Overview of Vaccine Adjuvants: Introduction, History, and Current Status.

Science.gov (United States)

Shah, Ruchi R; Hassett, Kimberly J; Brito, Luis A

2017-01-01

Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

Renal-sparing strategies in cardiac transplantation

DEFF Research Database (Denmark)

Gustafsson, Finn; Ross, Heather J

2009-01-01

PURPOSE OF REVIEW: Renal dysfunction due to calcineurin inhibitor (CNI) toxicity is a major clinical problem in cardiac transplantation. The aim of the article is to review the efficacy and safety of various renal sparing strategies in cardiac transplantation. RECENT FINDINGS: Small studies have...... reduction in terms of preserving renal function. Patients with longstanding CNI treatment or proteinuria are less likely to respond favourably to a switch from a CNI-based regimen to a proliferation signal inhibitor-based regimen. SUMMARY: Each cardiac transplant recipient with renal dysfunction must...... documented that late initiation of CNI is safe in patients treated with induction therapy at the time of transplantation. Use of mycophenolate is superior when compared with azathioprine to allow for CNI reduction. More substantial reduction in CNI levels is safe and effective with the introduction...

A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

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Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

2016-02-03

New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modified Sleeve Technique in Aortic Valve-Sparing Operation for Marfan Syndrome.

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Wu, Yung-Szu; Hsieh, Shih-Rong; Wang, Chung-Chi; Tsai, Chung-Lin

2018-03-22

We devised a simple modification of the Florida Sleeve procedure to perform aortic valve-sparing surgery. This technique is simple, quick, effective, and safe. We used this technique in operations performed on two young patients with Marfan syndrome. The initial and short-term results were satisfactory.

Pancreas-sparing duodenectomy for an obstructive adenocarcinoma of the duodenum.

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Lam, D; Croome, Kp; Hernandez-Alejandro, R

2012-08-01

A duodenal adenocarcinoma arising from the junction of the second and third portion of the duodenum, which was resected by pancreas-sparing duodenectomy, is reported. The completely obstructing tumour was circumferential and measured 6.5cm x 3.5cm x 1.0 cm. There was no evidence of pancreas invasion, nor any lymph node metastasis. Pancreas-sparing duodenectomy was performed, with dissection of the pancreaticoduodenal lymph nodes. The proximal duodenum was transected just distal to the ampula of Vater and jejunum was transected just distal to the ligament of Treitz. A hand-sewn side-to-side anastomosis for the duodenojejunostomy was performed. There were no postoperative complications. Pathology reported a duodenal adenocarcinoma resected with negative margins. Pancreaticoduodenectomy is the treatment of choice for a duodenal adenocarcinoma, however, pancreas-sparing duodenectomy may be a safe alternative for duodenal tumours not involving the 2(nd) portion, especially in elderly patients with multiple medical comorbidities. © JSCR.

Hypothesis driven development of new adjuvants: short peptides as immunomodulators.

Science.gov (United States)

Dong, Jessica C; Kobinger, Gary P

2013-04-01

To date, vaccinations have been one of the key strategies in the prevention and protection against infectious pathogens. Traditional vaccines have well-known limitations such as safety and efficacy issues, which consequently deems it inappropriate for particular populations and may not be an effective strategy against all pathogens. This evidence highlights the need to develop more efficacious vaccination regiments. Higher levels of protection can be achieved by the addition of immunostimulating adjuvants. Many adjuvants elicit strong, undefined inflammation, which produces increased immunogenicity but may also lead to undesirable effects. Hypothesis driven development of adjuvants is needed to achieve a more specific and directed immune response required for optimal and safe vaccine-induced immune protection. An example of such hypothesis driven development includes the use of short immunomodulating peptides as adjuvants. These peptides have the ability to influence the immune response and can be extrapolated for adjuvant use, but requires further investigation.

Inactivated Eyedrop Influenza Vaccine Adjuvanted with Poly(I:C Is Safe and Effective for Inducing Protective Systemic and Mucosal Immunity.

Directory of Open Access Journals (Sweden)

Eun-Do Kim

Full Text Available The eye route has been evaluated as an efficient vaccine delivery routes. However, in order to induce sufficient antibody production with inactivated vaccine, testing of the safety and efficacy of the use of inactivated antigen plus adjuvant is needed. Here, we assessed various types of adjuvants in eyedrop as an anti-influenza serum and mucosal Ab production-enhancer in BALB/c mice. Among the adjuvants, poly (I:C showed as much enhancement in antigen-specific serum IgG and mucosal IgA antibody production as cholera toxin (CT after vaccinations with trivalent hemagglutinin-subunits or split H1N1 vaccine antigen in mice. Vaccination with split H1N1 eyedrop vaccine antigen plus poly(I:C showed a similar or slightly lower efficacy in inducing antibody production than intranasal vaccination; the eyedrop vaccine-induced immunity was enough to protect mice from lethal homologous influenza A/California/04/09 (H1N1 virus challenge. Additionally, ocular inoculation with poly(I:C plus vaccine antigen generated no signs of inflammation within 24 hours: no increases in the mRNA expression levels of inflammatory cytokines nor in the infiltration of mononuclear cells to administration sites. In contrast, CT administration induced increased expression of IL-6 cytokine mRNA and mononuclear cell infiltration in the conjunctiva within 24 hours of vaccination. Moreover, inoculated visualizing materials by eyedrop did not contaminate the surface of the olfactory bulb in mice; meanwhile, intranasally administered materials defiled the surface of the brain. On the basis of these findings, we propose that the use of eyedrop inactivated influenza vaccine plus poly(I:C is a safe and effective mucosal vaccine strategy for inducing protective anti-influenza immunity.

Enhancement of the Immunogenicity and Protective Efficacy of a Mucosal Influenza Subunit Vaccine by the Saponin Adjuvant GPI-0100

NARCIS (Netherlands)

Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

2012-01-01

Identification of safe and effective adjuvants remains an urgent need for the development of inactivated influenza vaccines for mucosal administration. Here, we used a murine challenge model to evaluate the adjuvant activity of GPI-0100, a saponin-derived adjuvant, on influenza subunit vaccine

21 CFR 178.3010 - Adjuvant substances used in the manufacture of foamed plastics.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvant substances used in the manufacture of... substances used in the manufacture of foamed plastics. The following substances may be safely used as adjuvants in the manufacture of foamed plastics intended for use in contact with food, subject to any...

Management of ventilator associated pneumonia with a new antibiotic adjuvant entity (ceftriaxone+sulbactam+disodium edetate) - A novel approach to spare carbapenems.

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Sathe, Prachee; Maddani, Sagar; Kulkarni, Shilpa; Munshi, Nita

2017-10-01

Ventilator associated pneumonia (VAP) is one of the most serious nosocomial infections in Intensive Care Unit (ICU). The aim of this study was to evaluate a new approach to spare the carbapenems for the management of patients diagnosed with VAP due to Acinetobacter baumannii (A. baumannii). This retrospective study was conducted on VAP patients presenting for treatment at tertiary care centre between May 2014 and March 2016. The case sheets of patients who have been treated for VAP with meropenem, antibiotic adjuvant entity (AAE) and colistin were analysed. Out of 113 patients analysed, 24 (21.3%) patients were having VAP due to MDR A. baumannii. Microbial sensitivity has shown that 87.5% of patients were sensitive to AAE and colistin whereas all of them were resistant to meropenem, imipenem and gentamycin. The mean treatment durations were 12.4±2.1, 13.2±2.4 and 14.3±2.1days for AAE, meropenem+colistin and AAE+colistin treatment groups. In AAE susceptible patients, the mean treatment duration and cost could be reduced by 23-24% and 43-53% if AAE is used empirically. In AAE-resistant patients, the mean treatment duration and cost could be reduced by 21% and 26% if AAE+colistin regime is used empirically instead of meropenem followed by AAE+colistin. Clinical assessment with microbial eradication and pharmaco-economic evaluation clearly shows benefits in using AAE empirically in the management of A. baumannii infected VAP cases. Copyright © 2017 Elsevier Inc. All rights reserved.

Primary Buttonhole Mastopexy and Nipple-Sparing Mastectomy: A Preliminary Report.

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Salibian, Arthur H; Harness, Jay K; Mowlds, Donald S

2016-10-01

Patients undergoing nipple-sparing mastectomy and immediate-implant based reconstruction occasionally require a mastopexy based on their breast size and degree of ptosis. Previous reports have shown the feasibility of mastopexy-nipple-sparing mastectomy in selected patients to raise the nipple up to 5 cm. Major mastopexy with nipple transposition more than 6 cm in conjunction with nipple-sparing mastectomy for therapeutic indications has not been described. The authors review their experience with primary buttonhole mastopexy performed in conjunction with nipple-sparing mastectomy. Between 2008 and 2014, 16 patients (32 breasts) underwent bilateral primary mastopexy and nipple-sparing mastectomy with immediate staged implant-based reconstruction. The Passot buttonhole technique was used for the mastopexy in all patients, raising the nipple from 7 to 12 cm. Tumor-related data, risk factors, breast size, degree of ptosis, expander size, fill volume, selection criteria, and complications are discussed. The average follow-up period was 33 months (range, 14 to 80 months). There were no tumor recurrences, and all patients completed their reconstruction. Two patients required removal of the expander and delayed reconstruction because of infection and implant exposure due to nipple-areola loss. The reasons for nipple-areola loss and technical modifications to enhance skin viability by retaining a thin layer of subareolar breast tissue for removal during the second-stage implant exchange are discussed. Primary mastopexy using the buttonhole technique performed together with nipple-sparing mastectomy is a safe procedure with predictable results in patients with very large or ptotic breasts requiring lifts greater than 6 cm. The success of the combined procedure depends on preserving a thin layer of subareolar breast tissue and removing it at the time of implant exchange.

REPLACEMENT SPARE PART INVENTORY MONITORING USING ADAPTIVE NEURO FUZZY INFERENCE SYSTEM

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Hartono Hartono

2016-01-01

Full Text Available Abstract   The amount of inventory is determined on the basis of the demand. So that users can know the demand forecasts need to be done on the request. This study uses the data to implement a replacement parts on the electronic module production equipment in the telecommunications transmission systems, switching, access and power, ie by replacing the electronic module in the system is trouble  or damaged parts of a good electronic module spare parts inventory, while the faulty electronic modules shipped to the Repair Center for repaired again, so that the results of these improvements can replenish spare part  inventory. Parameters speed on improvement process of electronic module broken (repaired, in the form of an average repair time at the repair centers, in order to get back into the electronic module that is ready for used as spare parts in compliance with the safe supply inventory  warehouse.  This research using the method  of  Adaptive Neuro Fuzzy Inference System (ANFIS in developing a decision support system for inventory control of spare parts available in Warehouse Inventory taking into account several parameters supporters, namely demand, improvement and fulfillment of spare parts and repair time. This study uses a recycling input parameter repair faulty electronic module of the customer to immediately replace the module in inventory warehouse,  do improvements in the Repair Center. So the acceleration restoration factor is very influential as the input spare parts inventory supply in the warehouse and using the Adaptive Neuro-Fuzzy Inference System (ANFIS method.   Keywords: ANFIS, inventory control, replacement

Aortic valve-sparing surgery in Marfan syndrome.

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Nachum, Eyal; Shinfeld, Amichay; Kogan, Alexander; Preisman, Sergey; Levin, Shany; Raanani, Ehud

2013-08-01

Patients with Marfan syndrome are referred for cardiac surgery due to root aneurysm with or without aortic valve regurgitation. Because these patients are young and frequently present with normal-appearing aortic cusps, valve sparing is often recommended. However, due to the genetic nature of the disease, the durability of such surgery remains uncertain. Between February 2004 and June 2012, 100 patients in our department suffering from aortic aneurysm with aortic valve regurgitation underwent elective aortic valve-sparing surgery. Of them, 30 had Marfan syndrome, were significantly younger (30 +/- 13 vs. 53 +/- 16 years), and had a higher percentage of root aneurysm, compared with ascending aorta aneurysm in their non-Marfan counterparts. We evaluated the safety, durability, clinical and echocardiographic mid-term results of these patients. While no early deaths were reported in either group, there were a few major early complications in both groups. At follow-up (reaching 8 years with a mean of 34 +/- 26 months) there were no late deaths, and few major late complications in the Marfan group. Altogether, 96% and 78% of the patients were in New York Heart Association functional class I-II in the Marfan and non-Marfan groups respectively. None of the Marfan patients needed reoperation on the aortic valve. Freedom from recurrent aortic valve regurgitation > 3+ was 94% in the Marfan patients. Aortic valve-sparing surgery in Marfan symdrome patients is safe and yields good mid-term clinical outcomes.

Carbohydrate fatty acid monosulphate esters are safe and effective adjuvants for humoral responses

NARCIS (Netherlands)

Hilgers, L.A.T.; Platenburg, P.; Bajramovic, J.; Veth, J.; Sauerwein, R.; Roeffen, W.; Pohl, M.; Amerongen, G. van; Stittelaar, K.J.; Bosch, J.F. van den

2017-01-01

Carbohydrate fatty acid sulphate esters (CFASEs) formulated in a squalane-in-water emulsion are effective adjuvants for humoral responses to a wide range of antigens in various animal species but rise in body temperature and local reactions albeit mild or minimal hampers application in humans. In

Incorporating single-side sparing in models for predicting parotid dose sparing in head and neck IMRT

International Nuclear Information System (INIS)

Yuan, Lulin; Wu, Q. Jackie; Yin, Fang-Fang; Yoo, David; Jiang, Yuliang; Ge, Yaorong

2014-01-01

Purpose: Sparing of single-side parotid gland is a common practice in head-and-neck (HN) intensity modulated radiation therapy (IMRT) planning. It is a special case of dose sparing tradeoff between different organs-at-risk. The authors describe an improved mathematical model for predicting achievable dose sparing in parotid glands in HN IMRT planning that incorporates single-side sparing considerations based on patient anatomy and learning from prior plan data. Methods: Among 68 HN cases analyzed retrospectively, 35 cases had physician prescribed single-side parotid sparing preferences. The single-side sparing model was trained with cases which had single-side sparing preferences, while the standard model was trained with the remainder of cases. A receiver operating characteristics (ROC) analysis was performed to determine the best criterion that separates the two case groups using the physician's single-side sparing prescription as ground truth. The final predictive model (combined model) takes into account the single-side sparing by switching between the standard and single-side sparing models according to the single-side sparing criterion. The models were tested with 20 additional cases. The significance of the improvement of prediction accuracy by the combined model over the standard model was evaluated using the Wilcoxon rank-sum test. Results: Using the ROC analysis, the best single-side sparing criterion is (1) the predicted median dose of one parotid is higher than 24 Gy; and (2) that of the other is higher than 7 Gy. This criterion gives a true positive rate of 0.82 and a false positive rate of 0.19, respectively. For the bilateral sparing cases, the combined and the standard models performed equally well, with the median of the prediction errors for parotid median dose being 0.34 Gy by both models (p = 0.81). For the single-side sparing cases, the standard model overestimates the median dose by 7.8 Gy on average, while the predictions by the combined

Adjuvants for vaccines to drugs of abuse and addiction.

Science.gov (United States)

Alving, Carl R; Matyas, Gary R; Torres, Oscar; Jalah, Rashmi; Beck, Zoltan

2014-09-22

Immunotherapeutic vaccines to drugs of abuse, including nicotine, cocaine, heroin, oxycodone, methamphetamine, and others are being developed. The theoretical basis of such vaccines is to induce antibodies that sequester the drug in the blood in the form of antibody-bound drug that cannot cross the blood brain barrier, thereby preventing psychoactive effects. Because the drugs are haptens a successful vaccine relies on development of appropriate hapten-protein carrier conjugates. However, because induction of high and prolonged levels of antibodies is required for an effective vaccine, and because injection of T-independent haptenic drugs of abuse does not induce memory recall responses, the role of adjuvants during immunization plays a critical role. As reviewed herein, preclinical studies often use strong adjuvants such as complete and incomplete Freund's adjuvant and others that cannot be, or in the case of many newer adjuvants, have never been, employed in humans. Balanced against this, the only adjuvant that has been included in candidate vaccines in human clinical trials to nicotine and cocaine has been aluminum hydroxide gel. While aluminum salts have been widely utilized worldwide in numerous licensed vaccines, the experience with human responses to aluminum salt-adjuvanted vaccines to haptenic drugs of abuse has suggested that the immune responses are too weak to allow development of a successful vaccine. What is needed is an adjuvant or combination of adjuvants that are safe, potent, widely available, easily manufactured, and cost-effective. Based on our review of the field we recommend the following adjuvant combinations either for research or for product development for human use: aluminum salt with adsorbed monophosphoryl lipid A (MPLA); liposomes containing MPLA [L(MPLA)]; L(MPLA) adsorbed to aluminum salt; oil-in-water emulsion; or oil-in-water emulsion containing MPLA. Copyright © 2014. Published by Elsevier Ltd.

Effect of Nerve-Sparing Radical Prostatectomy on Urinary Continence in Patients With Preoperative Erectile Dysfunction

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Yong Hyun Park

2016-03-01

Full Text Available Purpose: We aimed to assess whether nerve-sparing radical prostatectomy (nsRP is associated with improved recovery of urinary continence compared to non–nerve-sparing radical prostatectomy (nnsRP in patients with localized prostate cancer and preoperative erectile dysfunction. Methods: A total of 360 patients with organ-confined prostate cancer and an International Index of Erectile Function score of less than 17 were treated with nsRP or nnsRP in Seoul St. Mary’s Hospital. Patients who received neoadjuvant or adjuvant androgen deprivation therapy or had a history of prostate-related surgery were excluded. Recovery of urinary continence was assessed at 0, 1, 3, 6, and 12 months. Postoperative recovery of continence was defined as zero pad usage. The association between nerve-sparing status and urinary continence was assessed by using univariate and multivariate Cox regression analyses after controlling for known predictive factors. Results: Urinary continence recovered in 279 patients (77.5% within the mean follow-up period of 22.5 months (range, 6–123 months. Recovery of urinary continence was reported in 74.6% and 86.4% of patients after nnsRP and nsRP, respectively, at 12 months (P=0.022. All groups had comparable perioperative criteria and had no significant preoperative morbidities. Age, American Society of Anesthesiologists score, and nerve-sparing status were significantly associated with recovery of urinary continence on univariate analysis. On multivariate analysis, age (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.002–1.478; P=0.026 and nerve-sparing status (HR, 0.713; 95% CI, 0.548–0.929; P=0.012 were independently associated with recovery of urinary continence. Conclusions: nsRP, as compared to nnsRP, improves recovery rates of urinary incontinence and decreases surgical morbidity without compromising pathologic outcomes.

