 77.12 to 77.4 Gy RBE. Conclusions: Local control with this treatment is high in patients radiated at the time of primary presentation. Spinal cord dose constraints appear to be safe. Sacral nerves receiving 77.12-77.4 Gy RBE are at risk for late toxicity.« less

Risk factors for recurrence of scabies: a retrospective study of scabies patients in a long-term care hospital.

PubMed

Makigami, Kuniko; Ohtaki, Noriko; Ishii, Norihisa; Tamashiro, Tetsuko; Yoshida, Sadao; Yasumura, Seiji

2011-09-01

A considerable number of patients suffer recurrence of scabies. To elucidate risk factors for recurrence of scabies, we compared patients who experienced scabies recurrence and those who suffered scabies only once. We conducted a retrospective review of medical records of all scabies patients in a long-term care hospital for the elderly (300 beds; six wards) for a period of 42 months to determine frequency of scabies onsets, underlying diseases, history of treatment, and demographic data such as age and sex. One hundred and forty-eight patients and five hospital staff members suffered scabies during the 42-month study period. All staff members and 98 patients had no recurrence, while 50 patients experienced at least one recurrence of scabies. The cumulative number of scabies diagnoses was 228. The rates of scabies onset and recurrence were considerably different among wards. The dementia unit showed the highest rate of onset and recurrence. In addition to frequent exposure to infectious sources, problematic behavior, such as lying in other patients beds, might cause the high recurrence rate in dementia units. Higher serum total lymphocyte count and topical use of γ-benzene hexachloride were associated with lower risk of scabies recurrence. Recurrence of scabies is not uncommon among elderly patients in institutional settings. Impaired immunity may be a risk factor for recurrence of scabies. Groups with a high onset rate of scabies pose a high likelihood of recurrence. Problematic behavior of demented patients may increase the risk of recurrence. Use of effective topical treatment may effectively prevent recurrence. © 2011 Japanese Dermatological Association.

A Study of 4-level DC-DC Boost Inverter with Passive Component Reduction Consideration

NASA Astrophysics Data System (ADS)

Kasiran, A. N.; Ponniran, A.; Harimon, M. A.; Hamzah, H. H.

2018-04-01

This study is to analyze design principles of boost inductor and capacitor used in the 4-level DC-DC boost converter to realize size reduction of passive component referring to their attributes. The important feature of this circuit is that most of the boost-up energy is transferred from the capacitor-clamped to the output side which the small inductance can be used at the input side. The inductance of the boost inductor is designed by referring the inductor current ripple. On the other hand, the capacitance of the capacitor-clamped is designed by considering voltage stress on semiconductor devices and also the used switching frequency. Besides that, according to the design specifications, the required inductance in 4-level DC-DC boost converter is decreased compared to a conventional conventional DC-DC boost converter. Meanwhile, voltage stress on semiconductor device is depending on the maximum voltage ripple of the capacitor-clamped. A 50 W 4-level DC-DC boost converter prototype has been constructed. The results show that the inductor current ripple was 1.15 A when the inductors, 1 mH and 0.11 mH were used in the conventional and 4-level DC-DC boost converters, respectively. Thus, based on the experimental results, it shows that the reduction of passive components by referring to their attributes in 4-level DC-DC boost converter is achieved. Moreover, the decreasing of voltage stress on the semiconductor devices is an advantage for the selection of low ON-resistance of the devices which will contribute to the reduction of the semiconductor conduction loss. The integration result of boost converter and H-bridge inverter is also shown.

Morbidity and prostate-specific antigen control of external beam radiation therapy plus low-dose-rate brachytherapy boost for low, intermediate, and high-risk prostate cancer.

PubMed

Koontz, Bridget F; Chino, Junzo; Lee, W Robert; Hahn, Carol A; Buckley, Niall; Huang, Samuel; Kim, Jay; Reagan, Robert; Joyner, Raymond; Anscher, Mitchell S

2009-01-01

Dose escalation has been shown beneficial in prostate cancer. Brachytherapy (BT) provides an opportunity for dose escalation beyond what can be safely delivered using only teletherapy methods. The purpose of this study was to determine cancer control and morbidity of external beam radiation therapy (EBRT) plus low-dose-rate (LDR) BT boost in patients with prostate cancer treated at Duke University Health System. Between June 1997 and August 2007, 199 patients were consecutively treated at our facility with 46Gy EBRT followed by 100Gy palladium-103 ((103)Pd) or 120Gy iodine-125 ((125)I) LDR prostate implant. Treatment characteristics and followup data were retrospectively analyzed. Intermediate risk was defined as T2b-c, Gleason score 7 (GS 7), or prostate-specific antigen (PSA) of 10.1-19.9ng/mL. High risk was defined as GS 8-10, PSA>20, T3+, or two intermediate risk factors. The Radiation Therapy Oncology Group toxicity scale was used to report morbidity for gastrointestinal (GI) and genitourinary (GU) effects. PSA recurrence was defined as nadir+2ng/mL. Median followup was 4.2 years for all patients, 4.8 years for high-risk patients. Risk categories were as follows: 20% low risk, 47% intermediate risk, and 33% high risk. Forty five percent of patients received adjuvant androgen deprivation therapy (ADT). The median length of time since end of ADT to last followup was 2.7 years in all patients, 2.0 years for high-risk patients. Five-year biochemical relapse-free survival was 87% for all, 81% for high-risk patients. PSA control was similar at 92% for all and 86% for high-risk patients. Five-year actuarial risk of any and Grade 3 late GI morbidity was 38% and 7% respectively, and any and Grade 3 late GU morbidity was 21% and 3%, respectively. There were no significant differences in risk of Grade 2+GI or GU morbidity with choice of isotope. EBRT plus LDR BT has acceptable morbidity and, with 5-year followup, provides excellent cancer control even in high-risk patients.

CYP3A induction and inhibition by different antiretroviral regimens reflected by changes in plasma 4beta-hydroxycholesterol levels.

PubMed

Josephson, F; Bertilsson, L; Böttiger, Y; Flamholc, L; Gisslén, M; Ormaasen, V; Sönnerborg, A; Diczfalusy, U

2008-08-01

A member of the major human cytochrome P450 superfamily of hemoproteins, CYP3A4/5, converts cholesterol into 4beta-hydroxycholesterol. We studied plasma 4beta-hydroxycholesterol levels prior to and 4 weeks after initiating antiretroviral therapy that included efavirenz, ritonavir-boosted atazanavir or ritonavir-boosted lopinavir with the aim of exploring the usefulness of plasma 4beta-hydroxycholesterol levels as an endogenous biomarker of CYP3A activity. Efavirenz is an inducer of CYP3A, whereas the ritonavir-boosted regimens are net inhibitors of CYP3A. In patients treated with efavirenz, the median plasma 4beta-hydroxycholesterol level increased by 46 ng/mL (p = 0.004; n = 11). In contrast, patients given ritonavir-boosted atazanavir showed a median decrease in plasma 4beta-hydroxycholesterol of -9.4 ng/mL (p = 0.0003; n = 22), and those given ritonavir-boosted lopinavir showed a median change from baseline of -5.8 ng/mL (p = 0.38; n = 19). There were significant between-group differences in the effects of antiretroviral treatment on plasma 4beta-hydroxycholesterol levels (p < 0.0001). Changes in plasma 4beta-hydroxycholesterol following the initiation of efavirenz- or atazanavir/ritonavir-based antiretroviral therapy reflected the respective net increase and decrease of CYP3A activity of these regimens. The plasma 4beta-hydroxycholesterol level did not indicate a net CYP3A inhibition in the lopinavir/ritonavir arm, possibly because of concomitant enzyme induction.

Recurrence Effects in the Parametric Spring Pendulum.

ERIC Educational Resources Information Center

Falk, Lars

1978-01-01

Gives a perturbation analysis to recurrence effects of the spring pendulum. The recurrence depends on two conservation laws which determine the motion in an intermediate region; oscillations outside this region are unstable and must return. Gives the relation to Fermi-Pasta-Ulam problem together with the explicit solution. (Author/GA)

Effect of delayed anthrax vaccine dose on Bacillus anthracis protective antigen IgG response and lethal toxin neutralization activity.

PubMed

Pittman, Phillip R; Fisher, Diana; Quinn, Xiaofei; Schmader, Trevor; Barrera-Oro, Julio G

2013-10-17

We describe the Bacillus anthracis protective antigen IgG antibody response and the B. anthracis lethal toxin neutralization activity to a delayed dose of anthrax vaccine adsorbed (AVA, BioThrax(®)) using validated assays. 373 individuals received 1, 2, or 3 priming doses, 18-24 months afterward, they received a delayed dose of AVA. Overall, 23.6% of subjects showed detectable anti-PA IgG before the boost, compared to 99.2% (P<0.0001) 28 days after the boost. Geometric mean anti-PA IgG concentration (GMC) was 1.66 μg/mL before and 887.82 μg/mL after the boost (P<0.0001). The proportion of individuals with four-fold increase in GMC following the boost ranged from 93.8% to 100%. Robust anti-PA IgG levels and B. anthracis lethal toxin neutralization activity are induced when an AVA dose is delayed as long as two years. These data support continuing with the vaccination schedule when a dose is delayed as long as two years rather than restarting the series. Published by Elsevier Ltd.

Boosted dark matter signals uplifted with self-interaction

DOE PAGES

Kong, Kyoungchul; Mohlabeng, Gopolang; Park, Jong -Chul

2015-04-01

We explore detection prospects of a non-standard dark sector in the context of boosted dark matter. We focus on a scenario with two dark matter particles of a large mass difference, where the heavier candidate is secluded and interacts with the standard model particles only at loops, escaping existing direct and indirect detection bounds. Yet its pair annihilation in the galactic center or in the Sun may produce boosted stable particles, which could be detected as visible Cherenkov light in large volume neutrino detectors. In such models with multiple candidates, self-interaction of dark matter particles is naturally utilized in themore » assisted freeze-out mechanism and is corroborated by various cosmological studies such as N-body simulations of structure formation, observations of dwarf galaxies, and the small scale problem. We show that self-interaction of the secluded (heavier) dark matter greatly enhances the capture rate in the Sun and results in promising signals at current and future experiments. We perform a detailed analysis of the boosted dark matter events for Super-Kamiokande, Hyper-Kamiokande and PINGU, including notable effects such as evaporation due to self-interaction and energy loss in the Sun.« less

Boosted dark matter signals uplifted with self-interaction

NASA Astrophysics Data System (ADS)

Kong, Kyoungchul; Mohlabeng, Gopolang; Park, Jong-Chul

2015-04-01

We explore detection prospects of a non-standard dark sector in the context of boosted dark matter. We focus on a scenario with two dark matter particles of a large mass difference, where the heavier candidate is secluded and interacts with the standard model particles only at loops, escaping existing direct and indirect detection bounds. Yet its pair annihilation in the galactic center or in the Sun may produce boosted stable particles, which could be detected as visible Cherenkov light in large volume neutrino detectors. In such models with multiple candidates, self-interaction of dark matter particles is naturally utilized in the assisted freeze-out mechanism and is corroborated by various cosmological studies such as N-body simulations of structure formation, observations of dwarf galaxies, and the small scale problem. We show that self-interaction of the secluded (heavier) dark matter greatly enhances the capture rate in the Sun and results in promising signals at current and future experiments. We perform a detailed analysis of the boosted dark matter events for Super-Kamiokande, Hyper-Kamiokande and PINGU, including notable effects such as evaporation due to self-interaction and energy loss in the Sun.

The Obesity Paradox in Recurrent Attacks of Gout in Observational Studies: Clarification and Remedy

PubMed Central

Nguyen, Uyen-Sa D. T.; Zhang, Yuqing; Louie-Gao, Qiong; Niu, Jingbo; Felson, David T.; LaValley, Michael P.; Choi, Hyon K.

2016-01-01

Objective Obesity is strongly associated with incident gout risk; its association with risk of recurrent gout attacks has been null or weak, constituting an obesity paradox. We sought to demonstrate and overcome the methodologic issues associated with the obesity paradox for risk of recurrent gout attacks. Methods Using the MRFIT database, we decomposed the total effect of obesity into its direct and indirect (i.e., mediated) effects using marginal structural models. We also estimated the total effect of BMI change from baseline among incident gout patients. Results Of 11,816 gout-free subjects at baseline, we documented 408 incident gout cases, with 132 developing recurrent gout attacks over a 7-year follow-up. The adjusted odds ratio (OR) for incident gout among obese individuals was 2.6, while that for recurrent gout attacks among gout patients was 0.98 (i.e., the obesity paradox). These ORs correlated well with the ORs for the indirect and direct effects of obesity on risk of recurrent gout attacks (i.e., 2.83 and 0.98, respectively). Compared with no BMI change, the OR of losing vs. gaining >5% of baseline BMI was 0.61 and 1.60 for recurrent gout attacks, respectively (P for trend <0.01), suggesting a dose-response association. Conclusion The obesity paradox for risk of recurrent gout attacks is explained by the absence of the direct effect, which is often measured in conventional analyses and misinterpreted as the intended total effect of interest. In contrast, the BMI change analysis correctly estimated the intended total effect of BMI, and revealed a dose-response relationship. PMID:27331767

Dose-Effect Relationships for Recurrence of Keloid and Pterygium After Surgery and Radiotherapy

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

Kal, Henk B.; Veen, Ronald E.; Juergenliemk-Schulz, Ina M.

2009-05-01

Purpose: To show radiation dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. Methods and Materials: Using PubMed, we performed a retrospective review of articles reporting incidences and/or dose-response relationships for recurrence of keloid and pterygium after radiotherapy following surgery. The irradiation regimens identified were normalized by use of the linear-quadratic model; biologically effective doses (BEDs) were calculated. Results: For keloid recurrence after radiotherapy following keloid removal, with either teletherapy or brachytherapy, the recurrence rate after having delivered a BED greater than 30 Gy is less than 10%. For pterygium recurrence after bare sclera surgery and {supmore » 90}Sr {beta}-irradiation, a BED of about 30 Gy seems to be sufficient also to reduce the recurrence rate to less than 10%. Conclusions: Most of the doses in the radiotherapy schemes used for prevention of keloid recurrence after surgery are too low. In contrast, the doses applied in most regimens to prevent pterygium recurrence are too high. A scheme with a BED of 30 to 40 Gy seems to be sufficient to prevent recurrences of keloid as well as pterygium.« less

The impact of HIV and ART on recurrent tuberculosis in a sub-Saharan setting.

PubMed

Houben, Rein M G J; Glynn, Judith R; Mboma, Sebastian; Mzemba, Themba; Mwaungulu, Nimrod J; Mwaungulu, Lorren; Mwenibabu, Michael; Mpunga, James; French, Neil; Crampin, Amelia C

2012-11-13

To estimate the impact of antiretroviral therapy (ART) on the incidence of recurrent tuberculosis (TB) in an African population. A long-term population cohort in Karonga District, northern Malawi. Patients who had completed treatment for laboratory-confirmed TB diagnosed since 1996 were visited annually to record vital status, ART use and screen for TB. Survival analysis estimated the effect of HIV/ART status at completion of treatment on mortality and recurrence. Analyses were stratified by time since treatment completion to estimate the effects on relapse (predominates during first year) and reinfection disease (predominates later). Among 1133 index TB cases contributing 4353 person-years of follow-up, there were 307 deaths and 103 laboratory-confirmed recurrences (recurrence rate 4.6 per 100 person-years). Half the recurrences occurred in the first year since completing treatment. HIV infection increased the recurrence rate [rate ratio adjusted for age, sex, period and TB type 2.69, 95% confidence interval (CI) 1.69-4.26], but with less effect in the first year (adjusted rate ratio 1.71, 95% CI 0.87-3.35) than subsequently (adjusted rate ratio 4.2, 95% CI 2.16-8.15). Recurrence rates on ART were intermediate between those of HIV-negative individuals and HIV-positive individuals without ART. Compared with HIV-positive individuals without ART, the adjusted rate ratio was 0.74 (95% CI 0.27-2.06) in the first year, and 0.43 (95% CI 0.11-1.73) later. The increased incidence of TB recurrence observed in HIV-positive patients appeared to be reduced by ART. The effects are mostly on later (likely reinfection) disease so the impact of ART on reducing recurrence will be highest in high TB incidence settings.

14 CFR 27.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Power boost and power-operated control...

14 CFR 27.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2011-01-01 2011-01-01 false Power boost and power-operated control...

14 CFR 29.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Systems § 29.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Power boost and power-operated control...

14 CFR 27.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2012-01-01 2012-01-01 false Power boost and power-operated control...

14 CFR 27.695 - Power boost and power-operated control system.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Systems § 27.695 Power boost and power-operated control system. (a) If a power boost or power-operated... failure of all engines. (b) Each alternate system may be a duplicate power portion or a manually operated... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Power boost and power-operated control...

On the Effect of Variability on Fermi, Pasta and Ulam Matrices

NASA Astrophysics Data System (ADS)

Nelson, Heather; Choubey, Bhaskar

The first numerical experiment by Fermi, Pasta, Ulam and Tsingou in 1955 observed recurrence in an array of non-linear systems. This has led to a large number of nonlinear numerical experiments with various new results from a chain of ideal oscillators. FPUT arrays consists of linear oscillators connected nonlinearly which leads to recurrence of energy mode with time. However, if such a system were to be physically constructed, inherent process variations would introduce a manufacturing tolerance into the parameters of the system. This abstract reports investigation into the effects of these tolerances on the FPU matrices. It has been observed that tolerance in the oscillators can degrade the observance of recurrence and with a chain of even 64 oscillators, recurrence cannot be observed with tolerances more than 10%. It has also been observed that linear oscillators tolerances have more effects on recurrence than those of the nonlinear coupling. Even with very small tolerances of +/- 1% on the linear components, one start to observe variations in the quality and magnitude of the recurrence and at +/- 5%, recurrence is starting to break down.

Amniotic membrane transplantation with conjunctival autograft for recurrent pterygium.

PubMed

Shimazaki, Jun; Kosaka, Koichi; Shimmura, Shigeto; Tsubota, Kazuo

2003-01-01

To study the effect of amniotic membrane transplantation (AMT) combined with either limbal autograft transplantation (LAT) or conjunctival autograft transplantation (CAT) in recurrent pterygium. Retrospective, noncomparative, interventional case series. Twenty-seven eyes of 27 patients with recurrent pterygium. The mean number of prior surgeries was 3.1 (range, 1-10). Fifteen eyes each had restriction of ocular movement and symblepharon before surgery. Patients were treated by AMT with either LAT (n = 15) or CAT (n = 12). Recurrence of pterygium, improvement in ocular movement, and symblepharon formation. Twenty-three (85.2%) of 27 eyes showed no recurrence with a mean observation period of 67.0 weeks. Fourteen eyes (93.3%) each showed improvement in ocular movement restriction and symblepharon after AMT. In four eyes that developed recurrence, three had LAT and one had CAT combined with AMT, suggesting that there was no difference in surgical outcome between LAT and CAT. AMT with CAT is a safe and effective method for recurrent pterygium, especially that associated with ocular movement restriction and symblepharon. Considering the potential adverse effects associated with limbal excision, AMT plus CAT may be preferred over AMT plus LAT.

Effective Induction of Simian Immunodeficiency Virus-Specific Cytotoxic T Lymphocytes in Macaques by Using a Multiepitope Gene and DNA Prime-Modified Vaccinia Virus Ankara Boost Vaccination Regimen

PubMed Central

Hanke, Tomas; Samuel, Rachel V.; Blanchard, Tom J.; Neumann, Veronica C.; Allen, Todd M.; Boyson, Jon E.; Sharpe, Sally A.; Cook, Nicola; Smith, Geoffrey L.; Watkins, David I.; Cranage, Martin P.; McMichael, Andrew J.

1999-01-01

DNA and modified vaccinia virus Ankara (MVA) are vaccine vehicles suitable and safe for use in humans. Here, by using a multicytotoxic T-lymphocyte (CTL) epitope gene and a DNA prime-MVA boost vaccination regimen, high levels of CTLs specific for a single simian immunodeficiency virus (SIV) gag-derived epitope were elicited in rhesus macaques. These vaccine-induced CTLs were capable of killing SIV-infected cells in vitro. Fluorescence-activated cell sorter analysis using soluble tetrameric major histocompatibility complex-peptide complexes showed that the vaccinated animals had 1 to 5% circulating CD8+ lymphocytes specific for the vaccine epitope, frequencies comparable to those in SIV-infected monkeys. Upon intrarectal challenge with pathogenic SIVmac251, no evidence for protection was observed in at least two of the three vaccinated animals. This study does not attempt to define correlates of protective immunity nor design a protective vaccine against immunodeficiency viruses, but it demonstrates clearly that the DNA prime-MVA boost regimen is an effective protocol for induction of CTLs in macaques. It also shows that powerful tools for studying the role of CTLs in the control of SIV and human immunodeficiency virus infections are now available: epitope-based vaccines, a protocol for an effective induction of CTLs in primates, and a simple and sensitive method for quantitation of epitope-specific T cells. The advantages of the DNA prime-MVA boost regimen as well as the correlations of tetramer staining of peripheral blood lymphocytes with CTL killing in vitro and postchallenge control of viremia are discussed. PMID:10438842

Effects of injection parameters, boost, and swirl ratio on gasoline compression ignition operation at idle and low-load conditions

DOE PAGES

Kodavasal, Janardhan; Kolodziej, Christopher P.; Ciatti, Stephen A.; ...

2016-11-03

In this study, we study the effects of injector nozzle inclusion angle, injection pressure, boost, and swirl ratio on gasoline compression ignition combustion. Closed-cycle computational fluid dynamics simulations using a 1/7th sector mesh representing a single cylinder of a four-cylinder 1.9 L diesel engine, operated in gasoline compression ignition mode with 87 anti-knock index (AKI) gasoline, were performed. Two different operating conditions were studied—the first is representative of idle operation (4 mg fuel/cylinder/cycle, 850 r/min), and the second is representative of a low-load condition (10 mg fuel/cylinder/cycle, 1500 r/min). The mixture preparation and reaction space from the simulations were analyzedmore » to gain insights into the effects of injection pressure, nozzle inclusion angle, boost, and swirl ratio on achieving stable low-load to idle gasoline compression ignition operation. It was found that narrower nozzle inclusion angles allow for more reactivity or propensity to ignition (determined qualitatively by computing constant volume ignition delays) and are suitable over a wider range of injection timings. Under idle conditions, it was found that lower injection pressures helped to reduce overmixing of the fuel, resulting in greater reactivity and ignitability (ease with which ignition can be achieved) of the gasoline. However, under the low-load condition, lower injection pressures did not increase ignitability, and it is hypothesized that this is because of reduced chemical residence time resulting from longer injection durations. Reduced swirl was found to maintain higher in-cylinder temperatures through compression, resulting in better ignitability. It was found that boosting the charge also helped to increase reactivity and advanced ignition timing.« less

Effects of injection parameters, boost, and swirl ratio on gasoline compression ignition operation at idle and low-load conditions

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

Kodavasal, Janardhan; Kolodziej, Christopher P.; Ciatti, Stephen A.

In this study, we study the effects of injector nozzle inclusion angle, injection pressure, boost, and swirl ratio on gasoline compression ignition combustion. Closed-cycle computational fluid dynamics simulations using a 1/7th sector mesh representing a single cylinder of a four-cylinder 1.9 L diesel engine, operated in gasoline compression ignition mode with 87 anti-knock index (AKI) gasoline, were performed. Two different operating conditions were studied—the first is representative of idle operation (4 mg fuel/cylinder/cycle, 850 r/min), and the second is representative of a low-load condition (10 mg fuel/cylinder/cycle, 1500 r/min). The mixture preparation and reaction space from the simulations were analyzedmore » to gain insights into the effects of injection pressure, nozzle inclusion angle, boost, and swirl ratio on achieving stable low-load to idle gasoline compression ignition operation. It was found that narrower nozzle inclusion angles allow for more reactivity or propensity to ignition (determined qualitatively by computing constant volume ignition delays) and are suitable over a wider range of injection timings. Under idle conditions, it was found that lower injection pressures helped to reduce overmixing of the fuel, resulting in greater reactivity and ignitability (ease with which ignition can be achieved) of the gasoline. However, under the low-load condition, lower injection pressures did not increase ignitability, and it is hypothesized that this is because of reduced chemical residence time resulting from longer injection durations. Reduced swirl was found to maintain higher in-cylinder temperatures through compression, resulting in better ignitability. It was found that boosting the charge also helped to increase reactivity and advanced ignition timing.« less

Familiarity speeds up visual short-term memory consolidation.

PubMed

Xie, Weizhen; Zhang, Weiwei

2017-06-01

Existing long-term memory (LTM) can boost the number of retained representations over a short delay in visual short-term memory (VSTM). However, it is unclear whether and how prior LTM affects the initial process of transforming fragile sensory inputs into durable VSTM representations (i.e., VSTM consolidation). The consolidation speed hypothesis predicts faster consolidation for familiar relative to unfamiliar stimuli. Alternatively, the perceptual boost hypothesis predicts that the advantage in perceptual processing of familiar stimuli should add a constant boost for familiar stimuli during VSTM consolidation. To test these competing hypotheses, the present study examined how the large variance in participants' prior multimedia experience with Pokémon affected VSTM for Pokémon. In Experiment 1, the amount of time allowed for VSTM consolidation was manipulated by presenting consolidation masks at different intervals after the onset of to-be-remembered Pokémon characters. First-generation Pokémon characters that participants were more familiar with were consolidated faster into VSTM as compared with recent-generation Pokémon characters that participants were less familiar with. These effects were absent in participants who were unfamiliar with both generations of Pokémon. Although familiarity also increased the number of retained Pokémon characters when consolidation was uninterrupted but still incomplete due to insufficient encoding time in Experiment 1, this capacity effect was absent in Experiment 2 when consolidation was allowed to complete with sufficient encoding time. Together, these results support the consolidation speed hypothesis over the perceptual boost hypothesis and highlight the importance of assessing experimental effects on both processing and representation aspects of VSTM. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

L2-Boosting algorithm applied to high-dimensional problems in genomic selection.

PubMed

González-Recio, Oscar; Weigel, Kent A; Gianola, Daniel; Naya, Hugo; Rosa, Guilherme J M

2010-06-01

The L(2)-Boosting algorithm is one of the most promising machine-learning techniques that has appeared in recent decades. It may be applied to high-dimensional problems such as whole-genome studies, and it is relatively simple from a computational point of view. In this study, we used this algorithm in a genomic selection context to make predictions of yet to be observed outcomes. Two data sets were used: (1) productive lifetime predicted transmitting abilities from 4702 Holstein sires genotyped for 32 611 single nucleotide polymorphisms (SNPs) derived from the Illumina BovineSNP50 BeadChip, and (2) progeny averages of food conversion rate, pre-corrected by environmental and mate effects, in 394 broilers genotyped for 3481 SNPs. Each of these data sets was split into training and testing sets, the latter comprising dairy or broiler sires whose ancestors were in the training set. Two weak learners, ordinary least squares (OLS) and non-parametric (NP) regression were used for the L2-Boosting algorithm, to provide a stringent evaluation of the procedure. This algorithm was compared with BL [Bayesian LASSO (least absolute shrinkage and selection operator)] and BayesA regression. Learning tasks were carried out in the training set, whereas validation of the models was performed in the testing set. Pearson correlations between predicted and observed responses in the dairy cattle (broiler) data set were 0.65 (0.33), 0.53 (0.37), 0.66 (0.26) and 0.63 (0.27) for OLS-Boosting, NP-Boosting, BL and BayesA, respectively. The smallest bias and mean-squared errors (MSEs) were obtained with OLS-Boosting in both the dairy cattle (0.08 and 1.08, respectively) and broiler (-0.011 and 0.006) data sets, respectively. In the dairy cattle data set, the BL was more accurate (bias=0.10 and MSE=1.10) than BayesA (bias=1.26 and MSE=2.81), whereas no differences between these two methods were found in the broiler data set. L2-Boosting with a suitable learner was found to be a competitive alternative for genomic selection applications, providing high accuracy and low bias in genomic-assisted evaluations with a relatively short computational time.

Radiation-related quality of life parameters after targeted intraoperative radiotherapy versus whole breast radiotherapy in patients with breast cancer: results from the randomized phase III trial TARGIT-A.

PubMed

Welzel, Grit; Boch, Angela; Sperk, Elena; Hofmann, Frank; Kraus-Tiefenbacher, Uta; Gerhardt, Axel; Suetterlin, Marc; Wenz, Frederik

2013-01-07

Intraoperative radiotherapy (IORT) is a new treatment approach for early stage breast cancer. This study reports on the effects of IORT on radiation-related quality of life (QoL) parameters. Two hundred and thirty women with stage I-III breast cancer (age, 31 to 84 years) were entered into the study. A single-center subgroup of 87 women from the two arms of the randomized phase III trial TARGIT-A (TARGeted Intra-operative radioTherapy versus whole breast radiotherapy for breast cancer) was analyzed. Furthermore, results were compared to non-randomized control groups: n = 90 receiving IORT as a tumor bed boost followed by external beam whole breast radiotherapy (EBRT) outside of TARGIT-A (IORT-boost), and n = 53 treated with EBRT followed by an external-beam boost (EBRT-boost). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaires C30 (QLQ-C30) and BR23 (QLQ-BR23). The mean follow-up period in the TARGIT-A groups was 32 versus 39 months in the non-randomized control groups. Patients receiving IORT alone reported less general pain (21.3 points), breast (7.0 points) and arm (15.1 points) symptoms, and better role functioning (78.7 points) as patients receiving EBRT (40.9; 19.0; 32.8; and 60.5 points, respectively, P < 0.01). Patients receiving IORT alone also had fewer breast symptoms than TARGIT-A patients receiving IORT followed by EBRT for high risk features on final pathology (IORT-EBRT; 7.0 versus 29.7 points, P < 0.01). There were no significant differences between TARGIT-A patients receiving IORT-EBRT compared to non-randomized IORT-boost or EBRT-boost patients and patients receiving EBRT without a boost. In the randomized setting, important radiation-related QoL parameters after IORT were superior to EBRT. Non-randomized comparisons showed equivalent parameters in the IORT-EBRT group and the control groups.

Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA Prime-Modified Vaccinia Virus Ankara Boost HIV-1 Vaccine Regimen.

PubMed

Bauer, Asli; Podola, Lilli; Mann, Philipp; Missanga, Marco; Haule, Antelmo; Sudi, Lwitiho; Nilsson, Charlotta; Kaluwa, Bahati; Lueer, Cornelia; Mwakatima, Maria; Munseri, Patricia J; Maboko, Leonard; Robb, Merlin L; Tovanabutra, Sodsai; Kijak, Gustavo; Marovich, Mary; McCormack, Sheena; Joseph, Sarah; Lyamuya, Eligius; Wahren, Britta; Sandström, Eric; Biberfeld, Gunnel; Hoelscher, Michael; Bakari, Muhammad; Kroidl, Arne; Geldmacher, Christof

2017-09-15

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gag p37 and two vaccinations with MVA-CMDR encoding subtype A Gag p55 Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ + ) Gag-specific T-cell responses were dominated by CD4 + T cells ( P < 0.001 compared to CD8 + T cells) that coexpressed interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-α) (63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude median response to Gag p24 regions, more conserved between prime and boost, compared to those of regions within Gag p15 (not primed) and Gag p17 (less conserved; P < 0.0001 for both). Four regions within Gag p24 each were targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA- and DNA Gag-encoded immunogens ( P = 0.04, r 2 = 0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T-cell response that was dominated by polyfunctional CD4 + T cells and that targeted multiple antigenic regions within the conserved Gag p24 protein. IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses. Copyright © 2017 American Society for Microbiology.

The effect of mode and context on survey results: Analysis of data from the Health Survey for England 2006 and the Boost Survey for London

PubMed Central

2010-01-01

Background Health-related data at local level could be provided by supplementing national health surveys with local boosts. Self-completion surveys are less costly than interviews, enabling larger samples to be achieved for a given cost. However, even when the same questions are asked with the same wording, responses to survey questions may vary by mode of data collection. These measurement differences need to be investigated further. Methods The Health Survey for England in London ('Core') and a London Boost survey ('Boost') used identical sampling strategies but different modes of data collection. Some data were collected by face-to-face interview in the Core and by self-completion in the Boost; other data were collected by self-completion questionnaire in both, but the context differed. Results were compared by mode of data collection using two approaches. The first examined differences in results that remained after adjusting the samples for differences in response. The second compared results after using propensity score matching to reduce any differences in sample composition. Results There were no significant differences between the two samples for prevalence of some variables including long-term illness, limiting long-term illness, current rates of smoking, whether participants drank alcohol, and how often they usually drank. However, there were a number of differences, some quite large, between some key measures including: general health, GHQ12 score, portions of fruit and vegetables consumed, levels of physical activity, and, to a lesser extent, smoking consumption, the number of alcohol units reported consumed on the heaviest day of drinking in the last week and perceived social support (among women only). Conclusion Survey mode and context can both affect the responses given. The effect is largest for complex question modules but was also seen for identical self-completion questions. Some data collected by interview and self-completion can be safely combined. PMID:20868528

Analysis, control and design of a non-inverting buck-boost converter: A bump-less two-level T-S fuzzy PI control.

PubMed

Almasi, Omid Naghash; Fereshtehpoor, Vahid; Khooban, Mohammad Hassan; Blaabjerg, Frede

2017-03-01

In this paper, a new modified fuzzy Two-Level Control Scheme (TLCS) is proposed to control a non-inverting buck-boost converter. Each level of fuzzy TLCS consists of a tuned fuzzy PI controller. In addition, a Takagi-Sugeno-Kang (TSK) fuzzy switch proposed to transfer the fuzzy PI controllers to each other in the control system. The major difficulty in designing fuzzy TLCS which degrades its performance is emerging unwanted drastic oscillations in the converter output voltage during replacing the controllers. Thereby, the fuzzy PI controllers in each level of TLCS structure are modified to eliminate these oscillations and improve the system performance. Some simulations and digital signal processor based experiments are conducted on a non-inverting buck-boost converter to support the effectiveness of the proposed TLCS in controlling the converter output voltage. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Boosting the Direct CP Measurement of the Higgs-Top Coupling.

PubMed

Buckley, Matthew R; Gonçalves, Dorival

2016-03-04

Characterizing the 125 GeV Higgs boson is a critical component of the physics program at the LHC Run II. In this Letter, we consider tt[over ¯]H associated production in the dileptonic mode. We demonstrate that the difference in azimuthal angle between the leptons from top decays can directly reveal the CP structure of the top-Higgs coupling with the sensitivity of the measurement substantially enhanced in the boosted Higgs regime. We first show how to access this channel via H→bb[over ¯] jet-substructure tagging, then demonstrate the ability of the new variable to measure CP. Our analysis includes all signal and background samples simulated via the MC@NLO algorithm including hadronization and underlying-event effects. Using a boosted Higgs substructure with dileptonic tops, we find that the top-Higgs coupling strength and the CP structure can be directly probed with achievable luminosity at the 13 TeV LHC.

Real-time detection with AdaBoost-svm combination in various face orientation

NASA Astrophysics Data System (ADS)

Fhonna, R. P.; Nasution, M. K. M.; Tulus

2018-03-01

Most of the research has used algorithm AdaBoost-SVM for face detection. However, to our knowledge so far there is no research has been facing detection on real-time data with various orientations using the combination of AdaBoost and Support Vector Machine (SVM). Characteristics of complex and diverse face variations and real-time data in various orientations, and with a very complex application will slow down the performance of the face detection system this becomes a challenge in this research. Face orientation performed on the detection system, that is 900, 450, 00, -450, and -900. This combination method is expected to be an effective and efficient solution in various face orientations. The results showed that the highest average detection rate is on the face detection oriented 00 and the lowest detection rate is in the face orientation 900.

A High Voltage Ratio and Low Ripple Interleaved DC-DC Converter for Fuel Cell Applications

PubMed Central

Chang, Long-Yi; Chao, Kuei-Hsiang; Chang, Tsang-Chih

2012-01-01

This paper proposes a high voltage ratio and low ripple interleaved boost DC-DC converter, which can be used to reduce the output voltage ripple. This converter transfers the low DC voltage of fuel cell to high DC voltage in DC link. The structure of the converter is parallel with two voltage-doubler boost converters by interleaving their output voltages to reduce the voltage ripple ratio. Besides, it can lower the current stress for the switches and inductors in the system. First, the PSIM software was used to establish a proton exchange membrane fuel cell and a converter circuit model. The simulated and measured results of the fuel cell output characteristic curve are made to verify the correctness of the established simulation model. In addition, some experimental results are made to validate the effectiveness in improving output voltage ripple of the proposed high voltage ratio interleaved boost DC-DC converters. PMID:23365536

A high voltage ratio and low ripple interleaved DC-DC converter for fuel cell applications.

PubMed

Chang, Long-Yi; Chao, Kuei-Hsiang; Chang, Tsang-Chih

2012-01-01

This paper proposes a high voltage ratio and low ripple interleaved boost DC-DC converter, which can be used to reduce the output voltage ripple. This converter transfers the low DC voltage of fuel cell to high DC voltage in DC link. The structure of the converter is parallel with two voltage-doubler boost converters by interleaving their output voltages to reduce the voltage ripple ratio. Besides, it can lower the current stress for the switches and inductors in the system. First, the PSIM software was used to establish a proton exchange membrane fuel cell and a converter circuit model. The simulated and measured results of the fuel cell output characteristic curve are made to verify the correctness of the established simulation model. In addition, some experimental results are made to validate the effectiveness in improving output voltage ripple of the proposed high voltage ratio interleaved boost DC-DC converters.

Rheumatoid arthritis significantly increased recurrence risk after ischemic stroke/transient ischemic attack.

PubMed

Chen, Yih-Ru; Hsieh, Fang-I; Lien, Li-Ming; Hu, Chaur-Jong; Jeng, Jiann-Shing; Peng, Giia-Sheun; Tang, Sung-Chun; Chi, Nai-Fang; Sung, Yueh-Feng; Chiou, Hung-Yi

2018-06-02

The effect of RA on recurrent stroke is unknown. Therefore, we examined effects of rheumatoid arthritis (RA) on risk of stroke recurrence and investigated the interaction between RA and traditional cardiovascular risk factors on recurrence risk after ischemic stroke (IS) or transient ischemic attack (TIA). Of 3190 patients with IS or TIA recruited in this cohort study, 638 were comorbid with RA and 2552 without RA. Stroke recurrence, RA, lifestyle, lipid variables and other comorbidities were identified through linkage between a nationwide stroke database in Taiwan and the National Health Insurance claims database. Cox proportional hazard models with competing risk adjustment were used to evaluate the relationship between RA and recurrent stroke. Patients with RA showed a significantly increased risk of recurrent stroke, particular in recurrent IS/TIA. The increased risk of recurrent IS/TIA in RA patients may through the changes of triglycerides (TG)/high-density lipoprotein cholesterol (HDL-C) ratio. A positive additive interaction was observed between RA and current smoking on the risk of recurrent IS/TIA. Significantly increased risks for recurrent IS/TIA were observed among RA patients who smoked > 40 years or those who smoked > 20 cigarettes/day. This study provides the first evidence that RA significantly increased recurrence IS/TIA risk. The changes of TG/HDL-C ratio may play some roles in the recurrence IS/TIA risk in RA patients. In addition, our results suggest that smoking increases the risk of recurrent IS/TIA in RA patients and reinforces the need for aggressive smoking cessation efforts in RA patients.

Of channels and pumps: different ways to boost the aldosterone?

PubMed

Bandulik, S

2017-07-01

The mineralocorticoid aldosterone is a major factor controlling the salt and water balance and thereby also the arterial blood pressure. Accordingly, primary aldosteronism (PA) characterized by an inappropriately high aldosterone secretion is the most common form of secondary hypertension. The physiological stimulation of aldosterone synthesis in adrenocortical glomerulosa cells by angiotensin II and an increased plasma K + concentration depends on a membrane depolarization and an increase in the cytosolic Ca 2+ activity. Recurrent gain-of-function mutations of ion channels and transporters have been identified in a majority of cases of aldosterone-producing adenomas and in familial forms of PA. In this review, the physiological role of these genes in the regulation of aldosterone synthesis and the altered function of the mutant proteins as well are described. The specific changes of the membrane potential and the cellular ion homoeostasis in adrenal cells expressing the different mutants are compared, and their impact on autonomous aldosterone production and proliferation is discussed. © 2016 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Classification of time-series images using deep convolutional neural networks

NASA Astrophysics Data System (ADS)

Hatami, Nima; Gavet, Yann; Debayle, Johan

2018-04-01

Convolutional Neural Networks (CNN) has achieved a great success in image recognition task by automatically learning a hierarchical feature representation from raw data. While the majority of Time-Series Classification (TSC) literature is focused on 1D signals, this paper uses Recurrence Plots (RP) to transform time-series into 2D texture images and then take advantage of the deep CNN classifier. Image representation of time-series introduces different feature types that are not available for 1D signals, and therefore TSC can be treated as texture image recognition task. CNN model also allows learning different levels of representations together with a classifier, jointly and automatically. Therefore, using RP and CNN in a unified framework is expected to boost the recognition rate of TSC. Experimental results on the UCR time-series classification archive demonstrate competitive accuracy of the proposed approach, compared not only to the existing deep architectures, but also to the state-of-the art TSC algorithms.

Effectiveness of repeat hepatic resection for patients with recurrent intrahepatic cholangiocarcinoma: Factors associated with long-term outcomes.

PubMed

Si, Anfeng; Li, Jun; Xing, Xianglei; Lei, Zhengqing; Xia, Yong; Yan, Zhenlin; Wang, Kui; Shi, Lehua; Shen, Feng

2017-04-01

Tumor recurrence after liver resection for intrahepatic cholangiocarcinoma is common. The effective treatment for recurrent intrahepatic cholangiocarcinoma remains to be established. This study evaluated the short- and long-term prognoses of patients after repeat hepatic resection for recurrent intrahepatic cholangiocarcinoma. Data for 72 patients who underwent R0 repeat hepatic resection for recurrent intrahepatic cholangiocarcinoma at the Eastern Hepatobiliary Surgery Hospital between 2005 and 2013 were analyzed. Tumor re-recurrence, recurrence-to-death survival, and overall survival were calculated and compared using the Kaplan-Meier method and the log-rank test. Independent risk factors were identified by Cox regression analysis. Operative morbidity and mortality rates were 18.1% and 1.4%, respectively. The 1-, 2-, and 3-year re-recurrence rates were 53.2%, 80.2%, and 92.6%, respectively, and the corresponding recurrence-to-death survival was 82.9%, 53.0%, and 35.3%, respectively. The 1-, 3-, and 5-year overall survival was 97.2%, 67.0%, and 41.9%, respectively. Patients with a time to recurrence of >1 year from the initial hepatectomy achieved higher 1-, 2-, and 3-year recurrence-to-death survival than patients with a time to recurrence of ≤1 year (92.5%, 61.7%. and 46.6% vs 70.4%, 42.2%, and 23.0%, P = .022). Multivariate analysis identified that recurrent tumor >3 cm (hazard ratio: 2.346; 95% confidence interval: 1.288-4.274), multiple recurrent nodules (2.304; 1.049-5.059), cirrhosis (3.165; 1.543-6.491), and a time to recurrence of ≤1 year (1.872; 1.055-3.324) were independent risk factors of recurrence-to-death survival. Repeat hepatic resection for recurrent intrahepatic cholangiocarcinoma was safe and produced long-term survival outcomes in selected patients based on prognostic stratification with the presence of the independent risk factors of recurrence-to-death survival. Copyright © 2016 Elsevier Inc. All rights reserved.

RBOOST: RIEMANNIAN DISTANCE BASED REGULARIZED BOOSTING

PubMed Central

Liu, Meizhu; Vemuri, Baba C.

2011-01-01

Boosting is a versatile machine learning technique that has numerous applications including but not limited to image processing, computer vision, data mining etc. It is based on the premise that the classification performance of a set of weak learners can be boosted by some weighted combination of them. There have been a number of boosting methods proposed in the literature, such as the AdaBoost, LPBoost, SoftBoost and their variations. However, the learning update strategies used in these methods usually lead to overfitting and instabilities in the classification accuracy. Improved boosting methods via regularization can overcome such difficulties. In this paper, we propose a Riemannian distance regularized LPBoost, dubbed RBoost. RBoost uses Riemannian distance between two square-root densities (in closed form) – used to represent the distribution over the training data and the classification error respectively – to regularize the error distribution in an iterative update formula. Since this distance is in closed form, RBoost requires much less computational cost compared to other regularized Boosting algorithms. We present several experimental results depicting the performance of our algorithm in comparison to recently published methods, LP-Boost and CAVIAR, on a variety of datasets including the publicly available OASIS database, a home grown Epilepsy database and the well known UCI repository. Results depict that the RBoost algorithm performs better than the competing methods in terms of accuracy and efficiency. PMID:21927643

Intelligent sensing sensory quality of Chinese rice wine using near infrared spectroscopy and nonlinear tools

NASA Astrophysics Data System (ADS)

Ouyang, Qin; Chen, Quansheng; Zhao, Jiewen

2016-02-01

The approach presented herein reports the application of near infrared (NIR) spectroscopy, in contrast with human sensory panel, as a tool for estimating Chinese rice wine quality; concretely, to achieve the prediction of the overall sensory scores assigned by the trained sensory panel. Back propagation artificial neural network (BPANN) combined with adaptive boosting (AdaBoost) algorithm, namely BP-AdaBoost, as a novel nonlinear algorithm, was proposed in modeling. First, the optimal spectra intervals were selected by synergy interval partial least square (Si-PLS). Then, BP-AdaBoost model based on the optimal spectra intervals was established, called Si-BP-AdaBoost model. These models were optimized by cross validation, and the performance of each final model was evaluated according to correlation coefficient (Rp) and root mean square error of prediction (RMSEP) in prediction set. Si-BP-AdaBoost showed excellent performance in comparison with other models. The best Si-BP-AdaBoost model was achieved with Rp = 0.9180 and RMSEP = 2.23 in the prediction set. It was concluded that NIR spectroscopy combined with Si-BP-AdaBoost was an appropriate method for the prediction of the sensory quality in Chinese rice wine.

Antibiotics for preventing recurrent sore throat.

PubMed

Ng, Gareth J Y; Tan, Stephanie; Vu, Anh N; Del Mar, Chris B; van Driel, Mieke L

2015-07-14

Antibiotics are sometimes used to prevent recurrent sore throat, despite concern about resistance. However, there is conflicting primary evidence regarding their effectiveness. To assess the effects of antibiotics in patients with recurrent sore throat. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 5); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 25 June 2015. Randomised controlled trials (RCTs) of antibiotics in adults and children suffering from pre-existing recurrent sore throat, defined as three or more sore throats in a year, examining the incidence of sore throat recurrence, with follow-up of at least 12 months post-antibiotic therapy. Two authors independently assessed trial quality and extracted data. Multiple attempts to contact the authors of one study yielded no response. We identified no trials that met the inclusion criteria for the review. We discarded the majority of the references retrieved from our search following screening of the title and abstract. We formally excluded four studies following review of the full-text report. There is insufficient evidence to determine the effectiveness of antibiotics for preventing recurrent sore throat. This finding must be balanced against the known adverse effects and cost of antibiotic therapy, when considering antibiotics for this purpose. There is a need for high quality RCTs that compare the effects of antibiotics versus placebo in adults and children with pre-existing recurrent sore throat on the following outcomes: incidence of sore throat recurrence, adverse effects, days off work and absence from school, and the incidence of complications. Future studies should be conducted and reported according to the CONSORT statement.

Comparative Cost-effectiveness of Strategies to Prevent Postoperative Clinical Recurrence of Crohn's Disease

PubMed Central

Doherty, Glen A.; Miksad, Rebecca A.; Cheifetz, Adam S.; Moss, Alan C.

2012-01-01

Background A number of treatments have been shown to reduce the risk of postoperative recurrence of Crohn's disease (CD). The optimal strategy is unknown. The aim was to evaluate the comparative cost-effectiveness of postoperative strategies to prevent clinical recurrence of CD. Methods Three prophylactic strategies were compared to “no prophylaxis”; mesalamine, azathioprine (AZA) / 6-mercaptopurine (6-MP), and infliximab. The probability of clinical recurrence, endoscopic recurrence, and therapy discontinuation due to adverse drug reactions (ADRs) were extracted from randomized controlled trials (RCTs). Quality-of-life scores and treatment costs were derived from published data. The primary model evaluated quality-adjusted life years (QALYs) and cost-effectiveness at 1 year after surgery. Sensitivity analysis assessed the impact of a range of recurrence rates on cost-effectiveness. An exploratory analysis evaluated cost-effectiveness outcomes 5 years after surgery. Results A strategy of “no prophylaxis” was the least expensive one at 1 and 5 years after surgery. Compared to this approach, AZA/6-MP had the most favorable incremental cost-effectiveness ratio (ICER) ($299,188/QALY gained), and yielded the highest net health benefits of the medication strategies at 1 year. Sensitivity analysis determined that the ICER of AZA/6-MP was preferable to mesalamine up to a recurrence rate of 52%, but mesalamine dominated at higher rates. In the 5-year exploratory analysis, mesalamine had the most favorable ICER over 5 years ($244,177/QALY gained). Conclusions Compared to no prophylactic treatment, AZA/6-MP has the most favorable ICER in the prevention of clinical recurrence of postoperative CD up to 1 year. At 5 years, mesalamine had the most favorable ICER in this model. PMID:21905173

Optical devices

DOEpatents

Chaves, Julio C.; Falicoff, Waqidi; Minano, Juan C.; Benitez, Pablo; Dross, Oliver; Parkyn, Jr., William A.

2010-07-13

An optical manifold for efficiently combining a plurality of blue LED outputs to illuminate a phosphor for a single, substantially homogeneous output, in a small, cost-effective package. Embodiments are disclosed that use a single or multiple LEDs and a remote phosphor, and an intermediate wavelength-selective filter arranged so that backscattered photoluminescence is recycled to boost the luminance and flux of the output aperture. A further aperture mask is used to boost phosphor luminance with only modest loss of luminosity. Alternative non-recycling embodiments provide blue and yellow light in collimated beams, either separately or combined into white.

Tuberculosis vaccines in clinical trials

PubMed Central

Rowland, Rosalind; McShane, Helen

2011-01-01

Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

AC to DC Bridgeless Boost Converter for Ultra Low Input Energy Harvesting

NASA Astrophysics Data System (ADS)

Dawam, A. H. A.; Muhamad, M.

2018-03-01

This paper presents design of circuit which converts low input AC voltage to a higher output DC voltage. A buck-boost topology and boost topology are combined to condition cycle of an AC input voltage. the unique integration of a combining circuit of buck-boost and boost circuit have been proposed in order to introduce a new direct ac-dc power converter topology without conventional diode bridge rectifier. The converter achieved to convert a milli-volt scale of input AC voltage into a volt scale of output DC voltages which is from 400mV to 3.3V.

A cost-effectiveness and budget impact analysis of first-line fidaxomicin for patients with Clostridium difficile infection (CDI) in Germany.

PubMed

Watt, Maureen; McCrea, Charles; Johal, Sukhvinder; Posnett, John; Nazir, Jameel

2016-10-01

Clostridium difficile infection (CDI) represents a significant economic healthcare burden, especially the cost of recurrent disease. Fidaxomicin produced significantly lower recurrence rates and higher sustained cure rates in clinical trials. We evaluated the cost-effectiveness and budget impact of fidaxomicin compared with vancomycin in Germany in the first-line treatment of patient subgroups with CDI at increased risk of recurrence. A semi-Markov model was used to compare the cost-effectiveness and budget impact of fidaxomicin vs. vancomycin from a payer perspective in Germany. The model cycle length was 10 days. The time horizon was 1 year. Model inputs were probability of clinical cure, 30-day probability of recurrence, and 30-day attributable mortality based on evidence from two randomized controlled trials comparing fidaxomicin and vancomycin in patients with CDI. Cost-effectiveness outcomes were cost per quality-adjusted life year gained, cost per bed-day saved, and cost per recurrence avoided. Despite higher drug acquisition costs, fidaxomicin was dominant in the cancer subgroup (less costly and more effective) and cost-effective in the other subgroups, with incremental cost-effectiveness ratios vs. vancomycin ranging from €26,900 to €44,500. Hospitalization costs of the first-line treatment of CDI with fidaxomicin vs. vancomycin were lower in every patient subgroup, resulting in budget impacts ranging from -€1325 (in patients ≥65 years) to -€2438 (in cancer patients). Reductions in the cost of treating recurrence with fidaxomicin ranged from -€574.32 per patient in those receiving concomitant antibiotics to -€1500.68 per patient in renally impaired patients. In patient subgroups with CDI at increased recurrence risk, fidaxomicin was cost-effective vs. vancomycin, and less costly and more effective in patients with cancer.

Long-Term Results of Concomitant Boost Radiation Plus Concurrent Cisplatin for Advanced Head and Neck Carcinomas: A Phase II Trial of the Radiation Therapy Oncology Group (RTOG 99-14)

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

Garden, Adam S.; Harris, Jonathan M.S.; Trotti, Andy

2008-08-01

Purpose: The feasibility of combining concomitant boost-accelerated radiation regimen (AFX-C) with cisplatin was previously demonstrated in this Phase II trial. This article reports the long-term toxicity, relapse patterns, and survival in patients with advanced head and neck carcinoma. Methods and Materials: Between April and November 2000, 84 patients with Stage III-IV HNC were enrolled, and 76 patients were analyzable. Radiation consisted of 72 Gy over 6 weeks. Cisplatin dose was 100 mg/m{sup 2} on Days 1 and 22. Tumor and clinical status were assessed, and acute-late toxicities were graded. Results: The median follow-up for surviving patients is 4.3 years. Themore » 2- and 4-year locoregional failure rates were 33% and 36%, respectively, and the 2- and 4-year survival rates were 70% and 54%, respectively. The worst overall late Grade 3 or 4 toxicity rate was 42%. The prevalence rates of a gastrostomy at any time during follow-up, at 12 months, and at 48 months were 83%, 41%, and 17%, respectively. Five of 36 patients (14%) alive and without disease at last follow-up were gastrostomy-tube dependent. Conclusion: These data of long-term follow-up of patients treated with AFX-C with cisplatin show encouraging results with regard to locoregional disease control and survival, with few recurrences after 2 years. The late toxicity rates are relatively high. However, although prolonged dysphagia was noted in our preliminary report, its prevalence does decreased over time. A Phase III trial comparing AFX-C plus cisplatin against standard radiation plus cisplatin has completed accrual.« less

Breast-Conserving Treatment in the Elderly: Long-Term Results of Adjuvant Hypofractionated and Normofractionated Radiotherapy

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

Kirova, Youlia M.; Campana, Francois; Savignoni, Alexia

2009-09-01

Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). Methods and Materials: Between 1995 and 1999, 367 women aged {>=}70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed bymore » a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9-140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results.« less

Divided attention enhances explicit but not implicit conceptual memory: an item-specific account of the attentional boost effect.

PubMed

Spataro, Pietro; Mulligan, Neil W; Bechi Gabrielli, Giulia; Rossi-Arnaud, Clelia

2017-02-01

The Attentional Boost Effect (ABE) refers to the counterintuitive finding that words encoded with to-be-responded targets in a divided-attention condition are remembered better than words encoded with distractors. Previous studies suggested that the ABE-related enhancement of verbal memory depends upon the activation of abstract lexical representations. In the present study, we extend this hypothesis by embedding it in the context of a broader perspective, which proposes that divided attention in the ABE paradigm affects item-specific, but not relational, processing. To this purpose, we examined the ABE in the matched tasks of category-cued recall (CCRT: explicit memory) and category exemplar generation (CEGT: implicit memory). In addition, study time was varied (500, 1500 or 4000 ms), to further determine whether the attentional boost manipulation could influence late-phase elaborative processing. In agreement with the predictions of the item-specific account, the results showed that exemplars encoded with targets were recalled better than exemplars encoded with distractors in the CCRT, but not in the CEGT. Moreover, performance in the CCRT increased with study time, whereas the size of the ABE-related enhancement tended to decrease, further confirming that this effect hinges upon early phase encoding processes.

Boosting for detection of gene-environment interactions.

PubMed

Pashova, H; LeBlanc, M; Kooperberg, C

2013-01-30

In genetic association studies, it is typically thought that genetic variants and environmental variables jointly will explain more of the inheritance of a phenotype than either of these two components separately. Traditional methods to identify gene-environment interactions typically consider only one measured environmental variable at a time. However, in practice, multiple environmental factors may each be imprecise surrogates for the underlying physiological process that actually interacts with the genetic factors. In this paper, we develop a variant of L(2) boosting that is specifically designed to identify combinations of environmental variables that jointly modify the effect of a gene on a phenotype. Because the effect modifiers might have a small signal compared with the main effects, working in a space that is orthogonal to the main predictors allows us to focus on the interaction space. In a simulation study that investigates some plausible underlying model assumptions, our method outperforms the least absolute shrinkage and selection and Akaike Information Criterion and Bayesian Information Criterion model selection procedures as having the lowest test error. In an example for the Women's Health Initiative-Population Architecture using Genomics and Epidemiology study, the dedicated boosting method was able to pick out two single-nucleotide polymorphisms for which effect modification appears present. The performance was evaluated on an independent test set, and the results are promising. Copyright © 2012 John Wiley & Sons, Ltd.

Steroids for preventing recurrence of acute severe migraine headaches: a meta-analysis.

PubMed

Huang, Y; Cai, X; Song, X; Tang, H; Huang, Y; Xie, S; Hu, Y

2013-08-01

Recurrence of migraine headaches after treatment is common. The evidence regarding steroids for preventing migraine headache recurrence is controversial. This meta-analysis examined the effectiveness of steroids for prevention of recurrent headaches. Databases (PubMed, Embase and the Cochrane Library) and conference proceedings were searched for randomized controlled trials comparing steroids and placebo in the treatment of migraine headaches. Two independent reviewers assessed studies and extracted data. Relative risks (RRs) of headache recurrence and adverse events were calculated and reported with 95% confidence intervals (95% CIs). Eight studies with 905 patients were included. Pooled analysis showed that when steroids were added to standard abortive therapy they reduced the rate of moderate or severe headache recurrence after 24-72 h of follow-up evaluation (RR = 0.71; 95% CI = 0.59-0.86). There was no significant benefit of steroids compared with placebo in the proportion of totally resolved migraines (RR = 1.11; 95% CI = 0.94-1.32). The side effects of steroids are mild and not significant except for dizziness. Subgroup meta-analysis showed that parenteral dexamethasone tends to be more effective in reducing moderate or severe recurrent headaches (RR = 0.68; 95% CI = 0.55-0.84). However, no significant differences were found between oral administration and parenteral administration of steroids (P = 0.37). When steroids are added to standard abortive therapy for migraine headaches, they are effective and safe for preventing moderate or severe headache recurrence. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS.

Comparison of composite prostate radiotherapy plan doses with dependent and independent boost phases.

PubMed

Narayanasamy, Ganesh; Avila, Gabrielle; Mavroidis, Panayiotis; Papanikolaou, Niko; Gutierrez, Alonso; Baacke, Diana; Shi, Zheng; Stathakis, Sotirios

2016-09-01

Prostate cases commonly consist of dual phase planning with a primary plan followed by a boost. Traditionally, the boost phase is planned independently from the primary plan with the risk of generating hot or cold spots in the composite plan. Alternatively, boost phase can be planned taking into account the primary dose. The aim of this study was to compare the composite plans from independently and dependently planned boosts using dosimetric and radiobiological metrics. Ten consecutive prostate patients previously treated at our institution were used to conduct this study on the Raystation™ 4.0 treatment planning system. For each patient, two composite plans were developed: a primary plan with an independently planned boost and a primary plan with a dependently planned boost phase. The primary plan was prescribed to 54 Gy in 30 fractions to the primary planning target volume (PTV1) which includes prostate and seminal vesicles, while the boost phases were prescribed to 24 Gy in 12 fractions to the boost planning target volume (PTV2) that targets only the prostate. PTV coverage, max dose, median dose, target conformity, dose homogeneity, dose to OARs, and probabilities of benefit, injury, and complication-free tumor control (P+) were compared. Statistical significance was tested using either a 2-tailed Student's t-test or Wilcoxon signed-rank test. Dosimetrically, the composite plan with dependent boost phase exhibited smaller hotspots, lower maximum dose to the target without any significant change to normal tissue dose. Radiobiologically, for all but one patient, the percent difference in the P+ values between the two methods was not significant. A large percent difference in P+ value could be attributed to an inferior primary plan. The benefits of considering the dose in primary plan while planning the boost is not significant unless a poor primary plan was achieved.

Basal Subtype of Invasive Breast Cancer Is Associated With a Higher Risk of True Recurrence After Conventional Breast-Conserving Therapy

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

Hattangadi-Gluth, Jona A.; Wo, Jennifer Y.; Nguyen, Paul L.

2012-03-01

Purpose: To determine whether breast cancer subtype is associated with patterns of ipsilateral breast tumor recurrence (IBTR), either true recurrence (TR) or elsewhere local recurrence (ELR), among women with pT1-T2 invasive breast cancer (IBC) who receive breast-conserving therapy (BCT). Methods and Materials: From Jan 1998 to Dec 2003, 1,223 women with pT1-T2N0-3 IBC were treated with BCT (lumpectomy plus whole-breast radiation). Ninety percent of patients received adjuvant systemic therapy, but none received trastuzumab. Biologic cancer subtypes were approximated by determining estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), and human epidermal growth factor receptor-2-positive (HER-2+) expression, classified as luminal A (ER+ ormore » PR+ and HER-2 negative [HER-2-]), luminal B (ER+ or PR+ and HER-2+), HER-2 (ER- and PR- and HER-2+), and basal (ER- and PR- and HER-2- ) subtypes. Imaging, pathology, and operative reports were reviewed by two physicians independently, including an attending breast radiologist. Readers were blinded to subtype and outcome. TR was defined as IBTR within the same quadrant and within 3 cm of the primary tumor. All others were defined as ELR. Results: At a median follow-up of 70 months, 24 patients developed IBTR (5-year cumulative incidence of 1.6%), including 15 TR and 9 ELR patients. At 5 years, basal (4.4%) and HER-2 (9%) subtypes had a significantly higher incidence of TR than luminal B (1.2%) and luminal A (0.2%) subtypes (p < 0.0001). On multivariate analysis, basal subtype (hazard ratio [HR], 4.8, p = 0.01), younger age at diagnosis (HR, 0.97; p = 0.05), and increasing tumor size (HR, 2.1; p = 0.04) were independent predictors of TR. Only younger age (HR, 0.95; p = 0.01) significantly predicted for ELR. Conclusions: Basal and HER-2 subtypes are significantly associated with higher rates of TR among women with pT1-T2 IBC after BCT. Younger age predicts for both TR and ELR. Strategies to reduce TR in basal breast cancers, such as increased boost doses, concomitant radiation and chemotherapy, or targeted therapy agents, should be explored.« less

AlignerBoost: A Generalized Software Toolkit for Boosting Next-Gen Sequencing Mapping Accuracy Using a Bayesian-Based Mapping Quality Framework

PubMed Central

Zheng, Qi; Grice, Elizabeth A.

2016-01-01

Accurate mapping of next-generation sequencing (NGS) reads to reference genomes is crucial for almost all NGS applications and downstream analyses. Various repetitive elements in human and other higher eukaryotic genomes contribute in large part to ambiguously (non-uniquely) mapped reads. Most available NGS aligners attempt to address this by either removing all non-uniquely mapping reads, or reporting one random or "best" hit based on simple heuristics. Accurate estimation of the mapping quality of NGS reads is therefore critical albeit completely lacking at present. Here we developed a generalized software toolkit "AlignerBoost", which utilizes a Bayesian-based framework to accurately estimate mapping quality of ambiguously mapped NGS reads. We tested AlignerBoost with both simulated and real DNA-seq and RNA-seq datasets at various thresholds. In most cases, but especially for reads falling within repetitive regions, AlignerBoost dramatically increases the mapping precision of modern NGS aligners without significantly compromising the sensitivity even without mapping quality filters. When using higher mapping quality cutoffs, AlignerBoost achieves a much lower false mapping rate while exhibiting comparable or higher sensitivity compared to the aligner default modes, therefore significantly boosting the detection power of NGS aligners even using extreme thresholds. AlignerBoost is also SNP-aware, and higher quality alignments can be achieved if provided with known SNPs. AlignerBoost’s algorithm is computationally efficient, and can process one million alignments within 30 seconds on a typical desktop computer. AlignerBoost is implemented as a uniform Java application and is freely available at https://github.com/Grice-Lab/AlignerBoost. PMID:27706155

Recurrence time statistics for finite size intervals

NASA Astrophysics Data System (ADS)

Altmann, Eduardo G.; da Silva, Elton C.; Caldas, Iberê L.

2004-12-01

We investigate the statistics of recurrences to finite size intervals for chaotic dynamical systems. We find that the typical distribution presents an exponential decay for almost all recurrence times except for a few short times affected by a kind of memory effect. We interpret this effect as being related to the unstable periodic orbits inside the interval. Although it is restricted to a few short times it changes the whole distribution of recurrences. We show that for systems with strong mixing properties the exponential decay converges to the Poissonian statistics when the width of the interval goes to zero. However, we alert that special attention to the size of the interval is required in order to guarantee that the short time memory effect is negligible when one is interested in numerically or experimentally calculated Poincaré recurrence time statistics.

Multiview boosting digital pathology analysis of prostate cancer.

PubMed

Kwak, Jin Tae; Hewitt, Stephen M

2017-04-01

Various digital pathology tools have been developed to aid in analyzing tissues and improving cancer pathology. The multi-resolution nature of cancer pathology, however, has not been fully analyzed and utilized. Here, we develop an automated, cooperative, and multi-resolution method for improving prostate cancer diagnosis. Digitized tissue specimen images are obtained from 5 tissue microarrays (TMAs). The TMAs include 70 benign and 135 cancer samples (TMA1), 74 benign and 89 cancer samples (TMA2), 70 benign and 115 cancer samples (TMA3), 79 benign and 82 cancer samples (TMA4), and 72 benign and 86 cancer samples (TMA5). The tissue specimen images are segmented using intensity- and texture-based features. Using the segmentation results, a number of morphological features from lumens and epithelial nuclei are computed to characterize tissues at different resolutions. Applying a multiview boosting algorithm, tissue characteristics, obtained from differing resolutions, are cooperatively combined to achieve accurate cancer detection. In segmenting prostate tissues, the multiview boosting method achieved≥ 0.97 AUC using TMA1. For detecting cancers, the multiview boosting method achieved an AUC of 0.98 (95% CI: 0.97-0.99) as trained on TMA2 and tested on TMA3, TMA4, and TMA5. The proposed method was superior to single-view approaches, utilizing features from a single resolution or merging features from all the resolutions. Moreover, the performance of the proposed method was insensitive to the choice of the training dataset. Trained on TMA3, TMA4, and TMA5, the proposed method obtained an AUC of 0.97 (95% CI: 0.96-0.98), 0.98 (95% CI: 0.96-0.99), and 0.97 (95% CI: 0.96-0.98), respectively. The multiview boosting method is capable of integrating information from multiple resolutions in an effective and efficient fashion and identifying cancers with high accuracy. The multiview boosting method holds a great potential for improving digital pathology tools and research. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of homologous and heterologous prime-boost vaccine approaches using Modified Vaccinia Ankara and soluble protein to induce neutralizing antibodies by the human cytomegalovirus pentamer complex in mice.

PubMed

Chiuppesi, Flavia; Wussow, Felix; Scharf, Louise; Contreras, Heidi; Gao, Han; Meng, Zhuo; Nguyen, Jenny; Barry, Peter A; Bjorkman, Pamela J; Diamond, Don J

2017-01-01

Since neutralizing antibodies (NAb) targeting the human cytomegalovirus (HCMV) pentamer complex (PC) potently block HCMV host cell entry, anti-PC NAb induction is thought to be important for a vaccine formulation to prevent HCMV infection. By developing a vaccine strategy based on soluble PC protein and using a previously generated Modified Vaccinia Ankara vector co-expressing all five PC subunits (MVA-PC), we compared HCMV NAb induction by homologous immunization using prime-boost vaccine regimen employing only PC protein or MVA-PC and heterologous immunization using prime-boost combinations of PC protein and MVA-PC. Utilizing a recently isolated anti-PC NAb, we produced highly pure soluble PC protein that displayed conformational and linear neutralizing epitopes, interfered with HCMV entry, and was recognized by antibodies induced by HCMV during natural infection. Mice vaccinated by different immunization routes with the purified PC protein in combination with a clinically approved adjuvant formulation elicited high-titer and durable HCMV NAb. While MVA-PC and soluble PC protein either alone or in combination elicited robust HCMV NAb, significantly different potencies of these vaccine approaches were observed in dependence on immunization schedule. Using only two immunizations, vaccination with MVA-PC alone or prime-boost combinations of MVA-PC and PC protein was significantly more effective in stimulating HCMV NAb than immunization with PC protein alone. In contrast, with three immunizations, NAb induced by soluble PC protein either alone or combined with two boosts of MVA-PC increased to levels that exceeded NAb titer stimulated by MVA-PC alone. These results provide insights into the potency of soluble protein and MVA to elicit NAb by the HCMV PC via homologous and heterologous prime-boost immunization, which may contribute to develop clinically deployable vaccine strategies to prevent HCMV infection.