Intranasal Immunization Using Mannatide as a Novel Adjuvant for an Inactivated Influenza Vaccine and Its Adjuvant Effect Compared with MF59.

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Shu-Ting Ren

Full Text Available Intranasal vaccination is more potent than parenteral injection for the prevention of influenza. However, because the poor efficiency of antigen uptake across the nasal mucosa is a key issue, immunostimulatory adjuvants are essential for intranasal vaccines. The immunomodulator mannatide or polyactin (PA has been used for the clinical treatment of impaired immunity in China, but its adjuvant effect on an inactivated trivalent influenza vaccine (ITIV via intranasal vaccination is unclear. To explore the adjuvant effect of PA, an inactivated trivalent influenza virus with or without PA or MF59 was instilled intranasally once a week in BALB/c mice. Humoral immunity was assessed by both the ELISA and hemagglutination inhibition (HI methods using antigen-specific antibodies. Splenic lymphocyte proliferation and the IFN-γ level were measured to evaluate cell-mediated immunity. The post-vaccination serum HI antibody geometric mean titers (GMTs for the H1N1 and H3N2 strains, antigen-specific serum IgG and IgA GMTs, mucosal SIgA GMT, splenic lymphocyte proliferation, and IFN-γ were significantly increased in the high-dose PA-adjuvanted vaccine group. The seroconversion rate and the mucosal response for the H3N2 strain were significantly elevated after high-dose PA administration. These adjuvant effects of high-dose PA for the influenza vaccine were comparable with those of the MF59 adjuvant, and abnormal signs or pathological changes were not found in the evaluated organs. In conclusion, PA is a novel mucosal adjuvant for intranasal vaccination with the ITIV that has safe and effective mucosal adjuvanticity in mice and successfully induces both serum and mucosal antibody responses and a cell-mediated response.

IMRT for adjuvant radiation in gastric cancer: A preferred plan?

International Nuclear Information System (INIS)

Ringash, Jolie; Perkins, Greg; Brierley, James; Lockwood, Gina; Islam, Mohammad; Catton, Pamela; Cummings, Bernard; Kim, John; Wong, Rebecca; Dawson, Laura

2005-01-01

Purpose: To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over conformal planning for postoperative adjuvant radiotherapy in patients with gastric carcinoma. Methods and Materials: Twenty patients who had undergone treatment planning with conformal beam arrangements for 4500 cGy adjuvant radiotherapy between 2000 and 2001 underwent repeat planning using IMRT techniques. Conformal five-field plans were compared with seven- to nine-field coplanar sliding-window IMRT plans. For each patient, the cumulative dose-volume histograms and organ-dose summaries (without distributions or digitally reconstructed radiographs) were provided to two independent, 'blinded' GI radiation oncologists. The oncologists indicated which plan provided better planning target volume coverage and critical organ sparing, any safety concerns with either plan, and which plan they would choose to treat the patient. Results: In 18 (90%) of 20 cases, both oncologists chose the same plan. Cases with disagreement were given to a third 'blinded' reviewer. A 'preferred plan' could be determined in 19 (95%) of 20 cases. IMRT was preferred in 17 (89%) of 19 cases. In 4 (20%) of 20 IMRT plans at least one radiation oncologist had safety concerns because of the spinal cord dose (3 cases) or small bowel dose (2 cases). Of 42 ratings, IMRT was thought to provide better planning target volume coverage in 36 (86%) and better sparing of the spinal cord in 31 (74%) of 42, kidneys in 29 (69%), liver in 30 (71%), and heart in 29 (69%) of 42 ratings. The median underdose volume (1.7 vs. 4.1 cm 3 ), maximal dose to the spinal cord (36.85 vs. 45.65 Gy), and dose to 50% of the liver (17.29 vs. 27.97), heart (12.89 vs. 15.50 Gy), and left kidney (15.50 vs. 16.06 Gy) were lower with IMRT than with the conformal plans. Conclusion: Compared with the conformal plans, oncologists frequently preferred IMRT plans when using dose-volume histogram data. The advantages of IMRT plans include both

ROLE OF ADJUVANT INTRAVESICAL CHEMOTHERAPY IN THE COMBINED ORGAN-SPARING TREATMENT OF NON-MUSCLE-INVASIVE BLADDER CANCER

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A. Yu. Zubko

2014-01-01

Full Text Available Objective: to enhance the efficiency of combined treatment for non-muscle-invasive bladder cancer ((NMIBC and to assess the results of its treatment using transurethral resection (TUR as monotherapy and in combination with intravesical adjuvant chemotherapy (CT.Subjects and methods. The results of treatment were analyzed in 59 patients with NMIBC. Twenty-two patients underwent TUR in Group 1; TUR and single intravesical injection of drugs were performed in 19 patients in Group 2; 18 patients had TUR and long-term intravesical CT.Results and discussion. The recurrence rates were 59.1, 57.9, and 38.89 % in Groups 1, 2, and 3, respectively. Intravesical CT was found to appreciably affect the prevention of recurrence in the area of resection. The rate of this recurrence was 31.81, 26.32, and 5.56 % in Groups 1, 2, and 3, respectively. Conclusion. Adjuvant intravesical chemotherapy CT is an effective method to prevent recurrent bladder cancer.

The surface charge of liposomal adjuvants is decisive for their interactions with the Calu-3 and A549 airway epithelial cell culture models

DEFF Research Database (Denmark)

Ingvarsson, Pall Thor; Rasmussen, Ida Svahn; Viaene, Michelle

2014-01-01

One of the main reasons for the unmet medical need for mucosal vaccines is the lack of safe and efficacious mucosal adjuvants. The cationic liposome-based adjuvant system composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) is a versatile adjuvant that has shown...

Nephron-sparing surgery and percutaneous biopsies in renal-cell carcinoma: a global impression among endourologists

NARCIS (Netherlands)

Kummerlin, Intan P. E. D.; Borrego, Jaime; Wink, Margot H.; van Dijk, Marleen M.; Wijkstra, Hessel; de La Rosette, Jean J. M. C. H.; Laguna, M. Pilar

2007-01-01

BACKGROUND AND PURPOSE: On the one hand, nephron-sparing surgery (NSS) in small renal tumors is a safe and effective alternative to radical nephrectomy. On the other hand, the role of preoperative percutaneous needle biopsies (PNB) remains controversial. The purpose of this study was to evaluate the

Nephron-sparing surgery and percutaneous biopsies in renal-cell carcinoma : a global impression among endourologists

NARCIS (Netherlands)

Kummerlin, I.; Borrego, J.; Wink, M.H.; Dijk, van M.M.; Wijkstra, H.; Rosette, de la J.J.M.C.H.; Laguna, M.P.

2010-01-01

Background and Purpose: On the one hand, nephron-sparing surgery (NSS) in small renal tumors is a safe and effective alternative to radical nephrectomy. On the other hand, the role of preoperative percutaneous needle biopsies (PNB) remains controversial. The purpose of this study was to evaluate the

Submandibular gland-sparing radiation therapy for locally advanced oropharyngeal squamous cell carcinoma: patterns of failure and xerostomia outcomes

International Nuclear Information System (INIS)

Gensheimer, Michael F; Liao, Jay J; Garden, Adam S; Laramore, George E; Parvathaneni, Upendra

2014-01-01

Saliva from submandibular glands (SMG) is necessary to minimize xerostomia. It is unclear whether SMG can be safely spared in patients undergoing bilateral neck radiotherapy for locally advanced oropharyngeal cancer without increasing the risk of marginal recurrence. We evaluated the outcomes of contralateral submandibular gland (cSMG) sparing intensity-modulated radiation therapy (IMRT). All patients with stage III/IV oropharyngeal squamous cell carcinoma treated with bilateral neck IMRT from 2006–2012 at our institution were included. Appropriately selected patients with favorable primary tumor characteristics and no definite contralateral neck disease were treated with cSMG-sparing IMRT. Patterns of failure and xerostomia outcomes were retrospectively analyzed. 114 patients were treated. 89% had stage IV disease and 89% received definitive radiation therapy. 76 patients (67%) received cSMG sparing IMRT. With a median follow-up of 30 months, there were 10 local, 9 regional, and 10 distant recurrences. 2-year overall survival was 86% and 2-year loco-regional control was 87%. In cSMG spared patients, the mean cSMG dose was 30.7 Gy. Late grade 2+ xerostomia was significantly reduced in the cSMG spared group compared to those without SMG sparing (6 months: 23% vs. 72%, 12 months: 6% vs. 41%, 24 months: 3% vs. 36%, all p < 0.0007). There were no peri-SMG marginal recurrences in the cSMG-spared cohort. cSMG sparing IMRT did not increase marginal failures in this series of locally advanced oropharyngeal SCC patients. Xerostomia was significantly reduced in cSMG spared patients

Total Maxillary Reconstruction With a Bi-Paddle Double-Barrel Osteocutaneous Fibular Flap and Arteriovenous Saphenous Loop After a Globe-Sparing Total Maxillectomy Due to Osteosarcoma.

Science.gov (United States)

Tseng, Wan-Ling; Chang, Tzu-Yen; Hung, Kuo-Shu; Chen, Szu-Han; Hsiao, Jenn-Ren; Lee, Yao-Chou

2017-01-01

The titanium mesh or bone graft is usually used for orbital support after a globe-sparing total maxillectomy. However, its use can invite complications, such as infection, exposure, and absorption, especially for patients who require adjuvant radiotherapy. Here, the authors present a patient who received total maxillary reconstruction with an osteocutaneous fibular flap. A 53-year-old man with the diagnosis of maxillary osteosarcoma received a globe-sparing total maxillectomy. A bi-paddle double-barrel osteocutaneous fibular flap was used for orbital support, alveolar ridge recreation, and oro-sino-nasal separation. The short pedicle length inherent in the double-barrel design of the fibular flap was overcome by creating an arteriovenous saphenous loop. The postoperative recovery was uneventful. During the 9 months follow-up, the patient was tumor-free and satisfied with his appearance, speech, and intake functions. Reconstruction with a bi-paddle double-barrel osteocutaneous fibular flap after a globe-sparing total maxillectomy can achieve satisfactory aesthetic and functional results.

Adjuvant effect in aquaculture fish of cell-wall glycolipids isolated from acid-fast bacteria.

Science.gov (United States)

Matsumoto, Megumi; Araki, Kyosuke; Nishimura, Sayaka; Kuriyama, Hideki; Nakanishi, Teruyuki; Shiozaki, Kazuhiro; Takeuchi, Yutaka; Yamamoto, Atsushi

2018-08-01

Mycobacteriosis and nocardiosis in cultured fish caused by infections with acid-fast bacteria, are responsible for large economic losses globally. In this study, we suggest a novel adjuvant using glycolipids that activates host immune systems. The immune response to glycolipids stimulation was investigated using ginbuna crucian carp. Ginbuna vaccinated with FKC (formalin-killed cells) + glycolipids isolated from Mycobacterium sp., upregulated inflammatory- and Th1-related cytokines, and a DTH (delayed-type hypersensitivity) response was confirmed only in ginbuna vaccinated with FKC + glycolipids. These observations suggest that glycolipids activated host innate and cell-mediated immunity. Subsequently, we evaluated the adjuvant effect of glycolipids against amberjack nocardiosis. In a challenge test, a higher survival rate was observed in amberjack vaccinated with FKC + glycolipids emulsified with conventional oil adjuvant than in fish vaccinated with FKC + oil adjuvant without glycolipids. Therefore, glycolipids potentially could be used as a practical, economical and safe adjuvant for aquaculture fish. Copyright © 2018. Published by Elsevier Ltd.

Safe current in home and spare time. Sicherer Strom in Heim und Freizeit. Vortraege

Energy Technology Data Exchange (ETDEWEB)

1982-01-01

The papers read at the meeting of the Association of Electrical Engineers (VDE) in May 1982 are intended on the one hand to create awareness of sources of danger and, on the other hand, to demonstrate and discuss how safety can be further enhanced by consistent use of standardization and enlightenment. They are titled as follows: Power accidents in home and spare time; Physiological aspects of accidents; Tasks of the state in consumer protection; Consumer protection through laws and standards; Test institutions and test-marks; Installation technology at home and abroad; Protective measures; Teaching and learning safety; Training for electricians and continuation training.

Skin Sparing Mastectomy and Immediate Breast Reconstruction (SSMIR for early breast cancer: Eight years single institution experience

Directory of Open Access Journals (Sweden)

Bobin Jean

2008-04-01

Full Text Available Abstract Background Skin Sparing Mastectomy (SSM and immediate breast reconstruction has become increasingly popular as an effective treatment for patients with breast carcinoma. The aim of this study was to evaluate the clinical outcome of skin sparing mastectomy in early breast cancer at a single population-based institution. Methods Records of ninety-five consecutive patients with operable breast cancer who had skin-sparing mastectomy and immediate breast reconstructions between 1995 and 2003 were reviewed. Patient and tumor characteristic, type of reconstruction, postoperative complications, aesthetic results and incidence of recurrence were analyzed. Results Mean age of the patients was 51.6(range 33–72 years. The AJCC pathologic stages were 0 (n = 51, 53.7%, I (n = 20, 21.1%, and II (n = 2, 2.1%. Twenty of the patients had recurrent disease (21.1%. The immediate breast reconstructions were performed with autologus tissue including latissimus dorsi musculocutaneous flap in 63 (66.3% patients and transverse rectus abdominis myocutaneous (TRAM flap in 4 (4.2% patients. Implants were used in 28 (29.4% patients. The average hospital stay was 7.7 days. Flap complication occurred in seven (10.4% patients resulting in four (6% re-operations and there were no delay in accomplishing postoperative adjuvant therapy. At a median follow-up of 69 months (range 48 to 144, local recurrence was seen in one patient (1.1% and systemic recurrence was seen in two patients (2.1%. Conclusion Skin sparing mastectomy and immediate breast reconstruction for early breast cancer is associated with low morbidity and low rate of local recurrence.

The mechanism of action of MF59 - an innately attractive adjuvant formulation.

Science.gov (United States)

O'Hagan, D T; Ott, G S; De Gregorio, E; Seubert, A

2012-06-19

MF59 is a safe and effective vaccine adjuvant which was originally approved to be included in a licensed influenza vaccine to be used in the elderly in Europe in 1997. The MF59 adjuvanted influenza vaccine (Fluad™) is now licensed in more than 20 countries worldwide and more than 85 million doses have been administered. More recently the vaccine adjuvant has also been shown to be safe and effective in young children and resulted in a significant increase in influenza vaccine efficacy in a controlled clinical trial in Europe. Since the early days of its discovery we have explored the mechanism of action of MF59, using a variety of available techniques. In recent years we have explored more thoroughly the mechanism of action using new and more sophisticated techniques. It is remarkable how consistent the data has been, using a variety of different approaches both in several small animal models and also using human immune cells in vitro. Here we present a summary of all the work performed to date on the mechanism of action of MF59 and we present a unified theory based on the accumulated data of how it exerts its adjuvant effects. A key element of the mechanism of action appears to be the creation of a transient 'immunocompetent' local environment at the injection site, resulting in the recruitment of key immune cells, which are able to take up antigen and adjuvant and transport them to the local lymph nodes, where the immune response is induced. This recruitment appears to be triggered by the induction of a chemokine driven gradient by the impact of MF59 on local cells, which are activated to secrete further chemokines, which are recruitment factors for more immune cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Preclinical evaluation of the saponin derivative GPI-0100 as an immunostimulating and dose-sparing adjuvant for pandemic influenza vaccines

NARCIS (Netherlands)

Liu, Heng; Bungener, Laura; ter Veer, Wouter; Coller, Beth-Ann; Wilschut, Jan; Huckriede, Anke

2011-01-01

With the current global influenza vaccine production capacity the large demand for vaccines in case of a pandemic can only be fulfilled when antigen dose sparing strategies are employed. Here we used a murine challenge model to evaluate the potential of GPI-0100, a semi-synthetic saponin derivative,

Sparing of the submandibular glands by intensity modulated radiotherapy in the treatment of head and neck cancer

International Nuclear Information System (INIS)

Saarilahti, Kauko; Kouri, Mauri; Collan, Juhani; Kangasmaeki, Aki; Atula, Timo; Joensuu, Heikki; Tenhunen, Mikko

2006-01-01

Background and purpose: The submandibular glands produce most of the unstimulated saliva output and are the key in prevention of radiation-related xerostomia. We investigated whether sparing of the submandibular function is feasible with intensity modulated radiotherapy (IMRT). Patients and methods: Thirty-six patients diagnosed with head and neck cancer were treated with IMRT and had at least one parotid gland excluded from the planning target volume. In a subset, of these patients (n=18) where the risk of cancer recurrence in the contralateral submandibular region was judged low, the contralateral submandibular gland was spared from full-dose irradiation. The total unstimulated and stimulated salivary flow rates and adverse effects were monitored. Results: Twelve months following IMRT mean unstimulated saliva flow was 60% of the baseline value among patients who had one submandibular gland spared and 25% among those who did not (P=0.006). Patients whose contralateral submandibular was spared reported less grade two or three xerostomia (4 vs. 11; P=0.018), and used less saliva substitutes. No cancer recurrences were detected at the vicinity of the spared glands during a median follow-up time of 31 months. Conclusions: Submandibular gland sparing with IMRT is safe in selected patients treated for head and neck cancer. It is effective in prevention of radiation-associated xerostomia

Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania.