External beam boost versus interstitial high-dose-rate brachytherapy boost in the adjuvant radiotherapy following breast-conserving therapy in early-stage breast cancer: a dosimetric comparison

PubMed Central

Melchert, Corinna; Kovács, György

2016-01-01

Purpose This study aims to compare the dosimetric data of local tumor's bed dose escalation (boost) with photon beams (external beam radiation therapy – EBRT) versus high-dose-rate interstitial brachytherapy (HDR-BT) after breast-conserving treatment in women with early-stage breast cancer. Material and methods We analyzed the treatment planning data of 136 irradiated patients, treated between 2006 and 2013, who underwent breast-conserving surgery and adjuvant whole breast irradiation (WBI; 50.4 Gy) and boost (HDR-BT: 10 Gy in one fraction [n = 36]; EBRT: 10 Gy in five fractions [n = 100]). Organs at risk (OAR; heart, ipsilateral lung, skin, most exposed rib segment) were delineated. Dosimetric parameters were calculated with the aid of dose-volume histograms (DVH). A non-parametric test was performed to compare the two different boost forms. Results There was no difference for left-sided cancers regarding the maximum dose to the heart (HDR-BT 29.8% vs. EBRT 29.95%, p = 0.34). The maximum doses to the other OAR were significantly lower for HDR-BT (Dmax lung 47.12% vs. 87.7%, p < 0.01; rib 61.17% vs. 98.5%, p < 0.01; skin 57.1% vs. 94.75%, p < 0.01; in the case of right-sided breast irradiation, dose of the heart 6.00% vs. 16.75%, p < 0.01). Conclusions Compared to EBRT, local dose escalation with HDR-BT presented a significant dose reduction to the investigated OAR. Only left-sided irradiation showed no difference regarding the maximum dose to the heart. Reducing irradiation exposure to OAR could result in a reduction of long-term side effects. Therefore, from a dosimetric point of view, an interstitial boost complementary to WBI via EBRT seems to be more advantageous in the adjuvant radiotherapy of breast cancer. PMID:27648082

How Travel Demand Affects Detection of Non-Recurrent Traffic Congestion on Urban Road Networks

NASA Astrophysics Data System (ADS)

Anbaroglu, B.; Heydecker, B.; Cheng, T.

2016-06-01

Occurrence of non-recurrent traffic congestion hinders the economic activity of a city, as travellers could miss appointments or be late for work or important meetings. Similarly, for shippers, unexpected delays may disrupt just-in-time delivery and manufacturing processes, which could lose them payment. Consequently, research on non-recurrent congestion detection on urban road networks has recently gained attention. By analysing large amounts of traffic data collected on a daily basis, traffic operation centres can improve their methods to detect non-recurrent congestion rapidly and then revise their existing plans to mitigate its effects. Space-time clusters of high link journey time estimates correspond to non-recurrent congestion events. Existing research, however, has not considered the effect of travel demand on the effectiveness of non-recurrent congestion detection methods. Therefore, this paper investigates how travel demand affects detection of non-recurrent traffic congestion detection on urban road networks. Travel demand has been classified into three categories as low, normal and high. The experiments are carried out on London's urban road network, and the results demonstrate the necessity to adjust the relative importance of the component evaluation criteria depending on the travel demand level.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection

PubMed Central

Nathwani, Dilip; Cornely, Oliver A.; Van Engen, Anke K.; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A. O.

2014-01-01

Objectives Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. Methods A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20 000/QALY and £30 000/QALY. One-way and probabilistic sensitivity analyses were performed. Results Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14 515 and £14 344, respectively) and in patients with a first recurrence (£16 535 and £16 926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16 529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30 000/QALY was 60% for severe CDI and 68% in a first recurrence. Conclusions Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. PMID:25096079

I-55 integrated diversion traffic management benefit study.

DOT National Transportation Integrated Search

2014-11-01

Traffic congestion, recurrent and non-recurrent, creates significant economic losses and environmental impacts. : Integrated Corridor Management (ICM) is a U.S.DOT research initiative that has been proven to effectively relieve : recurrent congestion...

Risk of recurrence of idiopathic calcium kidney stones: analysis of data from the literature.

PubMed

Ferraro, Pietro Manuel; Curhan, Gary C; D'Addessi, Alessandro; Gambaro, Giovanni

2017-04-01

Nephrolithiasis is a frequent condition. While it is generally accepted that such condition carries a risk of recurrence over time, the exact risk and its predictors have been rarely quantitated. We aimed to estimate recurrence of kidney stones, overall and in specific subgroups, from randomized controlled trials (RCTs) of calcium stone formers. Systematic review of RCTs of adult patients with idiopathic calcium kidney stones. Recurrence rates analyzed in subgroups based on type of intervention and other characteristics, using Poisson regression models. The analysis included 21 RCTs with 2168 participants over a median follow-up of 3.2 years (range 0.5-9.7). The median recurrence of kidney stones was 15 per 100 person-years (range 0-110). Recurrence was higher in those with two or more previous stone episodes compared to those with a single episode at enrolment (16 vs. 6 per 100 person-years, p < 0.001) and in those untreated or treated with dietary changes compared to those treated with drugs (26 vs. 23 vs. 9 per 100 person-years, p < 0.001). The effect of drugs on recurrence seemed to be beneficial only among those with two or more previous stone episodes. The overall recurrence rate of stones depends on factors such as previous stone history and type of treatment. Dietary approaches seem to be more effective among single stone formers, whereas drugs seem to be more effective among recurrent stone formers.

Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

PubMed Central

Jiang, George; Shi, Meng; Conteh, Solomon; Richie, Nancy; Banania, Glenna; Geneshan, Harini; Valencia, Anais; Singh, Priti; Aguiar, Joao; Limbach, Keith; Kamrud, Kurt I.; Rayner, Jonathan; Smith, Jonathan; Bruder, Joseph T.; King, C. Richter; Tsuboi, Takafumi; Takeo, Satoru; Endo, Yaeta; Doolan, Denise L.; Richie, Thomas L.; Weiss, Walter R.

2009-01-01

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost. PMID:19668343

Close Margins Less Than 2 mm Are Not Associated With Higher Risks of 10-Year Local Recurrence and Breast Cancer Mortality Compared With Negative Margins in Women Treated With Breast-Conserving Therapy.

PubMed

Tyler, Susan; Truong, Pauline T; Lesperance, Mary; Nichol, Alan; Baliski, Chris; Warburton, Rebecca; Tyldesley, Scott

2018-03-13

The 2014 Society of Surgical Oncology-American Society for Radiation Oncology consensus suggested "no ink on tumor" is a sufficient surgical margin for invasive breast cancer treated with breast-conserving surgery (BCS). Whether close margins <2 mm are associated with inferior outcomes remains controversial. This study evaluated 10-year outcomes by margin status in a population-based cohort treated with BCS and adjuvant radiation therapy (RT). The subjects were 10,863 women with invasive cancer categorized as pT1 to T3, any N, and M0 referred from 2001 to 2011, an era in which the institutional policy was to re-excise close or positive margins, except in select cases. All women underwent BCS and whole-breast RT with or without boost RT. Local recurrence (LR) and breast cancer-specific survival (BCSS) were examined using competing-risk analysis in cohorts with negative (≥2 mm; n = 9241, 85%), close (<2 mm; n = 1310, 12%), or positive (tumor touching ink; n = 312, 3%) margins. Multivariable analysis and matched-pair analysis were performed. The median follow-up period was 8 years. Systemic therapy was used in 87% of patients. Boost RT was used in 34.1%, 76.9%, and 79.5% of patients with negative, close, and positive margins, respectively. In the negative, close, and positive margin cohorts, the 10-year cumulative incidence of LR was 1.8%, 2.0%, and 1.1%, respectively (P = .759). Corresponding BCSS estimates were 93.9%, 91.8%, and 87.9%, respectively (P < .001). On multivariable analysis, close margins were not associated with increased LR (hazard ratio, 1.25; 95% confidence interval 0.79-1.97; P = .350) or reduced BCSS (hazard ratio, 1.25; 95% confidence interval 0.98-1.58, P = .071) relative to negative margins. On matched-pair analysis, close margin cases had similar LR (P = .114) and BCSS (P = .100) to negative margin controls. Select cases with close or positive margins in this population-based analysis had similar LR and BCSS to cases with negative margins. While these findings do not endorse omitting re-excision for all cases, the data support a policy of accepting carefully selected cases with close margins for adjuvant RT without re-excision. Copyright © 2018 Elsevier Inc. All rights reserved.

Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown

PubMed Central

Alami Chentoufi, Aziz; Kritzer, Elizabeth; Yu, David M.; Nesburn, Anthony B.; BenMohamed, Lbachir

2012-01-01

The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally “protected” exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4+ and CD8+ T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation “asymptomatic” clinical herpes vaccines, and discuss future mucosal “asymptomatic” prime-boost vaccines that could optimize local protective immunity. PMID:22548113

Intelligent sensing sensory quality of Chinese rice wine using near infrared spectroscopy and nonlinear tools.

PubMed

Ouyang, Qin; Chen, Quansheng; Zhao, Jiewen

2016-02-05

The approach presented herein reports the application of near infrared (NIR) spectroscopy, in contrast with human sensory panel, as a tool for estimating Chinese rice wine quality; concretely, to achieve the prediction of the overall sensory scores assigned by the trained sensory panel. Back propagation artificial neural network (BPANN) combined with adaptive boosting (AdaBoost) algorithm, namely BP-AdaBoost, as a novel nonlinear algorithm, was proposed in modeling. First, the optimal spectra intervals were selected by synergy interval partial least square (Si-PLS). Then, BP-AdaBoost model based on the optimal spectra intervals was established, called Si-BP-AdaBoost model. These models were optimized by cross validation, and the performance of each final model was evaluated according to correlation coefficient (Rp) and root mean square error of prediction (RMSEP) in prediction set. Si-BP-AdaBoost showed excellent performance in comparison with other models. The best Si-BP-AdaBoost model was achieved with Rp=0.9180 and RMSEP=2.23 in the prediction set. It was concluded that NIR spectroscopy combined with Si-BP-AdaBoost was an appropriate method for the prediction of the sensory quality in Chinese rice wine. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Kopeliovich, B. Z.; Institut fuer Theoretische Physik der Universitaet, Philosophenweg 19, D-69120 Heidelberg; Potashnikova, I. K.

Two novel QCD effects, double-color filtering and mutual boosting of the saturation scales in colliding nuclei, affect the transparency of the nuclei for quark dipoles in comparison with proton-nucleus collisions. The former effect increases the survival probability of the dipoles, since color filtering in one nucleus makes the other one more transparent. The second effect acts in the opposite direction and is stronger; it makes the colliding nuclei more opaque than in the case of pA collisions. As a result of parton saturation in nuclei the effective scale is shifted upward, which leads to an increase of the gluon densitymore » at small x. This in turn leads to a stronger transverse momentum broadening in AA compared with pA collisions, i.e., to an additional growth of the saturation momentum. Such a mutual boosting leads to a system of reciprocity equations, which result in a saturation scale, a few times higher in AA than in pA collisions at the energies of the large hadron collider (LHC). Since the dipole cross section is proportional to the saturation momentum squared, the nuclei become much more opaque for dipoles in AA than in pA collisions. For the same reason gluon shadowing turns out to be boosted to a larger magnitude compared with the product of the gluon shadowing factors in each of the colliding nuclei. All these effects make it more difficult to establish a baseline for anomalous J/{Psi} suppression in heavy ion collisions at high energies.« less

Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

PubMed

Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

2017-09-01

The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

How citation boosts promote scientific paradigm shifts and nobel prizes.

PubMed

Mazloumian, Amin; Eom, Young-Ho; Helbing, Dirk; Lozano, Sergi; Fortunato, Santo

2011-05-04

Nobel Prizes are commonly seen to be among the most prestigious achievements of our times. Based on mining several million citations, we quantitatively analyze the processes driving paradigm shifts in science. We find that groundbreaking discoveries of Nobel Prize Laureates and other famous scientists are not only acknowledged by many citations of their landmark papers. Surprisingly, they also boost the citation rates of their previous publications. Given that innovations must outcompete the rich-gets-richer effect for scientific citations, it turns out that they can make their way only through citation cascades. A quantitative analysis reveals how and why they happen. Science appears to behave like a self-organized critical system, in which citation cascades of all sizes occur, from continuous scientific progress all the way up to scientific revolutions, which change the way we see our world. Measuring the "boosting effect" of landmark papers, our analysis reveals how new ideas and new players can make their way and finally triumph in a world dominated by established paradigms. The underlying "boost factor" is also useful to discover scientific breakthroughs and talents much earlier than through classical citation analysis, which by now has become a widespread method to measure scientific excellence, influencing scientific careers and the distribution of research funds. Our findings reveal patterns of collective social behavior, which are also interesting from an attention economics perspective. Understanding the origin of scientific authority may therefore ultimately help to explain how social influence comes about and why the value of goods depends so strongly on the attention they attract.

Prevention of post-operative recurrence of Crohn's disease.

PubMed

Vaughn, Byron Philip; Moss, Alan Colm

2014-02-07

Endoscopic and clinical recurrence of Crohn's disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.

Maximum power point tracking techniques for wind energy systems using three levels boost converter

NASA Astrophysics Data System (ADS)

Tran, Cuong Hung; Nollet, Frédéric; Essounbouli, Najib; Hamzaoui, Abdelaziz

2018-05-01

This paper presents modeling and simulation of three level Boost DC-DC converter in Wind Energy Conversion System (WECS). Three-level Boost converter has significant advantage compared to conventional Boost. A maximum power point tracking (MPPT) method for a variable speed wind turbine using permanent magnet synchronous generator (PMSG) is also presented. Simulation of three-level Boost converter topology with Perturb and Observe algorithm and Fuzzy Logic Control is implemented in MATLAB/SIMULINK. Results of this simulation show that the system with MPPT using fuzzy logic controller has better performance to the Perturb and Observe algorithm: fast response under changing conditions and small oscillation.

Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries.

PubMed

Damm, Oliver; Ultsch, Bernhard; Horn, Johannes; Mikolajczyk, Rafael T; Greiner, Wolfgang; Wichmann, Ole

2015-06-05

A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies. A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries. A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold. While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.

Revisiting the Effect of Anthropomorphizing a Social Cause Campaign.

PubMed

Williams, Lisa A; Masser, Barbara; Sun, Jessie

2015-01-01

Recent research suggests that anthropomorphism can be harnessed as a tool to boost intentions to comply with social cause campaigns. Drawing on the human tendency to extend moral concern to entities portrayed as humanlike, it has been argued that adding personified features to a social campaign elevates anticipated guilt at failing to comply, and this subsequently boosts intentions to comply with that campaign. The present research aimed to extend extant research by disentangling the effects of emotional and non-emotional anthropomorphism, and differentiating amongst other emotional mechanisms of the anthropomorphism-compliance effect (namely, anticipated pride and anticipated regret). Experiment 1 (N = 294) compared the effectiveness of positive, negative, and emotionally-neutral anthropomorphized campaign posters for boosting campaign compliance intentions against non-anthropomorphized posters. We also measured potential mechanisms including anticipated guilt, regret, and pride. Results failed to support the anthropomorphism-compliance effect, and no changes in anticipated emotion according to anthropomorphism emerged. Experiments 2 (N = 150) and 3 (N = 196) represented further tests of the anthropomorphism-compliance effect. Despite high statistical power and efforts to closely replicate the conditions under which the anthropomorphism-compliance effect had been previously observed, no differences in compliance intention or anticipated emotion according to anthropomorphism emerged. A meta-analysis of the effects of anthropomorphism on compliance and anticipated emotion across the three experiments revealed effect size estimates that did not differ significantly from zero. The results of these three experiments suggest that the anthropomorphism-compliance effect is fragile and perhaps subject to contextual and idiographic influences. Thus, this research provides important insight and impetus for future research on the applied and theoretical utility of anthropomorphizing social cause campaigns.

Revisiting the Effect of Anthropomorphizing a Social Cause Campaign

PubMed Central

Williams, Lisa A.; Masser, Barbara; Sun, Jessie

2015-01-01

Recent research suggests that anthropomorphism can be harnessed as a tool to boost intentions to comply with social cause campaigns. Drawing on the human tendency to extend moral concern to entities portrayed as humanlike, it has been argued that adding personified features to a social campaign elevates anticipated guilt at failing to comply, and this subsequently boosts intentions to comply with that campaign. The present research aimed to extend extant research by disentangling the effects of emotional and non-emotional anthropomorphism, and differentiating amongst other emotional mechanisms of the anthropomorphism-compliance effect (namely, anticipated pride and anticipated regret). Experiment 1 (N = 294) compared the effectiveness of positive, negative, and emotionally-neutral anthropomorphized campaign posters for boosting campaign compliance intentions against non-anthropomorphized posters. We also measured potential mechanisms including anticipated guilt, regret, and pride. Results failed to support the anthropomorphism-compliance effect, and no changes in anticipated emotion according to anthropomorphism emerged. Experiments 2 (N = 150) and 3 (N = 196) represented further tests of the anthropomorphism-compliance effect. Despite high statistical power and efforts to closely replicate the conditions under which the anthropomorphism-compliance effect had been previously observed, no differences in compliance intention or anticipated emotion according to anthropomorphism emerged. A meta-analysis of the effects of anthropomorphism on compliance and anticipated emotion across the three experiments revealed effect size estimates that did not differ significantly from zero. The results of these three experiments suggest that the anthropomorphism-compliance effect is fragile and perhaps subject to contextual and idiographic influences. Thus, this research provides important insight and impetus for future research on the applied and theoretical utility of anthropomorphizing social cause campaigns. PMID:26406494

Priming T-cell responses with recombinant measles vaccine vector in a heterologous prime-boost setting in non-human primates.

PubMed

Bolton, Diane L; Santra, Sampa; Swett-Tapia, Cindy; Custers, Jerome; Song, Kaimei; Balachandran, Harikrishnan; Mach, Linh; Naim, Hussein; Kozlowski, Pamela A; Lifton, Michelle; Goudsmit, Jaap; Letvin, Norman; Roederer, Mario; Radošević, Katarina

2012-09-07

Licensed live attenuated virus vaccines capable of expressing transgenes from other pathogens have the potential to reduce the number of childhood immunizations by eliciting robust immunity to multiple pathogens simultaneously. Recombinant attenuated measles virus (rMV) derived from the Edmonston Zagreb vaccine strain was engineered to express simian immunodeficiency virus (SIV) Gag protein for the purpose of evaluating the immunogenicity of rMV as a vaccine vector in rhesus macaques. rMV-Gag immunization alone elicited robust measles-specific humoral and cellular responses, but failed to elicit transgene (Gag)-specific immune responses, following aerosol or intratracheal/intramuscular delivery. However, when administered as a priming vaccine to a heterologous boost with recombinant adenovirus serotype 5 expressing the same transgene, rMV-Gag significantly enhanced Gag-specific T lymphocyte responses following rAd5 immunization. Gag-specific humoral responses were not enhanced, however, which may be due to either the transgene or the vector. Cellular response priming by rMV against the transgene was highly effective even when using a suboptimal dose of rAd5 for the boost. These data demonstrate feasibility of using rMV as a priming component of heterologous prime-boost vaccine regimens for pathogens requiring strong cellular responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

Treatment of recurrent complicated urinary tract infections in children with vesicoureteral reflux.

PubMed

Wu, Tsung-Hua; Huang, Fang-Liang; Fu, Lin-Shien; Chou, Chia-Man; Chien, Ya-Li; Huang, Chung-Ming; Lin, Chin-Fu; Chen, Po-Yen

2016-10-01

Urinary tract infections (UTIs) in children with vesicoureteral reflux (VUR) are often caused by uropathogens with a high rate of drug resistance and are associated with a high rate of recurrence with a single pathogen. In this study, we evaluated the incidence of recurrent UTI and the drug resistance pattern of Escherichia coli in children with VUR. We also evaluated whether combination therapy comprising fosomycin plus one other antimicrobial agent is effective for treatment of recurrent UTIs. We retrospectively reviewed the medical records of all children with VUR who developed at least one episode of UTI during the period January 1, 2003 to December 31, 2013 at a single medical center. The effectiveness of fosfomycin plus amikicin for Enterobacteriaceae or ceftazidime for Pseudomonas aeruginosa infections was prospectively studied in six children with recurrent relapsing UTIs. The study population comprised 129 children (age range, from 1month to 15 years; mean ± standard deviation, 2.37 ± 2.91 years) with VUR who developed at least one UTI during the 10-year study period; 68 (52.7%) had recurrent UTIs. The presence of an underlying urinary tract anomaly was predictive of recurrence (p = 0.028). The rates of susceptibility of E. coli to cefazolin (p < 0.001) and cefotaxime (p < 0.001) were significantly lower in patients with recurrent UTIs. Combination therapy with fosfomycin plus amikacin or ceftazidime was shown to be an effective therapeutic option for recurrent UTIs due to a single uropathogen. The rates of susceptibility of E. coli to commonly used antimicrobials were significantly lower in children who developed more than one episode of UTI. The empiric choice of cefazolin or cefotaxime was usually ineffective. Administration of fosfomycin plus amikacin or ceftazidime was an effective therapeutic and preventive strategy in children with VUR and recurrent relapsing UTI. Copyright © 2014. Published by Elsevier B.V.

Boosting the Light: X-ray Physics in Confinement

ScienceCinema

Rhisberger, Ralf [HASYLAB/ DESY

2017-12-09

Remarkable effects are observed if light is confined to dimensions comparable to the wavelength of the light. The lifetime of atomic resonances excited by the radiation is strongly reduced in photonic traps, such as cavities or waveguides. Moreover, one observes an anomalous boost of the intensity scattered from the resonant atoms. These phenomena results from the strong enhancement of the photonic density of states in such geometries. Many of these effects are currently being explored in the regime of vsible light due to their relevance for optical information processing. It is thus appealing to study these phenomena also for much shorter wavelengths. This talk illuminates recent experiments where synchrotron x-rays were trapped in planar waveguides to resonantly excite atomos ([57]Fe nuclei_ embedded in them. In fact, one observes that the radiative decay of these excited atoms is strongly accelerated. The temporal acceleration of the decay goes along with a strong boost of the radiation coherently scattered from the confined atmos. This can be exploited to obtain a high signal-to-noise ratio from tiny quantities of material, leading to manifold applications in the investigation of nanostructured materials. One application is the use of ultrathin probe layers to image the internal structure of magnetic layer systems.

Boosting the growth of the probiotic strain Lactobacillus paracasei ssp. paracasei F19.

PubMed

Brignone, Desideria; Radmann, Pia; Behr, Jürgen; Vogel, Rudi F

2017-08-01

Single so-called booster substances were added to the fermentation medium of the probiotic strain Lactobacillus (L.) paracasei ssp. paracasei F19 to enhance its growth. A wide screening was carried out in microtiter plates and a statistical analysis of the growth parameters was performed. CFU counts were used to correlate the increase in OD 590nm with the increase in viable cell number. Sodium ascorbate, sodium pyruvate, manganese sulfate and cysteine had a remarkable boosting effect on the growth of L. paracasei F19. Three of the boosters increased the growth rate of the strain and led to a higher cell density and biomass yield in laboratory conditions. Cysteine significantly shortened the lag phase, therefore reducing the fermentation times. The boosters were tested on four additional Lactobacillus species and their growth boosting activity was retained. To investigate whether the growth boosters could improve the tolerance of L. paracasei F19 to the adverse condition in the GI tract, additional tests were performed. Sodium ascorbate and sodium pyruvate exerted a certain antioxidant effect, as they improved the tolerance of L. paracasei F19 to H 2 O 2 . Sodium ascorbate enhanced the growth of the strain in low pH.

Nanoengineering of 2D tin sulfide nanoflake arrays incorporated on polyaniline nanofibers with boosted capacitive behavior

NASA Astrophysics Data System (ADS)

Wang, Huanhuan; Chao, DongLiang; Liu, Jilei; Lin, Jianyi; Shen, Ze Xiang

2018-07-01

Nanoscale engineering plays an important role in designing novel electrode architecture and boosting energy storage in supercapacitors. Herein, we demonstrate the fabrication of freestanding tin sulfide based supercapacitor electrode using facile nucleation substrate control, i.e. polyaniline network. This is the first time that tin sulfide based material is fabricated as a binder-free electrode for supercapacitors. The first combination of tin sulfide and polyaniline also evokes synergistic effect to enhance the performance as the polyaniline nanofibers facilitate the growth of tin sulfide flakes in nanosize which is further proved helpful for improving the capacity and stability of the electrode. The as-obtained electrode of tin sulfide nanoflake arrays incorporated on polyaniline nanofibers (365 F g‑1 at 10 mV s‑1) exhibits superior electrochemical performance compared with micro-scaled tin sulfide (32 F g‑1 at 10 mV s‑1). The significantly improved pseudocapacitive and diffusive contributions of polyaniline nanofibers incorporated electrode are identified by quantitative kinetics analysis due to greatly decreased particle size and introduced mesopores, nanoclusters, and exposed edges. Profited from effective nanostructure engineering, a Na+ intercalation mechanism is also pointed out in boosting the electrochemical performance.

Syntactic priming during sentence comprehension: evidence for the lexical boost.

PubMed

Traxler, Matthew J; Tooley, Kristen M; Pickering, Martin J

2014-07-01

Syntactic priming occurs when structural information from one sentence influences processing of a subsequently encountered sentence (Bock, 1986; Ledoux et al., 2007). This article reports 2 eye-tracking experiments investigating the effects of a prime sentence on the processing of a target sentence that shared aspects of syntactic form. The experiments were designed to determine the degree to which lexical overlap between prime and target sentences produced larger effects, comparable to the widely observed "lexical boost" in production experiments (Pickering & Branigan, 1998; Pickering & Ferreira, 2008). The current experiments showed that priming effects during online comprehension were in fact larger when a verb was repeated across the prime and target sentences (see also Tooley et al., 2009). The finding of larger priming effects with lexical repetition supports accounts under which syntactic form representations are connected to individual lexical items (e.g., Tomasello, 2003; Vosse & Kempen, 2000, 2009). PsycINFO Database Record (c) 2014 APA, all rights reserved.

The Decoy Effect as a Nudge: Boosting Hand Hygiene With a Worse Option.

PubMed

Li, Meng; Sun, Yan; Chen, Hui

2018-05-01

This article provides the first test of the decoy effect as a nudge to influence real-world behavior. The decoy effect is the phenomenon that an additional but worse option can boost the appeal of an existing option. It has been widely demonstrated in hypothetical choices, but its usefulness in real-world settings has been subject to debate. In three longitudinal experiments in food-processing factories, we tested two decoy sanitation options that were worse than the existing sanitizer spray bottle. Results showed that the presence of a decoy, but not an additional copy of the original sanitizer bottle in a different color, drastically increased food workers' hand sanitizer use from the original sanitizer bottle and, consequently, improved workers' passing rate in hand sanitary tests from 60% to 70% to above 90% for 20 days. These findings indicate that the decoy effect can be a powerful nudge technique to influence real-world behavior.

Multiscale recurrence quantification analysis of order recurrence plots

NASA Astrophysics Data System (ADS)

Xu, Mengjia; Shang, Pengjian; Lin, Aijing

2017-03-01

In this paper, we propose a new method of multiscale recurrence quantification analysis (MSRQA) to analyze the structure of order recurrence plots. The MSRQA is based on order patterns over a range of time scales. Compared with conventional recurrence quantification analysis (RQA), the MSRQA can show richer and more recognizable information on the local characteristics of diverse systems which successfully describes their recurrence properties. Both synthetic series and stock market indexes exhibit their properties of recurrence at large time scales that quite differ from those at a single time scale. Some systems present more accurate recurrence patterns under large time scales. It demonstrates that the new approach is effective for distinguishing three similar stock market systems and showing some inherent differences.

Treatment effect of TUSPLV on recurrent varicocele

PubMed Central

Yan, Tian-Zhong; Wu, Xiao-Qiang; Wang, Zhi-Wei

2017-01-01

The aim of the study was to analyze the treatment effect of transumbilical single-port laparoscopic varicocelectomy (TUSPLV) on recurrent varicocele (VC). In order to compare the surgical effects of TUSPLV to traditional retroperitoneal ligation of the internal spermatic vein, 64 patients with recurrent VC were enrolled and divided into the control group (n=30) and the observation group (n=34). Patients in the control group underwent surgery using traditional retroperitoneal ligation of the internal spermatic vein, while those in the observation group underwent surgery using TUSPLV. The results showed that the time of operation and bleeding volume in the observation group were significantly lower. The occurrence and recurrence rates of periprocedural complications were considerably lower in the observation group. Differences were statistically significant (P<0.05). In terms of the pregnancy rate, the difference between the 2 groups had no statistical significance (P>0.05). We concluded that employing TUSPLV to treat recurrent VC was safe and effective. PMID:28123466

Modeling and Analysis of Power Processing Systems (MAPPS). Volume 2: Appendices

NASA Technical Reports Server (NTRS)

Lee, F. C.; Radman, S.; Carter, R. A.; Wu, C. H.; Yu, Y.; Chang, R.

1980-01-01

The computer programs and derivations generated in support of the modeling and design optimization program are presented. Programs for the buck regulator, boost regulator, and buck-boost regulator are described. The computer program for the design optimization calculations is presented. Constraints for the boost and buck-boost converter were derived. Derivations of state-space equations and transfer functions are presented. Computer lists for the converters are presented, and the input parameters justified.

Recurrent Shoulder Instability in a Young, Active, Military Population and Its Professional Implications.

PubMed

Flint, James H; Pickett, Adam; Owens, Brett D; Svoboda, Steven J; Peck, Karen Y; Cameron, Kenneth L; Biery, John; Giuliani, Jeffrey; Rue, John-Paul

Shoulder instability is a topic of significant interest within the sports medicine literature, particularly regarding recurrence rates and the ideal treatment indications and techniques. Little has been published specifically addressing the occupational implications of symptomatic recurrent shoulder instability. Previous arthroscopic repair will continue to be a significant predisposing factor for recurrent instability in a young, active population, and that recurrent instability may have a negative effect on college graduation and postgraduate occupational selection. Case series. Level 4. We conducted a retrospective review of approved medical waivers for surgical treatment of anterior shoulder dislocation or instability prior to matriculation at the US Military Academy or the US Naval Academy for the graduating classes of 2010 to 2013. Statistical analysis was performed to determine the incidence and risk factors for recurrence and to determine the impact on graduation rate and occupation selection. Fifty-nine patients were evaluated; 34% developed recurrent anterior instability. Patients with previous arthroscopic repair had a significantly higher incidence of recurrence (38%, P = 0.044). Recurrent shoulder instability did not significantly affect graduation rates or self-selected occupation ( P ≥ 0.05). There is a significant rate of recurrent shoulder instability after primary surgical repair, particularly among young, active individuals. In addition, arthroscopic repair resulted in a significantly higher recurrence rate compared with open repair in our population. Surgical repair for shoulder instability should not necessarily preclude young individuals from pursuing (or being considered for) occupations that may place them at greater risk of recurrence. The risk of recurrent instability is greater than the rate typically described, which may suggest that some subpopulations are at greater risk than others. A unique data point regarding instability is the effect on occupation selection.

Bezlotoxumab: A Review in Preventing Clostridium difficile Infection Recurrence.

PubMed

Deeks, Emma D

2017-10-01

Bezlotoxumab (Zinplava™) is a fully human monoclonal antibody against Clostridium difficile toxin B indicated for the prevention of C. difficile infection (CDI) recurrence in patients with a high recurrence risk. It is the first agent approved for recurrence prevention and is administered as a single intravenous infusion in conjunction with standard-of-care (SoC) antibacterial treatment for CDI. In well-designed, placebo-controlled, phase 3 trials (MODIFY 1 and 2), a single infusion of bezlotoxumab, given in combination with SoC antibacterial therapy for CDI in adults, was effective in reducing CDI recurrence in the 12 weeks post-treatment, with this benefit being seen mainly in the patients at high recurrence risk. Bezlotoxumab did not impact the efficacy of the antibacterials being used to treat the CDI and, consistent with its benefits on CDI recurrence, appeared to reduce the need for subsequent antibacterials, thus minimizing further gut microbiota disruption. Longer term, there were no further CDI recurrences over 12 months' follow-up among patients who had received bezlotoxumab in MODIFY 2 and entered an extension substudy. Bezlotoxumab has low immunogenicity and is generally well tolerated, although the potential for heart failure in some patients requires consideration; cost-effectiveness data for bezlotoxumab are awaited with interest. Thus, a single intravenous infusion of bezlotoxumab during SoC antibacterial treatment for CDI is an emerging option for reducing CDI recurrence in adults at high risk of recurrence.

Facial Affect Recognition Using Regularized Discriminant Analysis-Based Algorithms

NASA Astrophysics Data System (ADS)

Lee, Chien-Cheng; Huang, Shin-Sheng; Shih, Cheng-Yuan

2010-12-01

This paper presents a novel and effective method for facial expression recognition including happiness, disgust, fear, anger, sadness, surprise, and neutral state. The proposed method utilizes a regularized discriminant analysis-based boosting algorithm (RDAB) with effective Gabor features to recognize the facial expressions. Entropy criterion is applied to select the effective Gabor feature which is a subset of informative and nonredundant Gabor features. The proposed RDAB algorithm uses RDA as a learner in the boosting algorithm. The RDA combines strengths of linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA). It solves the small sample size and ill-posed problems suffered from QDA and LDA through a regularization technique. Additionally, this study uses the particle swarm optimization (PSO) algorithm to estimate optimal parameters in RDA. Experiment results demonstrate that our approach can accurately and robustly recognize facial expressions.

Episodic acyclovir therapy to abort recurrent attacks of genital herpes simplex infection.

PubMed

Whatley, J D; Thin, R N

1991-05-01

Frequent recurrence of genital herpes simplex infection can be a distressing condition. Continuous suppressive oral acyclovir is effective but expensive. Hitherto episodic therapy has given disappointing results. An open comparative study of patient initiated therapy is reported here. Acyclovir 200 mg five times daily for five days aborted 44% of recurrences and shortened 38% by greater than or equal to 50%, giving useful response in 82% of 34 recurrences. Acyclovir 400 mg twice daily for five days aborted 60% and shortened 17% giving useful benefit in 77% of 20 recurrences. Acyclovir 200 mg twice a day for five days gave unsatisfactory results. Patients were selected for frequent recurrences and a recognized prodrome, and care was taken to help to identify early prodromal symptoms. In these patients acyclovir in dosages of 200 mg five times daily for five days and 400 mg bd for five days proved convenient and cost effective.

Heterogeneous recurrence monitoring and control of nonlinear stochastic processes

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

Yang, Hui, E-mail: huiyang@usf.edu; Chen, Yun

Recurrence is one of the most common phenomena in natural and engineering systems. Process monitoring of dynamic transitions in nonlinear and nonstationary systems is more concerned with aperiodic recurrences and recurrence variations. However, little has been done to investigate the heterogeneous recurrence variations and link with the objectives of process monitoring and anomaly detection. Notably, nonlinear recurrence methodologies are based on homogeneous recurrences, which treat all recurrence states in the same way as black dots, and non-recurrence is white in recurrence plots. Heterogeneous recurrences are more concerned about the variations of recurrence states in terms of state properties (e.g., valuesmore » and relative locations) and the evolving dynamics (e.g., sequential state transitions). This paper presents a novel approach of heterogeneous recurrence analysis that utilizes a new fractal representation to delineate heterogeneous recurrence states in multiple scales, including the recurrences of both single states and multi-state sequences. Further, we developed a new set of heterogeneous recurrence quantifiers that are extracted from fractal representation in the transformed space. To that end, we integrated multivariate statistical control charts with heterogeneous recurrence analysis to simultaneously monitor two or more related quantifiers. Experimental results on nonlinear stochastic processes show that the proposed approach not only captures heterogeneous recurrence patterns in the fractal representation but also effectively monitors the changes in the dynamics of a complex system.« less

[Immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve].

PubMed

Feng, Yun; Yang, Dazhang; Liu, Dandan; Chen, Jian; Bi, Qingling; Luo, Keqiang

2014-08-01

To explore the application of immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve. Ten patients with thyroid cancer invading unilateral recurrent laryngeal nerve underwent radical surgery and immediate recurrent laryngeal nerve reconstruction. The reconstructive surgical approach included recurrent laryngeal nerve decompression surgery, end-to-end anastomosis of the recurrent laryngeal nerve, anastomosis of ansa cervicalis nerve to the recurrent laryngeal nerve, and nerve-muscle pedicle (NMP) technique. Among the ten patients, one underwent nerve decompression, one underwent end-to-end anastomosis of the recurrent laryngeal nerve, seven had anastomosis of ansa cervicalis to recurrent laryngeal nerve, and one case had anastomosis of ansa cervicalis to recurrent laryngeal nerve combined with nerve-muscle pedicle (NMP) technique. The effect of surgery was evaluated by videolaryngoscopy, maximum phonation time (MPT), phonation efficiency index (PEI) and voice assessment. T-test was used in the statistical analysis. All of the 10 patients had no complications including tumor recurrence and hypoparathyroidism after the surgery. Their hoarseness symptoms were improved, and the patients returned to normal or near-normal voice. Postoperative videolaryngoscopy showed that paralyzed vocal cord returned to normal muscle tone and volume, and the vocal cord vibration and mucosal wave were symmetric and the patients got good glottal closure. The pre- and post-operative maximum phone times of the patients were (4.52 ± 0.89) s and (11.91 ± 1.87) s, respectively (P < 0.01). The pre- and post-operative phonation efficiency indices were (1.37 ± 0.43) s/L and (4.02 ± 1.33) s/L, respectively (P < 0.05). In patients with thyroid cancer invading unilateral recurrent laryngeal nerve, immediate recurrent laryngeal nerve reconstruction following radical surgery of thyroid cancer can effectively achieve recovery in phonation function and improve the quality of life of the patients.

Radiobiological and treatment planning study of a simultaneously integrated boost for canine nasal tumors using helical tomotherapy.

PubMed

Gutíerrez, Alonso N; Deveau, Michael; Forrest, Lisa J; Tomé, Wolfgang A; Mackie, Thomas R

2007-01-01

Feasibility of delivering a simultaneously integrated boost to canine nasal tumors using helical tomotherapy to improve tumor control probability (TCP) via an increase in total biological equivalent uniform dose (EUD) was evaluated. Eight dogs with varying size nasal tumors (5.8-110.9 cc) were replanned to 42 Gy to the nasal cavity and integrated dose boosts to gross disease of 45.2, 48.3, and 51.3 Gy in 10 fractions. EUD values were calculated for tumors and mean normalized total doses (NTD(mean)) for organs at risk (OAR). Normal Tissue Complication Probability (NTCP) values were obtained for OARs, and estimated TCP values were computed using a logistic dose-response model and based on deliverable EUD boost doses. Significant increases in estimated TCP to 54%, 74%, and 86% can be achieved with 10%, 23%, and 37% mean relative EUD boosts to the gross disease, respectively. NTCP values for blindness of either eye and for brain necrosis were < 0.01% for all boosts. Values for cataract development were 31%, 42%, and 46% for studied boost schemas, respectively. Average NTD(mean) to eyes and brain for mean EUD boosts were 10.2, 11.3, and 12.1 Gy3, and 7.5, 7.2, and 7.9 Gy2, respectively. Using helical tomotherapy, simultaneously integrated dose boosts can be delivered to increase the estimated TCP at 1-year without significantly increasing the NTD(mean) to eyes and brain. Delivery of these treatments in a prospective trial may allow quantification of a dose-response relationship in canine nasal tumors.

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

Murphy, Colin; Anderson, Penny R.; Li Tianyu

Purpose: We examined the impact of radiation tumor bed boost parameters in early-stage breast cancer on local control and cosmetic outcomes. Methods and Materials: A total of 3,186 women underwent postlumpectomy whole-breast radiation with a tumor bed boost for Tis to T2 breast cancer from 1970 to 2008. Boost parameters analyzed included size, energy, dose, and technique. Endpoints were local control, cosmesis, and fibrosis. The Kaplan-Meier method was used to estimate actuarial incidence, and a Cox proportional hazard model was used to determine independent predictors of outcomes on multivariate analysis (MVA). The median follow-up was 78 months (range, 1-305 months).more » Results: The crude cosmetic results were excellent in 54%, good in 41%, and fair/poor in 5% of patients. The 10-year estimate of an excellent cosmesis was 66%. On MVA, independent predictors for excellent cosmesis were use of electron boost, lower electron energy, adjuvant systemic therapy, and whole-breast IMRT. Fibrosis was reported in 8.4% of patients. The actuarial incidence of fibrosis was 11% at 5 years and 17% at 10 years. On MVA, independent predictors of fibrosis were larger cup size and higher boost energy. The 10-year actuarial local failure was 6.3%. There was no significant difference in local control by boost method, cut-out size, dose, or energy. Conclusions: Likelihood of excellent cosmesis or fibrosis are associated with boost technique, electron energy, and cup size. However, because of high local control and rare incidence of fair/poor cosmesis with a boost, the anatomy of the patient and tumor cavity should ultimately determine the necessary boost parameters.« less

Three-dimensional conformal simultaneously integrated boost technique for breast-conserving radiotherapy.

PubMed

van der Laan, Hans Paul; Dolsma, Wil V; Maduro, John H; Korevaar, Erik W; Hollander, Miranda; Langendijk, Johannes A

2007-07-15

To compare the target coverage and normal tissue dose with the simultaneously integrated boost (SIB) and the sequential boost technique in breast cancer, and to evaluate the incidence of acute skin toxicity in patients treated with the SIB technique. Thirty patients with early-stage left-sided breast cancer underwent breast-conserving radiotherapy using the SIB technique. The breast and boost planning target volumes (PTVs) were treated simultaneously (i.e., for each fraction, the breast and boost PTVs received 1.81 Gy and 2.3 Gy, respectively). Three-dimensional conformal beams with wedges were shaped and weighted using forward planning. Dose-volume histograms of the PTVs and organs at risk with the SIB technique, 28 x (1.81 + 0.49 Gy), were compared with those for the sequential boost technique, 25 x 2 Gy + 8 x 2 Gy. Acute skin toxicity was evaluated for 90 patients treated with the SIB technique according to Common Terminology Criteria for Adverse Events, version 3.0. PTV coverage was adequate with both techniques. With SIB, more efficiently shaped boost beams resulted in smaller irradiated volumes. The mean volume receiving > or =107% of the breast dose was reduced by 20%, the mean volume outside the boost PTV receiving > or =95% of the boost dose was reduced by 54%, and the mean heart and lung dose were reduced by 10%. Of the evaluated patients, 32.2% had Grade 2 or worse toxicity. The SIB technique is proposed for standard use in breast-conserving radiotherapy because of its dose-limiting capabilities, easy implementation, reduced number of treatment fractions, and relatively low incidence of acute skin toxicity.

Recurrent Primary Biliary Cirrhosis: Peritransplant Factors and Ursodeoxycholic Acid Treatment Post-Liver Transplant

PubMed Central

Guy, Jennifer E.; Qian, Peiqing; Lowell, Jeffrey A.; Peters, Marion G.

2014-01-01

Primary biliary cirrhosis (PBC) recurs after orthotopic liver transplantation (OLT) in up to one-third of patients. These patients are typically asymptomatic, can be identified by abnormal liver biochemistries, and have evidence of histologic recurrence on liver biopsy. The effect of treatment on recurrence has not been determined. This pilot study evaluates the factors associated with recurrent PBC and describes our experience using ursodeoxycholic acid treatment in this patient population. Forty-eight patients with PBC were followed for at least 1 yr post-OLT, and 27 patients (56%) developed abnormal serum alkaline phosphatase. Seventeen patients (35%) had evidence of recurrent PBC by liver biopsy. Patients with recurrent PBC had a trend toward longer warm ischemia times and more episodes of acute cellular rejection in the first year posttransplant, but this was not significant in multivariate analysis. Donor or recipient age, donor and recipient cytomegalovirus status, and dose of immunosuppression did not correlate with recurrence of PBC. Those patients diagnosed with recurrent PBC were placed on ursodeoxycholic acid, 15 mg/kg daily, with improvement in serum alkaline phosphatase in the majority. In conclusion, recurrent PBC is not infrequent post-OLT, and ursodeoxycholic acid can be used with some benefit post-OLT. Treatment effects on long-term survival are not known. PMID:16184542

Recurrence rate and patient satisfaction of CO2 laser evaporation of lesions in patients with hidradenitis suppurativa: a retrospective study.

PubMed

Mikkelsen, Peter Riis; Dufour, Deirde Nathalie; Zarchi, Kian; Jemec, Gregor B E

2015-02-01

Hidradenitis suppurativa (HS) is a debilitating disease and is difficult to treat. Validation of surgical techniques is therefore of great importance in the management of HS. Carbon dioxide (CO2) laser evaporation has been shown effective, but larger-scale studies are scarce. To determine the recurrence rate, time to recurrence, and factors influencing disease recurrence in skin treated with CO2 laser evaporation, and healing by secondary intention; and patients' satisfaction with treatment. Fifty-eight patients treated with CO2 laser evaporation were interviewed regarding recurrence and satisfaction after a mean of 25.7 months. Seventeen of 58 (29%) reported recurrence of HS lesions within the borders of the treated areas after a mean of 12.7 months. Obesity was a risk factor for recurrence with a hazard ratio of 4.53. Fifty-five patients (95%) reported some or great improvement, and 91% would recommend the CO2 laser surgery to other HS patients. This study supports the claim that CO2 laser treatment is an effective modality for recurrent HS lesions in a majority of patients. The authors identified obesity as a risk factor for recurrence. Self-reported satisfaction is high, and only 3 of 58 report no change in the condition. None reported a worsening.

WE-AB-202-10: Modelling Individual Tumor-Specific Control Probability for Hypoxia in Rectal Cancer

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

Warren, S; Warren, DR; Wilson, JM

Purpose: To investigate hypoxia-guided dose-boosting for increased tumour control and improved normal tissue sparing using FMISO-PET images Methods: Individual tumor-specific control probability (iTSCP) was calculated using a modified linear-quadratic model with rectal-specific radiosensitivity parameters for three limiting-case assumptions of the hypoxia / FMISO uptake relationship. {sup 18}FMISO-PET images from 2 patients (T3N0M0) from the RHYTHM trial (Investigating Hypoxia in Rectal Tumours NCT02157246) were chosen to delineate a hypoxic region (GTV-MISO defined as tumor-to-muscle ratio > 1.3) within the anatomical GTV. Three VMAT treatment plans were created in Eclipse (Varian): STANDARD (45Gy / 25 fractions to PTV4500); BOOST-GTV (simultaneous integrated boostmore » of 60Gy / 25fr to GTV +0.5cm) and BOOST-MISO (60Gy / 25fr to GTV-MISO+0.5cm). GTV mean dose (in EQD2), iTSCP and normal tissue dose-volume metrics (small bowel, bladder, anus, and femoral heads) were recorded. Results: Patient A showed small hypoxic volume (15.8% of GTV) and Patient B moderate hypoxic volume (40.2% of GTV). Dose escalation to 60Gy was achievable, and doses to femoral heads and small bowel in BOOST plans were comparable to STANDARD plans. For patient A, a reduced maximum bladder dose was observed in BOOST-MISO compared to BOOST-GTV (D0.1cc 49.2Gy vs 54.0Gy). For patient B, a smaller high dose volume was observed for the anus region in BOOST-MISO compared to BOOST-GTV (V55Gy 19.9% vs 100%), which could potentially reduce symptoms of fecal incontinence. For BOOST-MISO, the largest iTSCPs (A: 95.5% / B: 90.0%) assumed local correlation between FMISO uptake and hypoxia, and approached iTSCP values seen for BOOST-GTV (A: 96.1% / B: 90.5%). Conclusion: Hypoxia-guided dose-boosting is predicted to improve local control in rectal tumors when FMISO is spatially correlated to hypoxia, and to reduce dose to organs-at-risk compared to boosting the whole GTV. This could lead to organ-preserving treatment strategies for locally-advanced rectal cancer, thereby improving quality of life. Oxford Cancer Imaging Centre (OCIC); Cancer Research UK (CRUK); Medical Research Council (MRC)« less

HIV drug resistance surveillance for prioritizing treatment in resource-limited settings

PubMed Central

Walensky, Rochelle P.; Weinstein, Milton C.; Yazdanpanah, Yazdan; Losina, Elena; Mercincavage, Lauren M.; Touré, Siaka; Divi, Nomita; Anglaret, Xavier; Goldie, Sue J.; Freedberg, Kenneth A.

2008-01-01

Background Sentinel testing programs for HIV drug resistance in resource-limited settings can inform policy on antiretroviral therapy (ART) and drug sequencing. Objective To examine the value of resistance surveillance in influencing recommendations toward effective and cost-effective sequencing of ART regimens. Methods A state-transition model of HIV infection was adapted to simulate clinical care in Côte d’Ivoire and evaluate the incremental cost-effectiveness of (1) no ART; (2) ART beginning with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen followed by a boosted protease inhibitor (PI)-based regimen; and (3) ART beginning with a boosted PI-based regimen followed by an NNRTI-based regimen. Results At a 5% prevalence of NNRTI resistance, a strategy that started with a PI-based regimen had a smaller health benefit and higher cost-effectiveness ratio than a strategy that started with an NNRTI-based regimen (cost-effectiveness ratio $910/year of life saved). Results consistently favored initiation with an NNRTI-based regimen, regardless of the population prevalence of NNRTI resistance (up to 76%) and the efficacy of an NNRTI-based regimen in the setting of resistance. The most influential parameters on the cost-effectiveness of sequencing strategies were boosted PI-based regimen costs and the efficacy of this regimen when used as second-line therapy. Conclusions Drug costs and treatment efficacies, but not NNRTI resistance levels, were most influential in determining optimal HIV drug sequencing in Côte d’Ivoire. Results of surveillance for NNRTI resistance should not be used as a major guide to treatment policy in resource-limited settings. PMID:17457091

Boosting Learning Algorithm for Stock Price Forecasting

NASA Astrophysics Data System (ADS)

Wang, Chengzhang; Bai, Xiaoming

2018-03-01

To tackle complexity and uncertainty of stock market behavior, more studies have introduced machine learning algorithms to forecast stock price. ANN (artificial neural network) is one of the most successful and promising applications. We propose a boosting-ANN model in this paper to predict the stock close price. On the basis of boosting theory, multiple weak predicting machines, i.e. ANNs, are assembled to build a stronger predictor, i.e. boosting-ANN model. New error criteria of the weak studying machine and rules of weights updating are adopted in this study. We select technical factors from financial markets as forecasting input variables. Final results demonstrate the boosting-ANN model works better than other ones for stock price forecasting.

Inelastic Boosted Dark Matter at direct detection experiments

NASA Astrophysics Data System (ADS)

Giudice, Gian F.; Kim, Doojin; Park, Jong-Chul; Shin, Seodong

2018-05-01

We explore a novel class of multi-particle dark sectors, called Inelastic Boosted Dark Matter (iBDM). These models are constructed by combining properties of particles that scatter off matter by making transitions to heavier states (Inelastic Dark Matter) with properties of particles that are produced with a large Lorentz boost in annihilation processes in the galactic halo (Boosted Dark Matter). This combination leads to new signals that can be observed at ordinary direct detection experiments, but require unconventional searches for energetic recoil electrons in coincidence with displaced multi-track events. Related experimental strategies can also be used to probe MeV-range boosted dark matter via their interactions with electrons inside the target material.

Optical manifold for light-emitting diodes

DOEpatents

Chaves, Julio C.; Falicoff, Waqidi; Minano, Juan C.; Benitez, Pablo; Parkyn, Jr., William A.; Alvarez, Roberto; Dross, Oliver

2008-06-03

An optical manifold for efficiently combining a plurality of blue LED outputs to illuminate a phosphor for a single, substantially homogeneous output, in a small, cost-effective package. Embodiments are disclosed that use a single or multiple LEDs and a remote phosphor, and an intermediate wavelength-selective filter arranged so that backscattered photoluminescence is recycled to boost the luminance and flux of the output aperture. A further aperture mask is used to boost phosphor luminance with only modest loss of luminosity. Alternative non-recycling embodiments provide blue and yellow light in collimated beams, either separately or combined into white.

Dynamics of multirate sampled data control systems. [for space shuttle boost vehicle

NASA Technical Reports Server (NTRS)

Naylor, J. R.; Hynes, R. J.; Molnar, D. O.

1974-01-01

The effect was investigated of the synthesis approach (single or multirate) on the machine requirements for a digital control system for the space shuttle boost vehicle. The study encompassed four major work areas: synthesis approach trades, machine requirements trades, design analysis requirements and multirate adaptive control techniques. The primary results are two multirate autopilot designs for the low Q and maximum Q flight conditions that exhibits equal or better performance than the analog and single rate system designs. Also, a preferred technique for analyzing and synthesizing multirate digital control systems is included.

Program scheme using common source lines in channel stacked NAND flash memory with layer selection by multilevel operation

NASA Astrophysics Data System (ADS)

Kim, Do-Bin; Kwon, Dae Woong; Kim, Seunghyun; Lee, Sang-Ho; Park, Byung-Gook

2018-02-01

To obtain high channel boosting potential and reduce a program disturbance in channel stacked NAND flash memory with layer selection by multilevel (LSM) operation, a new program scheme using boosted common source line (CSL) is proposed. The proposed scheme can be achieved by applying proper bias to each layer through its own CSL. Technology computer-aided design (TCAD) simulations are performed to verify the validity of the new method in LSM. Through TCAD simulation, it is revealed that the program disturbance characteristics is effectively improved by the proposed scheme.

Helicobacter pylori recurrence after eradication in Latin America: Implications for gastric cancer prevention

PubMed Central

Corral, Juan E; Mera, Robertino; Dye, Corey W; Morgan, Douglas R

2017-01-01

AIM To estimate Helicobacter pylori (H. pylori) recurrence rate in Latin America, a region with a significant H. pylori prevalence and gastric cancer burden. METHODS PubMed, LILACS, SciELO, Cochrane databases and abstracts from relevant meetings were reviewed. Information collected included: Participants’ characteristics, recruitment strategy, diagnostic modality, treatment arms, follow-up and recurrence rates. Recurrence was calculated using 100-patients-year rates, and data were pooled using a random effects model. The I2 statistic assessed between study heterogeneity. Meta-regression analyses evaluated for effect modifying variables. RESULTS Literature search yielded 163 articles. Twelve studies involving 4848 patients from 9 countries met inclusion criteria. Four hundred and thirty-two reinfections were recorded in 5487 person-years of follow-up. Pooled analysis showed a recurrence rate of 7.9 cases per 100 person-years (95%CI: 5.3-10.5). Meta-regression revealed that neither the antibiotic schema, a second antibiotic course, nor the diagnostic modality had an impact on the observed risk of recurrence. The recurrence rate in the first year after treatment, predominantly recrudescence, was 11.2 (6.1-16.4) per 100 patient years. Recurrence in subsequent years, was only 6.2 (3.8-8.7). CONCLUSION H. pylori recurrence rates in Latin America are significant, and with geographic variability, yet are acceptable based upon the current literature for consideration of large scale intervention trials. Further research in Latin America is warranted to evaluate the efficacy, cost-effectiveness, and potential adverse outcomes of proposed eradication programs. PMID:28451066

Ag85A-specific CD4+ T cell lines derived after boosting BCG-vaccinated cattle with Ad5-85A possess both mycobacterial growth inhibition and anti-inflammatory properties.

PubMed

Metcalfe, Hannah J; Biffar, Lucia; Steinbach, Sabine; Guzman, Efrain; Connelley, Tim; Morrison, Ivan; Vordermeier, H Martin; Villarreal-Ramos, Bernardo

2018-05-11

There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 + T cells post-boosting. Here, the capacity of Ag85A-specific CD4 + T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 + T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 + T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology. Copyright © 2018 Department for Environment Food and Rural Affairs. Published by Elsevier Ltd.. All rights reserved.

Climate and Lightning: An updated TRMM-LIS Analysis

NASA Technical Reports Server (NTRS)

Petersen, Walter A.; Buechler, D. E.

2009-01-01

The TRMM Lightning Imaging Sensor (LIS) has sampled global tropical and sub-tropical lightning flash densities for approximately 11 years. These data were originally processed and results presented by the authors in the 3rd AMS MALD Conference held in 2007 using both pre and post TRMM-boost lightning data. These data were normalized for the orbit boost by scaling the pre-boost data by a fixed constant based on the different swath areas for the pre and post-boost years (post-boost after 2001). Inevitably, one must question this simple approach to accounting for the orbit boost when sampling such a noisy quantity. Hence we are in the process of reprocessing the entire 11-year TRMM LIS dataset to reduce the orbit swath of the post-boost era to that of the pre-boost in order to eliminate sampling bias in the dataset. Study of the diurnal/seasonal/annual sampling suggests that those biases are already minimal and should not contribute to error in examination of annual trends. We will present new analysis of the 11-year annual trends in total lightning flash density for all latitudinal belts and select regions/regimes of the tropics as related to conventional climate signals and precipitation contents in the same period. The results should enable us to address, in some fashion, the sensitivity of the lightning flash density to subtle changes in climate.

Proton Radiotherapy for Pediatric Central Nervous System Germ Cell Tumors: Early Clinical Outcomes

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

MacDonald, Shannon M., E-mail: smacdonald@partners.or; Trofimov, Alexei; Safai, Sairos

Purpose: To report early clinical outcomes for children with central nervous system (CNS) germ cell tumors treated with protons; to compare dose distributions for intensity-modulated photon radiotherapy (IMRT), three-dimensional conformal proton radiation (3D-CPT), and intensity-modulated proton therapy with pencil beam scanning (IMPT) for whole-ventricular irradiation with and without an involved-field boost. Methods and Materials: All children with CNS germinoma or nongerminomatous germ cell tumor who received treatment at the Massachusetts General Hospital between 1998 and 2007 were included in this study. The IMRT, 3D-CPT, and IMPT plans were generated and compared for a representative case. Results: Twenty-two patients were treatedmore » with 3D-CPT. At a median follow-up of 28 months, there were no CNS recurrences; 1 patient had a recurrence outside the CNS. Local control, progression-free survival, and overall survival rates were 100%, 95%, and 100%, respectively. Comparable tumor volume coverage was achieved with IMRT, 3D-CPT, and IMPT. Substantial normal tissue sparing was seen with any form of proton therapy as compared with IMRT. The use of IMPT may yield additional sparing of the brain and temporal lobes. Conclusions: Preliminary disease control with proton therapy compares favorably to the literature. Dosimetric comparisons demonstrate the advantage of proton radiation over IMRT for whole-ventricle radiation. Superior dose distributions were accomplished with fewer beam angles utilizing 3D-CPT and scanned protons. Intensity-modulated proton therapy with pencil beam scanning may improve dose distribution as compared with 3D-CPT for this treatment.« less

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer.

PubMed

Wang, Shu-Lian; Liao, Zhongxing; Liu, Helen; Ajani, Jaffer; Swisher, Stephen; Cox, James D; Komaki, Ritsuko

2006-09-14

To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed local recurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fistula. Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Multibeam inverse intensity-modulated radiotherapy (IMRT) for whole breast irradiation: a single center experience in China.

PubMed

Yang, Zhaozhi; Zhang, Li; Chen, Xingxing; Ma, Jinli; Mei, Xin; Chen, Jiayi; Yu, Xiaoli; Guo, Xiaomao

2015-10-27

To present the clinical experience in our cancer center with multibeam inverse intensity-modulated radiotherapy (IMRT) for early stage breast cancer (BC) patients with whole breast irradiation (WBI). We retrospectively analyzed 622 patients with Stage 0 to III BC treated from 2008 to 2011 with wide local excision and WBI, using an inverse IMRT technique. All of the patients were prescribed a total dose of 50 Gy to the whole breast in 2-Gy fractions, followed by a tumor bed boost of 10 Gy in 5 fractions using an electron beam. Of all of the patients, 132 (21.2%) received whole breast plus regional lymph node (RLN) irradiation. 438 of 622 patients had records of acute skin toxicity based on common terminology criteria (CTC) for adverse events. Two hundred eighty (64%) patients had Grade 0/1 toxicity, 153 (35%) had Grade 2 and only 4 patients experienced grade 3 toxicity. Seventy patients (16%) had moist desquamation. Univariate analysis revealed that breast planning target volume was the only predictive factor for Grade ≥2 acute dermatitis (P = 0.002). After 4 years, 170 patients reported cosmetic results by self-assessment, of whom 151 (89%) patients reported good/excellent cosmetic results, and 17 (11%) patients reported fair assessments. For invasive cancer, the four-year rate of freedom from locoregional recurrence survival was 98.3%. Regarding carcinoma in situ, no patients experienced recurrence. BC patients who underwent conservative surgery followed by inverse IMRT plan exhibited acceptable acute toxicities and clinical outcomes. Longer follow-up is needed.

Automated Detection of Driver Fatigue Based on AdaBoost Classifier with EEG Signals.

PubMed

Hu, Jianfeng

2017-01-01

Purpose: Driving fatigue has become one of the important causes of road accidents, there are many researches to analyze driver fatigue. EEG is becoming increasingly useful in the measuring fatigue state. Manual interpretation of EEG signals is impossible, so an effective method for automatic detection of EEG signals is crucial needed. Method: In order to evaluate the complex, unstable, and non-linear characteristics of EEG signals, four feature sets were computed from EEG signals, in which fuzzy entropy (FE), sample entropy (SE), approximate Entropy (AE), spectral entropy (PE), and combined entropies (FE + SE + AE + PE) were included. All these feature sets were used as the input vectors of AdaBoost classifier, a boosting method which is fast and highly accurate. To assess our method, several experiments including parameter setting and classifier comparison were conducted on 28 subjects. For comparison, Decision Trees (DT), Support Vector Machine (SVM) and Naive Bayes (NB) classifiers are used. Results: The proposed method (combination of FE and AdaBoost) yields superior performance than other schemes. Using FE feature extractor, AdaBoost achieves improved area (AUC) under the receiver operating curve of 0.994, error rate (ERR) of 0.024, Precision of 0.969, Recall of 0.984, F1 score of 0.976, and Matthews correlation coefficient (MCC) of 0.952, compared to SVM (ERR at 0.035, Precision of 0.957, Recall of 0.974, F1 score of 0.966, and MCC of 0.930 with AUC of 0.990), DT (ERR at 0.142, Precision of 0.857, Recall of 0.859, F1 score of 0.966, and MCC of 0.716 with AUC of 0.916) and NB (ERR at 0.405, Precision of 0.646, Recall of 0.434, F1 score of 0.519, and MCC of 0.203 with AUC of 0.606). It shows that the FE feature set and combined feature set outperform other feature sets. AdaBoost seems to have better robustness against changes of ratio of test samples for all samples and number of subjects, which might therefore aid in the real-time detection of driver fatigue through the classification of EEG signals. Conclusion: By using combination of FE features and AdaBoost classifier to detect EEG-based driver fatigue, this paper ensured confidence in exploring the inherent physiological mechanisms and wearable application.

Automated Detection of Driver Fatigue Based on AdaBoost Classifier with EEG Signals

PubMed Central

Hu, Jianfeng

2017-01-01

Purpose: Driving fatigue has become one of the important causes of road accidents, there are many researches to analyze driver fatigue. EEG is becoming increasingly useful in the measuring fatigue state. Manual interpretation of EEG signals is impossible, so an effective method for automatic detection of EEG signals is crucial needed. Method: In order to evaluate the complex, unstable, and non-linear characteristics of EEG signals, four feature sets were computed from EEG signals, in which fuzzy entropy (FE), sample entropy (SE), approximate Entropy (AE), spectral entropy (PE), and combined entropies (FE + SE + AE + PE) were included. All these feature sets were used as the input vectors of AdaBoost classifier, a boosting method which is fast and highly accurate. To assess our method, several experiments including parameter setting and classifier comparison were conducted on 28 subjects. For comparison, Decision Trees (DT), Support Vector Machine (SVM) and Naive Bayes (NB) classifiers are used. Results: The proposed method (combination of FE and AdaBoost) yields superior performance than other schemes. Using FE feature extractor, AdaBoost achieves improved area (AUC) under the receiver operating curve of 0.994, error rate (ERR) of 0.024, Precision of 0.969, Recall of 0.984, F1 score of 0.976, and Matthews correlation coefficient (MCC) of 0.952, compared to SVM (ERR at 0.035, Precision of 0.957, Recall of 0.974, F1 score of 0.966, and MCC of 0.930 with AUC of 0.990), DT (ERR at 0.142, Precision of 0.857, Recall of 0.859, F1 score of 0.966, and MCC of 0.716 with AUC of 0.916) and NB (ERR at 0.405, Precision of 0.646, Recall of 0.434, F1 score of 0.519, and MCC of 0.203 with AUC of 0.606). It shows that the FE feature set and combined feature set outperform other feature sets. AdaBoost seems to have better robustness against changes of ratio of test samples for all samples and number of subjects, which might therefore aid in the real-time detection of driver fatigue through the classification of EEG signals. Conclusion: By using combination of FE features and AdaBoost classifier to detect EEG-based driver fatigue, this paper ensured confidence in exploring the inherent physiological mechanisms and wearable application. PMID:28824409

Change in Seroma Volume During Whole-Breast Radiation Therapy

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

Sharma, Rajiv; Spierer, Marnee; Mutyala, Subhakar

2009-09-01

Purpose: After breast-conserving surgery, a seroma often forms in the surgical cavity. If not drained, it may affect the volume of tumor bed requiring a boost after whole-breast radiation therapy (WBRT). Our objective was to evaluate the change in seroma volume that occurs during WBRT, before boost planning. Methods and Materials: A retrospective review was performed of women receiving breast-conserving therapy with evidence of seroma at the time of WBRT planning. Computed tomography (CT) simulation was performed before WBRT and before the tumor bed boost. All patients received either a hypofractionated (42.4 Gy/16 fraction + 9.6 Gy/4 fraction boost) ormore » standard fractionated (50.4 Gy/28 fraction + 10 Gy/5 fraction boost) regimen. Seroma volumes were contoured and compared on CT at the time of WBRT simulation and tumor bed boost planning. Results: Twenty-four patients with evidence of seroma were identified and all patients received WBRT without drainage of the seroma. Mean seroma volume before WBRT and at boost planning were significantly different at 65.7 cm{sup 3} (SD, 50.5 cm{sup 3}) and 35.6 cm{sup 3} (SD, 24.8 cm{sup 3}), respectively (p < 0.001). Mean and median reduction in seroma volume during radiation were 39.6% (SD, 23.8%) and 46.2% (range, 10.7-76.7%), respectively. Fractionation schedule was not correlated with change in seroma volume. Length of time from surgery to start of radiation therapy showed an inverse correlation with change in seroma volume (Pearson correlation r = -0.53, p < 0.01). Conclusions: The volume of seroma changes significantly during WBRT. Consequently, the accuracy of breast boost planning is likely affected, as is the volume of normal breast tissue irradiated. CT-based boost planning before boost irradiation is suggested to ensure appropriate coverage.« less

Notch3-specific inhibition using siRNA knockdown or GSI sensitizes paclitaxel-resistant ovarian cancer cells.

PubMed

Kang, Haeyoun; Jeong, Ju-Yeon; Song, Ji-Ye; Kim, Tae Heon; Kim, Gwangil; Huh, Jin Hyung; Kwon, Ah-Young; Jung, Sang Geun; An, Hee Jung

2016-07-01

Notch signaling plays an important role in ovarian cancer chemoresistance, which is responsible for recurrence. Gamma-secretase inhibitor (GSI) is a broad-spectrum Notch inhibitor, but it has serious side effects. The efficacy of Notch3-specific inhibition in paclitaxel-resistant ovarian cancers was assessed in this study, which has not yet been evaluated relative to GSI. To analyze the effect of Notch3-specific inhibition on paclitaxel-resistant ovarian cancers, we compared cell viability, apoptosis, cell migration, angiogenesis, cell cycle, and spheroid formation after treatment with either Notch3 siRNA or GSI in paclitaxel-resistant SKpac cells and parental SKOV3 cells. Expression levels of survival, cell cycle, and apoptosis-related proteins were measured and compared between groups. Notch3 was significantly overexpressed in chemoresistant cancer tissues and cell lines relative to chemosensitive group. In paclitaxel-resistant cancer cells, Notch inhibition significantly reduced viability, migration, and angiogenesis and increased apoptosis, thereby boosting sensitivity to paclitaxel. Spheroid formation was also significantly reduced. Both Notch3 siRNA-treated cells and GSI-treated cells arrested in the G2/M phase of the cell cycle. Proteins of cell survival, cyclin D1 and cyclin D3 were reduced, whereas p21 and p27 were elevated. Both GSI and Notch3 siRNA treatment reduced expression of anti-apoptotic proteins (BCL-W, BCL2, and BCL-XL) and increased expression of pro-apoptotic proteins (Bad, Bak, Bim, Bid, and Bax). These results indicate that Notch3-specific inhibition sensitizes paclitaxel-resistant cancer cells to paclitaxel treatment, with an efficacy comparable to that of GSI. This approach would be likely to avoid the side effects of broad-spectrum GSI treatment. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Reirradiation on recurrent cervical cancer case: Treatment response and side effects

NASA Astrophysics Data System (ADS)

Siregar, M. F.; Supriana, N.; Nuranna, L.; Prihartono, J.