Science.gov (United States)

Fox, Christopher B; Huynh, Chuong; O'Hara, Michael K; Onu, Adrian

2013-03-15

Many developing countries lack or have inadequate pandemic influenza vaccine manufacturing capacity. In the 2009 H1N1 pandemic, this led to delayed and inadequate vaccine coverage in the developing world. Thus, bolstering developing country influenza vaccine manufacturing capacity is urgently needed. The Cantacuzino Institute in Bucharest, Romania has been producing seasonal influenza vaccine since the 1970s, and has the capacity to produce ∼5 million doses of monovalent vaccine in the event of an influenza pandemic. Inclusion of an adjuvant in the vaccine could enable antigen dose sparing, expanding vaccine coverage and potentially allowing universal vaccination of the Romanian population and possibly neighboring countries. However, adjuvant formulation and manufacturing know-how are difficult to access. This manuscript describes the successful transfer of oil-in-water emulsion adjuvant manufacturing and quality control technologies from the Infectious Disease Research Institute in Seattle, USA to the Cantacuzino Institute. By describing the challenges and accomplishments of the project, it is hoped that the knowledge and experience gained will benefit other institutes involved in similar technology transfer projects designed to facilitate increased vaccine manufacturing capacity in developing countries. Copyright © 2012 Elsevier Ltd. All rights reserved.

Human Phase 1 trial of low-dose inactivated seasonal influenza vaccine formulated with Advax™ delta inulin adjuvant.

Science.gov (United States)

Gordon, David L; Sajkov, Dimitar; Honda-Okubo, Yoshikazu; Wilks, Samuel H; Aban, Malet; Barr, Ian G; Petrovsky, Nikolai

2016-07-19

Influenza vaccines are usually non-adjuvanted but addition of adjuvant may improve immunogenicity and permit dose-sparing, critical for vaccine supply in the event of an influenza pandemic. The aim of this first-in-man study was to determine the effect of delta inulin adjuvant on the safety and immunogenicity of a reduced dose seasonal influenza vaccine. Healthy male and female adults aged 18-65years were recruited to participate in a randomized controlled study to compare the safety, tolerability and immunogenicity of a reduced-dose 2007 Southern Hemisphere trivalent inactivated influenza vaccine formulated with Advax™ delta inulin adjuvant (LTIV+Adj) when compared to a full-dose of the standard TIV vaccine which does not contain an adjuvant. LTIV+Adj provided equivalent immunogenicity to standard TIV vaccine as assessed by hemagglutination inhibition (HI) assays against each vaccine strain as well as against a number of heterosubtypic strains. HI responses were sustained at 3months post-immunisation in both groups. Antibody landscapes against a large panel of H3N2 influenza viruses showed distinct age effects whereby subjects over 40years old had a bimodal baseline HI distribution pattern, with the highest HI titers against the very oldest H3N2 isolates and with a second HI peak against influenza isolates from the last 5-10years. By contrast, subjects >40years had a unimodal baseline HI distribution with peak recognition of H3N2 isolates from approximately 20years ago. The reduced dose TIV vaccine containing Advax adjuvant was well tolerated and no safety issues were identified. Hence, delta inulin may be a useful adjuvant for use in seasonal or pandemic influenza vaccines. Australia New Zealand Clinical Trial Registry: ACTRN12607000599471. Copyright © 2016 Elsevier Ltd. All rights reserved.

Electronic spare-parts catalogue, an elementary module of spare-parts supply; Elektronischer Ersatzteilkatalog als elementarer Baustein der Ersatzteilversorgung

Energy Technology Data Exchange (ETDEWEB)

Nienhaus, Karl; Bartnitzki, Thomas [RWTH Aachen (Germany). Inst. fuer Maschinentechnik der Rohstoffindustrie; Stoll, Andrea [Bucyrus HEX GmbH, Dortmund (Germany). Abt. Technische Dokumentation

2011-01-15

Developments in recent years in the supply of spare parts at Bucyrus HEX GmbH have revealed the increasing importance of quick and error-free ordering of spare parts by means of electronic spare-parts catalogues. The spare-parts catalogue has meanwhile become the central component in order to enter eCommerce with the after sales services. These higher requirements will lead to further optimisation and automation of the publishing process on the manufacturer's side and to quicker acceptance of the new digital media and the linking of the electronic spare-parts catalogues to maintenance planning systems on the customer's side. The authors agree that these are exciting times with regard to electronic spare-parts catalogues. (orig.)

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

Science.gov (United States)

Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

2010-01-01

To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p3D-CRT plans. The doses to the liver and bowel reduced significantly (p3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

Tabletted guar gum microspheres of piroxicam for targeted adjuvant therapy for colonic adenocarcinomas.

Science.gov (United States)

Vats, Anima; Pathak, Kamla

2012-11-01

In recent years, nonsteroidal anti-inflammatory drugs have been found to be cogent as an adjuvant therapeutic agent in mitigating colorectal cancer. Thus, this present investigation was aimed to formulate an oral, targeted tablet of piroxicam microspheres for sustained and targeted adjuvant therapy for colonic adenocarcinomas. Crosslinked guar gum microspheres of piroxicam were directly compressed into matrix tablet and coated with Eudragit S100. The optimized tablet that displayed 0% release in simulated gastric fluid, 15% in simulated intestinal fluid and 97.1% in simulated colonic fluid underwent roentgenographic study in rabbits to check its safe transit to the colon. x-ray images revealed intactness of the tablet until it reached the colon where the tablet matrix eroded. The designed, conceptual formulation emerged as potential carrier for targeted adjuvant therapy of piroxicam.

Neoadjuvant and adjuvant chemotherapy for locally advanced bladder carcinoma. Development of novel bladder preservation approach, Osaka Medical College regimen

International Nuclear Information System (INIS)

Azuma, Haruhito; Inamoto, Teruo; Takahara, Kiyoshi; Ibuki, Naokazu; Nomi, Hayahito; Yamamoto, Kazuhiro; Narumi, Yoshihumi; Ubai, Takanobu

2012-01-01

Cisplatin-based chemotherapy has been widely used in a neoadjuvant as well as adjuvant setting. Furthermore, trimodal approaches including complete transurethral resection of the bladder tumor followed by combined chemotherapy and radiation have generally been performed as bladder preservation therapy. However, none of the protocols have achieved a 5-year survival rate of more than 70%. Additionally, the toxicity of chemotherapy and/or a decreased quality of life due to urinary diversion cannot be ignored, as most patients with bladder cancer are elderly. We therefore newly developed the novel trimodal approach of ''combined therapy using balloon-occluded arterial infusion of anticancer agent and hemodialysis with concurrent radiation, which delivers an extremely high concentration of anticancer agent to the site of a tumor without systemic adverse effects (''Osaka Medical College regimen'' referred to as the OMC regimen). We initially applied the OMC regimen as neoadjuvant chemotherapy for locally advanced bladder cancer. However, since more than 85% of patients with histologically-proven urothelial cancer achieved complete response with no evidence of recurrence after a mean follow-up of 170 (range 21-814) weeks, we have been applying the OMC-regimen as a new approach for bladder sparing therapy. We summarize the advantage and/or disadvantage of chemotherapy in neoadjuvant as well as adjuvant settings, and show the details of our newly developed bladder sparing approach OMC regimen in this review. (author)

Successful adjuvant-free vaccination of BALB/c mice with mutated amyloid β peptides

Directory of Open Access Journals (Sweden)

Wahi Monika M

2008-02-01

Full Text Available Abstract Background A recent human clinical trial of an Alzheimer's disease (AD vaccine using amyloid beta (Aβ 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine. Results All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue. Conclusion Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.

A pilot study of sphincter-sparing management of adenocarcinoma of the rectum.

Science.gov (United States)

Steele, G; Busse, P; Huberman, M S; LeClair, J M; Falchuk, Z M; Mayer, R J; Bothe, A; Ravikumar, T S; Stone, M; Jessup, J M

1991-06-01

After analysis of 26 prospectively accrued patients with distal rectal adenocarcinomas who underwent sphincter preservation treatment, we have concluded that tumors that invade only the submucosa can safely be treated with surgery alone and that tumors that invade the muscularis or further can be safely treated with surgery combined with chemoradiotherapy. None of the patients had either local or distant recurrence, with a median follow-up of 21 months. All patients have been fully continent. The results, although preliminary, imply that resection of distal rectal adenocarcinoma with sphincter preservation, and adjuvant therapy when appropriate, have achieved local and distant control equal to the conventional Miles' abdominoperineal resection, but without the need for a permanent colostomy.

Esophagus and contralateral lung-sparing IMRT for locally advanced lung cancer in the community hospital setting

Directory of Open Access Journals (Sweden)

Johnny eKao

2015-06-01

Full Text Available Background: The optimal technique for performing lung IMRT remains poorly defined. We hypothesize that improved dose distributions associated with normal tissue sparing IMRT can allow for safe dose escalation resulting in decreased acute and late toxicity. Methods: We performed a retrospective analysis of 82 consecutive lung cancer patients treated with curative intent from 1/10 to 9/14. From 1/10 to 4/12, 44 patients were treated with the community standard of 3-dimensional conformal radiotherapy or IMRT without specific esophagus or contralateral lung constraints (standard RT. From 5/12 to 9/14, 38 patients were treated with normal tissue-sparing IMRT with selective sparing of contralateral lung and esophagus. The study endpoints were dosimetry, toxicity and overall survival.Results: Despite higher mean prescribed radiation doses in the normal tissue-sparing IMRT cohort (64.5 Gy vs. 60.8 Gy, p=0.04, patients treated with normal tissue-sparing IMRT had significantly lower lung V20, V10, V5, mean lung, maximum esophagus and mean esophagus doses compared to patients treated with standard RT (p≤0.001. Patients in the normal tissue-sparing IMRT group had reduced acute grade ≥3 esophagitis (0% vs. 11%, p<0.001, acute grade ≥2 weight loss (2% vs. 16%, p=0.04, late grade ≥2 pneumonitis (7% vs. 21%, p=0.02. The 2-year overall survival was 52% with normal tissue-sparing IMRT arm compared to 28% for standard RT (p=0.015.Conclusion: These data provide proof of principle that suboptimal radiation dose distributions are associated with significant acute and late lung and esophageal toxicity that may result in hospitalization or even premature mortality. Strict attention to contralateral lung and esophageal dose volume constraints are feasible in the community hospital setting without sacrificing disease control.

Spare Items validation

International Nuclear Information System (INIS)

Fernandez Carratala, L.

1998-01-01

There is an increasing difficulty for purchasing safety related spare items, with certifications by manufacturers for maintaining the original qualifications of the equipment of destination. The main reasons are, on the top of the logical evolution of technology, applied to the new manufactured components, the quitting of nuclear specific production lines and the evolution of manufacturers quality systems, originally based on nuclear codes and standards, to conventional industry standards. To face this problem, for many years different Dedication processes have been implemented to verify whether a commercial grade element is acceptable to be used in safety related applications. In the same way, due to our particular position regarding the spare part supplies, mainly from markets others than the american, C.N. Trillo has developed a methodology called Spare Items Validation. This methodology, which is originally based on dedication processes, is not a single process but a group of coordinated processes involving engineering, quality and management activities. These are to be performed on the spare item itself, its design control, its fabrication and its supply for allowing its use in destinations with specific requirements. The scope of application is not only focussed on safety related items, but also to complex design, high cost or plant reliability related components. The implementation in C.N. Trillo has been mainly curried out by merging, modifying and making the most of processes and activities which were already being performed in the company. (Author)

Valve-sparing aortic root replacement†

NARCIS (Netherlands)

Koolbergen, David R.; Manshanden, Johan S. J.; Bouma, Berto J.; Blom, Nico A.; Mulder, Barbara J. M.; de Mol, Bas A. J. M.; Hazekamp, Mark G.

2015-01-01

To evaluate our results of valve-sparing aortic root replacement and associated (multiple) valve repair. From September 2003 to September 2013, 97 patients had valve-sparing aortic root replacement procedures. Patient records and preoperative, postoperative and recent echocardiograms were reviewed.

Development of Novel Protocol for Preclinical Monitoring the Release of Adjuvants Encapsulated Mucosal Delivery Carriers

Directory of Open Access Journals (Sweden)

Mohamed Ibrahim-Saeed

2015-12-01

Full Text Available This work contributes in vaccines down-stream process by introducing a novel platform for in-vitro monitoring of vaccine-adjuvant delivery profile as a crucial preclinical optimizing step in mucosal vaccines. Nano and micro particles of Calcium phosphate (Cap vaccine-adjuvant were encapsulated in Chitosan and Alginate polymeric carriers. Adjuvants release profiles monitored in a permeable bag at 37°C, pH 2, incubated in isotonic buffer for 96 hours. The released Calcium in the outer buffer was monitored and compared in-addition to the carrier’s swelling and biophysical properties. The adjuvants and carriers did not interfere with the proliferation of cultured hepatocytes an indicator of their safe use; Chitosan’s viscosity and swelling were higher than Alginate. Chitosan’s Zeta-potential was significantly high positive, while Cap and Alginate were negative. The prepared CaP and Chitosan particles were in nano-size, while the ready-made CaP adjuvant and Alginate were in micro-size using zeta-seizer and scanning electron-micrograph. The release of nano-size particle was in ascending, extended and controlled manner compared to micro-size adjuvant. Moreover, nano-adjuvant release profile from Chitosan was superior compared to Alginate. The core controlling factors in vaccine-adjuvant sustained release includes; smaller adjuvant particles (nano-size, carrier’s low swelling, high viscosity and importantly carrier-adjuvant entrapment reversibility. Chitosan offers sustained ascending superior capacity in releasing Nano-Cap adjuvant. This novel in-vitro pre-clinical study answer a crucial downstream preparative step for optimizing mucosal vaccines before their direct routine in-vivo trial on animal regardless of adjuvant’s particle size or delivery kinetics.

Evolution in Monitoring of Free Flap Autologous Breast Reconstruction after Nipple-Sparing Mastectomy: Is There a Best Way?

Science.gov (United States)

Frey, Jordan D; Stranix, John T; Chiodo, Michael V; Alperovich, Michael; Ahn, Christina Y; Allen, Robert J; Choi, Mihye; Karp, Nolan S; Levine, Jamie P

2018-05-01

Free flap monitoring in autologous reconstruction after nipple-sparing mastectomy remains controversial. The authors therefore examined outcomes in nipple-sparing mastectomy with buried free flap reconstruction versus free flap reconstruction incorporating a monitoring skin paddle. Autologous free flap reconstructions with nipple-sparing mastectomy performed from 2006 to 2015 were identified. Demographics and operative results were analyzed and compared between buried flaps and those with a skin paddle for monitoring. Two hundred twenty-one free flaps for nipple-sparing mastectomy reconstruction were identified: 50 buried flaps and 171 flaps incorporating a skin paddle. The most common flaps used were deep inferior epigastric perforator (64 percent), profunda artery perforator (12.1 percent), and muscle-sparing transverse rectus abdominis myocutaneous flaps (10.4 percent). Patients undergoing autologous reconstructions with a skin paddle had a significantly greater body mass index (p = 0.006). Mastectomy weight (p = 0.017) and flap weight (p < 0.0001) were significantly greater in flaps incorporating a skin paddle. Comparing outcomes, there were no significant differences in flap failure (2.0 percent versus 2.3 percent; p = 1.000) or percentage of flaps requiring return to the operating room (6.0 percent versus 4.7 percent; p = 0.715) between groups. Buried flaps had an absolute greater mean number of revision procedures per nipple-sparing mastectomy (0.82) compared with the skin paddle group (0.44); however, rates of revision procedures per nipple-sparing mastectomy were statistically equivalent between the groups (p = 0.296). Although buried free flap reconstruction in nipple-sparing mastectomy has been shown to be safe and effective, the authors' technique has evolved to favor incorporating a skin paddle, which allows for clinical monitoring and can be removed at the time of secondary revision. Therapeutic, III.

Condition based spare parts supply

NARCIS (Netherlands)

Lin, X.; Basten, Robertus Johannes Ida; Kranenburg, A.A.; van Houtum, Geert-Jan

2012-01-01

We consider a spare parts stock point that serves an installed base of machines. Each machine contains the same critical component, whose degradation behavior is described by a Markov process. We consider condition based spare parts supply, and show that an optimal, condition based inventory policy

Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy.

Science.gov (United States)

Verstappen, Ralph; Djedovic, Gabriel; Morandi, Evi Maria; Heiser, Dietmar; Rieger, Ulrich Michael; Bauer, Thomas

2018-03-01

A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

Assessment of efficacy and safety of various adjuvant formulations with a total soluble extract of Trichinella spiralis

Directory of Open Access Journals (Sweden)

Aucouturier J.

2001-06-01

Full Text Available Trichinellosis, a re-emerging zoonosis in several countries and pig, is the main species responsible for its transmission to human. Vaccination of swine could be an alternative to prevent the risk of human contamination. In order to develop an efficient and safe inactivate vaccine, the choice of the adjuvant is an important issue. The aim of this study was to develop and select potent and safe adjuvants by screening them in an experimental model with a crude soluble antigen from L1 muscular larvae (ML of Trichinella spiralis (Ts. The efficacy was checked by the quantification of specific antibody levels. Specific and non-specific IgE antibody levels were also assessed. Safety was checked by the assessment of the local reaction at the injection site.Various Montanide® ISA adjuvant formulations including water in oil, oil in water and multiphasic emulsions, but also nanoparticles or microbeads were tested. The results clearly showed differences between the antibody responses induced by the adjuvants and demonstrated the necessity to use an adjuvant to obtain a specific IgG (IgG1or lgG2a response directed against the total soluble extract of Ts. All the formulations enhanced the humoral immune response. The origin of the oil contained in the emulsions played an important role on the efficacy. Indeed emulsions based on mineral oils were more efficient than those based on metabolisable oils. However it was linked with stronger local reactions. Multiphasic and oil in water emulsions but also nanoparticles failed to induce 1gG2a antibody levels. Microbeads and water in oil formulations based on mineral oils were more efficient. This experimentation allowed then the selection of several adjuvants which efficacy will be further Investigated by a challenge test and an analysis of the cellular populations involved in the mechanism of the immune response.