2017-08-01

Management of recurrent cervical cancer by reirradiation after radiation treatment remains controversial. In Indonesia, there is currently no data about reirradiation tumor response and side effects. This study aims to assess the tumor response to and side effects of reirradiation, the effect of time interval between first radiation treatment and cancer recurrence on the tumor response and side effects, and the effect of tumor size on tumor response. A cohort retrospective study with no comparison was done with the Radiotherapy Department at Cipto Mangunkusumo General Hospital, Jakarta. Participants were recurrent cervical cancer patients undergoing reirradiation. Data was collected from patients’ medical records and follow-up phone calls. Twenty-two patients participated in this study. Nine patients (40.9%) had complete responses, 10 patients (45.5%) had partial responses, 1 patient (4.5%) had a stable response, and 2 patients (9.1%) had tumor progressions. In general, 15 patients (68.2%) had no to light side effects (grade 0-2 RTOG) and 7 patients (31.8%) had severe side effects (grade 3-4 RTOG). Four patients (18.1%) had severe gastrointestinal acute side effects, 6 patients (27.3%) had severe gastrointestinal late side effects, 2 patients (9.1%) had severe urogenital side effects, and there were no patients had severe urogenital late side effects. There was no significant difference in tumor response between patients with time interval between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was no significant difference in tumor response between patients with tumor size ≤4 cm vs. >4 cm. Reirradiation can be considered as a modality in recurrent cervical cancer management since good tumor response was achieved and the majority of patients had no to light side effects (grade 0-2 RTOG). This study found no correlation between tumor response, side effects, and time gap between first radiation treatment and recurrence of <12 months vs. ≥12 months. There was also no correlation between tumor response and tumor size of ≤4 cm vs. > 4 cm.

Recurrent Dreams and Psychosocial Adjustment in Preteenaged Children

PubMed Central

Gauchat, Aline; Zadra, Antonio; Tremblay, Richard E.; Zelazo, Philip David; Séguin, Jean R.

2014-01-01

Research indicates that recurrent dreams in adults are associated with impoverished psychological well-being. Whether similar associations exist in children remains unknown. The authors hypothesized that children reporting recurrent dreams would show poorer psychosocial adjustment than children without recurrent dreams. One hundred sixty-eight 11-year-old children self-reported on their recurrent dreams and on measures of psychosocial adjustment. Although 35% of children reported having experienced a recurrent dream during the past year, our hypothesis was only partially supported. Multivariate analyses revealed a marginally significant interaction between gender and recurrent dream presence and a significant main effect of gender. Univariate analyses revealed that boys reporting recurrent dreams reported significantly higher scores on reactive aggression than those who did not (d = 0.58). This suggests that by age 11 years, the presence of recurrent dreams may already reflect underlying emotional difficulties in boys but not necessarily in girls. Challenges in addressing this developmental question are discussed. PMID:24976740

Clinical and patient reported outcomes of bleaching effectiveness.

PubMed

Klaric Sever, Eva; Budimir, Zrinka; Cerovac, Matea; Stambuk, Mario; Par, Matej; Negovetic Vranic, Dubravka; Tarle, Zrinka

2018-01-01

The objective of this study is to evaluate clinical and patient reported outcomes of different bleaching products. Thirty participants were randomly divided into three bleaching groups (n = 10). Bleaching was performed with high concentrations of hydrogen peroxide (HP) - Boost (40%) and Dash (30%), and with prefabricated splints Bite&White (6% HP). Tooth colour was measured before, immediately after, and 1 and 6 months after the bleaching by using classical shade guide and spectrophotometer. Tooth hypersensitivity was self-rated by patients on the Wong-Baker's face scale. Patient satisfaction was evaluated on a 7-point Likert-type scales that measured perceived performance and importance of different characteristics of bleaching treatment. All products were effective in teeth colour change (ΔE > 3.3), which was significantly higher for Boost (p = .016) and Dash (p = .024) than Bite&White treatment. Perception of hypersensitivity was the highest in Boost group, followed by Dash and Bite&White treatment. Most of the patients were satisfied with final tooth colour, length and comfort during treatment, but were dissatisfied with the stability of bleached tooth colour. Materials with the higher concentrations of bleaching agent demonstrated greater bleaching effectiveness than at-home bleaching product, but also a greater hypersensitivity. Lengthening the treatment process, but achieving a more stable tooth colour may improve the perceived value of a bleaching service.

The multistage vaccine H56 boosts the effects of BCG to protect cynomolgus macaques against active tuberculosis and reactivation of latent Mycobacterium tuberculosis infection

PubMed Central

Lin, Philana Ling; Dietrich, Jes; Tan, Esterlina; Abalos, Rodolfo M.; Burgos, Jasmin; Bigbee, Carolyn; Bigbee, Matthew; Milk, Leslie; Gideon, Hannah P.; Rodgers, Mark; Cochran, Catherine; Guinn, Kristi M.; Sherman, David R.; Klein, Edwin; Janssen, Christopher; Flynn, JoAnne L.; Andersen, Peter

2011-01-01

It is estimated that one-third of the world’s population is infected with Mycobacterium tuberculosis. Infection typically remains latent, but it can reactivate to cause clinical disease. The only vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG), is largely ineffective, and ways to enhance its efficacy are being developed. Of note, the candidate booster vaccines currently under clinical development have been designed to improve BCG efficacy but not prevent reactivation of latent infection. Here, we demonstrate that administering a multistage vaccine that we term H56 in the adjuvant IC31 as a boost to vaccination with BCG delays and reduces clinical disease in cynomolgus macaques challenged with M. tuberculosis and prevents reactivation of latent infection. H56 contains Ag85B and ESAT-6, which are two of the M. tuberculosis antigens secreted in the acute phase of infection, and the nutrient stress–induced antigen Rv2660c. Boosting with H56/IC31 resulted in efficient containment of M. tuberculosis infection and reduced rates of clinical disease, as measured by clinical parameters, inflammatory markers, and improved survival of the animals compared with BCG alone. Boosted animals showed reduced pulmonary pathology and extrapulmonary dissemination, and protection correlated with a strong recall response against ESAT-6 and Rv2660c. Importantly, BCG/H56-vaccinated monkeys did not reactivate latent infection after treatment with anti-TNF antibody. Our results indicate that H56/IC31 boosting is able to control late-stage infection with M. tuberculosis and contain latent tuberculosis, providing a rationale for the clinical development of H56. PMID:22133873

Prime-boost BCG vaccination with DNA vaccines based in β-defensin-2 and mycobacterial antigens ESAT6 or Ag85B improve protection in a tuberculosis experimental model

PubMed Central

Cervantes-Villagrana, Alberto R.; Hernández-Pando, Rogelio; Biragyn, Arya; Castañeda-Delgado, Julio; Bodogai, Monica; Martínez-Fierro, Margarita; Sada, Eduardo; Trujillo, Valentin; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

2018-01-01

The World Health Organization (WHO) has estimated that there are about 8 million new cases annually of active Tuberculosis (TB). Despite its irregular effectiveness (0–89%), the Bacillus Calmette-Guérin) BCG is the only vaccine available worldwide for prevention of TB; thus, the design is important of novel and more efficient vaccination strategies. Considering that β-defensin-2 is an antimicrobial peptide that induces dendritic cell maturation through the TLR-4 receptor and that both ESAT-6 and Ag85B are immunodominant mycobacterial antigens and efficient activators of the protective immune response, we constructed two DNA vaccines by the fusion of the gene encoding β-defensin-2 and antigens ESAT6 (pDE) and 85B (pDA). After confirming efficient local antigen expression that induced high and stable Interferon gamma (IFN-γ) production in intramuscular (i.m.) vaccinated Balb/c mice, groups of mice were vaccinated with DNA vaccines in a prime-boost regimen with BCG and with BCG alone, and 2 months later were challenged with the mild virulence reference strain H37Rv and the highly virulent clinical isolate LAM 5186. The level of protection was evaluated by survival, lung bacilli burdens, and extension of tissue damage (pneumonia). Vaccination with both DNA vaccines showed similar protection to that of BCG. After the challenge with the highly virulent Mycobacterium tuberculosis strain, animals that were prime-boosted with BCG and then boosted with both DNA vaccines showed significant higher survival and less tissue damage than mice vaccinated only with BCG. These results suggest that improvement of BCG vaccination, such as the prime-boost DNA vaccine, represents a more efficient vaccination scheme against TB. PMID:23196205

Evaluation of Plaque pH Changes Following Consumption of Health Drinks by Children: A Pilot Study

PubMed Central

Garg, Dhruv; Srikant, N; Bhandary, Meghna; Nayak, Anupama P; Rao, Arathi; Suprabha, BS

2017-01-01

Introduction With increased trend among people to choose a healthy diet, there is an increased consumption of health drinks by children. Thus, it is important to know their cariogenicity. Aim To evaluate the effect of consumption of health drinks viz., Horlicks, Boost and Complan on plaque pH in children. Materials and Methods The study consisted of four groups: Group I (control)- 10% sucrose solution, Group II- Horlicks, Group III- Boost, Group IV- Complan. Samples of plaque from representative teeth were collected and pH was measured using an electrode outside the mouth. After baseline pH was recorded, children were given their respective drinks and were asked to consume slowly over a period of three to five minutes following swish with 20 ml of the test drink for one minute. The pH was then recorded after 10, 20, 30, 40 and 60 minutes of the post consumption period. Obtained values were subjected to one-way ANOVA test for multiple group comparison followed by Post-Hoc Tukey’s test for group wise comparison. Results Twenty minutes after consumption of Complan and Boost, pH was decreased, but not to the critical pH value as in case of sucrose. The pH was found to be slightly increased, 20 minutes post Horlicks consumption. Post 60 minutes consumption of all the drinks including sucrose solution, the pH was increased in comparison to post 20 minutes. However, 60 minutes post consumption of Boost and Horlicks, pH increased above the baseline. Conclusion Consumption of health drinks viz., Complan and Boost did not lower the plaque pH to the level of critical pH. Consumption of Horlicks increased the plaque pH. PMID:28658897

How attentional boost interacts with reward: the effect of dopaminergic medications in Parkinson's disease.

PubMed

Kéri, Szabolcs; Nagy, Helga; Levy-Gigi, Einat; Kelemen, Oguz

2013-12-01

There is widespread evidence that dopamine is implicated in the regulation of reward and salience. However, it is less known how these processes interact with attention and recognition memory. To explore this question, we used the attentional boost test in patients with Parkinson's disease (PD) before and after the administration of dopaminergic medications. Participants performed a visual letter detection task (remembering rewarded target letters and ignoring distractor letters) while also viewing a series of photos of natural and urban scenes in the background of the letters. The aim of the game was to retrieve the target letter after each trial and to win as much virtual money as possible. The recognition of background scenes was not rewarded. We enrolled 26 drug-naïve, newly diagnosed patients with PD and 25 healthy controls who were evaluated at baseline and follow-up. Patients with PD received dopamine agonists (pramipexole, ropinirole, rotigotine) during the 12-week follow-up period. At baseline, we found intact attentional boost in patients with PD: they were able to recognize target-associated scenes similarly to controls. At follow-up, patients with PD outperformed controls for both target- and distractor-associated scenes, but not when scenes were presented without letters. The alerting, orienting and executive components of attention were intact in PD. Enhanced attentional boost was replicated in a smaller group of patients with PD (n = 15) receiving l-3,4-dihydroxyphenylalanine (L-DOPA). These results suggest that dopaminergic medications facilitate attentional boost for background information regardless of whether the central task (letter detection) is rewarded or not. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection

PubMed Central

Lapointe-Shaw, Lauren; Tran, Kim L.; Coyte, Peter C.; Hancock-Howard, Rebecca L.; Powis, Jeff; Poutanen, Susan M.; Hota, Susy

2016-01-01

Objective To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. Perspective Public insurer for all hospital and physician services. Setting Ontario, Canada. Methods A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. Results Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. Conclusion Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective. PMID:26901316

Cost-Effectiveness Analysis of Six Strategies to Treat Recurrent Clostridium difficile Infection.

PubMed

Lapointe-Shaw, Lauren; Tran, Kim L; Coyte, Peter C; Hancock-Howard, Rebecca L; Powis, Jeff; Poutanen, Susan M; Hota, Susy

2016-01-01

To assess the cost-effectiveness of six treatment strategies for patients diagnosed with recurrent Clostridium difficile infection (CDI) in Canada: 1. oral metronidazole; 2. oral vancomycin; 3.oral fidaxomicin; 4. fecal transplantation by enema; 5. fecal transplantation by nasogastric tube; and 6. fecal transplantation by colonoscopy. Public insurer for all hospital and physician services. Ontario, Canada. A decision analytic model was used to model costs and lifetime health effects of each strategy for a typical patient experiencing up to three recurrences, over 18 weeks. Recurrence data and utilities were obtained from published sources. Cost data was obtained from published sources and hospitals in Toronto, Canada. The willingness-to-pay threshold was $50,000/QALY gained. Fecal transplantation by colonoscopy dominated all other strategies in the base case, as it was less costly and more effective than all alternatives. After accounting for uncertainty in all model parameters, there was an 87% probability that fecal transplantation by colonoscopy was the most beneficial strategy. If colonoscopy was not available, fecal transplantation by enema was cost-effective at $1,708 per QALY gained, compared to metronidazole. In addition, fecal transplantation by enema was the preferred strategy if the probability of recurrence following this strategy was below 8.7%. If fecal transplantation by any means was unavailable, fidaxomicin was cost-effective at an additional cost of $25,968 per QALY gained, compared to metronidazole. Fecal transplantation by colonoscopy (or enema, if colonoscopy is unavailable) is cost-effective for treating recurrent CDI in Canada. Where fecal transplantation is not available, fidaxomicin is also cost-effective.

Intraoperative recurrent laryngeal nerve monitoring: a useful method for patients with esophageal cancer.

PubMed

Zhong, D; Zhou, Y; Li, Y; Wang, Y; Zhou, W; Cheng, Q; Chen, L; Zhao, J; Li, X; Yan, X

2014-07-01

It is well accepted that recurrent laryngeal nerve paralysis is a severe complication of esophagectomy or lymphadenectomy performed adjacent to the recurrent laryngeal nerves. Herein, determination of the effectiveness of implementing continuous recurrent laryngeal nerve monitoring to reduce the incidence of recurrent laryngeal nerve paralysis after esophagectomy was sought. A total of 115 patients diagnosed with esophageal cancer were enrolled in the thoracic section of the Tangdu Hospital of the Fourth Military Medical University from April 2008 to April 2009. Clinical parameters of patients, the morbidity, and the mortality following esophageal resection were recorded and compared. After the surgery, a 2-year follow up was completed. It was found that recurrent laryngeal nerve paralysis and postoperative pneumonia were more frequently diagnosed in the patients that did not receive continuous recurrent laryngeal nerve monitoring (6/61 vs. 0/54). Furthermore, positive mediastinal lymph nodes (P = 0.015), total mediastinal lymph nodes (P < 0.001), positive total lymph nodes (P = 0.027), and total lymph nodes (P < 0.001) were more often surgically removed in the patients with continuous recurrent laryngeal nerve monitoring. These patients also had a higher 2-year survival rate (P = 0.038) after surgery. It was concluded that continuous intraoperative recurrent laryngeal nerve monitoring is technically safe and effectively identifies the recurrent laryngeal nerves. This may be a helpful method for decreasing the incidence of recurrent laryngeal nerve paralysis and postoperative pneumonia, and for improving the efficiency of lymphadenectomy. © 2012 Copyright the Authors. Journal compilation © 2012, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.

Economic Evaluation of a Problem Solving Intervention to Prevent Recurrent Sickness Absence in Workers with Common Mental Disorders

PubMed Central

Arends, Iris; Bültmann, Ute; van Rhenen, Willem; Groen, Henk; van der Klink, Jac J. L.

2013-01-01

Objectives Workers with common mental disorders (CMDs) frequently experience recurrent sickness absence but scientifically evaluated interventions to prevent recurrences are lacking. The objectives of this study are to evaluate the cost-effectiveness and cost-benefit of a problem solving intervention aimed at preventing recurrent sickness absence in workers with CMDs compared to care as usual. Methods An economic evaluation was conducted alongside a cluster-randomised controlled trial with 12 months follow-up. Treatment providers were randomised to either a 2-day training in the SHARP-at work intervention, i.e. a problem solving intervention, or care as usual. Effect outcomes were the incidence of recurrent sickness absence and time to recurrent sickness absence. Self-reported health care utilisation was measured by questionnaires. A cost-effectiveness analysis (CEA) from the societal perspective and a cost-benefit analysis (CBA) from the employer’s perspective were conducted. Results The CEA showed that the SHARP-at work intervention was more effective but also more expensive than care as usual. The CBA revealed that employer’s occupational health care costs were significantly higher in the intervention group compared to care as usual. Overall, the SHARP-at work intervention showed no economic benefit compared to care as usual. Conclusions As implementation of the SHARP-at work intervention might require additional investments, health care policy makers need to decide if these investments are worthwhile considering the results that can be accomplished in reducing recurrent sickness absence. PMID:23951270

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande.

PubMed

Kachulis, C; Abe, K; Bronner, C; Hayato, Y; Ikeda, M; Iyogi, K; Kameda, J; Kato, Y; Kishimoto, Y; Marti, Ll; Miura, M; Moriyama, S; Nakahata, M; Nakano, Y; Nakayama, S; Okajima, Y; Orii, A; Pronost, G; Sekiya, H; Shiozawa, M; Sonoda, Y; Takeda, A; Takenaka, A; Tanaka, H; Tasaka, S; Tomura, T; Akutsu, R; Kajita, T; Kaneyuki, K; Nishimura, Y; Okumura, K; Tsui, K M; Labarga, L; Fernandez, P; Blaszczyk, F D M; Gustafson, J; Kearns, E; Raaf, J L; Stone, J L; Sulak, L R; Berkman, S; Tobayama, S; Goldhaber, M; Elnimr, M; Kropp, W R; Mine, S; Locke, S; Weatherly, P; Smy, M B; Sobel, H W; Takhistov, V; Ganezer, K S; Hill, J; Kim, J Y; Lim, I T; Park, R G; Himmel, A; Li, Z; O'Sullivan, E; Scholberg, K; Walter, C W; Ishizuka, T; Nakamura, T; Jang, J S; Choi, K; Learned, J G; Matsuno, S; Smith, S N; Amey, J; Litchfield, R P; Ma, W Y; Uchida, Y; Wascko, M O; Cao, S; Friend, M; Hasegawa, T; Ishida, T; Ishii, T; Kobayashi, T; Nakadaira, T; Nakamura, K; Oyama, Y; Sakashita, K; Sekiguchi, T; Tsukamoto, T; Abe, K E; Hasegawa, M; Suzuki, A T; Takeuchi, Y; Yano, T; Hayashino, T; Hiraki, T; Hirota, S; Huang, K; Jiang, M; Nakamura, K E; Nakaya, T; Quilain, B; Patel, N D; Wendell, R A; Anthony, L H V; McCauley, N; Pritchard, A; Fukuda, Y; Itow, Y; Murase, M; Muto, F; Mijakowski, P; Frankiewicz, K; Jung, C K; Li, X; Palomino, J L; Santucci, G; Vilela, C; Wilking, M J; Yanagisawa, C; Ito, S; Fukuda, D; Ishino, H; Kibayashi, A; Koshio, Y; Nagata, H; Sakuda, M; Xu, C; Kuno, Y; Wark, D; Di Lodovico, F; Richards, B; Tacik, R; Kim, S B; Cole, A; Thompson, L; Okazawa, H; Choi, Y; Ito, K; Nishijima, K; Koshiba, M; Totsuka, Y; Suda, Y; Yokoyama, M; Calland, R G; Hartz, M; Martens, K; Simpson, C; Suzuki, Y; Vagins, M R; Hamabe, D; Kuze, M; Yoshida, T; Ishitsuka, M; Martin, J F; Nantais, C M; Tanaka, H A; Konaka, A; Chen, S; Wan, L; Zhang, Y; Wilkes, R J; Minamino, A

2018-06-01

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Search for Boosted Dark Matter Interacting with Electrons in Super-Kamiokande

NASA Astrophysics Data System (ADS)

Kachulis, C.; Abe, K.; Bronner, C.; Hayato, Y.; Ikeda, M.; Iyogi, K.; Kameda, J.; Kato, Y.; Kishimoto, Y.; Marti, Ll.; Miura, M.; Moriyama, S.; Nakahata, M.; Nakano, Y.; Nakayama, S.; Okajima, Y.; Orii, A.; Pronost, G.; Sekiya, H.; Shiozawa, M.; Sonoda, Y.; Takeda, A.; Takenaka, A.; Tanaka, H.; Tasaka, S.; Tomura, T.; Akutsu, R.; Kajita, T.; Kaneyuki, K.; Nishimura, Y.; Okumura, K.; Tsui, K. M.; Labarga, L.; Fernandez, P.; Blaszczyk, F. d. M.; Gustafson, J.; Kearns, E.; Raaf, J. L.; Stone, J. L.; Sulak, L. R.; Berkman, S.; Tobayama, S.; Goldhaber, M.; Elnimr, M.; Kropp, W. R.; Mine, S.; Locke, S.; Weatherly, P.; Smy, M. B.; Sobel, H. W.; Takhistov, V.; Ganezer, K. S.; Hill, J.; Kim, J. Y.; Lim, I. T.; Park, R. G.; Himmel, A.; Li, Z.; O'Sullivan, E.; Scholberg, K.; Walter, C. W.; Ishizuka, T.; Nakamura, T.; Jang, J. S.; Choi, K.; Learned, J. G.; Matsuno, S.; Smith, S. N.; Amey, J.; Litchfield, R. P.; Ma, W. Y.; Uchida, Y.; Wascko, M. O.; Cao, S.; Friend, M.; Hasegawa, T.; Ishida, T.; Ishii, T.; Kobayashi, T.; Nakadaira, T.; Nakamura, K.; Oyama, Y.; Sakashita, K.; Sekiguchi, T.; Tsukamoto, T.; Abe, KE.; Hasegawa, M.; Suzuki, A. T.; Takeuchi, Y.; Yano, T.; Hayashino, T.; Hiraki, T.; Hirota, S.; Huang, K.; Jiang, M.; Nakamura, KE.; Nakaya, T.; Quilain, B.; Patel, N. D.; Wendell, R. A.; Anthony, L. H. V.; McCauley, N.; Pritchard, A.; Fukuda, Y.; Itow, Y.; Murase, M.; Muto, F.; Mijakowski, P.; Frankiewicz, K.; Jung, C. K.; Li, X.; Palomino, J. L.; Santucci, G.; Vilela, C.; Wilking, M. J.; Yanagisawa, C.; Ito, S.; Fukuda, D.; Ishino, H.; Kibayashi, A.; Koshio, Y.; Nagata, H.; Sakuda, M.; Xu, C.; Kuno, Y.; Wark, D.; Di Lodovico, F.; Richards, B.; Tacik, R.; Kim, S. B.; Cole, A.; Thompson, L.; Okazawa, H.; Choi, Y.; Ito, K.; Nishijima, K.; Koshiba, M.; Totsuka, Y.; Suda, Y.; Yokoyama, M.; Calland, R. G.; Hartz, M.; Martens, K.; Simpson, C.; Suzuki, Y.; Vagins, M. R.; Hamabe, D.; Kuze, M.; Yoshida, T.; Ishitsuka, M.; Martin, J. F.; Nantais, C. M.; Tanaka, H. A.; Konaka, A.; Chen, S.; Wan, L.; Zhang, Y.; Wilkes, R. J.; Minamino, A.; Super-Kamiokande Collaboration

2018-06-01

A search for boosted dark matter using 161.9 kt yr of Super-Kamiokande IV data is presented. We search for an excess of elastically scattered electrons above the atmospheric neutrino background, with a visible energy between 100 MeV and 1 TeV, pointing back to the Galactic center or the Sun. No such excess is observed. Limits on boosted dark matter event rates in multiple angular cones around the Galactic center and Sun are calculated. Limits are also calculated for a baseline model of boosted dark matter produced from cold dark matter annihilation or decay. This is the first experimental search for boosted dark matter from the Galactic center or the Sun interacting in a terrestrial detector.

Preventing recurrent ankle sprains: Is the use of an App more cost-effective than a printed Booklet? Results of a RCT.

PubMed

Van Reijen, M; Vriend, I; van Mechelen, W; Verhagen, E A

2018-02-01

Recurrent ankle sprains can be reduced by following a neuromuscular training (NMT) program via a printed Booklet or a mobile application. Regarding the high incidence of ankle sprains, cost-effectiveness regarding implementation can have a large effect on total societal costs. In this economic analysis, we evaluated whether the method of implementing a proven effective NMT program using an App or a Booklet resulted in differences in injury incidence rates leading to costs and hence to differences in cost-effectiveness. In total, 220 athletes with a previous ankle sprain were recruited for this randomized controlled trial with a follow-up of 12 months. Half of the athletes used the freely available "Strengthen your ankle" App and the other half received a printed Booklet. After the 8-week program, athletes were questioned monthly on their recurrent injuries. Primary outcome measures were incidence density of ankle injury and incremental cost-effectiveness ratio (ICER). During follow-up, 31 athletes suffered from a recurrent ankle sprain that led to costs resulting in a hazard ratio of 1.13 (95% CI: 0.56-2.27). The incremental cost-effectiveness ratio of the App group in comparison with the Booklet group was €361.52. The CE plane shows that there was neither a difference in effects nor in costs between both intervention methods. This study showed that the method of implementing the NMT program using an App or a Booklet led to similar cost-effectiveness ratios and the same occurrence of recurrent injuries leading to costs. Both the App and the Booklet can be used to prevent recurrent ankle injuries, showing no differences in (cost-) effectiveness at 12-month follow-up. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reconcile Planck-scale discreteness and the Lorentz-Fitzgerald contraction

NASA Astrophysics Data System (ADS)

Rovelli, Carlo; Speziale, Simone

2003-03-01

A Planck-scale minimal observable length appears in many approaches to quantum gravity. It is sometimes argued that this minimal length might conflict with Lorentz invariance, because a boosted observer can see the minimal length further Lorentz contracted. We show that this is not the case within loop quantum gravity. In loop quantum gravity the minimal length (more precisely, minimal area) does not appear as a fixed property of geometry, but rather as the minimal (nonzero) eigenvalue of a quantum observable. The boosted observer can see the same observable spectrum, with the same minimal area. What changes continuously in the boost transformation is not the value of the minimal length: it is the probability distribution of seeing one or the other of the discrete eigenvalues of the area. We discuss several difficulties associated with boosts and area measurement in quantum gravity. We compute the transformation of the area operator under a local boost, propose an explicit expression for the generator of local boosts, and give the conditions under which its action is unitary.

Improvement of the Immunogenicity of Porcine Circovirus Type 2 DNA Vaccine by Recombinant ORF2 Gene and CpG Motifs.

PubMed

Li, Jun; Shi, Jian-Li; Wu, Xiao-Yan; Fu, Fang; Yu, Jiang; Yuan, Xiao-Yuan; Peng, Zhe; Cong, Xiao-Yan; Xu, Shao-Jian; Sun, Wen-Bo; Cheng, Kai-Hui; Du, Yi-Jun; Wu, Jia-Qiang; Wang, Jin-Bao; Huang, Bao-Hua

2015-06-01

Nowadays, adjuvant is still important for boosting immunity and improving resistance in animals. In order to boost the immunity of porcine circovirus type 2 (PCV2) DNA vaccine, CpG motifs were inserted. In this study, the dose-effect was studied, and the immunity of PCV2 DNA vaccines by recombinant open reading frame 2 (ORF2) gene and CpG motifs was evaluated. Three-week-old Changbai piglets were inoculated intramuscularly with 200 μg, 400 μg, and 800 μg DNA vaccines containing 14 and 18 CpG motifs, respectively. Average gain and rectum temperature were recorded everyday during the experiments. Blood was collected from the piglets after vaccination to detect the changes of specific antibodies, interleukin-2, and immune cells every week. Tissues were collected for histopathology and polymerase chain reaction. The results indicated that compared to those of the control piglets, all concentrations of two DNA vaccines could induce PCV2-specific antibodies. A cellular immunity test showed that PCV2-specific lymphocytes proliferated the number of TH, TC, and CD3+ positive T-cells raised in the blood of DNA vaccine immune groups. There was no distinct pathological damage and viremia occurring in pigs that were inoculated with DNA vaccines, but there was some minor pathological damage in the control group. The results demonstrated that CpG motifs as an adjuvant could boost the humoral and cellular immunity of pigs to PCV2, especially in terms of cellular immunity. Comparing two DNA vaccines that were constructed, the one containing 18 CpG motifs was more effective. This is the first report that CpG motifs as an adjuvant insert to the PCV2 DNA vaccine could boost immunity.

Acellular pertussis vaccines effectiveness over time: A systematic review, meta-analysis and modeling study

PubMed Central

Chit, Ayman; Zivaripiran, Hossein; Shin, Thomas; Lee, Jason K. H.; Tomovici, Antigona; Macina, Denis; Johnson, David R.; Decker, Michael D.; Wu, Jianhong

2018-01-01

Background Acellular pertussis vaccine studies postulate that waning protection, particularly after the adolescent booster, is a major contributor to the increasing US pertussis incidence. However, these studies reported relative (ie, vs a population given prior doses of pertussis vaccine), not absolute (ie, vs a pertussis vaccine naïve population) efficacy following the adolescent booster. We aim to estimate the absolute protection offered by acellular pertussis vaccines. Methods We conducted a systematic review of acellular pertussis vaccine effectiveness (VE) publications. Studies had to comply with the US schedule, evaluate clinical outcomes, and report VE over discrete time points. VE after the 5-dose childhood series and after the adolescent sixth-dose booster were extracted separately and pooled. All relative VE estimates were transformed to absolute estimates. VE waning was estimated using meta-regression modeling. Findings Three studies reported VE after the childhood series and four after the adolescent booster. All booster studies reported relative VE (vs acellular pertussis vaccine-primed population). We estimate initial childhood series absolute VE is 91% (95% CI: 87% to 95%) and declines at 9.6% annually. Initial relative VE after adolescent boosting is 70% (95% CI: 54% to 86%) and declines at 45.3% annually. Initial absolute VE after adolescent boosting is 85% (95% CI: 84% to 86%) and declines at 11.7% (95% CI: 11.1% to 12.3%) annually. Interpretation Acellular pertussis vaccine efficacy is initially high and wanes over time. Observational VE studies of boosting failed to recognize that they were measuring relative, not absolute, VE and the absolute VE in the boosted population is better than appreciated. PMID:29912887

Algorithms that eliminate the effects of calibration artefact and trial-imposed offsets of Masimo oximeter in BOOST-NZ trial.

PubMed

Zahari, Marina; Lee, Dominic Savio; Darlow, Brian Alexander

2016-10-01

The displayed readings of Masimo pulse oximeters used in the Benefits Of Oxygen Saturation Targeting (BOOST) II and related trials in very preterm babies were influenced by trial-imposed offsets and an artefact in the calibration software. A study was undertaken to implement new algorithms that eliminate the effects of offsets and artefact. In the BOOST-New Zealand trial, oxygen saturations were averaged and stored every 10 s up to 36 weeks' post-menstrual age. Two-hundred and fifty-seven of 340 babies enrolled in the trial had at least two weeks of stored data. Oxygen saturation distribution patterns corresponding with a +3 % or -3 % offset in the 85-95 % range were identified together with that due to the calibration artefact. Algorithms involving linear and quadratic interpolations were developed, implemented on each baby of the dataset and validated using the data of a UK preterm baby, as recorded from Masimo oximeters with the original software and a non-offset Siemens oximeter. Saturation distributions obtained were compared for both groups. There were a flat region at saturations 85-87 % and a peak at 96 % from the lower saturation target oximeters, and at 93-95 and 84 % respectively from the higher saturation target oximeters. The algorithms lowered the peaks and redistributed the accumulated frequencies to the flat regions and artefact at 87-90 %. The resulting distributions were very close to those obtained from the Siemens oximeter. The artefact and offsets of the Masimo oximeter's software had been addressed to determine the true saturation readings through the use of novel algorithms. The implementation would enable New Zealand data be included in the meta-analysis of BOOST II trials, and be used in neonatal oxygen studies.

The effect of a social support boosting intervention on stress, coping, and social support in caregivers of children with HIV/AIDS.

PubMed

Hansell, P S; Hughes, C B; Caliandro, G; Russo, P; Budin, W C; Hartman, B; Hernandez, O C

1998-01-01

Caring for the human immunodeficiency virus (HIV)-infected child is challenging and affects the entire family system. Studies have shown that social support can mitigate caregiver stress and enhance coping; however, social support may not always result in a positive outcome for the recipient. To measure caregiver stress, coping, and social support, and to test the effect of a social support boosting intervention on levels of stress, coping, and social support among caregivers of children with HIV/acquired immune deficiency syndrome (AIDS). An experimental design was used with monthly social support boosting interventions implemented. The stratified randomized sample included 70 primary caregivers of children with HIV/AIDS. The sample strata were seropositive caregivers (biological parents) and seronegative caregivers (foster parents and extended family members). Study measures included the Derogatis Stress Profile, Family Crisis Oriented Personal Evaluation Scale, and the Tilden Interpersonal Relationship Inventory. Data were analyzed using descriptive statistics and repeated measure MANOVA. Statistically significant differences between the experimental and control groups were found on changes in the dependent variables over time when caregiver strata were included as a factor in the analysis; no statistically significant results were found when caregiver strata were combined. Univariate Ftests indicated that the level of social support for caregivers who were seronegative in the experimental group was significantly different from seronegative caregivers in the control group and seropositive caregivers in both groups. No significant treatment group differences were found for seropositive caregivers. Seronegative caregivers derived substantial benefit from the social support boosting intervention. Seronegative caregivers who acquire a child with HIV/AIDS are confronted with a complex stressful situation; the critical need to enhance their social support is achievable through the intervention tested in this study.

Cyclooxygenase-2 expression and recurrence of colorectal adenomas: effect of aspirin chemoprevention.