Spares management for improved maintenance

International Nuclear Information System (INIS)

Moncrief, E.C.; Schroder, R.M.

1987-01-01

A recent survey by the US Nuclear Regulatory Commission (NRC) of maintenance practices at US nuclear power plants confirms that spare parts availability is, to some extent, a problem at all but a few plants, and that 57% of the plants sometimes operated in a limiting condition for operation over the last year due to unavailability of spare parts. That's the bad news. The good news is that significant improvement is possible without ballooning inventory. The vast majority of total dollar value of spare parts inventory at power generation stations, whether nuclear or fossil, is rarely used (parts or components that are used 12 or less times per year including many with a history of no use for many years). Inventory Solutions of Akron, Ohio, has developed such a tool, called rarely used inventory stocking logic (RUSL) which is a user-friendly decision support tool for setting spare parts reorder points. Based on statistical computations enhanced to include the most advanced techniques developed for use in aerospace and military combat readiness, RUSL calculates the optimum stocking level to achieve the desired spare part availability at the station. In doing so, it considers the importance of the part in preventing an outage, as well as key economic ordering parameters, such as part cost, carrying cost, number of parts in service, historical observed usage, anticipated future usage, and lead time to replenish

Liposomal preparations of muramyl glycopeptides as immunomodulators and adjuvants.

Science.gov (United States)

Turánek, Jaroslav; Ledvina, Miroslav; Kasná, Andrea; Vacek, Antonín; Hríbalova, Vera; Krejcí, Josef; Miller, Andrew D

2006-04-12

The need for safe and structurally defined immunomodulators and adjuvants is increasing in connection with the recently observed marked increase in the prevalence of pathological conditions characterized by immunodeficiency. Important groups of such compounds are muramyl glycopeptides, analogs of muramyl dipeptide (MDP), glucosaminyl-muramyl dipeptide (GMDP), and desmuramylpeptides. We have designed and synthesized new types of analogs with changes in both the sugar and the peptide parts of the molecule that show a high immunostimulating and adjuvant activity and suppressed adverse side effects. The introduction of lipophilic residues has also improved their incorporation into liposomes, which represent a suitable drug carrier. The proliposome-liposome method is based on the conversion of the initial proliposome preparation into liposome dispersion by dilution with the aqueous phase. The description of a home-made stirred thermostated cell and its link-up with a liquid delivery system for a rapid and automated preparation of multilamellar liposomes at strictly controlled conditions (sterility, temperature, dilution rate and schedule) is presented. The cell has been designed for laboratory-scale preparation of liposomes (300-1000 mg of phospholipid per run) in a procedure taking less than 90 min. The method can be readily scaled up. Examples of adjuvant and immunostimulatory effect of liposomal preparation in mice model will be presented.

Advax™, a novel microcrystalline polysaccharide particle engineered from delta inulin, provides robust adjuvant potency together with tolerability and safety.

Science.gov (United States)

Petrovsky, Nikolai; Cooper, Peter D

2015-11-04

There is an ongoing need for new adjuvants to facilitate development of vaccines against HIV, tuberculosis, malaria and cancer, amongst many others. Unfortunately, the most potent adjuvants are often associated with toxicity and safety issues. Inulin, a plant-derived polysaccharide, has no immunological activity in its native soluble form but when crystallized into a stable microcrystalline particulate from (delta inulin) acquires potent adjuvant activity. Delta inulin has been shown to enhance humoral and cellular immune responses against a broad range of co-administered viral, bacterial, parasitic and toxin antigens. Inulin normally crystallizes as large heterogeneous particles with a broad size distribution and variable solubility temperatures. To ensure reproducible delta inulin particles with a consistent size distribution and temperature of solubility, a current Good Manufacturing Practice (cGMP) process was designed to produce Advax™ adjuvant. In its cCMP form, Advax™ adjuvant has proved successful in human trials of vaccines against seasonal and pandemic influenza, hepatitis B and insect sting anaphylaxis, enhancing antibody and T-cell responses while being safe and well tolerated. Advax™ adjuvant represents a novel human adjuvant that enhances both humoral and cellular immunity. This review describes the discovery and development of Advax™ adjuvant and research into its unique mechanism of action. Copyright © 2015 Elsevier Ltd. All rights reserved.

Immediate Breast Reconstruction with Expander Assisted Latissimus Dorsi Flap after Skin Sparing Mastectomy

International Nuclear Information System (INIS)

Abdalla, H.M.; Shallan, M.A.; Fouad, F.A.; Elsayed, A.A.

2006-01-01

Background and Purpose: The latissimus dorsi my-ocutaneous flap (LDMF) used to. be the standard practice far breast reconstruction; haw ever, with the increased use of tissue expanders and the development of the transverse rectus-abdomen's myocutaneaus flap for autologous tissue breast reconstruction, its use has decreased. To. reassess the role of the LDMF in breast reconstruction, a prospective study was performed to. evaluate women who. had a skin sparing mastectomy followed by immediate reconstruction with a latissimus dorsi flap and tissue expander implant. Patients and Methods: Twenty-five women with early breast cancer underwent immediate latissimus dorsi my-ocutaneaus flaps with tissue expander after skin sparing mastectamy. The ancalagic safety at skin sparing mastectamy, the pastaperative aesthetic results and camplicatians were evaluated. Results: Between May 2003 and April 2005, 25 can-secutive wamen diagnased with breast cancer underwent skin sparing mas tecta my and expander assisted immediate latissimus darsi breast recanstructian. Their median age was 42 years, ranging fram 34 to 48 years. The pracedure duratian ranged fram 2.5 to. 6 haurs, with a median at 3.9 haurs, hawever, expansian was campleted by 4 manths (range I to. 8 manths). Patients were discharged 7 days after surgery with a range af 5 to. 15 days. The camplicatian rate was law, manifesting with skin flap necrosis in 12%, waund infectian in 4%, and part site extrusian in 4%. There was no. flap lass. With the exceptian af serama farmatian, the danar site marbidity was law (seroma 40%, hematama 4%, back pain 8%, and limited arm mavement 4%). No. lacal recurrence was recorded. The aesthetic result af surgery was rated as excellent in 20%, gaad in 60%, fair in 24%, and paar in 4% af cases. The duratian af past-aperative fallaw up was 14.7 manths, ranging fram 6 to 24 manths. Conclusions: Skin sparing mastectamy and immediate breast recanstructian is an ancalagically safe technique. The use

Safety of long-term subcutaneous free flap skin banking after skin-sparing mastectomy

Directory of Open Access Journals (Sweden)

Ralph Verstappen

2018-03-01

Full Text Available Background A persistent problem in autologous breast reconstruction in skin-sparing mastectomies is skin restoration after skin necrosis or secondary oncological resection. As a solution to facilitate reconstruction, skin banking of free-flap skin has been proposed in cases where the overlying skin envelope must be resected, as this technique spares the patient an additional donor site. Herein, we present the largest series to date in which this method was used. We investigated its safety and the possibility of skin banking for prolonged periods of time. Methods All skin-sparing mastectomies and immediate autologous breast reconstructions from December 2009 until June 2013 at our institution were analysed. Results We identified 31 patients who underwent 33 free flap reconstructions in which skin banking was performed. Our median skin banking period was 7 days, with a maximum duration of 171 days. In 22.5% of cases, the banked skin was used to reconstruct overlying skin defects, and in 9.6% of cases to reconstruct the nipple-areolar complex. Microbiological and histological investigations of the banked skin revealed neither clinical infections nor malignancies. Conclusions In situ skin banking, even for prolonged periods of time, is a safe and cost-effective method to ensure that skin defects due to necrosis or secondary oncological resection can be easily reconstructed.

Adjuvants are key factors for the development of future vaccines: Lessons from the Finlay Adjuvant platform

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Oliver ePérez

2013-12-01

Full Text Available The development of effective vaccines against neglected diseases, especially those associated with poverty and social deprivation, is urgently needed. Modern vaccine technologies and a better understanding of the immune response have provided scientists with the tools for rational and safer design of subunit vaccines. Often, however, subunit vaccines do not elicit strong immune responses, highlighting the need to incorporate better adjuvants; this step therefore becomes a key factor for vaccine development. In this review we outline some key features of modern vaccinology that are linked with the development of better adjuvants. In line with the increased desire to obtain novel adjuvants for future vaccines, the Finlay Adjuvant Platform offers a novel approach for the development of new and effective adjuvants. The Finlay Adjuvants (AFs, AFPL (proteoliposome and AFCo (cochleate, were initially designed for parenteral and mucosal applications, and constitute potent adjuvants for the induction of Th1 responses against several antigens. This review summarizes the status of the Finlay technology in producing promising adjuvants for unsolved-vaccine diseases including mucosal approaches and therapeutic vaccines. Ideas related to adjuvant classification, adjuvant selection, and their possible influence on innate recognition via multiple toll-like receptors are also discussed.

Managing spares for improved availability

International Nuclear Information System (INIS)

Moncrief, E.C.; Schroder, R.M.

1987-01-01

A recent survey by the U.S. Nuclear Regulatory Commission of maintenance practices at U.S. nuclear power plants confirms that spare parts availability is, to some extent, a problem at all but a few plants. Fortunately, significant improvement is possible without ballooning inventory. The vast majority of total dollar value of spare parts inventory at power generation stations, whether nuclear or fossil, is rarely used (parts or components that are used 12 or less times per year including many with a history of no use for many years). Because rarely used inventory is not effectively managed with traditional inventory management techniques, opportunities exist both to increase availability and to reduce investment. But this requires a unique statistical tool that can recommend an unbiased, economic reorder point to be used in the materials management system. Inventory Solutions Inc. (ISI) of Akron, Ohio, has developed such a tool, rarely used inventory stocking logic (RUSL), which is a user friendly decision support tool for setting spare parts reorder points. RUSL, based on statistical computations enhanced to include the most advanced techniques developed for use in aerospace and military combat-readiness, calculates the optimum stocking level to achieve the desired spare part availability at the station

Nanoparticulate Tubular Immunostimulating Complexes: Novel Formulation of Effective Adjuvants and Antigen Delivery Systems

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Nina Sanina

2017-01-01

Full Text Available New generation vaccines, based on isolated antigens, are safer than traditional ones, comprising the whole pathogen. However, major part of purified antigens has weak immunogenicity. Therefore, elaboration of new adjuvants, more effective and safe, is an urgent problem of vaccinology. Tubular immunostimulating complexes (TI-complexes are a new type of nanoparticulate antigen delivery systems with adjuvant activity. TI-complexes consist of cholesterol and compounds isolated from marine hydrobionts: cucumarioside A2-2 (CDA from Cucumaria japonica and monogalactosyldiacylglycerol (MGDG from marine algae or seagrass. These components were selected due to immunomodulatory and other biological activities. Glycolipid MGDG from marine macrophytes comprises a high level of polyunsaturated fatty acids (PUFAs, which demonstrate immunomodulatory properties. CDA is a well-characterized individual compound capable of forming stable complex with cholesterol. Such complexes do not possess hemolytic activity. Ultralow doses of cucumariosides stimulate cell as well as humoral immunity. Therefore, TI-complexes comprising biologically active components turned out to be more effective than the strongest adjuvants: immunostimulating complexes (ISCOMs and complete Freund’s adjuvant. In the present review, we discuss results published in series of our articles on elaboration, qualitative and quantitative composition, ultrastructure, and immunostimulating activity of TI-complexes. The review allows immersion in the history of creating TI-complexes.

Radiation-sparing managements for cervical cancer: a developing countries perspective

Directory of Open Access Journals (Sweden)

de la Garza Jaime

2006-11-01

Full Text Available Abstract Cervical cancer is the seventh most frequent cancer worldwide but more than 80% of cases occur in developing countries. Till date, radiation therapy with external beam and brachytherapy remains as the core treatment for most stages of cervical cancer. However, radiation treatment protocols and equipment modelled on the best developed countries can be seldom applied directly to developing countries owing to financial constraints and lack of qualified personnel, thus, a substantial proportion of patients do not have access to even palliative radiation therapy. Treatment options when the standard therapy is either not available or difficult to reproduce in particular settings is highly desirable with the potential to save lives that otherwise could be lost by the lack of adequate treatment. These options of treatment ideally had to have show, 1 that these are not inferior to the "standard" in terms of either survival or quality of life; 2 that these can be delivered in settings were the "standard" is not available or if available its quality is poor; and 3 that the treatment option be accepted by the population to be treated. Based on these considerations, it is obvious that cervical cancer patients, particularly those who live in countries with limited resources and therefore may not have sufficient radiation therapy resources are in need of newer therapeutical options. There is now a considerable amount of information emanating from clinical studies where surgery has a major role in treating this disease. These forms of "radiation-sparing" treatments include total mesometrial resection that could make unnecessary the use of adjuvant radiation; neoadjuvant chemotherapy that could avoid the use of adjuvant radiation in around 85% of patients and preoperative chemoradiation that could make brachytherapy dispensable. The feasibility and therapeutical value of these potential forms of management need to be prospectively evaluated.

The short-term safety of adjuvant paclitaxel plus trastuzumab - A single centre experience.

Science.gov (United States)

Ates, Ozturk; Sunar, Veli; Aslan, Alma; Karatas, Fatih; Sahin, Suleyman; Altundag, Kadri

2017-01-01

HER2-amplified breast cancer (BC) has a poor prognosis. The combination of trastuzumab with chemotherapy in the adjuvant setting decreases recurrence and improves overall survival in HER2-positive BC. However, the role of adjuvant treatment in patients with HER2-amplified small BC without lymph node involvement is still under debate. The purpose of this study was to investigate the safety of adjuvant paclitaxel and trastuzumab (APT) in this group of patients. A total of 87 operated early BC patients without lymph node involvement (N0) were treated with APT for 12 weeks followed by trastuzumab alone for a total of 9 months. Clinicopathological features and adverse events were analyzed. The median patient age was 50 years (range 28- 82), and 51% of them were postmenopausal. The median tumor diameter was 2.4 cm (range 0.5-6), with 51% of the patients having tumor size between 2 and 3 cm. Eighty-one percent of patients had invasive ductal carcinoma (IDC), and 64% had grade 3 tumors. Adjuvant hormone therapy and adjuvant radiotherapy were administered to 65 and 54% of patients, respectively. At a median follow up of 13 months (range 6-38), one patient (1.1%, 95% CI 0-3.4) experienced an asymptomatic decrease in left ventricular ejection fraction (LVEF) and 3 patients (3.4%, 95% CI 0-6.9) experienced grade 3 neuropathy. APT appears to be a safe combination in early-stage, HER2-amplified and node-negative BC.

Increased immunogenicity of the MF59-adjuvanted influenza vaccine compared to a conventional subunit vaccine in elderly subjects

International Nuclear Information System (INIS)

Gasparini, R.; Pozzi, T.; Montomoli, E.; Fragapane, E.; Senatore, F.; Minutello, M.; Podda, A.

2001-01-01

Three-hundred and eight outpatient elderly subjects (≥ 65 years) were randomly assigned to receive the MF59-adjuvanted influenza vaccine (FLUAD; n = 204) or a conventional subunit influenza vaccine (AGRIPPAL S1; n = 104) in order to compare the safety and immunogenicity of the two vaccines. Although mild pain at the injection site was reported more frequently by subjects immunised with the adjuvanted vaccine, both vaccines were shown to be safe and well tolerated. The adjuvanted vaccine was more immunogenic as indicated by higher post-immunisation geometric mean titres (GMTs) and by higher proportions of subjects with post-immunisation ≥ four fold increases of antibody titres or subjects with ≥ 1/160 post-immunisation HI titres. These differences, statistically significant for all three strains after immunisation, indicated that, by addition of the MF59 adjuvant emulsion, conventional subunit influenza antigens acquire an enhanced immunogenicity without any clinically significant increase of their reactogenicity

Skin sparing mastectomy: Technique and suggested methods of reconstruction

International Nuclear Information System (INIS)

Farahat, A.M.; Hashim, T.; Soliman, H.O.; Manie, T.M.; Soliman, O.M.

2014-01-01

To demonstrate the feasibility and accessibility of performing adequate mastectomy to extirpate the breast tissue, along with en-block formal axillary dissection performed from within the same incision. We also compared different methods of immediate breast reconstruction used to fill the skin envelope to achieve the best aesthetic results. Methods: 38 patients with breast cancer underwent skin-sparing mastectomy with formal axillary clearance, through a circum-areolar incision. Immediate breast reconstruction was performed using different techniques to fill in the skin envelope. Two reconstruction groups were assigned; group 1: Autologus tissue transfer only (n= 24), and group 2: implant augmentation (n= 14). Autologus tissue transfer: The techniques used included filling in the skin envelope using Extended Latissimus Dorsi flap (18 patients) and Pedicled TRAM flap (6 patients). Augmentation with implants: Subpectoral implants(4 patients), a rounded implant placed under the pectoralis major muscle to augment an LD reconstructed breast. LD pocket (10 patients), an anatomical implant placed over the pectoralis major muscle within a pocket created by the LD flap. No contra-lateral procedure was performed in any of the cases to achieve symmetry. Results: All cases underwent adequate excision of the breast tissue along with en-block complete axillary clearance (when indicated), without the need for an additional axillary incision. Eighteen patients underwent reconstruction using extended LD flaps only, six had TRAM flaps, four had augmentation using implants placed below the pectoralis muscle along with LD flaps, and ten had implants placed within the LD pocket. Breast shape, volume and contour were successfully restored in all patients. Adequate degree of ptosis was achieved, to ensure maximal symmetry. Conclusions: Skin Sparing mastectomy through a circum-areolar incision has proven to be a safe and feasible option for the management of breast cancer in Egyptian

Second Line of Defense Spares Program

Energy Technology Data Exchange (ETDEWEB)

Henderson, Dale L.; Holmes, Aimee E.; Muller, George; Mercier, Theresa M.; Brigantic, Robert T.; Perkins, Casey J.; Cooley, Scott K.; Thorsen, Darlene E.

2012-11-20

During Fiscal Year 2012, a team from the Pacific Northwest National Laboratory (PNNL) conducted an assessment and analysis of the Second Line of Defense (SLD) Sustainability spare parts program. Spare parts management touches many aspects of the SLD Sustainability Program including contracting and integration of Local Maintenance Providers (LMP), equipment vendors, analyses and metrics on program performance, system state of health, and maintenance practices. Standardized spares management will provide better data for decisions during site transition phase and will facilitate transition to host country sustainability ownership. The effort was coordinated with related SLD Sustainability Program initiatives, including a configuration items baselining initiative, a metrics initiative, and a maintenance initiative. The spares study has also led to pilot programs for sourcing alternatives that include regional intermediate inventories and partnering agreements that leverage existing supply chains. Many partners from the SLD Sustainability program contributed to and were consulted in the course of the study. This document provides a description of the findings, recommendations, and implemented solutions that have resulted from the study.

3D-conformal-intensity modulated radiotherapy with compensators for head and neck cancer: clinical results of normal tissue sparing

Directory of Open Access Journals (Sweden)

Koscielny Sven

2006-06-01

Full Text Available Abstract Background To investigate the potential of parotic gland sparing of intensity modulated radiotherapy (3D-c-IMRT performed with metallic compensators for head and neck cancer in a clinical series by analysis of dose distributions and clinical measures. Materials and methods 39 patients with squamous cell cancer of the head and neck irradiated using 3D-c-IMRT were evaluable for dose distribution within PTVs and at one parotid gland and 38 patients for toxicity analysis. 10 patients were treated primarily, 29 postoperatively, 19 received concomittant cis-platin based chemotherapy, 20 3D-c-IMRT alone. Initially the dose distribution was calculated with Helax ® and photon fluence was modulated using metallic compensators made of tin-granulate (n = 22. Later the dose distribution was calculated with KonRad ® and fluence was modified by MCP 96 alloy compensators (n = 17. Gross tumor/tumor bed (PTV 1 was irradiated up to 60–70 Gy, [5 fractions/week, single fraction dose: 2.0–2.2 (simultaneously integrated boost], adjuvantly irradiated bilateral cervical lymph nodes (PTV 2 with 48–54 Gy [single dose: 1.5–1.8]. Toxicity was scored according the RTOG scale and patient-reported xerostomia questionnaire (XQ. Results Mean of the median doses at the parotid glands to be spared was 25.9 (16.3–46.8 Gy, for tin graulate 26 Gy, for MCP alloy 24.2 Gy. Tin-granulate compensators resulted in a median parotid dose above 26 Gy in 10/22, MCP 96 alloy in 0/17 patients. Following acute toxicities were seen (°0–2/3: xerostomia: 87%/13%, dysphagia: 84%/16%, mucositis: 89%/11%, dermatitis: 100%/0%. No grade 4 reaction was encountered. During therapy the XQ forms showed °0–2/3: 88%/12%. 6 months postRT chronic xerostomia °0–2/3 was observed in 85%/15% of patients, none with °4 xerostomia. Conclusion 3D-c-IMRT using metallic compensators along with inverse calculation algorithm achieves sufficient parotid gland sparing in virtually all advanced

Spare Parts Management of Aging Capital Products

NARCIS (Netherlands)

M. Hekimoğlu (Mustafa)

2015-01-01

textabstractSpare parts are critical for operations of capital products such as aircraft, refineries, trucks, etc/, which require maintenance regularly. Original Equipment Manufacturers (OEMs) bear the responsibility of undisrupted maintenance service and spare parts flow for their capital products.

[A Case of Advanced Transverse Colon Cancer with Nephrotic Syndrome Treated with Curative Resection and Complete Adjuvant Chemotherapy].

Science.gov (United States)

Sato, Nobutaka; Fuyuno, Seiya; Hatada, Teppei; Furuhashi, Takashi; Abe, Toshihiko

2017-05-01

A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

Core sampling system spare parts assessment

International Nuclear Information System (INIS)

Walter, E.J.

1995-01-01

Soon, there will be 4 independent core sampling systems obtaining samples from the underground tanks. It is desirable that these systems be available for sampling during the next 2 years. This assessment was prepared to evaluate the adequacy of the spare parts identified for the core sampling system and to provide recommendations that may remediate overages or inadequacies of spare parts

Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

Science.gov (United States)

Nedrud, John G; Bagheri, Nayer; Schön, Karin; Xin, Wei; Bergroth, Hilda; Eliasson, Dubravka Grdic; Lycke, Nils Y

2013-01-01

A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB). The protective efficacy of the selected peptides together with cholera toxin (CT) was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD) that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

One-stage nipple and breast reconstruction following areola-sparing mastectomy.

Science.gov (United States)

Kim, Hye Ri; Lim, Jin Soo; Kim, Sue Min; Jung, Sung No; Yoo, Gyeol; Rha, Eun Young

2013-09-01

Skin-sparing mastectomy with immediate breast reconstruction is increasingly becoming a proven surgical option for early-stage breast cancer patients. Areola-sparing mastectomy (ASM) has also recently become a popular procedure. The purpose of this article is to investigate the reconstructive and aesthetic issues experienced with one-stage nipple and breast reconstruction using ASM. Among the patients who underwent mastectomy between March 2008 and March 2010, 5 women with a low probability of nipple-areolar complex malignant involvement underwent ASM and immediate breast reconstruction with simultaneous nipple reconstruction using the modified C-V flap. The cosmetic outcomes of this series were reviewed by plastic surgeons and patient self-assessment and satisfaction were assessed via telephone interview. During the average 11-month follow-up period, there were no cases of cancer recurrence, the aesthetic outcomes were graded as excellent to very good, and all of the patients were satisfied. Two patients developed a gutter-like depression around the reconstructed nipple, and one patient developed skin erosion in a small area of the areola, which healed with conservative dressing. The other complications, such as necrosis of the skin flap or areola, seroma, hematoma, or fat necrosis did not occur. Since one-stage nipple and breast reconstruction following ASM is an oncologically safe, cost-effective, and aesthetically satisfactory procedure, it is a good surgical option for early breast cancer patients.

System-oriented inventory models for spare parts

NARCIS (Netherlands)

Basten, R.J.I.; Houtum, van G.J.J.A.N.

2014-01-01

Stocks of spare parts, located at appropriate locations, can prevent long downtimes of technical systems that are used in the primary processes of their users. Since such downtimes are typically very expensive, generally system-oriented service measures are used in spare parts inventory control.

Cardiac safety of trastuzumab as adjuvant treatment for Japanese patients with early breast cancer

International Nuclear Information System (INIS)

Ishihara, Mikiya; Mukai, Hirofumi; Nagai, Shunji; Mukohara, Toru

2009-01-01

Recently, randomized trials revealed that trastuzumab as adjuvant treatment was effective in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients. Safety information on adjuvant trastuzumab use in Japanese patients, especially cardiac toxicity data, is needed. We retrospectively reviewed 48 patients with early-stage HER2-positive breast cancer who were treated with curative surgery and adjuvant trastuzumab at the National Cancer Center Hospital East (Kashiwa, Japan). The cardiac safety as well as the short-term efficacy of trastuzumab were evaluated. The median age of the patients was 54 years. All patients received adjuvant or neoadjuvant cytotoxic chemotherapy. Twenty-seven patients (56%) received adjuvant radiation therapy. Forty-four patients (92%) received trastuzumab without concurrent cytotoxic chemotherapy and 4 patients (8%) on taxanes received trastuzumab concurrently. Twenty-five patients completed 1 year of trastuzumab treatment and 5 patients completed 2 years of trastuzumab treatment. Nine patients discontinued trastuzumab treatment, because of progressive disease (1 patient), decrease in left ventricular ejection fraction (LVEF; 2 patients), patient's refusal (4 patients), and other reasons (2 patients). There were five cardiac events. A decrease in LVEF to less than 50% was seen in 2 patients. The relationship between trastuzumab treatment and the cardiac events was unclear in 3 patients. The median follow-up time was 21.2 months. The disease-free survival (DFS) was 97.5% at 1 year and 92.9% at 2 years. The incidence of cardiac events caused by trastuzumab treatment was low in our analysis. Adjuvant trastuzumab treatment for up to at least 1 year should be safe for Japanese breast cancer patients. (author)

19 CFR 10.537 - Accessories, spare parts, or tools.

Science.gov (United States)

2010-04-01

... parts, or tools will be taken into account as originating or non-originating materials, as the case may... 19 Customs Duties 1 2010-04-01 2010-04-01 false Accessories, spare parts, or tools. 10.537 Section... Free Trade Agreement Rules of Origin § 10.537 Accessories, spare parts, or tools. Accessories, spare...

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

Directory of Open Access Journals (Sweden)

Samantha Sayers

2012-01-01

Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

Science.gov (United States)

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Efficacy and safety of short course adjuvant trastuzumab combination chemotherapy in breast cancer

Directory of Open Access Journals (Sweden)

Sachin S Hingmire

2017-01-01

Full Text Available Background: The adjuvant short course 9-week trastuzumab combination therapy for human epidermal receptor 2 positive breast cancer patients may often be considered as a cost-effective and safe option and has important implications for the Indian subcontinent as well as other developing countries. However, such regimens of shorter duration trastuzumab therapy like FinHer, offered in view of economic constraints, may not be able to achieve globally comparable cure rates in early breast cancer especially with high-risk women with more than 3 lymph node positive. Methods and Material: Outcome of 21 patients with HER2 positive breast cancer was treated with short course trastuzumab combination chemotherapy in the adjuvant setting was studied. Results: Out of 21 patients 15 are alive and disease free with a follow up of up to 73 months (median follow up 42 months.

Subcomponent vaccine based on CTA1-DD adjuvant with incorporated UreB class II peptides stimulates protective Helicobacter pylori immunity.

Directory of Open Access Journals (Sweden)

John G Nedrud

Full Text Available A mucosal vaccine against Helicobacter pylori infection could help prevent gastric cancers and peptic ulcers. While previous attempts to develop such a vaccine have largely failed because of the requirement for safe and effective adjuvants or large amounts of well defined antigens, we have taken a unique approach to combining our strong mucosal CTA1-DD adjuvant with selected peptides from urease B (UreB. The protective efficacy of the selected peptides together with cholera toxin (CT was first confirmed. However, CT is a strong adjuvant that unfortunately is precluded from clinical use because of its toxicity. To circumvent this problem we have developed a derivative of CT, the CTA1-DD adjuvant, that has been found safe in non-human primates and equally effective compared to CT when used intranasally. We genetically fused the selected peptides into the CTA1-DD plasmid and found after intranasal immunizations of Balb/c mice using purified CTA1-DD with 3 copies of an H. pylori urease T cell epitope (CTA1-UreB3T-DD that significant protection was stimulated against a live challenge infection. Protection was, however, weaker than with the gold standard, bacterial lysate+CT, but considering that we only used a single epitope in nanomolar amounts the results convey optimism. Protection was associated with enhanced Th1 and Th17 immunity, but immunizations in IL-17A-deficient mice revealed that IL-17 may not be essential for protection. Taken together, we have provided evidence for the rational design of an effective mucosal subcomponent vaccine against H. pylori infection based on well selected protective epitopes from relevant antigens incorporated into the CTA1-DD adjuvant platform.

[Aortic valve-sparing root reconstruction in Marfan syndrome].

Science.gov (United States)

Ogino, H; Sasaki, H; Hanafusa, Y; Hirata, M; Numata, S; Ando, M; Yagihara, T; Kitamura, S

2002-07-01

The outcome of aortic valve-sparing root reconstruction in Marfan syndrome was reviewed. Thirteen patients with Marfan syndrome underwent aortic valve-sparing root reconstruction for annuloaortic ectasia or aortic root dissection between 1994 and 1999. The grade of preoperative aortic regurgitation was I in 4, II in 2, III in 5, IV in 2 patients. The procedures of aortic valve-sparing were reimplantation in 7 and remodeling in 5 patients. There was no hospital and late death. Recurrence of aortic regurgitation greater than moderate grade developed in 1 patient immediately after the surgery and in the other 4 patients in the late stage. One patient of them required aortic valve replacement for it. Aortic valve-sparing root reconstruction is applicable in Marfan patients, although the indication should be cautious. Close observation is needed for recurrence of aortic regurgitation.

A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant

OpenAIRE

Janina Jiang; Guangchao Liu; Valerie A. Kickhoefer; Leonard H. Rome; Lin-Xi Li; Stephen J. McSorley; Kathleen A. Kelly

2017-01-01

Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting g...

N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride: An immune-enhancing adjuvant for hepatitis E virus recombinant polypeptide vaccine in mice.

Science.gov (United States)

Tao, Wei; Zheng, Hai-Qun; Fu, Ting; He, Zhuo-Jing; Hong, Yan

2017-08-03

Adjuvants are essential for enhancing vaccine potency by improving the humoral and/or cell-mediated immune response to vaccine antigens. This study was performed to evaluate the immuno-enhancing characteristic of N-(2-hydroxy) propyl-3-trimethylammonium chitosan chloride (HTCC), the cationically modified chitosan, as an adjuvant for hepatitis E virus (HEV) recombinant polypeptide vaccine. Animal experiments showed that HTCC provides adjuvant activity when co-administered with HEV recombinant polypeptide vaccine by intramuscularly route. Vaccination using HTCC as an adjuvant was associated with increases of the serum HEV-specific IgG antibodies, splenocytes proliferation and the growths of CD4 + CD8 - T lymphocytes and IFN-γ-secreting T lymphocytes in peripheral blood. These findings suggested that HTCC had strong immuno-enhancing effect. Our findings are the first to demonstrate that HTCC is safe and effective in inducing a good antibody response and stimulating Th1-biased immune responses for HEV recombinant polypeptide vaccine.

Renal Toxicity of Adjuvant Chemoradiotherapy With Cisplatin in Gastric Cancer

International Nuclear Information System (INIS)

Welz, Stefan; Hehr, Thomas; Kollmannsberger, Christian; Bokemeyer, Carsten; Belka, Claus; Budach, Wilfried

2007-01-01

Purpose: Adjuvant, 5-fluorouracil (5-FU)-based chemoradiotherapy for completely resected high-risk gastric adenocarcinoma has been shown to improve survival in a randomized Intergroup trial. However, the results still showed an unsatisfactory outcome. On the basis of previously reported results of a Phase II trial using a more aggressive, cisplatin-containing chemoradiotherapy schedule, we investigated the effects of this approach on long-term renal function. Patients and Methods: Between December 2000 and September 2003, 27 patients were treated at Tuebingen University in a Phase II multicenter trial investigating adjuvant chemoradiotherapy. The adjuvant chemoradiotherapy consisted of two cycles of adjuvant 5-FU, folinic acid, cisplatin (200 mg/m 2 ), and paclitaxel before and after radiotherapy (45 Gy in 1.8-Gy fractions) with daily concomitant 5-FU (225 mg/m 2 /24 h). A dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys was used. Renal function was assessed by the changes in creatinine and creatinine clearance during follow-up. Results: The prescribed 45 Gy was administered to 100% of the patients, and the cumulative cisplatin dose was 200 mg/m 2 in 74% of all patients. In 89%, the constraints concerning the renal absorbed doses were met. The median follow-up for the creatinine and clearance values was 30 and 26 months, respectively. The creatinine values tended to worsen over time without reaching critical levels. We were unable to demonstrate a significant dose-response relationship for renal damage in the tested dose range. Conclusions: Using a dose constraint of ≤12 Gy for 37.5% of the functional volume of both kidneys appears to be safe at a median follow-up of 2 years for a cumulative cisplatin dose of 200 mg/m 2 administered before and after simultaneous 5-FU and radiotherapy

One-Stage Nipple and Breast Reconstruction Following Areola-Sparing Mastectomy

Directory of Open Access Journals (Sweden)

Hye Ri Kim

2013-09-01

Full Text Available BackgroundSkin-sparing mastectomy with immediate breast reconstruction is increasingly becoming a proven surgical option for early-stage breast cancer patients. Areola-sparing mastectomy (ASM has also recently become a popular procedure. The purpose of this article is to investigate the reconstructive and aesthetic issues experienced with one-stage nipple and breast reconstruction using ASM.MethodsAmong the patients who underwent mastectomy between March 2008 and March 2010, 5 women with a low probability of nipple-areolar complex malignant involvement underwent ASM and immediate breast reconstruction with simultaneous nipple reconstruction using the modified C-V flap. The cosmetic outcomes of this series were reviewed by plastic surgeons and patient self-assessment and satisfaction were assessed via telephone interview.ResultsDuring the average 11-month follow-up period, there were no cases of cancer recurrence, the aesthetic outcomes were graded as excellent to very good, and all of the patients were satisfied. Two patients developed a gutter-like depression around the reconstructed nipple, and one patient developed skin erosion in a small area of the areola, which healed with conservative dressing. The other complications, such as necrosis of the skin flap or areola, seroma, hematoma, or fat necrosis did not occur.ConclusionsSince one-stage nipple and breast reconstruction following ASM is an oncologically safe, cost-effective, and aesthetically satisfactory procedure, it is a good surgical option for early breast cancer patients.