PubMed

Benamouzig, Robert; Uzzan, Bernard; Martin, Antoine; Deyra, Jacques; Little, Julian; Girard, Bernard; Chaussade, Stanislas

2010-05-01

Low-dose aspirin reduces the incidence of colorectal cancer and recurrence of adenomas. Cyclooxygenase-2 (COX-2), one of its main target enzymes, is reportedly over-expressed in colorectal adenomas. To assess COX-2 expression, in relation to adenoma recurrence and the protective effect of aspirin, in a large series of colorectal adenomas, recruited from a double-blind randomised controlled trial comparing recurrences after low-dose aspirin or placebo. Follow-up colonoscopies were performed after 1 and 4 years to assess adenoma recurrence. COX-2 expression was assessed by immunohistochemistry for each adenoma obtained at baseline colonoscopy, separately for epithelium, deep stroma and overall. Architecture, grade of dysplasia, K-ras mutation, p53 and cyclin D1 expression were studied. COX-2 expression could be assessed in 219 adenomas from 136 128 adenomas (58%) from 59 patients strongly expressed COX-2. Strong COX-2 expression predominated in adenomas larger than 10 mm (84/129 vs 44/90; p=0.02) and in adenomas showing high-grade dysplasia (22/29 vs 104/188; p=0.04). Deep stromal but not epithelial initial expression of COX-2 predicted adenoma recurrence in the whole population (30/72 patients or 42% strongly expressed deep stromal COX-2 compared with 16/64 or 25% without recurrent adenoma; p=0.04). The protective effect of aspirin was mainly observed in patients in whom COX-2 initial expression was low (RR for recurrence in patients taking aspirin with low COX-2 expression: 0.59; 95% CI 0.39 to 0.90; p=0.02). There was no significant effect of aspirin at the end of the trial. Over-expression of COX-2 was frequent and predominated in large and high-grade dysplasia adenomas. Deep stromal but not epithelial initial expression of COX-2 predicted recurrence of adenomas. Aspirin did not act preferentially on patients whose initial adenomas strongly expressed COX-2.

Cost-effectiveness analysis of fidaxomicin versus vancomycin in Clostridium difficile infection.

PubMed

Nathwani, Dilip; Cornely, Oliver A; Van Engen, Anke K; Odufowora-Sita, Olatunji; Retsa, Peny; Odeyemi, Isaac A O

2014-11-01

Fidaxomicin was non-inferior to vancomycin with respect to clinical cure rates in the treatment of Clostridium difficile infections (CDIs) in two Phase III trials, but was associated with significantly fewer recurrences than vancomycin. This economic analysis investigated the cost-effectiveness of fidaxomicin compared with vancomycin in patients with severe CDI and in patients with their first CDI recurrence. A 1 year time horizon Markov model with seven health states was developed from the perspective of Scottish public healthcare providers. Model inputs for effectiveness, resource use, direct costs and utilities were obtained from published sources and a Scottish expert panel. The main model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY), for fidaxomicin versus vancomycin; ICERs were interpreted using willingness-to-pay thresholds of £20,000/QALY and £30,000/QALY. One-way and probabilistic sensitivity analyses were performed. Total costs were similar with fidaxomicin and vancomycin in patients with severe CDI (£14,515 and £14,344, respectively) and in patients with a first recurrence (£16,535 and £16,926, respectively). Improvements in clinical outcomes with fidaxomicin resulted in small QALY gains versus vancomycin (severe CDI, +0.010; patients with first recurrence, +0.019). Fidaxomicin was cost-effective in severe CDI (ICER £16,529/QALY) and dominant (i.e. more effective and less costly) in patients with a first recurrence. The probability that fidaxomicin was cost-effective at a willingness-to-pay threshold of £30,000/QALY was 60% for severe CDI and 68% in a first recurrence. Fidaxomicin is cost-effective in patients with severe CDI and in patients with a first CDI recurrence versus vancomycin. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

The attentional boost effect and context memory.

PubMed

Mulligan, Neil W; Smith, S Adam; Spataro, Pietro

2016-04-01

Stimuli co-occurring with targets in a detection task are better remembered than stimuli co-occurring with distractors-the attentional boost effect (ABE). The ABE is of interest because it is an exception to the usual finding that divided attention during encoding impairs memory. The effect has been demonstrated in tests of item memory but it is unclear if context memory is likewise affected. Some accounts suggest enhanced perceptual encoding or associative binding, predicting an ABE on context memory, whereas other evidence suggests a more abstract, amodal basis of the effect. In Experiment 1, context memory was assessed in terms of an intramodal perceptual detail, the font and color of the study word. Experiment 2 examined context memory cross-modally, assessing memory for the modality (visual or auditory) of the study word. Experiments 3 and 4 assessed context memory with list discrimination, in which 2 study lists are presented and participants must later remember which list (if either) a test word came from. In all experiments, item (recognition) memory was also assessed and consistently displayed a robust ABE. In contrast, the attentional-boost manipulation did not enhance context memory, whether defined in terms of visual details, study modality, or list membership. There was some evidence that the mode of responding on the detection task (motoric response as opposed to covert counting of targets) may impact context memory but there was no evidence of an effect of target detection, per se. In sum, the ABE did not occur in context memory with verbal materials. (c) 2016 APA, all rights reserved).

RBoost: Label Noise-Robust Boosting Algorithm Based on a Nonconvex Loss Function and the Numerically Stable Base Learners.

PubMed

Miao, Qiguang; Cao, Ying; Xia, Ge; Gong, Maoguo; Liu, Jiachen; Song, Jianfeng

2016-11-01

AdaBoost has attracted much attention in the machine learning community because of its excellent performance in combining weak classifiers into strong classifiers. However, AdaBoost tends to overfit to the noisy data in many applications. Accordingly, improving the antinoise ability of AdaBoost plays an important role in many applications. The sensitiveness to the noisy data of AdaBoost stems from the exponential loss function, which puts unrestricted penalties to the misclassified samples with very large margins. In this paper, we propose two boosting algorithms, referred to as RBoost1 and RBoost2, which are more robust to the noisy data compared with AdaBoost. RBoost1 and RBoost2 optimize a nonconvex loss function of the classification margin. Because the penalties to the misclassified samples are restricted to an amount less than one, RBoost1 and RBoost2 do not overfocus on the samples that are always misclassified by the previous base learners. Besides the loss function, at each boosting iteration, RBoost1 and RBoost2 use numerically stable ways to compute the base learners. These two improvements contribute to the robustness of the proposed algorithms to the noisy training and testing samples. Experimental results on the synthetic Gaussian data set, the UCI data sets, and a real malware behavior data set illustrate that the proposed RBoost1 and RBoost2 algorithms perform better when the training data sets contain noisy data.

Riemann curvature of a boosted spacetime geometry

NASA Astrophysics Data System (ADS)

Battista, Emmanuele; Esposito, Giampiero; Scudellaro, Paolo; Tramontano, Francesco

2016-10-01

The ultrarelativistic boosting procedure had been applied in the literature to map the metric of Schwarzschild-de Sitter spacetime into a metric describing de Sitter spacetime plus a shock-wave singularity located on a null hypersurface. This paper evaluates the Riemann curvature tensor of the boosted Schwarzschild-de Sitter metric by means of numerical calculations, which make it possible to reach the ultrarelativistic regime gradually by letting the boost velocity approach the speed of light. Thus, for the first time in the literature, the singular limit of curvature, through Dirac’s δ distribution and its derivatives, is numerically evaluated for this class of spacetimes. Moreover, the analysis of the Kretschmann invariant and the geodesic equation shows that the spacetime possesses a “scalar curvature singularity” within a 3-sphere and it is possible to define what we here call “boosted horizon”, a sort of elastic wall where all particles are surprisingly pushed away, as numerical analysis demonstrates. This seems to suggest that such “boosted geometries” are ruled by a sort of “antigravity effect” since all geodesics seem to refuse to enter the “boosted horizon” and are “reflected” by it, even though their initial conditions are aimed at driving the particles toward the “boosted horizon” itself. Eventually, the equivalence with the coordinate shift method is invoked in order to demonstrate that all δ2 terms appearing in the Riemann curvature tensor give vanishing contribution in distributional sense.

Carotid recurrent stenosis and risk of ipsilateral stroke: a systematic review of the literature.

PubMed

Frericks, H; Kievit, J; van Baalen, J M; van Bockel, J H

1998-01-01

The main goal of follow-up after carotid endarterectomy is to prevent new strokes caused by recurrent stenosis. To determine the most cost-effective follow-up schedule, it is necessary to know the incidence of recurrent stenosis and the risk of stroke it carries. A systematic review of the literature was performed using standard meta-analytical techniques. Incidence of recurrent stenosis: The data were very heterogeneous. The risk of recurrent stenosis was 10% in the first year, 3% in the second, and 2% in the third. Long-term risk of recurrent stenosis is about 1% per year. Risk of stroke: The reported relative risks of stroke in patients with recurrent stenosis compared with patients without recurrent stenosis showed extreme heterogeneity and ranged from 10 to 0.10. The random effects summary estimator of relative risk was 1.88. The data were very heterogeneous, and much better data are needed to arrive at truly reliable estimates of these important parameters of follow-up. It is clear, though, that the risk of recurrent stenosis is highest in the first few years after carotid endarterectomy and very low in later years. By use of general decision-analytic arguments, it can be argued that, given the test characteristics of carotid ultrasound, a small number of tests can be done in the first few years and that testing for restenosis should not be done after 4 years.

Building the Emotional Intelligence of Groups.

ERIC Educational Resources Information Center

Druskat, Vanessa Urch; Wolff, Steven B.

2001-01-01

Research has found that individual emotional intelligence has a group analog and it is critical to groups' effectiveness. Teams can develop greater emotional intelligence and boost their overall performance. (JOW)

Enhanced charging kinetics of porous electrodes: surface conduction as a short-circuit mechanism.

PubMed

Mirzadeh, Mohammad; Gibou, Frederic; Squires, Todd M

2014-08-29

We use direct numerical simulations of the Poisson-Nernst-Planck equations to study the charging kinetics of porous electrodes and to evaluate the predictive capabilities of effective circuit models, both linear and nonlinear. The classic transmission line theory of de Levie holds for general electrode morphologies, but only at low applied potentials. Charging dynamics are slowed appreciably at high potentials, yet not as significantly as predicted by the nonlinear transmission line model of Biesheuvel and Bazant. We identify surface conduction as a mechanism which can effectively "short circuit" the high-resistance electrolyte in the bulk of the pores, thus accelerating the charging dynamics and boosting power densities. Notably, the boost in power density holds only for electrode morphologies with continuous conducting surfaces in the charging direction.

How Social Communications Influence Advertising Perception and Response in Online Communities?

PubMed Central

Zeng, Fue; Tao, Ran; Yang, Yanwu; Xie, Tingting

2017-01-01

This research aims to explore how social communications of online communities affect users’ perception and responses toward social media advertising. We developed a conceptual model based on the SBT, encapsulating 9 constructs and 10 hypothesis extracted from the extant social media advertising literature. Our research outcome proves that social communications can effectively boost users’ behaviors to be in accordance with an online social community, thus facilitate their acceptance and responses toward social media advertising, with users’ group intention as an intervening factor. From an operational standpoint, it’s an effective way to build and maintain social bonds between users and the community by boosting social communications, supporting fluent interpersonal communications. In addition, managers of an online community should elaborate on users’ group intentions to increase users’ advertising acceptance and response. PMID:28855879

Robust control of the DC-DC boost converter based on the uncertainty and disturbance estimator

NASA Astrophysics Data System (ADS)

Oucheriah, Said

2017-11-01

In this paper, a robust non-linear controller based on the uncertainty and disturbance estimator (UDE) scheme is successfully developed and implemented for the output voltage regulation of the DC-DC boost converter. System uncertainties, external disturbances and unknown non-linear dynamics are lumped as a signal that is accurately estimated using a low-pass filter and their effects are cancelled by the controller. This methodology forms the basis of the UDE-based controller. A simple procedure is also developed that systematically determines the parameters of the controller to meet certain specifications. Using simulation, the effectiveness of the proposed controller is compared against the sliding-mode control (SMC). Experimental tests also show that the proposed controller is robust to system uncertainties, large input and load perturbations.

How Social Communications Influence Advertising Perception and Response in Online Communities?

PubMed

Zeng, Fue; Tao, Ran; Yang, Yanwu; Xie, Tingting

2017-01-01

This research aims to explore how social communications of online communities affect users' perception and responses toward social media advertising. We developed a conceptual model based on the SBT, encapsulating 9 constructs and 10 hypothesis extracted from the extant social media advertising literature. Our research outcome proves that social communications can effectively boost users' behaviors to be in accordance with an online social community, thus facilitate their acceptance and responses toward social media advertising, with users' group intention as an intervening factor. From an operational standpoint, it's an effective way to build and maintain social bonds between users and the community by boosting social communications, supporting fluent interpersonal communications. In addition, managers of an online community should elaborate on users' group intentions to increase users' advertising acceptance and response.

An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates

PubMed Central

Wise, Megan C.; Hutnick, Natalie A.; Pollara, Justin; Myles, Devin J. F.; Williams, Constance; Yan, Jian; LaBranche, Celia C.; Khan, Amir S.; Sardesai, Niranjan Y.; Montefiori, David; Barnett, Susan W.; Zolla-Pazner, Susan; Ferrari, Guido

2015-01-01

ABSTRACT The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the risk of HIV-1 infection. We have made several improvements to the DNA platform and have previously shown that improved DNA vaccines alone are capable of inducing both binding and neutralizing antibodies in small-animal models. In this study, we explored how an improved DNA prime and recombinant protein boost would impact HIV-specific vaccine immunogenicity in rhesus macaques (RhM). After DNA immunization with either a single HIV Env consensus sequence or multiple constructs expressing HIV subtype-specific Env consensus sequences, we detected both CD4+ and CD8+ T-cell responses to all vaccine immunogens. These T-cell responses were further increased after protein boosting to levels exceeding those of DNA-only or protein-only immunization. In addition, we observed antibodies that exhibited robust cross-clade binding and neutralizing and antibody-dependent cellular cytotoxicity (ADCC) activity after immunization with the DNA prime-protein boost regimen, with the multiple-Env formulation inducing a more robust and broader response than the single-Env formulation. The magnitude and functionality of these responses emphasize the strong priming effect improved DNA immunogens can induce, which are further expanded upon protein boost. These results support further study of an improved synthetic DNA prime together with a protein boost for enhancing anti-HIV immune responses. IMPORTANCE Even with effective antiretroviral drugs, HIV remains an enormous global health burden. Vaccine development has been problematic in part due to the high degree of diversity and poor immunogenicity of the HIV Env protein. Studies suggest that a relevant HIV vaccine will likely need to induce broad cellular and humoral responses from a simple vaccine regimen due to the resource-limited setting in which the HIV pandemic is most rampant. DNA vaccination lends itself well to increasing the amount of diversity included in a vaccine due to the ease of manufacturing multiple plasmids and formulating them as a single immunization. By increasing the number of Envs within a formulation, we were able to show an increased breadth of responses as well as improved functionality induced in a nonhuman primate model. This increased breadth could be built upon, leading to better coverage against circulating strains with broader vaccine-induced protection. PMID:26085155

Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review

PubMed Central

Hallifax, R J; Yousuf, A; Jones, H E; Corcoran, J P; Psallidas, I; Rahman, N M

2017-01-01

Objectives Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. Design We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case–control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. Results Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0–2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. Conclusions Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies. PMID:27803156

Effectiveness of chemical pleurodesis in spontaneous pneumothorax recurrence prevention: a systematic review.

PubMed

Hallifax, R J; Yousuf, A; Jones, H E; Corcoran, J P; Psallidas, I; Rahman, N M

2017-12-01

Spontaneous pneumothorax is a common pathology. International guidelines suggest pleurodesis for non-resolving air leak or recurrence prevention at second occurrence. This study comprehensively reviews the existing literature regarding chemical pleurodesis efficacy. We systematically reviewed the literature to identify relevant randomised controlled trials (RCTs), case-control studies and case series. We described the findings of these studies and tabulated relative recurrence rates or ORs (in studies with control groups). Meta-analysis was not performed due to substantial clinical heterogeneity. Of 560 abstracts identified by our search strategy, 50 were included in our systematic review following screening. Recurrence rates in patients with chest tube drainage only were between 26.1% and 50.1%. Thoracoscopic talc poudrage (four studies (n=249)) provided recurrence rates of between 2.5% and 10.2% with the only RCT suggesting an OR of 0.10 compared with drainage alone. In comparison, talc administration during video-assisted thoracic surgery (VATS) from eight studies (n=2324) recurrence was between 0.0% and 3.2%, but the RCT did not demonstrate a significant difference compared with bleb/bullectomy alone. Minocycline appears similarly effective post-VATS (recurrence rates 0.0-2.9%). Prolonged air leak and recurrence prevention using tetracycline via chest drain (n=726) is likely to provide recurrence rates between 13.0% and 33.3% and autologous blood patch pleurodesis (n=270) between 15.6% and 18.2%. Chemical pleurodesis postsurgical treatment or via thoracoscopy appears to be most effective. Evidence for definitive success rates of each agent is limited by the small number of randomised trials or other comparative studies. 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/.

Can-CSC-GBE: Developing Cost-sensitive Classifier with Gentleboost Ensemble for breast cancer classification using protein amino acids and imbalanced data.

PubMed

Ali, Safdar; Majid, Abdul; Javed, Syed Gibran; Sattar, Mohsin

2016-06-01

Early prediction of breast cancer is important for effective treatment and survival. We developed an effective Cost-Sensitive Classifier with GentleBoost Ensemble (Can-CSC-GBE) for the classification of breast cancer using protein amino acid features. In this work, first, discriminant information of the protein sequences related to breast tissue is extracted. Then, the physicochemical properties hydrophobicity and hydrophilicity of amino acids are employed to generate molecule descriptors in different feature spaces. For comparison, we obtained results by combining Cost-Sensitive learning with conventional ensemble of AdaBoostM1 and Bagging. The proposed Can-CSC-GBE system has effectively reduced the misclassification costs and thereby improved the overall classification performance. Our novel approach has highlighted promising results as compared to the state-of-the-art ensemble approaches. Copyright © 2016 Elsevier Ltd. All rights reserved.

Women with breast cancer report substantially more disease- and treatment-related side or late effects than registered by clinical oncologists: a cross-sectional study of a standard follow-up program in an oncological department.

PubMed

Ellegaard, Mai-Britt Bjørklund; Grau, Cai; Zachariae, Robert; Jensen, Anders Bonde

2017-08-01

Follow-up after breast cancer treatment is standard due to the risk of development of new primary cancers and recurrent disease. The aim of the present study was to evaluate a standard follow-up program in an oncological department by assessing: (1) Symptoms or signs of new primary cancer or recurrent disease, (2) Disease- and treatment-related physical and psychosocial side or late effects, and (3) relevant actions by oncology staff. In a cross-sectional study, 194 women who came for follow-up visit after treatment for primary surgery were included. The clinical oncologists registered symptoms and signs of recurrent disease or new primary cancer. Side or late effects were both assessed by patient and the clinical oncologists. Loco-regional or distant signs of recurrent disease were suspected in eight (5%) patients. Further examinations revealed no disease recurrence. Most patients (93%) reported some degree of side or late effects. Statistically significant more side or late effects were reported by the women (average: 6.9) than registered by the clinical oncologists (average: 2.4), p < 0.001. The three most often patient-reported side or late effects were hot flushes (35%), fatigue (32%), and sleep disturbance (31%). None of the scheduled or additional visits resulted in detection of recurrent disease. Furthermore, the majority of patients reported side or late effects. Statistically significant more women reported side or late effects than registered by the clinical oncologists. This suggests the need for rethinking of the follow-up programs with more emphasis upon side or late effects of the treatment.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury.

PubMed

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-06-15

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury.

Routine exposure of recurrent laryngeal nerve in thyroid surgery can prevent nerve injury★

PubMed Central

Shen, Chenling; Xiang, Mingliang; Wu, Hao; Ma, Yan; Chen, Li; Cheng, Lan

2013-01-01

To determine the value of dissecting the recurrent laryngeal nerve during thyroid surgery with respect to preventing recurrent laryngeal nerve injury, we retrospectively analyzed clinical data from 5 344 patients undergoing thyroidectomy. Among these cases, 548 underwent dissection of the recurrent laryngeal nerve, while 4 796 did not. There were 12 cases of recurrent laryngeal nerve injury following recurrent laryngeal nerve dissection (injury rate of 2.2%) and 512 cases of recurrent laryngeal nerve injury in those not undergoing nerve dissection (injury rate of 10.7%). This difference remained statistically significant between the two groups in terms of type of thyroid disease, type of surgery, and number of surgeries. Among the 548 cases undergoing recurrent laryngeal nerve dissection, 128 developed anatomical variations of the recurrent laryngeal nerve (incidence rate of 23.4%), but no recurrent laryngeal nerve injury was found. In addition, the incidence of recurrent laryngeal nerve injury was significantly lower in patients with the inferior parathyroid gland and middle thyroid veins used as landmarks for locating the recurrent laryngeal nerve compared with those with the entry of the recurrent laryngeal nerve into the larynx as a landmark. These findings indicate that anatomical variations of the recurrent laryngeal nerve are common, and that dissecting the recurrent laryngeal nerve during thyroid surgery is an effective means of preventing nerve injury. PMID:25206452

A two-dose heterologous prime-boost vaccine regimen eliciting sustained immune responses to Ebola Zaire could support a preventive strategy for future outbreaks

PubMed Central

Shukarev, Georgi; Callendret, Benoit; Luhn, Kerstin; Douoguih, Macaya

2017-01-01

ABSTRACT The consequences of the 2013–16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated by over 18 months of active Ebola virus transmission, followed by sporadic resurgences potentially related to sexual transmission by survivors with viral persistence in body fluids following recovery. The need to develop and implement strategies to prevent and mitigate future outbreaks is now beyond dispute. The potential for unpredictable outbreaks of indeterminate duration, and control challenges posed by the possibility of sporadic re-emergence, mean that implementation of an effective vaccination program for outbreak containment necessitates a vaccine providing durable immunity. Heterologous prime-boost vaccine regimens deliver the same or similar antigens through different vaccine types, the first to prime and the second to boost the immune system. Ad26.ZEBOV/MVA-BN-Filo is an investigational Ebola Zaire vaccine regimen that uses this heterologous prime-boost approach. Preliminary Phase 1 data suggest that Ad26.ZEBOV/MVA-BN-Filo confers durable immunity for at least 240 d and is well-tolerated with a good safety profile. This regimen may therefore be suitable for prophylactic use in a regional or targeted population vaccination strategy, and could potentially aid prevention and control of future Ebola outbreaks. PMID:27925844

Using Chou's pseudo amino acid composition based on approximate entropy and an ensemble of AdaBoost classifiers to predict protein subnuclear location.

PubMed

Jiang, Xiaoying; Wei, Rong; Zhao, Yanjun; Zhang, Tongliang

2008-05-01

The knowledge of subnuclear localization in eukaryotic cells is essential for understanding the life function of nucleus. Developing prediction methods and tools for proteins subnuclear localization become important research fields in protein science for special characteristics in cell nuclear. In this study, a novel approach has been proposed to predict protein subnuclear localization. Sample of protein is represented by Pseudo Amino Acid (PseAA) composition based on approximate entropy (ApEn) concept, which reflects the complexity of time series. A novel ensemble classifier is designed incorporating three AdaBoost classifiers. The base classifier algorithms in three AdaBoost are decision stumps, fuzzy K nearest neighbors classifier, and radial basis-support vector machines, respectively. Different PseAA compositions are used as input data of different AdaBoost classifier in ensemble. Genetic algorithm is used to optimize the dimension and weight factor of PseAA composition. Two datasets often used in published works are used to validate the performance of the proposed approach. The obtained results of Jackknife cross-validation test are higher and more balance than them of other methods on same datasets. The promising results indicate that the proposed approach is effective and practical. It might become a useful tool in protein subnuclear localization. The software in Matlab and supplementary materials are available freely by contacting the corresponding author.

A two-dose heterologous prime-boost vaccine regimen eliciting sustained immune responses to Ebola Zaire could support a preventive strategy for future outbreaks.

PubMed

Shukarev, Georgi; Callendret, Benoit; Luhn, Kerstin; Douoguih, Macaya

2017-02-01

The consequences of the 2013-16 Ebola Zaire virus disease epidemic in West Africa were grave. The economies, healthcare systems and communities of Guinea, Sierra Leone and Liberia were devastated by over 18 months of active Ebola virus transmission, followed by sporadic resurgences potentially related to sexual transmission by survivors with viral persistence in body fluids following recovery. The need to develop and implement strategies to prevent and mitigate future outbreaks is now beyond dispute. The potential for unpredictable outbreaks of indeterminate duration, and control challenges posed by the possibility of sporadic re-emergence, mean that implementation of an effective vaccination program for outbreak containment necessitates a vaccine providing durable immunity. Heterologous prime-boost vaccine regimens deliver the same or similar antigens through different vaccine types, the first to prime and the second to boost the immune system. Ad26.ZEBOV/MVA-BN-Filo is an investigational Ebola Zaire vaccine regimen that uses this heterologous prime-boost approach. Preliminary Phase 1 data suggest that Ad26.ZEBOV/MVA-BN-Filo confers durable immunity for at least 240 d and is well-tolerated with a good safety profile. This regimen may therefore be suitable for prophylactic use in a regional or targeted population vaccination strategy, and could potentially aid prevention and control of future Ebola outbreaks.

Characterisation of a live Salmonella vaccine stably expressing the Mycobacterium tuberculosis Ag85B–ESAT6 fusion protein

PubMed Central

Hall, Lindsay J.; Clare, Simon; Pickard, Derek; Clark, Simon O.; Kelly, Dominic L.F.; Ghany, Moataz Abd El; Hale, Christine; Dietrich, Jes; Andersen, Peter; Marsh, Philip D.; Dougan, Gordon

2009-01-01

A recombinant Salmonella enterica serovar Typhimurium (S. Typhimurium) vaccine strain was constructed that stably expressed the Mycobacterium tuberculosis fusion antigen Ag85B–ESAT6 from the chromosome. Live oral vaccination of mice with the Salmonella/Ag85B–ESAT6 strain generated a potent anti-Ag85B–ESAT6 TH1 response with high antibody titres with a IgG2a-bias and significant IFN-γ production lasting over a 120-day period. When mice primed with the Salmonella/Ag85B–ESAT6 vaccine were mucosally boosted with the Ag85B–ESAT6 antigen and adjuvant the IFN-γ responses increased markedly. To determine the protective efficacy of this vaccine strain, guinea pigs were immunised and followed for a 30-week period after aerosol challenge with M. tuberculosis. The heterologous prime-boost strategy of live Salmonella vaccine followed by a systemic boost of antigen and adjuvant reduced the levels of M. tuberculosis bacteria in the lungs and spleen to the same extent as BCG. Additionally, this vaccination regimen was observed to be statistically equivalent in terms of protection to immunisation with BCG. Thus, live oral priming with the recombinant Salmonella/Ag85B–ESAT6 and boosting with Ag85B–ESAT6 plus the adjuvant LTK63 represents an effective mucosal vaccination regimen. PMID:19755145

Predicting Kindergarteners' Achievement and Motivation from Observational Measures of Teaching Effectiveness

ERIC Educational Resources Information Center

Mantzicopoulos, Panayota; Patrick, Helen; Strati, Anna; Watson, Jesse S.

2018-01-01

We investigated the premise that observation measures of instruction are indicators of effective teaching, using the definition of effectiveness articulated by departments of education: teaching that boosts student achievement. We argued that student motivation is equally as important as achievement in the evaluation of teaching effectiveness…

A novel joint-processing adaptive nonlinear equalizer using a modular recurrent neural network for chaotic communication systems.

PubMed

Zhao, Haiquan; Zeng, Xiangping; Zhang, Jiashu; Liu, Yangguang; Wang, Xiaomin; Li, Tianrui

2011-01-01

To eliminate nonlinear channel distortion in chaotic communication systems, a novel joint-processing adaptive nonlinear equalizer based on a pipelined recurrent neural network (JPRNN) is proposed, using a modified real-time recurrent learning (RTRL) algorithm. Furthermore, an adaptive amplitude RTRL algorithm is adopted to overcome the deteriorating effect introduced by the nesting process. Computer simulations illustrate that the proposed equalizer outperforms the pipelined recurrent neural network (PRNN) and recurrent neural network (RNN) equalizers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas

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

Richard, Patrick, E-mail: patrjr@uw.edu; Phillips, Mark; Smith, Wade

Purpose: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. Methods and Materials: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with themore » largest impact on the ICER. Results: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. Conclusions: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.« less

Effects of Antiepileptic Drugs on Spontaneous Recurrent Seizures in a Novel Model of Extended Hippocampal Kindling in Mice.

PubMed

Song, Hongmei; Tufa, Uilki; Chow, Jonathan; Sivanenthiran, Nila; Cheng, Chloe; Lim, Stellar; Wu, Chiping; Feng, Jiachun; Eubanks, James H; Zhang, Liang

2018-01-01

Epilepsy is a common neurological disorder characterized by naturally-occurring spontaneous recurrent seizures and comorbidities. Kindling has long been used to model epileptogenic mechanisms and to assess antiepileptic drugs. In particular, extended kindling can induce spontaneous recurrent seizures without gross brain lesions, as seen clinically. To date, the development of spontaneous recurrent seizures following extended kindling, and the effect of the antiepileptic drugs on these seizures are not well understood. In the present study we aim to develop a mouse model of extended hippocampal kindling for the first time. Once established, we plan to evaluate the effect of three different antiepileptic drugs on the development of the extended-hippocampal-kindled-induced spontaneous recurrent seizures. Male C57 black mice were used for chronic hippocampal stimulations or handling manipulations (twice daily for up to 70 days). Subsequently, animals underwent continuous video/EEG monitoring for seizure detection. Spontaneous recurrent seizures were consistently observed in extended kindled mice but no seizures were detected in the control animals. The aforementioned seizures were generalized events characterized by hippocampal ictal discharges and concurrent motor seizures. Incidence and severity of the seizures was relatively stable while monitored over a few months after termination of the hippocampal stimulation. Three antiepileptic drugs with distinct action mechanisms were tested: phenytoin, lorazepam and levetiracetam. They were applied via intra-peritoneal injections at anticonvulsive doses and their effects on the spontaneous recurrent seizures were analyzed 10-12 h post-injection. Phenytoin (25 mg/kg) and levetiracetam (400 mg/kg) abolished the spontaneous recurrent seizures. Lorazepam (1.5 mg/kg) decreased motor seizure severity but did not reduce the incidence and duration of corresponding hippocampal discharges, implicating its inhibitory effects on seizure spread. No gross brain lesions were observed in a set of extended hippocampal kindled mice submitted to histological evaluation. All these data suggests that our model could be considered as a novel mouse model of extended hippocampal kindling. Some limitations remain to be considered.

[Analysis of related factors of recurrent otitis media with effusion in children].

PubMed

Zhu, Z; Zheng, G X; Li, Q; Shi, Q L; Zhou, H G; Fang, R P

2017-08-05

Objective: To investigate the influencing factors of recurrent episodes of otitis media with effusion in children. Method: A retrospective summary of the clinical data of 210 cases of children with otitis media with effusion, 75 cases of recurrence after treatment, 135 cases were recovered, the recurrence of the related factors and after symptomatic treatment effect is analyzed. Result: Logistic regression analysis results found that adenoid hypertrophy (Ⅲ°, Ⅳ°), tonsil hypertrophy (Ⅳ°) and sinusitis (including choanal polyp), a positive allergens, upper respiratory tract infection, the stomach esophagus regurgitation, cleft palate, younger age has significant effect on recurrence of otitis media with effusion, have significant difference ( P < 0.05). And the influence of duration, gender, passive smoking history and previous medical history of otitis media with effusion has no obvious statistical significance ( P > 0.05). Through the comparison among different age groups, adenoidectomy Ⅲ °, Ⅳ ° hypertrophy tract infections in > 3-6 years old group has significant effect ( P < 0.05), recurrent respiratory tract infections in less than 3 years old group and the group of children aged > 3-6 years OME recurrence has significant effect ( P < 0.05). By tympanocentesis or tympanostomy tube insertion and according to different conditions to take symptomatic treatment, 75 cases (123 ears) were cured 96 ears (78.05%), 19 ears were improved (15.45%), the total effective rate was 93.50%, ineffective in 8 ears (6.50%). Conclusion: Adenoid hypertrophy (Ⅲ°, Ⅳ°), tonsil hypertrophy (Ⅳ°), sinusitis, nasal polyps, allergic diseases and upper respiratory tract infection gastroesophageal reflux, cleft palate and younger age may be adverse factors related to recurrent otitis media with effusion in children, the clinical doctors should pay attention to these symptoms, according to different causes, adopt individualized treatment plan, make children get the best treatment as soon as possible. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Botulinum Toxin for the Management of Sjögren Syndrome-Associated Recurrent Parotitis.

PubMed

O'Neil, Luke M; Palme, Carsten E; Riffat, Faruque; Mahant, Neil

2016-12-01

Recurrent parotitis is a rare manifestation of Sjögren syndrome. The management of recurrent parotitis is challenging because conservative methods may be of limited efficacy and invasive approaches carry the risk of complications. Botulinum toxin has been shown to reduce salivary flow, and consequently, the results of its use in the management of recurrent parotitis have been encouraging. A 65-year-old female patient with recurrent parotitis due to Sjögren syndrome was referred to us, complaining of weekly bouts of inflammation. She required a course of antibiotics monthly to control bacterial superinfections. We treated her with onabotulinumtoxinA injections into both parotid glands at regular intervals. After her second injection cycle, she denied further inflammatory bouts, has not required antibiotics in more than 36 months, and denied any side effects. Botulinum toxin may be a safe and effective method of treating Sjögren syndrome-associated recurrent parotitis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The effect of recurrent severe hypoglycemia on cognitive performance in children with type 1 diabetes: a meta-analysis.

PubMed

Blasetti, Annalisa; Chiuri, Rosa Maria; Tocco, Anna Maria; Di Giulio, Concetta; Mattei, Peter A; Ballone, Enzo; Chiarelli, Francesco; Verrotti, Alberto

2011-11-01

The purpose of this study was to investigate the existence and extent of cognitive impairment in type 1 diabetic children with episodes of recurrent severe hypoglycemia, using meta-analysis to synthesize data across studies. The meta-analysis sample included: 441 children with diabetes and recurrent severe hypoglycemia, 560 children with diabetes and without recurrent severe hypoglycemia. Overall, children with type 1 diabetes and recurrent severe hypoglycemia had slightly lower performance than diabetic children without severe hypoglycemia, only in some cognitive domains: intelligence, memory, learning, and verbal fluency/language. Greater impairment was found in memory and learning. No impairment was found for motor speed. Our results seem to confirm the hypothesis that recurrent severe hypoglycemia has a selective negative effect on the children's cognitive functions. However, these results must be considered with caution taking into account factors such as small sample sizes, the different definitions of severe hypoglycemia, and the variety of neuropsychological tests used.

Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication

MedlinePlus

... Boost from Existing Medication Spotlight on Research Experimental Treatment for Duchenne Muscular Dystrophy Gets Boost from Existing Medication By Colleen Labbe, M.S. | March 1, 2013 A mouse hanging on a wire during a test of muscle strength. Mice with a mutant dystrophin gene, which ...