Inventory Control of Spare Parts for Operating Nuclear Power plants

Energy Technology Data Exchange (ETDEWEB)

Park, Jong-Hyuck; Jang, Se-Jin; Hwang, Eui-Youp; Yoo, Sung-Soo; Yoo, Keun-Bae; Lee, Sang-Guk; Hong, Sung-Yull [Korea Electric Power Research Institute, Taejon (Korea, Republic of)

2006-07-01

Inventory control of spare parts plays an increasingly important role in operation management. The trade-off is clear: on one hand a large number of spare parts ties up a large amount of capital, while on the other hand too little inventory may result in extremely costly emergency actions. This is why during the last few decades inventory of spare parts control has been the topics of many publications. Recently management systems such as manufacturing resources planning (MRP) and enterprise resource planning (ERP) have been added. However, most of these contributions have similar theoretical background. This means the concepts and techniques are mainly based on mathematical assumptions and modeling inventory of spare parts situations Nuclear utilities in Korea have several problems to manage the optimum level of spare parts though they used MRP System. Because most of items have long lead time and they are imported from United States, Canada, France and so on. In this paper, we will examine the available inventory optimization models which are applicable to nuclear power plant and then select optimum model and assumptions to make inventory of spare parts strategies. Then we develop the computer program to select and determine optimum level of spare parts which should be automatically controlled by KHNP ERP system. The main contribution of this paper is an inventory of spare parts control model development, which can be applied to nuclear power plants in Korea.

Inventory Control of Spare Parts for Operating Nuclear Power plants

International Nuclear Information System (INIS)

Park, Jong-Hyuck; Jang, Se-Jin; Hwang, Eui-Youp; Yoo, Sung-Soo; Yoo, Keun-Bae; Lee, Sang-Guk; Hong, Sung-Yull

2006-01-01

Inventory control of spare parts plays an increasingly important role in operation management. The trade-off is clear: on one hand a large number of spare parts ties up a large amount of capital, while on the other hand too little inventory may result in extremely costly emergency actions. This is why during the last few decades inventory of spare parts control has been the topics of many publications. Recently management systems such as manufacturing resources planning (MRP) and enterprise resource planning (ERP) have been added. However, most of these contributions have similar theoretical background. This means the concepts and techniques are mainly based on mathematical assumptions and modeling inventory of spare parts situations Nuclear utilities in Korea have several problems to manage the optimum level of spare parts though they used MRP System. Because most of items have long lead time and they are imported from United States, Canada, France and so on. In this paper, we will examine the available inventory optimization models which are applicable to nuclear power plant and then select optimum model and assumptions to make inventory of spare parts strategies. Then we develop the computer program to select and determine optimum level of spare parts which should be automatically controlled by KHNP ERP system. The main contribution of this paper is an inventory of spare parts control model development, which can be applied to nuclear power plants in Korea

Comparative Safety and Efficacy Profile of a Novel Oil in Water Vaccine Adjuvant Comprising Vitamins A and E and a Catechin in Protective Anti-Influenza Immunity

Directory of Open Access Journals (Sweden)

Sapna Patel

2017-05-01

Full Text Available Non-replicating vaccines, such as those based on recombinant proteins, require adjuvants and delivery systems, which have thus far depended on mimicking pathogen danger signals and strong pro-inflammatory responses. In search of a safer and more efficacious alternative, we tested whether vaccinations with influenza recombinant hemagglutinin (HA mixed with a novel vegetable oil in water emulsion adjuvant (Natural Immune-enhancing Delivery System, NIDS, based on the immune-enhancing synergy of vitamins A and E and a catechin, could protect against intra-nasal challenge with live influenza virus. Vaccinations of inbred Brag Albino strain c (BALB/c mice, with HA mixed with NIDS compared to other adjuvants, i.e., a squalene oil in water emulsion (Sq. oil, and the Toll Like Receptor 3 (TLR3 agonist Poly (I:C, induced significantly lower select innate pro-inflammatory responses in serum, but induced significantly higher adaptive antibody and splenic T Helper 1 (TH1 or TH2, but not TH17, responses. Vaccinations with NIDS protected against infection, as measured by clinical scores, lung viral loads, and serum hemagglutination inhibition titers. The NIDS exhibited a strong dose sparing effect and the adjuvant action of NIDS was intact in the outbred CD1 mice. Importantly, vaccinations with the Sq. oil, but not NIDS, induced a significantly higher Serum Amyloid P component, an acute phase reactant secreted by hepatocytes, and total serum IgE. Thus, the NIDS may be used as a clinically safer and more efficacious vaccine adjuvant against influenza, and potentially other infectious diseases.

Nanoparticulate STING agonists are potent lymph node-targeted vaccine adjuvants.

Science.gov (United States)

Hanson, Melissa C; Crespo, Monica P; Abraham, Wuhbet; Moynihan, Kelly D; Szeto, Gregory L; Chen, Stephanie H; Melo, Mariane B; Mueller, Stefanie; Irvine, Darrell J

2015-06-01

Cyclic dinucleotides (CDNs) are agonists of stimulator of IFN genes (STING) and have potential as vaccine adjuvants. However, cyclic di-GMP (cdGMP) injected s.c. shows minimal uptake into lymphatics/draining lymph nodes (dLNs) and instead is rapidly distributed to the bloodstream, leading to systemic inflammation. Here, we encapsulated cdGMP within PEGylated lipid nanoparticles (NP-cdGMP) to redirect this adjuvant to dLNs. Compared with unformulated CDNs, encapsulation blocked systemic dissemination and markedly enhanced dLN accumulation in murine models. Delivery of NP-cdGMP increased CD8+ T cell responses primed by peptide vaccines and enhanced therapeutic antitumor immunity. A combination of a poorly immunogenic liposomal HIV gp41 peptide antigen and NP-cdGMP robustly induced type I IFN in dLNs, induced a greater expansion of vaccine-specific CD4+ T cells, and greatly increased germinal center B cell differentiation in dLNs compared with a combination of liposomal HIV gp41 and soluble CDN. Further, NP-cdGMP promoted durable antibody titers that were substantially higher than those promoted by the well-studied TLR agonist monophosphoryl lipid A and comparable to a much larger dose of unformulated cdGMP, without the systemic toxicity of the latter. These results demonstrate that nanoparticulate delivery safely targets CDNs to the dLNs and enhances the efficacy of this adjuvant. Moreover, this approach can be broadly applied to other small-molecule immunomodulators of interest for vaccines and immunotherapy.

48 CFR 217.7506 - Spare parts breakout program.

Science.gov (United States)

2010-10-01

..., DoD Supply Chain Materiel Management Regulation, Chapter 8, Section C8.3, for spare parts breakout... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Spare parts breakout program. 217.7506 Section 217.7506 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS...

Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Chang, A.E.; Steinberg, S.M.; Culnane, M.; Lampert, M.H.; Reggia, A.J.; Simpson, C.G.; Hicks, J.E.; White, D.E.; Yang, J.J.; Glatstein, E. (National Cancer Institute, Bethesda, MD (USA))

1989-09-01

We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone.

Functional and psychosocial effects of multimodality limb-sparing therapy in patients with soft tissue sarcomas

International Nuclear Information System (INIS)

Chang, A.E.; Steinberg, S.M.; Culnane, M.

1989-01-01

We have documented functional and psychosocial changes in patients with extremity soft tissue sarcomas who have undergone multimodality limb-sparing treatments. In 88 patients, parameters related to economic status, sexual activity, pain, limb function, and global quality of life (QOL) were recorded prior to surgery and every 6 months postoperatively. Changes from the preoperative assessment for every parameter were analyzed in each patient. Six months after surgery, there was a decrease in employment status, sexual activity, and in limb function in a significant number of patients. At 12 months, these decreases were still evident. Despite these changes, global QOL measured by a standardized test showed at least some improvement in a significant proportion of patients at 12 months. These findings highlight the difficulty in defining QOL. It could not be ascertained if radiation therapy and/or chemotherapy were causative factors in specific changes because of the small numbers of patients in each subgroup. However, among 60 patients with high-grade sarcomas, significant wound problems developed in 10 of 33 who received postoperative radiation therapy in combination with adjuvant doxorubicin and cyclophosphamide chemotherapy compared with one of 27 patients who received adjuvant chemotherapy alone (P = .016). Also, among high-grade sarcoma patients with 12-month follow-up, six of 19 patients who received radiation therapy and chemotherapy developed joint contractures compared with zero of 15 patients who received chemotherapy alone (P less than .04). The combination of postoperative radiation therapy and chemotherapy appeared to be associated with significantly more tissue-related injury in patients with high-grade sarcomas compared with chemotherapy alone

Joint optimization of redundancy level and spare part inventories

International Nuclear Information System (INIS)

Sleptchenko, Andrei; Heijden, Matthieu van der

2016-01-01

We consider a “k-out-of-N” system with different standby modes. Each of the N components consists of multiple part types. Upon failure, a component can be repaired within a certain time by switching the failed part by a spare, if available. We develop both an exact and a fast approximate analysis to compute the system availability. Next, we jointly optimize the component redundancy level with the inventories of the various spare parts. We find that our approximations are very accurate and suitable for large systems. We apply our model to a case study at a public organization in Qatar, and find that we can improve the availability-to-cost ratio by reducing the redundancy level and increasing the spare part inventories. In general, high redundancy levels appear to be useful only when components are relatively cheap and part replacement times are high. - Highlights: • We analyze a redundant system (k-out-of-N) with multiple parts and spares. • We jointly optimize the redundancy level and the spare part inventories. • We develop an exact method and an approximation to evaluate the system availability. • Adding spare parts and reducing the redundancy level cuts cost by 50% in a case study. • The availability is not very sensitive to the shape of the failure time distribution.

Vaccines, adjuvants and autoimmunity.

Science.gov (United States)

Guimarães, Luísa Eça; Baker, Britain; Perricone, Carlo; Shoenfeld, Yehuda

2015-10-01

Vaccines and autoimmunity are linked fields. Vaccine efficacy is based on whether host immune response against an antigen can elicit a memory T-cell response over time. Although the described side effects thus far have been mostly transient and acute, vaccines are able to elicit the immune system towards an autoimmune reaction. The diagnosis of a definite autoimmune disease and the occurrence of fatal outcome post-vaccination have been less frequently reported. Since vaccines are given to previously healthy hosts, who may have never developed the disease had they not been immunized, adverse events should be carefully accessed and evaluated even if they represent a limited number of occurrences. In this review of the literature, there is evidence of vaccine-induced autoimmunity and adjuvant-induced autoimmunity in both experimental models as well as human patients. Adjuvants and infectious agents may exert their immune-enhancing effects through various functional activities, encompassed by the adjuvant effect. These mechanisms are shared by different conditions triggered by adjuvants leading to the autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome). In conclusion, there are several case reports of autoimmune diseases following vaccines, however, due to the limited number of cases, the different classifications of symptoms and the long latency period of the diseases, every attempt for an epidemiological study has so far failed to deliver a connection. Despite this, efforts to unveil the connection between the triggering of the immune system by adjuvants and the development of autoimmune conditions should be undertaken. Vaccinomics is a field that may bring to light novel customized, personalized treatment approaches in the future. Copyright © 2015 Elsevier Ltd. All rights reserved.

An expert system for spare parts inventory control

International Nuclear Information System (INIS)

Kim, K.Y.; Chen, P.Y.C.; Okrent, D.

1987-01-01

This paper describes an expert system which can handle spare part requirements not only in corrective maintenance (CM) or preventive maintenance (PM), but also when failure rates of components or parts are updated by new data or by predictive maintenance (PDM), and which can also decide optimum stocking level of each spare part. This expert system provides a maintenance (or inventory) manager with an improved basis for decision making in the maintenance related to spare parts. The definitions of PM and PDM from NUREG-1212 (USNRC 1986) are used herein. This expert system used Intellignece/Compiler (Intelligence Ware, 1986) as a language/tool in the IBM-PC

Feasibility and safety of extended adjuvant temozolomide beyond six cycles for patients with glioblastoma.

Science.gov (United States)

Hsieh, S Yp; Chan, D Tm; Kam, M Km; Loong, H Hf; Tsang, W K; Poon, D Mc; Ng, S Cp; Poon, W S

2017-12-01

Temozolomide is the first chemotherapeutic agent proven effective for patients with newly diagnosed glioblastoma. The drug is well tolerated for its low toxicity. The current standard practice is concomitant chemoradiotherapy for 6 weeks followed by 6 cycles of adjuvant temozolomide. Some Caucasian studies have suggested that patients might benefit from extended adjuvant cycles of temozolomide (>6 cycles) to lengthen both progression-free survival and overall survival. In the present study, we compared differences in survival and toxicity profile between patients who received conventional 6-cycle temozolomide and those who received more than 6 cycles of temozolomide. Patients with newly diagnosed glioblastoma without progressive disease and completed concomitant chemoradiotherapy during a 4-year period were studied. Progression-free survival was compared using Kaplan-Meier survival curves. t Test, U test, and correlation were chosen accordingly to examine the impact of age, extent of resection, MGMT promoter methylation status and adjuvant cycles on progression-free survival. For factors with a P value of cycles of temozolomide (n=7) and 43.4 months for those who received more than 6 cycles (n=7) [P=0.007, log-rank test]. Two patients in the former group and one in the latter group encountered grade 1 toxicity and recovered following dose adjustment. Cycles of adjuvant temozolomide were correlated with progression-free survival (P=0.016, hazard ratio=0.68). Extended cycles of temozolomide are safe and feasible for Chinese patients with disease responsive to temozolomide.

Adjuvant endocrine therapy for premenopausal women with hormone-responsive breast cancer.

Science.gov (United States)

Mathew, Aju; Davidson, Nancy E

2015-11-01

Multiple strategies for endocrine treatment of premenopausal women with hormone-responsive breast cancer have been assessed and results have been presented over the last two years. These include tamoxifen for 5-10 years (ATLAS and aTTom), tamoxifen for 5 years followed by aromatase inhibitor (AI) for 5 years for women who have become postmenopausal (MA-17); ovarian ablation (OA) by surgery (EBCTCG overview); ovarian function suppression (OFS) by LHRH agonist (LHRH agonist meta-analysis); or combinations of approaches including OFS plus tamoxifen or AI (SOFT, TEXT, ABCSG 12 and E3193). Many of these trials have taken place in the backdrop of (neo)adjuvant chemotherapy which can confound interpretation because such therapy can suppress ovarian function either transiently or permanently. Nonetheless these trials suggest in aggregate that 10 years of tamoxifen are better than 5 years and that a program of extended adjuvant therapy of tamoxifen for 5 years followed by aromatase inhibitor for 5 years is effective for suitable candidates. The SOFT and E3193 trials do not show a major advantage for use of OFS + tamoxifen compared to tamoxifen alone. The joint SOFT/TEXT analysis and ABCGS12 trials both suggest that outcomes can be excellent with the use of combined endocrine therapy alone in properly selected patients but give conflicting results with regard to potential benefits for OFS + AI compared with OFS + tamoxifen. Further work will be needed to ascertain long-term outcomes, identify factors that predict who will benefit from extended adjuvant endocrine therapy, and assess role of OFS by medical or surgical means. It is clear, however, that endocrine therapy is a critical part of the adjuvant regimen for most premenopausal women with hormone-responsive breast cancer, and a subset of these women with luminal A-type tumors can be safely treated with endocrine therapy alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

A spare-parts inventory program for TRIGA reactors

Energy Technology Data Exchange (ETDEWEB)

Anderson, T V; Ringle, J C; Johnson, A G [Oregon State University (United States)

1974-07-01

As is fairly common with new reactor facilities, we had a few spare parts on hand as part of our original purchase when the OSU TRIGA first went critical in March of 1967. Within a year or so, however, it became apparent that we should critically examine our spare parts inventory in order to avoid unnecessary or prolonged outages due to lack of a crucial piece of equipment. Many critical components (those which must be present and operable according to our license or technical specifications) were considered, and a priority list of acquiring these was established. This first list was drawn up in March, 1969, two years after initial criticality, and some key components were ordered. The availability of funds was the overriding restriction then and now. This spare-parts list is reviewed and new components purchased annually; the average amount spent has been about $2,000 per year. This inventory has proved invaluable more than once; without it, we would have had lengthy shutdowns awaiting the arrival of the needed component. The sobering thought, however, is that our spare-parts inventory is still not complete-far from it, in fact, because this would be prohibitively expensive. It is very difficult to guess with 100% accuracy just which component might need replacing, and your $10,000 inventory of spare parts is useless in that instance if it doesn't include the needed part. An idea worth considering is to either (a) encourage General Atomic, through the collective voice of all TRIGA owners, to maintain a rather complete inventory of replacement parts, or (b) maintain an owner's spare-parts pool, financed by contributions from all the facilities. If either of these pools was established, the needed part could reach any facility within the U.S. within a few days, minimizing reactor outage time. (author)

A spare-parts inventory program for TRIGA reactors

International Nuclear Information System (INIS)

Anderson, T.V.; Ringle, J.C.; Johnson, A.G.

1974-01-01

As is fairly common with new reactor facilities, we had a few spare parts on hand as part of our original purchase when the OSU TRIGA first went critical in March of 1967. Within a year or so, however, it became apparent that we should critically examine our spare parts inventory in order to avoid unnecessary or prolonged outages due to lack of a crucial piece of equipment. Many critical components (those which must be present and operable according to our license or technical specifications) were considered, and a priority list of acquiring these was established. This first list was drawn up in March, 1969, two years after initial criticality, and some key components were ordered. The availability of funds was the overriding restriction then and now. This spare-parts list is reviewed and new components purchased annually; the average amount spent has been about $2,000 per year. This inventory has proved invaluable more than once; without it, we would have had lengthy shutdowns awaiting the arrival of the needed component. The sobering thought, however, is that our spare-parts inventory is still not complete-far from it, in fact, because this would be prohibitively expensive. It is very difficult to guess with 100% accuracy just which component might need replacing, and your $10,000 inventory of spare parts is useless in that instance if it doesn't include the needed part. An idea worth considering is to either (a) encourage General Atomic, through the collective voice of all TRIGA owners, to maintain a rather complete inventory of replacement parts, or (b) maintain an owner's spare-parts pool, financed by contributions from all the facilities. If either of these pools was established, the needed part could reach any facility within the U.S. within a few days, minimizing reactor outage time. (author)

Adjuvants and Their Mechanisms of Action

Directory of Open Access Journals (Sweden)

Masoumeh Foumani

2012-09-01

Full Text Available Adjuvants are chemicals, microbial components, or mammalian proteins that enhance the immune response to vaccine antigens. Reducing vaccine-related adverse effects and inducing specific types of immunity has led to the development of numerous new adjuvants. Adjuvants in experimental and commercial vaccines include aluminum salts (alum, oil emulsions, saponins, immune-stimulating complexes (ISCOMs, liposomes, microparticles, nonionic block copolymers, derivatized polysaccharides, cytokines, and a wide variety of bacterial derivatives. The mechanisms of action of these diverse compounds are different. Factors influencing the selection of an adjuvant include animal species, specific pathogen, vaccine antigen, route of immunization, and type of immunity needed. In this paper we review the current adjuvant types, structure and mechanism of action and their application in the design and production of animal and human vaccines to provide a source for students and researchers in related fields .

Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04.

Science.gov (United States)

O'Connell, Michael J; Colangelo, Linda H; Beart, Robert W; Petrelli, Nicholas J; Allegra, Carmen J; Sharif, Saima; Pitot, Henry C; Shields, Anthony F; Landry, Jerome C; Ryan, David P; Parda, David S; Mohiuddin, Mohammed; Arora, Amit; Evans, Lisa S; Bahary, Nathan; Soori, Gamini S; Eakle, Janice; Robertson, John M; Moore, Dennis F; Mullane, Michael R; Marchello, Benjamin T; Ward, Patrick J; Wozniak, Timothy F; Roh, Mark S; Yothers, Greg; Wolmark, Norman

2014-06-20

The optimal chemotherapy regimen administered concurrently with preoperative radiation therapy (RT) for patients with rectal cancer is unknown. National Surgical Adjuvant Breast and Bowel Project trial R-04 compared four chemotherapy regimens administered concomitantly with RT. Patients with clinical stage II or III rectal cancer who were undergoing preoperative RT (45 Gy in 25 fractions over 5 weeks plus a boost of 5.4 Gy to 10.8 Gy in three to six daily fractions) were randomly assigned to one of the following chemotherapy regimens: continuous intravenous infusional fluorouracil (CVI FU; 225 mg/m(2), 5 days per week), with or without intravenous oxaliplatin (50 mg/m(2) once per week for 5 weeks) or oral capecitabine (825 mg/m(2) twice per day, 5 days per week), with or without oxaliplatin (50 mg/m(2) once per week for 5 weeks). Before random assignment, the surgeon indicated whether the patient was eligible for sphincter-sparing surgery based on clinical staging. The surgical end points were complete pathologic response (pCR), sphincter-sparing surgery, and surgical downstaging (conversion to sphincter-sparing surgery). From September 2004 to August 2010, 1,608 patients were randomly assigned. No significant differences in the rates of pCR, sphincter-sparing surgery, or surgical downstaging were identified between the CVI FU and capecitabine regimens or between the two regimens with or without oxaliplatin. Patients treated with oxaliplatin experienced significantly more grade 3 or 4 diarrhea (P < .001). Administering capecitabine with preoperative RT achieved similar rates of pCR, sphincter-sparing surgery, and surgical downstaging compared with CVI FU. Adding oxaliplatin did not improve surgical outcomes but added significant toxicity. The definitive analysis of local tumor control, disease-free survival, and overall survival will be performed when the protocol-specified number of events has occurred. © 2014 by American Society of Clinical Oncology.

Favorable Outcome with Close Margins in Patients Undergoing Nipple/Skin Sparing Mastectomy with Immediate Breast Reconstruction: 5-year Follow-up

Directory of Open Access Journals (Sweden)

Enver Özkurt1

2018-02-01

Full Text Available Background: Implant-based breast reconstruction after mastectomy has recently been reported to be the preferred type of surgery among breast-specific surgeons and plastic surgeons. Aims: To explore the significant clinicopathological factors associated with long-term outcome related to local recurrences of the nipple among patients who underwent immediate breast reconstruction with tissue expander or implant after mastectomy. Study Design: Retrospective cohort. Methods: From January 2007 to January 2013, 51 breast cancer patients who underwent immediate breast reconstruction with tissue expander or implant were retrospectively analysed. Patients’ demographic data, clinicopathological characteristics, and clinical outcome by disease-free survival and disease-specific survival analyses were determined. Results: The median follow-up was 64 (31-114 months. Of the 57 mastectomies, 41 were skin sparing mastectomy (72% and 16 were nipple-areola sparing mastectomy (28%. Immediate breast reconstruction surgery included tissue expander (n=46, 81% or implant (n=11, 19% placement. The molecular subgroups of 47 invasive cancers were as follows: luminal A (n=23, 49%, luminal B (n=16, 34%, non-luminal HER2 (n=5, 10.6, triple negative breast cancer (n=3, 6.4%. The 5-years disease-specific survival, disease-free survival, and locoregional recurrence-free survival rates were 96.8%, 90%, and 97.6% respectively. Patients with luminal A cancer were found to have an improved 5-year disease-free survival time than other (luminal A; 100% vs. non-luminal A; 78%; p=0.028. Of the 14 nipple-areola sparing mastectomy, 13 had a close median tumour distance to nipple-areola complex (<20 mm with a 5-year locoregional recurrence free survival of 100%. Conclusion: Immediate breast reconstruction with implant or tissue expander can be safely applied in patients undergoing skin sparing mastectomy or nipple-areola sparing mastectomy. Patients with luminal-A type show the most

Sparing bilateral neck level IB in oropharyngeal carcinoma and xerostomia outcomes.

Science.gov (United States)

Tam, Moses; Riaz, Nadeem; Kannarunimit, Danita; Peña, Angela P; Schupak, Karen D; Gelblum, Daphna Y; Wolden, Suzanne L; Rao, Shyam; Lee, Nancy Y

2015-08-01

To assess whether sparing neck-level IB in target delineation of node-positive (N+) oropharyngeal carcinoma (OPC) can improve xerostomia outcomes without compromising locoregional control (LRC). A total of 125 N+ OPC patients with a median age of 57 years underwent chemoradiation between May 2010 and December 2011. A total of 74% of patients had T1-T2 disease, 26% T3-T4, 16% N1, 8% N2A, 48% N2B, 28% N2C; 53% base of tongue, 41% tonsil, and 6% other. Patients were divided into those who had target delineation sparing of bilateral level IB (the spared cohort) versus no sparing (the treated cohort). Sparing of contralateral high-level II nodes was also performed more consistently in the spared cohort. A prospective xerostomia questionnaire (patient reported) was given at each patient follow-up visit to this cohort of patients to assess late xerostomia. Clinical assessment (observer rated) at each patient follow-up visit was also recorded. The 2-year LRC for the spared and treated cohorts was 97.5% and 93.8%, respectively (median follow-up, 23.2 mo). No locoregional failures occurred outside of treatment fields. The spared cohort experienced significant benefits in patient-reported xerostomia summary scores (P=0.021) and observer-rated xerostomia scores (P=0.006). In addition, there were significant reductions in mean doses to the ipsilateral submandibular gland (63.9 vs. 70.5 Gy; Pxerostomia outcomes.

ERM immersion vaccination and adjuvants

DEFF Research Database (Denmark)

Skov, J.; Chettri, J. K.; Jaafar, R. M.

2015-01-01

Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

Treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy for prostate cancer

International Nuclear Information System (INIS)

Wadasaki, Koichi; Kaneyasu, Yuko; Kenjo, Masahiro; Matsuura, Kanji; Murakami, Yuji; Hashimoto, Yasutoshi; Ito, Katsuhide; Kiriu, Hiroshi; Ito, Atsushi

2007-01-01

The indications for and the efficacy of radiation therapy after radical operation for patients with prostate cancer are not clear. We analyzed the treatment results of adjuvant radiotherapy and salvage radiotherapy after radical prostatectomy. Between September 1997 and November 2004, 57 patients received adjuvant radiotherapy or salvage radiotherapy after radical prostatectomy. Fifteen patients received radiation therapy because of positive margins and/or extracapsular invasion in surgical specimens (adjuvant group). Forty-two patients received radiation therapy because of rising prostate-specific antigen (PSA) during follow-up (salvage group). Radiation therapy was delivered to the fossa of the prostate±seminal vesicles by a three-dimensional (3-D) conformal technique to a total dose of 60-66 Gy (median, 60 Gy). Biochemical control was defined as the maintenance of a PSA level of less than 0.2 ng/ml. The median follow-up period after radiation therapy was 33 months (range, 12-98 months). Three-year biochemical control rates were 87% for the adjuvant group and 61% for the salvage group. For patients in the salvage group treated without hormone therapy, the preradiation PSA value was the most significant factor for the biochemical control rate. The 3-year biochemical control rate was 93% in patients whose preradiation PSA was 0.5 ng/ml or less and 29% in patients whose preradiation PSA was more than 0.5 ng/ml. No severe adverse effects (equal to or more than grade 3) were seen in treated patients. Radiation therapy after radical prostatectomy seemed to be effective for adjuvant therapy and for salvage therapy in patients with a preradiation PSA of 0.5 ng/ml or less. Also, radiation to the fossa of the prostate±seminal vesicles, to a total dose of 60-66 Gy, using a three-dimensional (3-D) conformal technique, seemed to be safe. (author)

Limb sparing approach: Adjuvant radiation therapy in adults with intermediate or high-grade limb soft tissue sarcoma

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Merimsky, Ofer; Soyfer, Vjacheslav; Kovner, Felix; Bickels, Jacob; Issakov, Josephine; Flusser, Gideon; Meller, Isaac; Ofer, Oded; Kollender, Yehuda

2005-01-01

Background: Limb soft tissue sarcomas (STS) are currently treated with limb sparing surgery (LSS) followed by radiation therapy (RT). Patients and methods: Between October 1994 and October 2002, 133 adult patients with intermediate or high-grade limb STS were approached by LSS+RT. Results: RT related toxicity was manageable, with a low rate of severe effects. At 4-year median follow-up, there were 48 recurrences of any type, 23 of isolated local failure, and 35 of systemic spread w/o local failure. DFS and OS were influenced by disease stage II vs I, primary site in the upper limb vs lower limb, MPNST vs other types, induction therapy vs no induction, adequate resection vs marginal resection or involved margins, and good response to induction therapy vs bad response. DFS and OS were Patient's age and sex, tumor depth, acute or late toxicity of RT, or the interval of time between the date of definitive surgery and the start of RT did not affect DFS and or OS. Conclusions: The RT protocol is applicable in the era of complicated, expensive and time-consuming 3D therapy. Our results of LSS+RT in adults with limb HG STS are satisfactory

Nipple-Sparing Mastectomy Improves Long-Term Nipple But Not Skin Sensation After Breast Reconstruction: Quantification of Long-Term Sensation in Nipple Sparing Versus Non-nipple Sparing Mastectomy.

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Rodriguez-Unda, Nelson A; Bello, Ricardo J; Clarke-Pearson, Emily M; Sanyal, Abanti; Cooney, Carisa M; Manahan, Michele A; Rosson, Gedge D

2017-06-01

Changes in breast sensation after reconstruction are expected. Return of breast sensation after reconstruction and whether nipple-sparing mastectomy offers a substantial benefit in terms of sensation has been inconsistently documented in the literature. We conducted the current study using the pressure-specified sensory device to quantify postoperative breast sensation in patients undergoing nipple-sparing versus non-nipple-sparing mastectomy. Consecutive adult women who underwent nipple-sparing (NSM) and non-NSM (NNSM) and were at least 18 months postreconstruction were included. Breast measurements were taken in 4 quadrants (upper/lower lateral, upper/lower medial) and nipple. Averaged skin cutaneous thresholds [(UL+LL+UM+LM)/4] and nipple sensation between NSM and NNSM were compared as the primary outcome measure. A generalized estimating equations model was used; univariate and multivariate variable analyses were done when appropriate. Forty-four patients (74 breasts) were examined (53 NNSM vs 21 NSM). The groups were further subdivided into autologous versus implant-based reconstruction. Averaged cutaneous skin thresholds for quadrants were better for the NSM, 51.8(±24.5) g/mm versus NNSM, 56.5(±25.7) g/mm, although this difference was not statistically significant. However, NSM breasts measured higher nipple or nipple area sensitivity, 44.5(±30.8) g/mm versus NNSM, 83.8(±27.4) g/mm (P sensation was the number of revision surgeries, especially after third revision. Breast sensation is decreased after reconstruction in both NSM and NNSM, but nipple sensation or nipple area is better preserved in NSM breasts. Number of revision surgeries (>3) was a predictor of decreased sensation.

Immune response in domestic ducks following intradermal delivery of inactivated vaccine against H5N1 highly pathogenic avian influenza virus adjuvanted with oligodeoxynucleotides containing CpG motifs.

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Yuk, Seong-Su; Lee, Dong-Hun; Park, Jae-Keun; To, Eredene-Ochir; Kwon, Jung-Hoon; Noh, Jin-Yong; Gomis, Susantha; Song, Chang-Seon

2015-08-01

Ducks are a natural reservoir for H5N1 highly pathogenic avian influenza (HPAI) viruses, which produces a range of clinical outcomes from asymptomatic infections to severe disease with mortality. Vaccination against HPAI is one of the few methods available for controlling avian influenza virus (AIV) infection in domestic ducks; therefore, it is necessary to improve vaccine efficacy against HPAI in domestic ducks. However, few studies have focused on enhancing the immune response by testing alternative administration routes and adjuvants. While attempting to maximize the efficacy of a vaccine, it is important to select an appropriate vaccine delivery route and adjuvant to elicit an enhanced immune response. Although several studies have indicated that the vaccination of ducks against HPAI viruses has offered protection against lethal virus challenge, the immunogenicity of the vaccine still requires improvement. In this study, we characterized the immune response following a novel vaccination strategy against H5N1 HPAI virus in domestic ducks. Our novel intradermal delivery system and the application of the cytosine-phosphodiester-guanine (CpG) oligodeoxynucleotide (ODN) adjuvant allowed us to obtain information regarding the sustained vaccine immunity. Compared with the intramuscular route of vaccination, the intradermal route resulted in higher antibody titer as well as lower antibody deviation following secondary vaccination. In addition, the use of a CpG-ODN adjuvant had a dose-sparing effect on antibody titer. Furthermore, when a high dose of antigen was used, the CpG-ODN-adjuvanted vaccine maintained a high mean antibody titer. This data demonstrates that intradermal immunization combined with administration of CpG-ODN as an adjuvant may be a promising strategy for improving vaccine efficacy in domestic ducks. © 2015 Poultry Science Association Inc.

Endogenous and Exogenous Natural Adjuvants for Vaccine Development.

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Bolhassani, Azam; Talebi, Somayeh; Anvar, Ali

2017-01-01

Objective & Background: Various adjuvants are usually co-injected with an antigen for stimulation of effective immune responses. Adjuvants are able to elicit innate immune responses at the injection site. Depending on the activated type of innate responses, adjuvants can modify the quality and quantity of adaptive immune responses. Their mechanisms of action in vaccine development include: a) enhancement of the total antibody titers; b) reduction of the antigen dose; c) induction of potent cell-mediated immunity; d) increase in the speed and duration of the protective response; e) stimulation of mucosal immunity; and f) cross-protection. Up to now, different exogenous adjuvants have been identified to boost immune responses including inorganic compounds, mineral oil, bacterial products, non-bacterial organics, detergents or Quil A, plant saponins, Freund's complete or incomplete adjuvants, and delivery systems. However, some immune responses can be generated in the absence of the exogenous adjuvants. Indeed, endogenous adjuvants released from the cells were known as the danger signals and immunogenic compounds. Several main endogenous adjuvants contain cytokines, chemokines, alarmins, dendritic cells (DCs), toll like receptor (TLR) ligands or agonists, and antibodies. In this review, the immune activities of the natural adjuvants especially endogenous adjuvants and their mechanisms of action are discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A hot-spare injector for the APS linac

International Nuclear Information System (INIS)

Lewellen, J. W.

1999-01-01

Last year a second-generation SSRL-type thermionic cathode rf gun was installed in the Advanced Photon Source (APS) linac. This gun (referred to as ''gun2'') has been successfully commissioned and now serves as the main injector for the APS linac, essentially replacing the Koontz-type DC gun. To help ensure injector availability, particularly with the advent of top-up mode operation at the APS, a second thermionic-cathode rf gun will be installed in the APS linac to act as a hot-spare beam source. The hot-spare installation includes several unique design features, including a deep-orbit Panofsky-style alpha magnet. Details of the hot-spare beamline design and projected performance are presented, along with some plans for future performance upgrades

Graft-Sparing Strategy for Thoracic Prosthetic Graft Infection.

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Uchino, Gaku; Yoshida, Takeshi; Kakii, Bunpachi; Furui, Masato

2018-04-01

 Thoracic prosthetic graft infection is a rare but serious complication with no standard management. We reported our surgical experience on graft-sparing strategy for thoracic prosthetic graft infection.  This study included patients who underwent graft-sparing surgery for thoracic prosthetic graft infection at Matsubara Tokushukai Hospital in Japan from January 2000 to October 2017.  There were 17 patients included in the analyses, with a mean age at surgery of 71.0 ± 10.5 years; 11 were men. In-hospital mortality was observed in five patients (29.4%).  Graft-sparing surgery for thoracic prosthetic graft infection is an alternative option particularly for early graft infection after hemiarch replacement. Georg Thieme Verlag KG Stuttgart · New York.

Valve-sparing aortic root replacement†.