Alternative Fuels Data Center: Electric Trolley Boosts Business in

Science.gov Websites

Bakersfield, CaliforniaA> Electric Trolley Boosts Business in Bakersfield, California to someone Business in Bakersfield, California Discover how Bakersfield's electric trolley is giving a green boost to downtown businesses. For information about this project, contact San Joaquin Valley Clean Cities. Download

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

Johns, Kenneth

BOOST 2013 was the 5th International Joint Theory/Experiment Workshop on Phenomenology, Reconstruction and Searches for Boosted Objects in High Energy Hadron Collisions. It was locally organized and hosted by the Experimental High Energy Physics Group at the University of Arizona and held at Flagstaff, Arizona on August 12-16, 2013. The workshop provided a forum for theorists and experimentalists to present and discuss the latest findings related to the reconstruction of boosted objects in high energy hadron collisions and their use in searches for new physics. This report gives the outcomes of the BOOST 2013 Workshop.

Use of nonlinear design optimization techniques in the comparison of battery discharger topologies for the space platform

NASA Technical Reports Server (NTRS)

Sable, Dan M.; Cho, Bo H.; Lee, Fred C.

1990-01-01

A detailed comparison of a boost converter, a voltage-fed, autotransformer converter, and a multimodule boost converter, designed specifically for the space platform battery discharger, is performed. Computer-based nonlinear optimization techniques are used to facilitate an objective comparison. The multimodule boost converter is shown to be the optimum topology at all efficiencies. The margin is greatest at 97 percent efficiency. The multimodule, multiphase boost converter combines the advantages of high efficiency, light weight, and ample margin on the component stresses, thus ensuring high reliability.

Design and dSpace interfacing of current fed high gain dc to dc boost converter for low voltage applications

NASA Astrophysics Data System (ADS)

Mukhopadhyay, Debraj; Das, Subhrajit; Arunkumar, G.; Elangovan, D.; Ragunath, G.

2017-11-01

In this paper a current fed interleaved DC - DC boost converter which has an isolated topology and used for high voltage step up is proposed. A basic DC to DC boost converter converts uncontrolled DC voltage into controlled DC voltage of higher magnitude. Whereas this topology has the advantages of lower input current ripple, lesser output voltage, lesser stress on switches, faster transient response, improved reliability and much lesser electromagnetic emission over the conventional DC to DC boost converter. Most important benefit of this interleaved DC to DC boost converter is much higher efficiency. The input current is divided into two paths, substantially ohmic loss (I2R) and inductor ac loss gets reduced and finally the system achieves much higher efficiency. With recent mandates on energy saving interleaved DC to DC boost converter may be used as a very powerful tool to maintain good power density keeping the input current manageable. Higher efficiency also allows higher switching frequency and as a result the topology becomes more compact and cost friendly. The proposed topology boosts 48v DC to 200 V DC. Switching frequency is 100 kHz and PSIM 9.1 Platform has been used for the simulation.

Conditional Random Field (CRF)-Boosting: Constructing a Robust Online Hybrid Boosting Multiple Object Tracker Facilitated by CRF Learning

PubMed Central

Yang, Ehwa; Gwak, Jeonghwan; Jeon, Moongu

2017-01-01

Due to the reasonably acceptable performance of state-of-the-art object detectors, tracking-by-detection is a standard strategy for visual multi-object tracking (MOT). In particular, online MOT is more demanding due to its diverse applications in time-critical situations. A main issue of realizing online MOT is how to associate noisy object detection results on a new frame with previously being tracked objects. In this work, we propose a multi-object tracker method called CRF-boosting which utilizes a hybrid data association method based on online hybrid boosting facilitated by a conditional random field (CRF) for establishing online MOT. For data association, learned CRF is used to generate reliable low-level tracklets and then these are used as the input of the hybrid boosting. To do so, while existing data association methods based on boosting algorithms have the necessity of training data having ground truth information to improve robustness, CRF-boosting ensures sufficient robustness without such information due to the synergetic cascaded learning procedure. Further, a hierarchical feature association framework is adopted to further improve MOT accuracy. From experimental results on public datasets, we could conclude that the benefit of proposed hybrid approach compared to the other competitive MOT systems is noticeable. PMID:28304366

Cost-Effectiveness of Fecal Microbiota Transplantation in the Treatment of Recurrent Clostridium Difficile Infection: A Literature Review.

PubMed

Arbel, Leor T; Hsu, Edmund; McNally, Keegan

2017-08-23

Clostridium difficile ( C. difficile ) is a common cause of antibiotic--associated diarrhea (AAD), being responsible for 15--25% of all AAD cases. The purpose of this literature review is to determine the cost-effectiveness of fecal microbiota transplantation (FMT) and how it compares in this regard to the standard treatments of choice for recurrent C. difficile infection (CDI). The review of the literature along with the evaluation of three comparative cost effective analyses yielded findings consistent with the view that FMT is the most cost-effective option in treating recurrent CDI. There are some (but considerably less) data indicating that FMT may be a cost effective strategy in treating initial CDI, as well. The superior cost-effectiveness of FMT as compared to the preferred standards of treatment for recurrent CDI suggest FMT use should become more integrated in routine clinical practice. Increased utilization of FMTs would allow for better control of this increasingly problematic disease as well as lower costs associated with its management.

Examining Whether Offspring Psychopathology Influences Illness Course in Mothers With Recurrent Depression Using a High-Risk Longitudinal Sample

PubMed Central

2016-01-01

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = −.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls’ symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. PMID:26854510

Examining whether offspring psychopathology influences illness course in mothers with recurrent depression using a high-risk longitudinal sample.

PubMed

Sellers, Ruth; Hammerton, Gemma; Harold, Gordon T; Mahedy, Liam; Potter, Robert; Langley, Kate; Thapar, Ajay; Rice, Frances; Thapar, Anita; Collishaw, Stephan

2016-02-01

Depression is known to be influenced by psychosocial stressors. For mothers with recurrent depressive illness, the presence of psychopathology in their children may have important effects on their own mental health. Although the impact of maternal depression on child mental health is well-established, no study to date, as far as we are aware, has examined the extent to which offspring psychopathology influences the course of depression in mothers with a history of recurrent depressive illness, what types of child psychopathology impact maternal mental health, or whether risks vary by child gender. Aims were to (a) Use a longitudinal design to examine whether adolescent psychopathology (depression, disruptive behavior disorder; DBD) predicts recurrence of a depressive episode and depression symptom course in women with a history of recurrent depression; and (b) To test if observed effects vary by child gender. 299 mothers with recurrent major depressive disorder and their adolescent offspring were assessed on 2 occasions, 29 months apart. Maternal depression and offspring psychopathology were assessed using semistructured interview measures. Cross-generational links across time were assessed using structural equation modeling. Analyses were adjusted for past severity of maternal depression. Offspring depression symptoms but not DBD symptoms at baseline predicted future episode recurrence in mothers. Depression symptoms in daughters (β = .16, p = .039) but not sons (β = -.07, p = .461), predicted an increase in maternal depression symptoms across time. Psychopathology in daughters is associated with long-term depressive symptoms in women (mothers) with a history of recurrent depression. Findings highlight the importance of careful assessment and management of mental health problems in adolescents for more effective management of maternal depression. This study suggests that offspring symptoms of depression may be important for the recurrence of maternal depression episodes. Girls' symptoms of depression may be a particularly important psychosocial stressor for the development of depressive symptoms in mothers with a history of recurrent depression. (c) 2016 APA, all rights reserved).

Impact of power index, hydroureteronephrosis, stone size, and composition on the efficacy of in situ boosted ESWL for primary proximal ureteral calculi.

PubMed

Singh, I; Gupta, N P; Hemal, A K; Dogra, P N; Ansari, M S; Seth, A; Aron, M

2001-07-01

The efficacy, safety, feasibility, and outcome of in situ treatment applied to select proximal ureteral calculi was assessed and analyzed with a view to avoiding auxiliary interventions and providing high clearance rates in the shortest possible time. We studied the impact of several clinically important variables, including power index, degree of hydroureteronephrosis (HDUN), stone size, and composition on the efficacy of sequential in situ boosted extracorporeal shock wave lithotripsy (ESWL) in a select group. The power index requirement for the in situ boosted protocol and the impact of the stone size/composition, degree of HDUN, and clearance rates were also analyzed. An in situ (no instrumentation) boosted protocol was applied to 130 primary unimpacted proximal ureteral calculi with no prior intervention. A typical session with the Siemens Lithostar Plus comprised 3000 shock waves, in installments of 500, deployed at a power setting of 1 to 4 kV with a gradual stepwise escalation. Sequential boosted additional sessions of ESWL were administered on days 2, 7, and 14, tailored to the degree of fragmentation, clearance status, and amount of residual stone bulk. Several parameters (shock waves, kilovolts used, fluoroscopy time, number of sessions, stone size, composition, fragmentation, clearance, and HDUN) were recorded and the results analyzed statistically. The results were excellent in 83.8%, with a mean duration to complete clearance of 11.3 days. In situ ESWL failed in 7.69%, and the auxiliary intervention rate was 10.7%. Pre-ESWL HDUN was present in 78.3%, the mean power index was 184.6/session/case, and the average stone burden was 8.9 mm(2). Calcium oxalate monohydrate was the most common stone (56%). Renal colic was the most common side effect observed. The power index, fragmentation at the first session, and stone size were found to be the most favorable significant variables affecting stone clearance. The degree of HDUN, number of sessions, and stone composition did not significantly impact the clearance rates. In situ boosted ESWL should be the first-line therapeutic modality in select unimpacted primary proximal ureteral stones.

Helical Tomotherapy With Simultaneous Integrated Boost After Laparoscopic Staging in Patients With Cervical Cancer: Analysis of Feasibility and Early Toxicity

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

Marnitz, Simone, E-mail: simone.marnitz@charite.de; Koehler, Christhardt; Burova, Elena

Purpose: To demonstrate the feasibility and safety of the simultaneous integrated boost technique for dose escalation in combination with helical tomotherapy in patients with cervical cancer. Methods and Materials: Forty patients (International Federation of Gynecology and Obstetrics Stage IB1 pN1-IVA) underwent primary chemoradiation with helical tomotherapy. Before therapy, 29/40 patients underwent laparoscopic pelvic and para-aortic lymphadenectomy. In 21%, 31%, and 3% of the patients, pelvic, pelvic and para-aortic, and skip metastases in the para-aortic region could be confirmed. All patients underwent radiation with 1.8-50.4 Gy to the tumor region and the pelvic (para-aortic) lymph node region (planning target volume-A), andmore » a simultaneous boost with 2.12-59.36 Gy to the boost region (planning target volume-B). The boost region was defined using titan clips during laparoscopic staging. In all other patients, standardized borders for the planning target volume-B were defined. High-dose-rate brachytherapy was performed in 39/40 patients. The mean biologic effective dose to the macroscopic tumor ranged from 87.5 to 97.5 Gy. Chemotherapy consisted of weekly cisplatin 40 mg/m{sup 2}. Dose-volume histograms and acute gastrointestinal, genitourinary, and hematologic toxicity were evaluated. Results: The mean treatment time was 45 days. The mean doses to the small bowel, rectum, and bladder were 28.5 {+-} 6.1 Gy, 47.9 {+-} 3.8 Gy, and 48 {+-} 3 Gy, respectively. Hematologic toxicity Grade 3 occurred in 20% of patients, diarrhea Grade 2 in 5%, and diarrhea Grade 3 in 2.5%. There was no Grade 3 genitourinary toxicity. All patients underwent curettage 3 months after chemoradiation, which confirmed complete pathologic response in 38/40 patients. Conclusions: The concept of simultaneous integrated boost for dose escalation in patients with cervical cancer is feasible, with a low rate of acute gastrointestinal and genitourinary toxicity. Whether dose escalation can be translated into improved outcome will be assessed after a longer follow-up time.« less

What to Expect During a Mastectomy Surgery

MedlinePlus

... Managing Side Effects and Supportive Care Managing Pain Quality of Life Survival and Risk of Recurrence Breast Cancer Recurrence ... Pain Managing Side Effects and Supportive Care Support Quality of Life Survivorship Topics Survivorship Topics Medical Care After Treatment ...

Postoperative radiotherapy and tumor recurrence after complete resection of stage II/III thymic tumor: a meta-analysis of cohort studies.

PubMed

Ma, Jietao; Sun, Xin; Huang, Letian; Xiong, Zhicheng; Yuan, Meng; Zhang, Shuling; Han, Cheng-Bo

2016-01-01

Whether postoperative radiotherapy (PORT) is effective for reducing the recurrence risk in patients who received complete resection of the stage II or III thymic tumors has not been determined. A meta-analysis was performed by combining the results of all available controlled trials. PubMed, Cochrane's Library, and the Embase databases were searched for studies which compared the recurrence data for patients with complete resection of the stage II or III thymic tumors assigned to an observing group, or a PORT group. A random effect model was applied to combine the results. Nineteen studies, all designed as retrospective cohort studies were included. These studies included 663 patients of PORT group and 617 patients of observing group. The recurrence rate for the patients in PORT group and observing group were 12.4% and 11.5%, respectively. Results of our study indicated that PORT has no significant influence on recurrent risk in patients with stage II or III thymic tumor after complete resection (odds ratio 1.02, 95% confidence interval 0.55-1.90, P=0.96). When stratified by stages, our meta-analyses did not indicate any significant effects of PORT on recurrent outcomes in either the stage II or the stage III patients. Moreover, subsequent analysis limited to studies only including patients with thymoma or thymic carcinoma also did not support the benefits of PORT on recurrent outcomes. Although derived from retrospective cohort studies, current evidence did not support any benefit of PORT on recurrent risk in patients with complete resection of the stage II or III thymic tumors.

Skin dose differences between intensity-modulated radiation therapy and volumetric-modulated arc therapy and between boost and integrated treatment regimens for treating head and neck and other cancer sites in patients

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

Penoncello, Gregory P.; Ding, George X., E-mail: george.ding@vanderbilt.edu

The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, andmore » 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm{sup 3} for head and neck plans and brain plans and a contiguous volume of 5 cm{sup 3} for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.« less

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

Jabbari, Siavash; Weinberg, Vivian K.; Kaprealian, Tania

Purpose: High dose rate (HDR) brachytherapy has been established as an excellent monotherapy or after external-beam radiotherapy (EBRT) boost treatment for prostate cancer (PCa). Recently, dosimetric studies have demonstrated the potential for achieving similar dosimetry with stereotactic body radiotherapy (SBRT) compared with HDR brachytherapy. Here, we report our technique, PSA nadir, and acute and late toxicity with SBRT as monotherapy and post-EBRT boost for PCa using HDR brachytherapy fractionation. Patients and Methods: To date, 38 patients have been treated with SBRT at University of California-San Francisco with a minimum follow-up of 12 months. Twenty of 38 patients were treated withmore » SBRT monotherapy (9.5 Gy Multiplication-Sign 4 fractions), and 18 were treated with SBRT boost (9.5 Gy Multiplication-Sign 2 fractions) post-EBRT and androgen deprivation therapy. PSA nadir to date for 44 HDR brachytherapy boost patients with disease characteristics similar to the SBRT boost cohort was also analyzed as a descriptive comparison. Results: SBRT was well tolerated. With a median follow-up of 18.3 months (range, 12.6-43.5), 42% and 11% of patients had acute Grade 2 gastrourinary and gastrointestinal toxicity, respectively, with no Grade 3 or higher acute toxicity to date. Two patients experienced late Grade 3 GU toxicity. All patients are without evidence of biochemical or clinical progression to date, and favorably low PSA nadirs have been observed with a current median PSA nadir of 0.35 ng/mL (range, <0.01-2.1) for all patients (0.47 ng/mL, range, 0.2-2.1 for the monotherapy cohort; 0.10 ng/mL, range, 0.01-0.5 for the boost cohort). With a median follow-up of 48.6 months (range, 16.4-87.8), the comparable HDR brachytherapy boost cohort has achieved a median PSA nadir of 0.09 ng/mL (range, 0.0-3.3). Conclusions: Early results with SBRT monotherapy and post-EBRT boost for PCa demonstrate acceptable PSA response and minimal toxicity. PSA nadir with SBRT boost appears comparable to those achieved with HDR brachytherapy boost.« less

Effects of long memory in the order submission process on the properties of recurrence intervals of large price fluctuations

NASA Astrophysics Data System (ADS)

Meng, Hao; Ren, Fei; Gu, Gao-Feng; Xiong, Xiong; Zhang, Yong-Jie; Zhou, Wei-Xing; Zhang, Wei

2012-05-01

Understanding the statistical properties of recurrence intervals (also termed return intervals in econophysics literature) of extreme events is crucial to risk assessment and management of complex systems. The probability distributions and correlations of recurrence intervals for many systems have been extensively investigated. However, the impacts of microscopic rules of a complex system on the macroscopic properties of its recurrence intervals are less studied. In this letter, we adopt an order-driven stock model to address this issue for stock returns. We find that the distributions of the scaled recurrence intervals of simulated returns have a power-law scaling with stretched exponential cutoff and the intervals possess multifractal nature, which are consistent with empirical results. We further investigate the effects of long memory in the directions (or signs) and relative prices of the order flow on the characteristic quantities of these properties. It is found that the long memory in the order directions (Hurst index Hs) has a negligible effect on the interval distributions and the multifractal nature. In contrast, the power-law exponent of the interval distribution increases linearly with respect to the Hurst index Hx of the relative prices, and the singularity width of the multifractal nature fluctuates around a constant value when Hx<0.7 and then increases with Hx. No evident effects of Hs and Hx are found on the long memory of the recurrence intervals. Our results indicate that the nontrivial properties of the recurrence intervals of returns are mainly caused by traders' behaviors of persistently placing new orders around the best bid and ask prices.

Microarray analysis of potential genes in the pathogenesis of recurrent oral ulcer.

PubMed

Han, Jingying; He, Zhiwei; Li, Kun; Hou, Lu

2015-01-01

Recurrent oral ulcer seriously threatens patients' daily life and health. This study investigated potential genes and pathways that participate in the pathogenesis of recurrent oral ulcer by high throughput bioinformatic analysis. RT-PCR and Western blot were applied to further verify screened interleukins effect. Recurrent oral ulcer related genes were collected from websites and papers, and further found out from Human Genome 280 6.0 microarray data. Each pathway of recurrent oral ulcer related genes were got through chip hybridization. RT-PCR was applied to test four recurrent oral ulcer related genes to verify the microarray data. Data transformation, scatter plot, clustering analysis, and expression pattern analysis were used to analyze recurrent oral ulcer related gene expression changes. Recurrent oral ulcer gene microarray was successfully established. Microarray showed that 551 genes involved in recurrent oral ulcer activity and 196 genes were recurrent oral ulcer related genes. Of them, 76 genes up-regulated, 62 genes down-regulated, and 58 genes up-/down-regulated. Total expression level up-regulated 752 times (60%) and down-regulated 485 times (40%). IL-2 plays an important role in the occurrence, development and recurrence of recurrent oral ulcer on the mRNA and protein levels. Gene microarray can be used to analyze potential genes and pathways in recurrent oral ulcer. IL-2 may be involved in the pathogenesis of recurrent oral ulcer.

Percutaneous Soft Tissue Release for Treating Chronic Recurrent Myofascial Pain Associated with Lateral Epicondylitis: 6 Case Studies

PubMed Central

Lin, Ming-Ta; Chou, Li-Wei; Chen, Hsin-Shui; Kao, Mu-Jung

2012-01-01

Objective. The purpose of this pilot study is to investigate the effectiveness of the percutaneous soft tissue release for the treatment of recurrent myofascial pain in the forearm due to recurrent lateral epicondylitis. Methods. Six patients with chronic recurrent pain in the forearm with myofascial trigger points (MTrPs) due to chronic lateral epicondylitis were treated with percutaneous soft tissue release of Lin's technique. Pain intensity (measured with a numerical pain rating scale), pressure pain threshold (measured with a pressure algometer), and grasping strength (measured with a hand dynamometer) were assessed before, immediately after, and 3 months and 12 months after the treatment. Results. For every individual case, the pain intensity was significantly reduced (P < 0.01) and the pressure pain threshold and the grasping strength were significantly increased (P < 0.01) immediately after the treatment. This significant effectiveness lasts for at least one year. Conclusions. It is suggested that percutaneous soft tissue release can be used for treating chronic recurrent lateral epicondylitis to avoid recurrence, if other treatment, such as oral anti-inflammatory medicine, physical therapy, or local steroid injection, cannot control the recurrent pain. PMID:23243428

Future Directions for the Early Detection of Colorectal Cancer Recurrence

PubMed Central

Walker, Avery S.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alex; Nissan, Aviram; Brucher, Bjorn; Champagne, Bradley J.; Steele, Scott R.

2014-01-01

Surgical resection remains a mainstay of treatment and is highly effective for localized colorectal cancer. However, ~30-40% of patients develop recurrence following surgery and 40-50% of recurrences are apparent within the first few years after initial surgical resection. Several variables factor into the ultimate outcome of these patients, including the extent of disease, tumor biology, and patient co-morbidities. Additionally, the time from initial treatment to the development of recurrence is strongly associated with overall survival, particularly in patients who recur within one year of their surgical resection. Current post-resection surveillance strategies involve physical examination, laboratory, endoscopic and imaging studies utilizing various high and low-intensity protocols. Ultimately, the goal is to detect recurrence as early as possible, and ideally in the asymptomatic localized phase, to allow initiation of treatment that may still result in cure. While current strategies have been effective, several efforts are evolving to improve our ability to identify recurrent disease at its earliest phase. Our aim with this article is to briefly review the options available and, more importantly, examine emerging and future options to assist in the early detection of colon and rectal cancer recurrence. PMID:24790655

The complexity of child protection recurrence: The case for a systems approach.

PubMed

Jenkins, Brian Q; Tilbury, Clare; Mazerolle, Paul; Hayes, Hennessey

2017-01-01

Research on child protection recurrence has found consistent child, family, and case characteristics associated with repeated involvement with the child protection system. Despite the considerable body of empirical research, knowledge about why recurrence occurs, and what can be done to reduce it, is limited. This paper reviews the empirical literature and analyses the approaches of prior recurrence research. Four related conceptual challenges are identified: (1) a tendency to conflate child protection recurrence with repeated child maltreatment; (2) uncertainty about how best to operationalize and measure child protection recurrence in research; (3) inconsistency between prevailing explanations for the most frequently observed patterns of recurrence; and (4) difficulty in developing coherent strategies to address child protection recurrence based on research. Addressing these challenges requires a greater consideration of the effects of decision-making in the child protection system on recurrence. This paper proposes a methodology based in systems theory and drawing on existing administrative data to examine the characteristics of the child protection system that may also produce recurrence. Copyright © 2016 Elsevier Ltd. All rights reserved.

Integration of a Radiosensitivity Molecular Signature Into the Assessment of Local Recurrence Risk in Breast Cancer

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

Torres-Roca, Javier F., E-mail: javier.torresroca@moffitt.org; Department of Chemical Biology and Molecular Medicine, Moffitt Cancer Center, Tampa, Florida; Fulp, William J.

Purpose: Recently, we developed radiosensitivity (RSI), a clinically validated molecular signature that estimates tumor radiosensitivity. In the present study, we tested whether integrating RSI with the molecular subtype refines the classification of local recurrence (LR) risk in breast cancer. Methods and Materials: RSI and molecular subtype were evaluated in 343 patients treated with breast-conserving therapy that included whole-breast radiation therapy with or without a tumor bed boost (dose range 45-72 Gy). The follow-up period for patients without recurrence was 10 years. The clinical endpoint was LR-free survival. Results: Although RSI did not uniformly predict for LR across the entire cohort, combining RSImore » and the molecular subtype identified a subpopulation with an increased risk of LR: triple negative (TN) and radioresistant (reference TN-radioresistant, hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.15-0.92, P=.02). TN patients who were RSI-sensitive/intermediate had LR rates similar to those of luminal (LUM) patients (HR 0.86, 95% CI 0.47-1.57, P=.63). On multivariate analysis, combined RSI and molecular subtype (P=.004) and age (P=.001) were the most significant predictors of LR. In contrast, integrating RSI into the LUM subtype did not identify additional risk groups. We hypothesized that radiation dose escalation was affecting radioresistance in the LUM subtype and serving as a confounder. An increased radiation dose decreased LR only in the luminal-resistant (LUM-R) subset (HR 0.23, 95% CI 0.05-0.98, P=.03). On multivariate analysis, the radiation dose was an independent variable only in the LUMA/B-RR subset (HR 0.025, 95% CI 0.001-0.946, P=.046), along with age (P=.008), T stage (P=.004), and chemotherapy (P=.008). Conclusions: The combined molecular subtype–RSI identified a novel molecular subpopulation (TN and radioresistant) with an increased risk of LR after breast-conserving therapy. We propose that the combination of RSI and molecular subtype could be useful in guiding radiation therapy–based decisions in breast cancer.« less

Selective Genomic Copy Number Imbalances and Probability of Recurrence in Early-Stage Breast Cancer

PubMed Central

Thompson, Patricia A.; Brewster, Abenaa M.; Kim-Anh, Do; Baladandayuthapani, Veerabhadran; Broom, Bradley M.; Edgerton, Mary E.; Hahn, Karin M.; Murray, James L.; Sahin, Aysegul; Tsavachidis, Spyros; Wang, Yuker; Zhang, Li; Hortobagyi, Gabriel N.; Mills, Gordon B.; Bondy, Melissa L.

2011-01-01

A number of studies of copy number imbalances (CNIs) in breast tumors support associations between individual CNIs and patient outcomes. However, no pattern or signature of CNIs has emerged for clinical use. We determined copy number (CN) gains and losses using high-density molecular inversion probe (MIP) arrays for 971 stage I/II breast tumors and applied a boosting strategy to fit hazards models for CN and recurrence, treating chromosomal segments in a dose-specific fashion (-1 [loss], 0 [no change] and +1 [gain]). The concordance index (C-Index) was used to compare prognostic accuracy between a training (n = 728) and test (n = 243) set and across models. Twelve novel prognostic CNIs were identified: losses at 1p12, 12q13.13, 13q12.3, 22q11, and Xp21, and gains at 2p11.1, 3q13.12, 10p11.21, 10q23.1, 11p15, 14q13.2-q13.3, and 17q21.33. In addition, seven CNIs previously implicated as prognostic markers were selected: losses at 8p22 and 16p11.2 and gains at 10p13, 11q13.5, 12p13, 20q13, and Xq28. For all breast cancers combined, the final full model including 19 CNIs, clinical covariates, and tumor marker-approximated subtypes (estrogen receptor [ER], progesterone receptor, ERBB2 amplification, and Ki67) significantly outperformed a model containing only clinical covariates and tumor subtypes (C-Index full model, train[test]  =  0.72[0.71] ± 0.02 vs. C-Index clinical + subtype model, train[test]  =  0.62[0.62] ± 0.02; p<10−6). In addition, the full model containing 19 CNIs significantly improved prognostication separately for ER–, HER2+, luminal B, and triple negative tumors over clinical variables alone. In summary, we show that a set of 19 CNIs discriminates risk of recurrence among early-stage breast tumors, independent of ER status. Further, our data suggest the presence of specific CNIs that promote and, in some cases, limit tumor spread. PMID:21858162

Effects of a traditional Chinese medicine, Longdanxiegan formula granule, on Toll-like receptor pathway in female guinea pigs with recurrent genital herpes.

PubMed

Kuang, Lin; Deng, Yihui; Liu, Xiaodan; Zou, Zhixiang; Mi, Lan

2016-04-01

The aim of the present study was to investigate the effects of Longdanxiegan formula granule (LDXGFG), a Chinese traditional medicine on Toll-like receptor (TLR) pathway in recurrent genital herpes. An experimental recurrent genital herpes model was constructed using herpes guinea pig model. The effect of LDXGFG on expression levels of TLR pathway genes were detected using real-time polymerase chain reaction. Furthermore, the dendritic cells and Langerhans cells were isolated and the TLR pathway genes of these cells were assayed after LDXGFG treatment. The result suggested two different expression patterns of TLR pathway genes in genital herpes and recurrent genital herpes, including upregulated genes and downregulated genes. TLR1, TLR4, TLR6, TLR7, TLR8, TLR9, and TLR10 showed a significant decrease while, TLR2, TLR3, and TLR5 increased in genital herpes and recurrent genital herpes guinea pigs. Meanwhile, the downregulated genes in genital herpes and recurrent genital herpes were stimulated by LDXGFG. By contrast, the upregulated genes decreased significantly after LDXGFG treatment. In both dendritic cells and Langerhans cells, the TLR pathway genes exhibited same pattern: the LDXGFG corrected the abnormal expression of TLR pathway genes. The present results suggest that LDXGFG is an alternative, inexpensive, and lasting-effect medicine for herpes simplex virus 2 infection. Copyright © 2016. Published by Elsevier B.V.

Estimating the effect of a rare time-dependent treatment on the recurrent event rate.

PubMed

Smith, Abigail R; Zhu, Danting; Goodrich, Nathan P; Merion, Robert M; Schaubel, Douglas E

2018-05-30

In many observational studies, the objective is to estimate the effect of treatment or state-change on the recurrent event rate. If treatment is assigned after the start of follow-up, traditional methods (eg, adjustment for baseline-only covariates or fully conditional adjustment for time-dependent covariates) may give biased results. We propose a two-stage modeling approach using the method of sequential stratification to accurately estimate the effect of a time-dependent treatment on the recurrent event rate. At the first stage, we estimate the pretreatment recurrent event trajectory using a proportional rates model censored at the time of treatment. Prognostic scores are estimated from the linear predictor of this model and used to match treated patients to as yet untreated controls based on prognostic score at the time of treatment for the index patient. The final model is stratified on matched sets and compares the posttreatment recurrent event rate to the recurrent event rate of the matched controls. We demonstrate through simulation that bias due to dependent censoring is negligible, provided the treatment frequency is low, and we investigate a threshold at which correction for dependent censoring is needed. The method is applied to liver transplant (LT), where we estimate the effect of development of post-LT End Stage Renal Disease (ESRD) on rate of days hospitalized. Copyright © 2018 John Wiley & Sons, Ltd.

Alternative Fuels Data Center: New York Coalition Helps Local Alternative

Science.gov Websites

Fuel Station Boost Revenue New York Coalition Helps Local Alternative Fuel Station Boost Revenue to someone by E-mail Share Alternative Fuels Data Center: New York Coalition Helps Local Alternative Fuel Station Boost Revenue on Facebook Tweet about Alternative Fuels Data Center: New York

Series Connected Buck-Boost Regulator

NASA Technical Reports Server (NTRS)

Birchenough, Arthur G. (Inventor)

2006-01-01

A Series Connected Buck-Boost Regulator (SCBBR) that switches only a fraction of the input power, resulting in relatively high efficiencies. The SCBBR has multiple operating modes including a buck, a boost, and a current limiting mode, so that an output voltage of the SCBBR ranges from below the source voltage to above the source voltage.

Using injectable hydrogel markers to assess resimulation for boost target volume definition in a patient undergoing whole-breast radiotherapy

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

Patel, Henal; Goyal, Sharad; Kim, Leonard, E-mail: kimlh@rutgers.edu

Several publications have recommended that patients undergoing whole-breast radiotherapy be resimulated for boost planning. The rationale for this is that the seroma may be smaller when compared with the initial simulation. However, the decision remains whether to use the earlier or later images to define an appropriate boost target volume. A patient undergoing whole-breast radiotherapy had new, injectable, temporary hydrogel fiducial markers placed 1 to 3 cm from the seroma at the time of initial simulation. The patient was resimulated 4.5 weeks later for conformal photon boost planning. Computed tomography (CT) scans acquired at the beginning and the end ofmore » whole-breast radiotherapy showed that shrinkage of the lumpectomy cavity was not matched by a corresponding reduction in the surrounding tissue volume, as demarcated by hydrogel markers. This observation called into question the usual interpretation of cavity shrinkage for boost target definition. For this patient, it was decided to define the boost target volume on the initial planning CT instead of the new CT.« less

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

Joshi, Jay Prakash

The objectives of this project are to calibrate the Advanced Experimental Fuel Counter (AEFC), benchmark MCNP simulations using experimental results, investigate the effects of change in fuel assembly geometry, and finally to show the boost in doubles count rates with 252Cf active soruces due to the time correlated induced fission (TCIF) effect.

Recurrent Violent Injury: Magnitude, Risk Factors, and Opportunities for Intervention from a Statewide Analysis

PubMed Central

Kaufman, Elinore; Rising, Kristin; Wiebe, Douglas J.; Ebler, David J.; Crandall, Marie L.; Delgado, M. Kit

2016-01-01

Introduction Though preventing recurrent violent injury is an important component of a public health approach to interpersonal violence, and a common focus of violence intervention programs, the true incidence of recurrent violent injury is unknown. Prior studies have reported recurrence rates from 0.8% to 44%, and risk factors for recurrence are not well established. Methods We used a statewide, all-payer database to perform a retrospective cohort study of emergency department visits for injury due to interpersonal violence in Florida, following patients injured in 2010 for recurrence through 2012. We assessed risk factors for recurrence with multivariable logistic regression and estimated time to recurrence with the Kaplan-Meier method. We tabulated hospital charges and costs for index and recurrent visits. Results Of 53,908 patients presenting for violent injury in 2010, 11.1% had a recurrent violent injury during the study period. Trauma centers treated 31.8%, including 55.9% of severe injuries. Among recurrers, 58.9% went to a different hospital for their second injury. Low income, homelessness, Medicaid or uninsurance, and Black race were associated with increased odds of recurrence. Patients with visits for mental and behavioral health and unintentional injury also had increased odds of recurrence. Index injuries accounted for $105 million in costs, and recurrent injuries accounted for another $25.3 million. Conclusions Recurrent violent injury is a common and costly phenomenon, and effective violence prevention programs are needed. Prevention must include the non-trauma centers where many patients seek care. PMID:27460511

Multipole expansions and Fock symmetry of the hydrogen atom

NASA Astrophysics Data System (ADS)

Meremianin, A. V.; Rost, J.-M.

2006-10-01

The main difficulty in utilizing the O(4) symmetry of the hydrogen atom in practical calculations is the dependence of the Fock stereographic projection on energy. This is due to the fact that the wavefunctions of the states with different energies are proportional to the hyperspherical harmonics (HSH) corresponding to different points on the hypersphere. Thus, the calculation of the matrix elements reduces to the problem of re-expanding HSH in terms of HSH depending on different points on the hypersphere. We solve this problem by applying the technique of multipole expansions for four-dimensional HSH. As a result, we obtain the multipole expansions whose coefficients are the matrix elements of the boost operator taken between hydrogen wavefunctions (i.e., hydrogen form factors). The explicit expressions for those coefficients are derived. It is shown that the hydrogen matrix elements can be presented as derivatives of an elementary function. Such an operator representation is convenient for the derivation of recurrence relations connecting matrix elements between states corresponding to different values of the quantum numbers n and l.

Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination.

PubMed

Hwang, Charles W; Steigleman, Walter A; Saucedo-Sanchez, Erika; Tuli, Sonal S

2013-04-01

In this study, the case of a patient who presented with reactivation of herpes zoster (HZ) keratitis and worsening of neurotrophic keratopathy, keratouveitis, and keratoconjunctivitis sicca after vaccination with live attenuated HZ vaccine (Zostavax) is described. This is a retrospective case review. A 63-year-old man, with a history of HZ keratouveitis and neurotrophic keratopathy that had been quiescent for 3.5 years off medication, presented with keratouveitis 2 weeks after Zostavax administration. Oral acyclovir and topical prednisolone acetate and cyclopentolate were started, with subsequent improvement in inflammation and visual acuity. However, the patient was unable to be tapered completely off the steroids. HZ keratouveitis is the result of cell-mediated immunity (CMI) directed toward viral antigens within the eye. The live attenuated HZ vaccine, Zostavax, boosts the recipient's CMI to prevent reactivation of HZ. However, patients with a history of HZ keratitis may have persistent viral antigens in their corneas and can develop recurrence of keratouveitis because of the vaccine-induced increase in CMI. Vaccination should be undertaken with caution in patients with a history of HZ ophthalmicus.

Can we predict Acute Medical readmissions using the BOOST tool? A retrospective case note review.

PubMed

Lee, Geraldine A; Freedman, Daniel; Beddoes, Penelope; Lyness, Emily; Nixon, Imogen; Srivastava, Vivek

2016-01-01

Readmissions within 30-days of hospital discharge are a problem. The aim was to determine if the Better Outcomes for Older Adults through Safe Transitions (BOOST) risk assessment tool was applicable within the UK. Patients over 65 readmitted were identified retrospectively via a casenote review. BOOST assessment was applied with 1 point for each risk factor. 324 patients were readmitted (mean age 77 years) with a median of 7 days between discharge and readmission. The median BOOST score was 3 (IQR 2-4) with polypharmacy evident in 88% and prior hospitalisation in 70%. The tool correctly predicted 90% of readmissions using two or more risk factors and 99.1% if one risk factor was included. The BOOST assessment tool appears appropriate in predicting readmissions however further analysis is required to determine its precision.

Longitudinal hydrodynamics from event-by-event Landau initial conditions

DOE PAGES

Sen, Abhisek; Gerhard, Jochen; Torrieri, Giorgio; ...

2015-02-02

Here we investigate three-dimensional ideal hydrodynamic evolution, with Landau initial conditions, incorporating event-by-event variation with many events and transverse density inhomogeneities. We show that the transition to boost-invariant flow occurs too late for realistic setups, with corrections of θ (20%-30%) expected at freeze-out for most scenarios. Moreover, the deviation from boost invariance is correlated with both transverse flow and elliptic flow, with the more highly transversely flowing regions also showing the most violation of boost invariance. Therefore, if longitudinal flow is not fully developed at the early stages of heavy ion collisions, hydrodynamics where boost invariance holds at midrapidity ismore » inadequate to extract transport coefficients of the quark-gluon plasma. We conclude by arguing that developing experimental probes of boost invariance is necessary, and suggest some promising directions in this regard.« less

The Effects of Discipline Responses in Delaying Toddler Misbehavior Recurrences.

ERIC Educational Resources Information Center

Larzelere, Robert E.; Schneider, William N.; Larson, David B.; Pike, Patricia L.

1996-01-01

Compares the effectiveness of maternal punishment (time out, spanking), reasoning, and a combination of the two. Results based on mothers' (N=40) structured diaries of toddler fighting and disobedience indicate that mild punishment, combined with reasoning, is an effective discipline response to toddler misbehavior in terms of recurrence of…

Dramatically Polarized Opinion on the Role of Brachytherapy Boost in Management of High-risk Prostate Cancer: A Survey of North American Genitourinary Expert Radiation Oncologists.

PubMed

McClelland, Shearwood; Sandler, Kiri A; Degnin, Catherine; Chen, Yiyi; Mitin, Timur

2018-06-01

Three randomized clinical trials have established brachytherapy (BT) boost in combination with external beam radiation therapy (EBRT) and androgen deprivation therapy (ADT) as superior to definitive EBRT and ADT alone in terms of biochemical control (but not overall survival) at the expense of increased toxicity in men with high-risk (HR) prostate cancer (PCa). The current view regarding these 2 treatment algorithms among North American genitourinary (GU) experts is not known. A survey was distributed to 88 practicing North American GU physicians serving on decision-making committees of cooperative group research organizations. Questions pertained to opinions regarding BT as monotherapy for low-risk PCa and BT boost for HR PCa. Responders were asked to self-identify as BT experts versus non-experts. Treatment recommendations were correlated with practice patterns using the Fisher exact test. Forty-two radiation oncologists completed the survey, of whom 23 (55%) recommend EBRT and ADT alone and 19 (45%) recommend addition of BT boost. Twenty-five participants (60%) identified themselves as BT experts. Nearly 90% of those recommending BT boost were BT experts versus approximately 10% of non-BT experts (P < .001). Responders who recommended BT monotherapy as first-choice treatment for low-risk PCa were more likely to recommend BT boost for HR PCa (P < .0001). There is a dramatic polarization in opinions regarding incorporation of BT boost into EBRT + ADT therapy for patients with HR PCa among North American GU radiation oncology experts, who serve on decision-making committees and influence the national treatment guidelines and future clinical trials. Those who identify themselves as BT experts are significantly more likely to recommend BT boost. These findings are likely to influence the national guidelines and implementation of BT boost in current and future North American PCa clinical studies. Copyright © 2018 Elsevier Inc. All rights reserved.

A boosting skin vaccination with dissolving microneedle patch encapsulating M2e vaccine broadens the protective efficacy of conventional influenza vaccines.

PubMed

Zhu, Wandi; Pewin, Winston; Wang, Chao; Luo, Yuan; Gonzalez, Gilbert X; Mohan, Teena; Prausnitz, Mark R; Wang, Bao-Zhong

2017-09-10

The biodegradable microneedle patch (MNP) is a novel technology for vaccine delivery that could improve the immunogenicity of vaccines. To broaden the protective efficiency of conventional influenza vaccines, a new 4M2e-tFliC fusion protein construct containing M2e sequences from different subtypes was generated. Purified fusion protein was encapsulate into MNPs with a biocompatible polymer for use as a boosting vaccine. The results demonstrated that mice receiving a conventional inactivated vaccine followed by a skin-applied dissolving 4M2e-tFliC MNP boost could better maintain the humoral antibody response than that by the conventional vaccine-prime alone. Compared with an intramuscular injection boost, mice receiving the MNP boost showed significantly enhanced cellular immune responses, hemagglutination-inhibition (HAI) titers, and neutralization titers. Increased frequency of antigen-specific plasma cells and long-lived bone marrow plasma cells was detected in the MNP boosted group as well, indicating that skin vaccination with 4M2e-tFliC facilitated a long-term antibody-mediated immunity. The 4M2e-tFliC MNP-boosted group also possessed enhanced protection against high lethal dose challenges against homologous A/PR/8/34 and A/Aichi/2/68 viruses and protection for a majority of immunized mice against a heterologous A/California/07/2009 H1N1 virus. High levels of M2e specific immune responses were observed in the 4M2e-tFliC MNP-boosted group as well. These results demonstrate that a skin-applied 4M2e-tFliC MNP boosting immunization to seasonal vaccine recipients may be a rapid approach for increasing the protective efficacy of seasonal vaccines in response to a significant drift seen in circulating viruses. The results also provide a new perspective for future exploration of universal influenza vaccines. Copyright © 2017 Elsevier B.V. All rights reserved.

Optical Coherence Tomography and Stent Boost Imaging Guided Bioresorbable Vascular Scaffold Overlapping for Coronary Chronic Total Occlusion Lesion

PubMed Central

Li, Hu; Choi, Cheol Ung; Oh, Dong Joo

2017-01-01

We report herein the optical coherence tomography (OCT) and stent boost imaging guided bioresorbable vascular scaffold (BVS) implantation for right coronary artery (RCA) chronic total occlusion (CTO) lesion. The gold standard for evaluating BVS expansion after percutaneous coronary intervention is OCT. However, stent boost imaging is a new technique that improves fluoroscopy-based assessments of stent overlapping, and the present case shows clinical usefulness of OCT and stent boost imaging guided ‘overlapping’ BVS implantation via antegrade approach for a typical RCA CTO lesion. PMID:28792157

Cost-effectiveness of Bezlotoxumab Compared With Placebo for the Prevention of Recurrent Clostridium difficile Infection.

PubMed

Prabhu, Vimalanand S; Dubberke, Erik R; Dorr, Mary Beth; Elbasha, Elamin; Cossrow, Nicole; Jiang, Yiling; Marcella, Stephen

2018-01-18

Clostridium difficile infection (CDI) is the most commonly recognized cause of recurrent diarrhea. Bezlotoxumab, administered concurrently with antibiotics directed against C. difficile (standard of care [SoC]), has been shown to reduce the recurrence of CDI, compared with SoC alone. This study aimed to assess the cost-effectiveness of bezlotoxumab administered concurrently with SoC, compared with SoC alone, in subgroups of patients at risk of recurrence of CDI. A computer-based Markov health state transition model was designed to track the natural history of patients infected with CDI. A cohort of patients entered the model with either a mild/moderate or severe CDI episode, and were treated with SoC antibiotics together with either bezlotoxumab or placebo. The cohort was followed over a lifetime horizon, and costs and utilities for the various health states were used to estimate incremental cost-effectiveness ratios (ICERs). Both deterministic and probabilistic sensitivity analyses were used to test the robustness of the results. The cost-effectiveness model showed that, compared with placebo, bezlotoxumab was associated with 0.12 quality-adjusted life-years (QALYs) gained and was cost-effective in preventing CDI recurrences in the entire trial population, with an ICER of $19824/QALY gained. Compared with placebo, bezlotoxumab was also cost-effective in the subgroups of patients aged ≥65 years (ICER of $15298/QALY), immunocompromised patients (ICER of $12597/QALY), and patients with severe CDI (ICER of $21430/QALY). Model-based results demonstrated that bezlotoxumab was cost-effective in the prevention of recurrent CDI compared with placebo, among patients receiving SoC antibiotics for treatment of CDI. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Parental involvement and association with adolescents' fruit and vegetable intake at follow-up: Process evaluation results from the multi-component school-based Boost intervention.

PubMed

Jørgensen, Sanne Ellegård; Jørgensen, Thea Suldrup; Aarestrup, Anne Kristine; Due, Pernille; Krølner, Rikke

2016-10-26

Based on the assumption of parental influence on adolescent behavior, multicomponent school-based dietary interventions often include a parental component. The effect of this intervention component is seldom reported and the evidence is inconsistent. We conducted a systematic process evaluation of the parental component and examined whether the leveal of parental involvement in a large multi-component intervention: the Boost study was associated with adolescents' fruit and vegetable (FV) intake at follow-up. The Boost study was targeting FV intake among 1,175 Danish 7 th graders (≈13- year-olds) in the school year 2010/11. The study included a school component: free FV in class and curricular activities; a local community component: fact sheets for sports- and youth clubs; and a parental component: presentation of Boost at a parent-school meeting, 6 newsletters to parents, 3 guided student-parent curricular activities, and a student-parent Boost event. Students whose parent replied to the follow-up survey (n = 347). Questionnaire data from students, parents and teachers at 20 intervention schools. Process evaluation measures: dose delivered, dose received, appreciation and level of parental involvement. Parental involvement was trichotomized into: low/no (0-2 points), medium (3 points) and high (4-6 points). The association between level of parental involvement and self-reported FV intake (24-h recall), was analyzed using multilevel regression analyses. The Boost study was presented at a parent-school meeting at all intervention schools. The dose delivered was low to moderate for the three other parental elements. Most parents appreciated the intervention and talked with their child about Boost (83.5 %). High, medium and low parental involvement was found among 30.5 %, 29.6 % and 39.4 % of the students respectively. Parental involvement was highest among women. More men agreed that the parental newsletters provided new information. Students with a medium and high level of parental involvement ate 47.5 and 95.2 g more FV per day compared to students with low level/no parental involvement (p = 0.02). Students with a high level of parental involvement ate significantly more FV at follow-up compared to students with a low level/no parental involvement. Parental involvement in interventions may improve adolescents' FV intake if challenges of implementation can be overcome. ISRCTN11666034 . Registered 06/01/2012. Retrospectively registered.

Prevention of recurrent urinary tract infections in women.

PubMed

2013-06-01

Around 40-50% of women experience at least one urinary tract infection (UTI) during their lifetime and 20-30% of these have a recurrence within 3-4 months of the initial infection.¹ Recurrent UTI (usually defined as three episodes in the last 12 months or two episodes in the last 6 months) can have a considerable impact on a woman's quality of life. Each episode of acute UTI in young women is typically associated with about 6 days of symptoms, 2.4 days of restricted activities and 0.4 days of bed rest.¹ Antibacterial prophylaxis is effective in preventing recurrent episodes, but at the expense of unwanted effects and a risk of promoting bacterial resistance. Here we assess the efficacy of different antibacterial regimens and non-antibacterial alternatives (cranberry, probiotics, oestrogens, immunostimulation, hyaluronic acid and chondroitin, acupuncture and herbs) in the prevention of recurrent uncomplicated UTIs in women.

Retrieval Practice Makes Procedure from Remembering: An Automatization Account of the Testing Effect

ERIC Educational Resources Information Center

Racsmány, Mihály; Szollosi, Ágnes; Bencze, Dorottya

2018-01-01

The "testing effect" refers to the striking phenomenon that repeated retrieval practice is one of the most effective learning strategies, and certainly more advantageous for long-term learning, than additional restudying of the same information. How retrieval can boost the retention of memories is still without unanimous explanation. In…

Boosted classification trees result in minor to modest improvement in the accuracy in classifying cardiovascular outcomes compared to conventional classification trees

PubMed Central

Austin, Peter C; Lee, Douglas S

2011-01-01

Purpose: Classification trees are increasingly being used to classifying patients according to the presence or absence of a disease or health outcome. A limitation of classification trees is their limited predictive accuracy. In the data-mining and machine learning literature, boosting has been developed to improve classification. Boosting with classification trees iteratively grows classification trees in a sequence of reweighted datasets. In a given iteration, subjects that were misclassified in the previous iteration are weighted more highly than subjects that were correctly classified. Classifications from each of the classification trees in the sequence are combined through a weighted majority vote to produce a final classification. The authors' objective was to examine whether boosting improved the accuracy of classification trees for predicting outcomes in cardiovascular patients. Methods: We examined the utility of boosting classification trees for classifying 30-day mortality outcomes in patients hospitalized with either acute myocardial infarction or congestive heart failure. Results: Improvements in the misclassification rate using boosted classification trees were at best minor compared to when conventional classification trees were used. Minor to modest improvements to sensitivity were observed, with only a negligible reduction in specificity. For predicting cardiovascular mortality, boosted classification trees had high specificity, but low sensitivity. Conclusions: Gains in predictive accuracy for predicting cardiovascular outcomes were less impressive than gains in performance observed in the data mining literature. PMID:22254181

Effect of nebulized budesonide on decreasing the recurrence of allergic fungal rhinosinusitis.

PubMed

Dai, Qi; Duan, Chen; Liu, Quan; Yu, Hongmeng

The aim of this study was to evaluate the clinical efficacy and the effects on decreasing the recurrence of AFRS (allergic fungal rhinosinusitis) of a budesonide inhalation suspension delivered via transnasal nebulization to patients following endoscopic sinus surgery. Thirty-five patients were recruited into this study. Final diagnoses were reached using Bent and Kuhn's criteria. The eligible patients were randomly divided into two groups: the budesonide transnasal nebulization group (group A) and the topical nasal steroids group (group B). Nasal symptoms, Lund-Mackay scores, and Kupferberg grades were evaluated before surgery, after surgery and during the follow-up to assess the effects of these two approaches. A total of 30 patients with AFRS who were eligible were included in the study. Four of the 15 patients in group B (26.67%) developed recurrent disease, whereas no patients in group A developed recurrent disease. This difference was statistically significant (p=0.032). Nebulized budesonide is an effective and safe treatment for patients with AFRS following endoscopic sinus surgery, as evidenced by the reduced recurrence rate observed in the budesonide transnasal nebulization group relative to the topical nasal steroids group. Copyright © 2017 Elsevier Inc. All rights reserved.

[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

[Treatment of recurrent laryngeal papilloma by submucosal resection and the effect on prognosis].

PubMed

Hu, Huiying; Zhang, Qingxiang; Sun, Guoyan; Yu, Zhenkun

2015-11-01

To investigate the efficacy of submucosal resection by CO2 laser in the treatment of recurrent laryngeal papilloma and the effect on prognosis. A total of 11 patients diagnosed as recurrent laryngeal papilloma were included in this review. Papilloma was marked before operation and checked under fibro-laryngoscope. Papilloma was resected completely including the submucosal tissure with CO2 laser or microequipment. In widespread papilloma, false membrane in raw surface were cleared 7-10 days after operation. Surgical specimens (including membrane) were detected by routine pathology, HPV typing and immunohistochemical pathologic examination. The patients were checked once a month in the first 3 months after operation, and then once for every 3 months. Once the hoarseness and other symptoms aggravated or the disease was recurrent, the patients were treated immediately. HPV viral DNA was found in 10/11 cases, with HPV11 (7/11 cases) and HPV6 (3/11 cases). Cases with regards to follow-up, from 6 months to 1 year, 3 cases were followed up 1 year after operation, without recurrence. Five patients including 2 children were followed up 6 to 12 months after operation, without recurrence. Two children underwent 2 or 3 operations, were followed-up more than 6 months withouting recurrence. Papilloma submucosal resection could decrease postoperative recurrence and is worth to be further investigated.

Thrombectomy for ischemic stroke: meta-analyses of recurrent strokes, vasospasms, and subarachnoid hemorrhages.

PubMed

Emprechtinger, Robert; Piso, Brigitte; Ringleb, Peter A

2017-03-01

Mechanical thrombectomy with stent retrievers is an effective treatment for patients with ischemic stroke. Results of recent meta-analyses report that the treatment is safe. However, the endpoints recurrent stroke, vasospasms, and subarachnoid hemorrhage have not been evaluated sufficiently. Hence, we extracted data on these outcomes from the five recent thrombectomy trials (MR CLEAN, ESCAPE, REVASCAT, SWIFT PRIME, and EXTEND IA published in 2015). Subsequently, we conducted meta-analyses for each outcome. We report the results of the fixed, as well as the random effects model. Three studies reported data on recurrent strokes. While the results did not reach statistical significance in the random effects model (despite a three times elevated risk), the fixed effects model revealed a significantly higher rate of recurrent strokes after thrombectomy. Four studies reported data on subarachnoid hemorrhage. The higher pooled rates in the intervention groups were statistically significant in both, the fixed and the random effects model. One study reported on vasospasms. We recorded 14 events in the intervention group and none in the control group. The efficacy of mechanical thrombectomy is not questioned, yet our results indicate an increased risk for recurrent strokes, subarachnoid hemorrhage, and vasospasms post-treatment. Therefore, we strongly recommend a thoroughly surveillance, concerning these adverse events in future clinical trials and routine registries.

Manuka honey as an effective treatment for chronic pilonidal sinus wounds.

PubMed

Thomas, M; Hamdan, M; Hailes, S; Walker, M

2011-11-01

A retrospective study to investigate the effectiveness of topical manuka honey in the treatment of chronic or recurrent pilonidal sinus disease (PSD), assessing the ability of this simple dressing technique to achieve complete wound healing, the time taken to achieve healing and the recurrence rate. All patients who received manuka honey dressing therapy following surgical intervention for chronic or recurrent PSD were identified over a 4-year period. In a retrospective review of case notes, data were collected on patient sex, age, nature of surgical procedures performed, time to achieve complete wound healing, and recurrences after completion of honey therapy. Seventeen patients were eligible for inclusion in the study. Mean time to commence honey therapy post-surgery was 93 days (5-517 days; median 33 days); 15 patients achieved complete wound healing, in a mean time of 65 days (14-264 days; median 49 days). Honey was discontinued in one patient due to an adverse event, and two patients experienced recurrence several months after completing honey therapy. Manuka honey dressing therapy provides an effective topical treatment for chronic/recurrent PSD. Further research is necessary to determine the optimum dressing protocol. The authors have no conflicts of interest to declare. There were no external sources of funding for this study.

The definition of biochemical failure in patients treated with definitive radiotherapy.

PubMed

Kattan, M W; Fearn, P A; Leibel, S; Potters, L

2000-12-01

The American Society for Therapeutic Radiology and Oncology (ASTRO) published a definition for biochemical failure following treatment of prostate cancer. Others have noted difficulties with interpreting this definition and recommended modifications to accommodate special recurrence patterns. We have compared various modifications to the original ASTRO definition on our series of 1213 patients treated with transperineal permanent prostate brachytherapy. The ASTRO modifications we considered adjusted for (1) early censoring of nonrecurrent patients with rising prostate-specific antigen levels (PSA), (2) cumulative rather than consecutive rises (without a decrease) as evidence of recurrence, (3) both of the above, and (4) waiting 2 years before data analysis. The Kaplan-Meier method was used to compute the effects on recurrence rate for patients treated with and without neoadjuvant hormones. With the original ASTRO definition, freedom from recurrence in our series of men who did not receive neoadjuvant hormones was 83% at 4 years. All of the modifications considered had statistically insignificant effects on freedom from recurrence rates, varying from 80% to 83% at 4 years. Patients treated with neoadjuvant hormones also showed very little sensitivity to the recurrence definition employed. Early censoring of equivocal patients and counting cumulative rather than consecutive rises in PSA (without a decrease) had little empiric effect on the ASTRO recurrence rates. However, we favor the addition of both these modifications to the ASTRO definition on conceptual grounds for evaluating patients following any modality (radiation or surgery), whereby a trend over multiple PSA values is used to judge failure.

Propensity Score Estimation With Boosted Regression for Evaluating Causal Effects in Observational Studies

ERIC Educational Resources Information Center

McCaffrey, Daniel F.; Ridgeway, Greg; Morral, Andrew R.

2004-01-01

Causal effect modeling with naturalistic rather than experimental data is challenging. In observational studies participants in different treatment conditions may also differ on pretreatment characteristics that influence outcomes. Propensity score methods can theoretically eliminate these confounds for all observed covariates, but accurate…

A hybrid model based on neural networks for biomedical relation extraction.

PubMed

Zhang, Yijia; Lin, Hongfei; Yang, Zhihao; Wang, Jian; Zhang, Shaowu; Sun, Yuanyuan; Yang, Liang

2018-05-01

Biomedical relation extraction can automatically extract high-quality biomedical relations from biomedical texts, which is a vital step for the mining of biomedical knowledge hidden in the literature. Recurrent neural networks (RNNs) and convolutional neural networks (CNNs) are two major neural network models for biomedical relation extraction. Neural network-based methods for biomedical relation extraction typically focus on the sentence sequence and employ RNNs or CNNs to learn the latent features from sentence sequences separately. However, RNNs and CNNs have their own advantages for biomedical relation extraction. Combining RNNs and CNNs may improve biomedical relation extraction. In this paper, we present a hybrid model for the extraction of biomedical relations that combines RNNs and CNNs. First, the shortest dependency path (SDP) is generated based on the dependency graph of the candidate sentence. To make full use of the SDP, we divide the SDP into a dependency word sequence and a relation sequence. Then, RNNs and CNNs are employed to automatically learn the features from the sentence sequence and the dependency sequences, respectively. Finally, the output features of the RNNs and CNNs are combined to detect and extract biomedical relations. We evaluate our hybrid model using five public (protein-protein interaction) PPI corpora and a (drug-drug interaction) DDI corpus. The experimental results suggest that the advantages of RNNs and CNNs in biomedical relation extraction are complementary. Combining RNNs and CNNs can effectively boost biomedical relation extraction performance. Copyright © 2018 Elsevier Inc. All rights reserved.

Moderating effects of perceived growth on the association between fear of cancer recurrence and health-related quality of life among adolescent and young adult cancer survivors.

PubMed

Cho, Dalnim; Park, Crystal L

2017-01-01

We examined whether (1) fear of cancer recurrence was related to lower health-related quality of life and (2) perceived growth moderated the link between fear of recurrence and health-related quality of life. About 292 adolescent and young adult cancer survivors (diagnosed with cancer at ages 15-34) completed a cross-sectional survey. Fear of recurrence was related to poorer physical and mental health-related quality of life. The negative association between fear of recurrence and mental health-related quality of life was moderated by perceived growth. Fostering perceived growth may mitigate the adverse associations of fear of recurrence and health-related quality of life.

Quality of Life in Women Undergoing Breast Irradiation in a Randomized, Controlled Clinical Trial Evaluating Different Tumor Bed Boost Fractionations

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

Finkel, Morgan A.; Cooper, Benjamin T.; Li, Xiaochun

Purpose: To identify differences in breast cancer patient-reported quality of life (QOL) between 2 radiation tumor bed boost dose regimens. Methods and Materials: Four hundred patients with stage 0, I, or II breast cancer who underwent segmental mastectomy with sentinel node biopsy and/or axillary node dissection were treated with either a daily or weekly boost. Patients were treated prone to 40.5 Gy/15 fractions to the whole breast, 5 days per week. Patients were randomized to a concomitant daily boost to the tumor bed of 0.5 Gy, or a weekly boost of 2 Gy on Friday. Patients completed 6 validated QOL survey instruments at baseline,more » last week of treatment (3 weeks), 45-60 days from the completion of radiation treatment, and at 2-year follow-up. Results: There were no statistically significance differences in responses to the 6 QOL instruments between the daily and weekly radiation boost regimens, even after adjustment for important covariates. However, several changes in responses over time occurred in both arms, including worsening functional status, cosmetic status, and breast-specific pain at the end of treatment as compared with before and 45 to 60 days after the conclusion of treatment. Conclusions: Whole-breast, prone intensity modulated radiation has similar outcomes in QOL measures whether given with a daily or weekly boost. This trial has generated the foundation for a current study of weekly versus daily radiation boost in women with early breast cancer in which 3-dimensional conformal radiation is allowed as a prospective stratification factor.« less

Ototoxicity After Intensity-Modulated Radiation Therapy and Cisplatin-Based Chemotherapy in Children With Medulloblastoma

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

Paulino, Arnold C., E-mail: apaulino@tmhs.or; Department of Pediatrics, Division of Hematology/Oncology, Texas Children's Hospital, Houston, TX; Baylor College of Medicine, Houston, TX

2010-12-01

Purpose: To report the incidence of Pediatric Oncology Group (POG) Grade 3 or 4 ototoxicity in a cohort of patients treated with craniospinal irradiation (CSI) followed by posterior fossa (PF) and/or tumor bed (TB) boost using intensity-modulated radiation therapy (IMRT). Methods and Materials: From 1998 to 2006, 44 patients with medulloblastoma were treated with CSI followed by IMRT to the PF and/or TB and cisplatin-based chemotherapy. Patients with standard-risk disease were treated with 18 to 23.4 Gy CSI followed by either a (1) PF boost to 36 Gy and TB boost to 54 to 55.8 Gy or (2) TB boostmore » to 55.8 Gy. Patients with high-risk disease received 36 to 39.6 Gy CSI followed by a (1) PF boost to 54 to 55.8 Gy, (2) PF boost to 45 Gy and TB boost to 55.8 Gy, or (3) TB boost to 55.8 Gy. Median audiogram follow-up was 41 months (range, 11-92.4 months). Results: POG Grade Ototoxicity 0, 1, 2, 3. and 4 was found in 29, 32, 11, 13. and 3 ears. respectively, with POG Grade 3 or 4 accounting for 18.2% of cases. There was a statistically significant difference in mean radiation dose (D{sub mean}) cochlea according to degree of ototoxicity, with D{sub mean} cochlea increasing with severity of hearing loss (p = 0.027). Conclusions: Severe ototoxicity was seen in 18.2% of ears in children treated with IMRT boost and cisplatin-based chemotherapy. Increasing dose to the cochlea was associated with increasing severity of hearing loss.« less

Treatment plan comparison between Tri-Co-60 magnetic-resonance image-guided radiation therapy and volumetric modulated arc therapy for prostate cancer

PubMed Central

Park, Jong Min; Park, So-Yeon; Choi, Chang Heon; Chun, Minsoo; Kim, Jin Ho; Kim, Jung-In

2017-01-01

To investigate the plan quality of tri-Co-60 intensity-modulated radiation therapy (IMRT) with magnetic-resonance image-guided radiation therapy compared with volumetric-modulated arc therapy (VMAT) for prostate cancer. Twenty patients with intermediate-risk prostate cancer, who received radical VMAT were selected. Additional tri-Co-60 IMRT plans were generated for each patient. Both primary and boost plans were generated with tri-Co-60 IMRT and VMAT techniques. The prescription doses of the primary and boost plans were 50.4 Gy and 30.6 Gy, respectively. The primary and boost planning target volumes (PTVs) of the tri-Co-60 IMRT were generated with 3 mm margins from the primary clinical target volume (CTV, prostate + seminal vesicle) and a boost CTV (prostate), respectively. VMAT had a primary planning target volume (primary CTV + 1 cm or 2 cm margins) and a boost PTV (boost CTV + 0.7 cm margins), respectively. For both tri-Co-60 IMRT and VMAT, all the primary and boost plans were generated that 95% of the target volumes would be covered by the 100% of the prescription doses. Sum plans were generated by summation of primary and boost plans. In sum plans, the average values of V70 Gy of the bladder of tri-Co-60 IMRT vs. VMAT were 4.0% ± 3.1% vs. 10.9% ± 6.7%, (p < 0.001). Average values of V70 Gy of the rectum of tri-Co-60 IMRT vs. VMAT were 5.2% ± 1.8% vs. 19.1% ± 4.0% (p < 0.001). The doses of tri-Co-60 IMRT delivered to the bladder and rectum were smaller than those of VMAT while maintaining identical target coverage in both plans. PMID:29207634

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

Chen, Xiaojian; Qiao, Qiao; Department of Radiotherapy, First Hospital of China Medical University, Shenyang

Purpose: To evaluate the efficiency of standard image-guided radiation therapy (IGRT) to account for lumpectomy cavity (LC) variation during whole-breast irradiation (WBI) and propose an adaptive strategy to improve dosimetry if IGRT fails to address the interfraction LC variations. Methods and Materials: Daily diagnostic-quality CT data acquired during IGRT in the boost stage using an in-room CT for 19 breast cancer patients treated with sequential boost after WBI in the prone position were retrospectively analyzed. Contours of the LC, treated breast, ipsilateral lung, and heart were generated by populating contours from planning CTs to boost fraction CTs using an auto-segmentationmore » tool with manual editing. Three plans were generated on each fraction CT: (1) a repositioning plan by applying the original boost plan with the shift determined by IGRT; (2) an adaptive plan by modifying the original plan according to a fraction CT; and (3) a reoptimization plan by a full-scale optimization. Results: Significant variations were observed in LC. The change in LC volume at the first boost fraction ranged from a 70% decrease to a 50% increase of that on the planning CT. The adaptive and reoptimization plans were comparable. Compared with the repositioning plans, the adaptive plans led to an improvement in target coverage for an increased LC case (1 of 19, 7.5% increase in planning target volume evaluation volume V{sub 95%}), and breast tissue sparing for an LC decrease larger than 35% (3 of 19, 7.5% decrease in breast evaluation volume V{sub 50%}; P=.008). Conclusion: Significant changes in LC shape and volume at the time of boost that deviate from the original plan for WBI with sequential boost can be addressed by adaptive replanning at the first boost fraction.« less

The quest for conditional independence in prospectivity modeling: weights-of-evidence, boost weights-of-evidence, and logistic regression

NASA Astrophysics Data System (ADS)

Schaeben, Helmut; Semmler, Georg

2016-09-01

The objective of prospectivity modeling is prediction of the conditional probability of the presence T = 1 or absence T = 0 of a target T given favorable or prohibitive predictors B, or construction of a two classes 0,1 classification of T. A special case of logistic regression called weights-of-evidence (WofE) is geologists' favorite method of prospectivity modeling due to its apparent simplicity. However, the numerical simplicity is deceiving as it is implied by the severe mathematical modeling assumption of joint conditional independence of all predictors given the target. General weights of evidence are explicitly introduced which are as simple to estimate as conventional weights, i.e., by counting, but do not require conditional independence. Complementary to the regression view is the classification view on prospectivity modeling. Boosting is the construction of a strong classifier from a set of weak classifiers. From the regression point of view it is closely related to logistic regression. Boost weights-of-evidence (BoostWofE) was introduced into prospectivity modeling to counterbalance violations of the assumption of conditional independence even though relaxation of modeling assumptions with respect to weak classifiers was not the (initial) purpose of boosting. In the original publication of BoostWofE a fabricated dataset was used to "validate" this approach. Using the same fabricated dataset it is shown that BoostWofE cannot generally compensate lacking conditional independence whatever the consecutively processing order of predictors. Thus the alleged features of BoostWofE are disproved by way of counterexamples, while theoretical findings are confirmed that logistic regression including interaction terms can exactly compensate violations of joint conditional independence if the predictors are indicators.

Induction of strong anti-HIV cellular immunity by a combination of Clostridium perfringens expressing HIV gag and virus like particles.

PubMed

Pegu, Poonam; Helmus, Ruth; Gupta, Phalguni; Tarwater, Patrick; Caruso, Lori; Shen, Chengli; Ross, Ted; Chen, Yue

2011-12-01

The lower gastrointestinal tract is a major mucosal site of HIV entry and initial infection. Thus, the induction of strong cellular immune responses at this mucosal site will be an important feature of an effective HIV vaccine. We have used a novel prime-boost vaccination approach to induce immune responses at mucosal sites. Orally delivered recombinant Clostridium perfringens expressing HIV-1 gag (Cp-Gag) was evaluated for induction of HIV-1 Gag specific T cell responses in a prime-boost model with intranasal inoculation of HIV-1 virus like particles (VLP). HIV-1 specific cellular immune responses in both the effector (Lamina propria) and inductive sites (Peyer's patches) of the gastrointestinal (GI) tract were significantly higher in mice immunized using Cp-Gag and VLPs in a prime-boost approach compared to mice immunized with either Cp-Gag or VLPs alone. Such cellular immune response was found to be mediated by both CD8(+) and CD4(+) T cells. Such a strong mucosal immune response could be very useful in developing a mucosal vaccine against HIV-1.