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Koolbergen, David R; Manshanden, Johan S J; Bouma, Berto J; Blom, Nico A; Mulder, Barbara J M; de Mol, Bas A J M; Hazekamp, Mark G

2015-02-01

To evaluate our results of valve-sparing aortic root replacement and associated (multiple) valve repair. From September 2003 to September 2013, 97 patients had valve-sparing aortic root replacement procedures. Patient records and preoperative, postoperative and recent echocardiograms were reviewed. Median age was 40.3 (range: 13.4-68.6) years and 67 (69.1%) were male. Seven (7.2%) patients were younger than 18 years, the youngest being 13.4 years. Fifty-four (55.7%) had Marfan syndrome, 2 (2.1%) other fibrous tissue diseases, 15 (15.5%) bicuspid aortic valve and 3 (3.1%) had earlier Fallot repair. The reimplantation technique was used in all, with a straight vascular prosthesis in 11 (26-34 mm) and the Valsalva prosthesis in 86 (26-32 mm). Concomitant aortic valve repair was performed in 43 (44.3%), mitral valve repair in 10 (10.3%), tricuspid valve repair in 5 (5.2%) and aortic arch replacement in 3 (3.1%). Mean follow-up was 4.2 ± 2.4 years. Follow-up was complete in all. One 14-year old patient died 1.3 years post-surgery presumably of ventricular arrhythmia. One patient underwent reoperation for aneurysm of the proximal right coronary artery after 4.9 years and 4 patients required aortic valve replacement, 3 of which because of endocarditis after 0.1, 0.8 and 1.3 years and 1 because of cusp prolapse after 3.8 years. No thrombo-embolic complications occurred. Mortality, root reoperation and aortic regurgitation were absent in 88.0 ± 0.5% at 5-year follow-up. Results of valve-sparing root replacement are good, even in association with a high incidence of concomitant valve repair. Valve-sparing aortic root replacement can be performed at a very young age as long as an adult size prosthesis can be implanted. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Testicular sparing surgery in small testis masses: A multinstitutional experience

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Andrea B. Galosi

2016-12-01

Full Text Available Introduction: The incidence of benign testicular tumors is increasing in particular in small lesion incidentally found at scrotal ultrasonography. Primary aim of this study was to perform radical surgery in malignant tumor. Secondary aim was to verify the efficacy of the diagnostic-therapeutic pathway recently adopted in management of small masses with testis sparing surgery in benign lesions. Materials and methods: In this multicenter study, we reviewed all patients with single testis lesion less than 15 mm at ultrasound as main diameter. We applied the diagnostic-therapeutic pathway described by Sbrollini et al. (Arch Ital Urol Androl 2014; 86:397 which comprises: 1 testicular tumor markers, 2 repeated scrotal ultrasound at the tertiary center, 3 surgical exploration with inguinal approach, intraoperative ultrasound, and intraoperative pathological examination. Definitive histology was reviewed by a dedicated uro-pathologist. Results: Twenty-eight patients completed this clinical flowchart. The mean lesion size was 9.3 mm (range 2.5-15. Testicular tumor markers were normal except in a case. Intraoperative ultrasound was necessary in 8/28 cases. We treated 11/28 (39.3% with immediate radical orchiectomy and 17/28 (60.7% with testis-sparing surgery. Definitive pathological results were: malignant tumor in 6 cases (seminoma, benign tumor in 10 cases (5 Leydig tumors, 2 Sertoli tumors, 1 epidermoid cyst, 1 adenomatoid tumor, 1 angiofibroma, benign disease in 11 (8 inflammation with haemorragic infiltration, 2 tubular atrophy, 1 fibrosis, and normal parenchyma in 1 case. We observed a good concordance between frozen section examination and definitive histology. Any malignant tumor was treated conservatively. Any delayed orchiectomy was necessary based on definitive histology. Conclusions: The incidence of benign lesions in 60% of small testis lesions with normal tumor markers makes orchiectomy an overtreatment. Testicular sparing surgery of single

Vaccination of dogs with six different candidate leishmaniasis vaccines composed of a chimerical recombinant protein containing ribosomal and histone protein epitopes in combination with different adjuvants.

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Poot, J; Janssen, L H M; van Kasteren-Westerneng, T J; van der Heijden-Liefkens, K H A; Schijns, V E J C; Heckeroth, A

2009-07-16

Chimerical protein "Q", composed of antigenic ribosomal and histone sequences, in combination with live BCG is a promising canine leishmaniasis vaccine candidate; one of the few vaccine candidates that have been tested successfully in dogs. Unfortunately, live BCG is not an appropriate adjuvant for commercial application due to safety problems in dogs. In order to find a safe adjuvant with similar efficacy to live BCG, muramyl dipeptide, aluminium hydroxide, Matrix C and killed Propionibacterium acnes in combination with either E. coli- or baculovirus-produced recombinant JPCM5_Q protein were tested. Groups of five or seven dogs were vaccinated with six different adjuvant-antigen combinations and challenged with a high dose intravenous injection of Leishmania infantum JPC strain promastigotes. All candidate vaccines proved to be safe, and both humoral and cellular responses to the recombinant proteins were detected at the end of the prime-boost vaccination scheme. However, clinical and parasitological data obtained during the 10 month follow-up period indicated that protection was not induced by either of the six candidate vaccines. Although no direct evidence was obtained, our data suggest that live BCG may have a significant protective effect against challenge with L. infantum in dogs.

Sparing land for biodiversity at multiple spatial scales

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Johan eEkroos

2016-01-01

Full Text Available A common approach to the conservation of farmland biodiversity and the promotion of multifunctional landscapes, particularly in landscapes containing only small remnants of non-crop habitats, has been to maintain landscape heterogeneity and reduce land-use intensity. In contrast, it has recently been shown that devoting specific areas of non-crop habitats to conservation, segregated from high-yielding farmland (‘land sparing’, can more effectively conserve biodiversity than promoting low-yielding, less intensively managed farmland occupying larger areas (‘land sharing’. In the present paper we suggest that the debate over the relative merits of land sparing or land sharing is partly blurred by the differing spatial scales at which it is suggested that land sparing should be applied. We argue that there is no single correct spatial scale for segregating biodiversity protection and commodity production in multifunctional landscapes. Instead we propose an alternative conceptual construct, which we call ‘multiple-scale land sparing’, targeting biodiversity and ecosystem services in transformed landscapes. We discuss how multiple-scale land sparing may overcome the apparent dichotomy between land sharing and land sparing and help to find acceptable compromises that conserve biodiversity and landscape multifunctionality.

Proteoliposome derived cochleate as novel adjuvant.

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Bracho, Gustavo; Lastre, Miriam; del Campo, Judith; Zayas, Caridad; González, Domingo; Gil, Danay; Acevedo, Reinaldo; Taboada, Carlos; Solís, Rosa L; Pérez, Oliver

2006-04-12

Cochleate structures (CS) consist in a highly stable lipid structures that have been reported to be a good antigen delivery system. The incorporation of pathogen associated molecular pattern (PAMP) from bacterial membranes into CS became in a promising approach to develop adjuvants, particularly mucosal adjuvants. Therefore, we prepare CS from proteoliposome (PL) obtained from Neisseria meningitidis B (PLCS) and evaluated it for its capability to stimulate the immune system as well as the adjuvant activity. The ability of PLCS to induce Thl polarization was also explored. The results and the easy capability for new antigen incorporation on CS support its use as adjuvant for immunization with a large variety of pathogen derived antigens and different routes of immunization.

Role of Adjuvant Radiosurgery after Thoracoscopic Microsurgical Resection of a Spinal Schwannoma

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Toba N. Niazi

2012-01-01

Full Text Available Stereotactic radiosurgery to benign tumors of the spine has not been advocated as a primary treatment modality because of the favorable prognosis for these lesions after gross-total resection. There is even less evidence regarding its use as an adjuvant to neurosurgical resection of benign recurrent spinal disease. We describe the case of a 30-year-old man with a thoracic spinal schwannoma who had an interval increase of his lesion five months after thoracoscopic microsurgical resection. The patient opted for noninvasive stereotactic radiosurgery in lieu of additional surgical excision and has had stable disease 15 months after radiosurgical treatment with the linear accelerator (LINAC system. In this setting, stereotactic radiosurgery provided a useful adjunct to thoracoscopic microsurgical resection. Future Class I and II evidence should be sought to evaluate the utility of stereotactic radiosurgery as a primary treatment modality or as an adjuvant for microneurosurgical resection of benign spinal lesions in patients who want noninvasive treatment after disease recurrence or who harbor medical comorbidities that would preclude them from being safe surgical candidates.

Applications of nanomaterials as vaccine adjuvants

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Zhu, Motao; Wang, Rongfu; Nie, Guangjun

2014-01-01

Vaccine adjuvants are applied to amplify the recipient's specific immune responses against pathogen infection or malignancy. A new generation of adjuvants is being developed to meet the demands for more potent antigen-specific responses, specific types of immune responses, and a high margin of safety. Nanotechnology provides a multifunctional stage for the integration of desired adjuvant activities performed by the building blocks of tailor-designed nanoparticles. Using nanomaterials for antigen delivery can provide high bioavailability, sustained and controlled release profiles, and targeting and imaging properties resulting from manipulation of the nanomaterials’ physicochemical properties. Moreover, the inherent immune-regulating activity of particular nanomaterials can further promote and shape the cellular and humoral immune responses toward desired types. The combination of both the delivery function and immunomodulatory effect of nanomaterials as adjuvants is thought to largely benefit the immune outcomes of vaccination. In this review, we will address the current achievements of nanotechnology in the development of novel adjuvants. The potential mechanisms by which nanomaterials impact the immune responses to a vaccine and how physicochemical properties, including size, surface charge and surface modification, impact their resulting immunological outcomes will be discussed. This review aims to provide concentrated information to promote new insights for the development of novel vaccine adjuvants. PMID:25483497

[Valve-sparing Replacement in Patients with Aortic Root Dilatation].

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Yamazaki, Kazuhiro; Minatoya, Kenji; Ueda, Ryoma; Takehara, Masato; Sakamoto, Kazuhisa; Ide, Yujiro; Kanemitsu, Hideo; Ueyama, Koji; Ikeda, Tadashi

2018-01-01

Valve-sparing root replacement is increasingly used to overcome drawbacks associated with valvular prostheses. In our institution, 7 patients underwent valve-sparing root replacement from August 2016 to July 2017. The mean age was 45 years (range, 14~69 years). Three patients had Marfan syndrome and 1 had Loeys-Dietz syndrome with acute aortic dissection. All patients underwent surgery with reimplantation technique using a Valsalva graft. Two patients required repair of aortic valve leaflet prolapse. All patients had an excellent clinical course, with mild or no aortic regurgitation and a decrease in end-diastolic volume on echocardiography. These results support the continued use of valve-sparing root replacement in selected patients.

Liposome-Based Adjuvants for Subunit Vaccines: Formulation Strategies for Subunit Antigens and Immunostimulators

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Signe Tandrup Schmidt

2016-03-01

Full Text Available The development of subunit vaccines has become very attractive in recent years due to their superior safety profiles as compared to traditional vaccines based on live attenuated or whole inactivated pathogens, and there is an unmet medical need for improved vaccines and vaccines against pathogens for which no effective vaccines exist. The subunit vaccine technology exploits pathogen subunits as antigens, e.g., recombinant proteins or synthetic peptides, allowing for highly specific immune responses against the pathogens. However, such antigens are usually not sufficiently immunogenic to induce protective immunity, and they are often combined with adjuvants to ensure robust immune responses. Adjuvants are capable of enhancing and/or modulating immune responses by exposing antigens to antigen-presenting cells (APCs concomitantly with conferring immune activation signals. Few adjuvant systems have been licensed for use in human vaccines, and they mainly stimulate humoral immunity. Thus, there is an unmet demand for the development of safe and efficient adjuvant systems that can also stimulate cell-mediated immunity (CMI. Adjuvants constitute a heterogeneous group of compounds, which can broadly be classified into delivery systems or immunostimulators. Liposomes are versatile delivery systems for antigens, and they can carefully be customized towards desired immune profiles by combining them with immunostimulators and optimizing their composition, physicochemical properties and antigen-loading mode. Immunostimulators represent highly diverse classes of molecules, e.g., lipids, nucleic acids, proteins and peptides, and they are ligands for pattern-recognition receptors (PRRs, which are differentially expressed on APC subsets. Different formulation strategies might thus be required for incorporation of immunostimulators and antigens, respectively, into liposomes, and the choice of immunostimulator should ideally be based on knowledge regarding the

Triacetin-based acetate supplementation as a chemotherapeutic adjuvant therapy in glioma.

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Tsen, Andrew R; Long, Patrick M; Driscoll, Heather E; Davies, Matthew T; Teasdale, Benjamin A; Penar, Paul L; Pendlebury, William W; Spees, Jeffrey L; Lawler, Sean E; Viapiano, Mariano S; Jaworski, Diane M

2014-03-15

Cancer is associated with epigenetic (i.e., histone hypoacetylation) and metabolic (i.e., aerobic glycolysis) alterations. Levels of N-acetyl-L-aspartate (NAA), the primary storage form of acetate in the brain, and aspartoacylase (ASPA), the enzyme responsible for NAA catalysis to generate acetate, are reduced in glioma; yet, few studies have investigated acetate as a potential therapeutic agent. This preclinical study sought to test the efficacy of the food additive Triacetin (glyceryl triacetate, GTA) as a novel therapy to increase acetate bioavailability in glioma cells. The growth-inhibitory effects of GTA, compared to the histone deacetylase inhibitor Vorinostat (SAHA), were assessed in established human glioma cell lines (HOG and Hs683 oligodendroglioma, U87 and U251 glioblastoma) and primary tumor-derived glioma stem-like cells (GSCs), relative to an oligodendrocyte progenitor line (Oli-Neu), normal astrocytes, and neural stem cells (NSCs) in vitro. GTA was also tested as a chemotherapeutic adjuvant with temozolomide (TMZ) in orthotopically grafted GSCs. GTA-induced cytostatic growth arrest in vitro comparable to Vorinostat, but, unlike Vorinostat, GTA did not alter astrocyte growth and promoted NSC expansion. GTA alone increased survival of mice engrafted with glioblastoma GSCs and potentiated TMZ to extend survival longer than TMZ alone. GTA was most effective on GSCs with a mesenchymal cell phenotype. Given that GTA has been chronically administered safely to infants with Canavan disease, a leukodystrophy due to ASPA mutation, GTA-mediated acetate supplementation may provide a novel, safe chemotherapeutic adjuvant to reduce the growth of glioma tumors, most notably the more rapidly proliferating, glycolytic and hypoacetylated mesenchymal glioma tumors. © 2013 UICC.

19 CFR 10.600 - Accessories, spare parts, or tools.

Science.gov (United States)

2010-04-01

...-Central America-United States Free Trade Agreement Rules of Origin § 10.600 Accessories, spare parts, or... parts, or tools are customary for the good. (a) Regional value content. If the good is subject to a regional value content requirement, the value of the accessories, spare parts, or tools is taken into...

Comparison of Dexmedetomidine and Fentanyl as an Adjuvant to Ropivacaine for Postoperative Epidural Analgesia in Pediatric Orthopedic Surgery.

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Park, Sang Jun; Shin, Seokyung; Kim, Shin Hyung; Kim, Hyun Woo; Kim, Seung Hyun; Do, Hae Yoon; Choi, Yong Seon

2017-05-01

Opioids are commonly used as an epidural adjuvant to local anesthetics, but are associated with potentially serious side effects, such as respiratory depression. The aim of this study was to compare the efficacy and safety of dexmedetomidine with that of fentanyl as an adjuvant to epidural ropivacaine in pediatric orthopedic surgery. This study enrolled 60 children (3-12 years old) scheduled for orthopedic surgery of the lower extremities and lumbar epidural patient-controlled analgesia (PCA). Children received either dexmedetomidine (1 μg/kg) or fentanyl (1 μg/kg) along with 0.2% ropivacaine (0.2 mL/kg) via an epidural catheter at 30 minutes before the end of surgery. Postoperatively, the children were observed for ropivacaine consumption via epidural PCA, postoperative pain intensity, need for rescue analgesics, emergence agitation, and other adverse effects. The mean dose of bolus epidural ropivacaine was significantly lower within the first 6 h after surgery in the dexmedetomidine group, compared with the fentanyl group (0.029±0.030 mg/kg/h vs. 0.053±0.039 mg/kg/h, p=0.012). The median pain score at postoperative 6 h was also lower in the dexmedetomidine group, compared to the fentanyl group [0 (0-1.0) vs. 1.0 (0-3.0), p=0.039]. However, there was no difference in the need for rescue analgesia throughout the study period between groups. The use of dexmedetomidine as an epidural adjuvant had a significantly greater analgesic and local anesthetic-sparing effect, compared to fentanyl, in the early postoperative period in children undergoing major orthopedic lower extremity surgery. © Copyright: Yonsei University College of Medicine 2017

Adjuvant chemo- and radiotherapy in gastrointestinal tumors

International Nuclear Information System (INIS)

Sendler, A.; Feldmann, H.J.; Fink, U.; Molls, M.; Siewert, J.R.

1995-01-01

In modern surgical oncology, adjuvant therapies are important complementary strategies. In local advanced carcinomas of the gastrointestinal tract, 5-year survival data are still disappointing despite standardized surgery. In this context, it has to be differentiated between adjuvant therapy following complete tumor exstirpation (so-called UICC R 0 resection) and additive therapies following incomplete tumor resections (UICC R 1 or R 2 resection). Modalities in the adjuvant setting are chemotherapy, radiotherapy or the combined radio-/chemotherapy. In esophageal and gastric cancer there is up to now no benefit of postoperative adjuvant therapy. In pancreatic cancer, there are studies indicating a benefit of combined radio-/chemotherapy after complete tumor resection. A standard adjuvant chemotherapeutic treatment is proven in colon cancer stage III (Dukes C) with levamisole and 5-FU. Completely resected rectal carcinoma should be treated postoperatively with combined radio-/chemotherapy. In the common clinical or practical setting, adjuvant therapy is indicated only in locally advanced gastrointestinal tumors following R 0 resection. Postoperative therapy following incomplete tumor resection has its reason only in a palliative intention. (orig.) [de

Adjuvant chemotherapy for rectal cancer: Is it needed?

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Milinis, Kristijonas; Thornton, Michael; Montazeri, Amir; Rooney, Paul S

2015-01-01

Adjuvant chemotherapy has become a standard treatment of advanced rectal cancer in the West. The benefits of adjuvant chemotherapy after surgery alone have been well established. However, controversy surrounds the use adjuvant chemotherapy in patients who received preoperative chemoradiotherapy, despite it being recommended by a number of international guidelines. Results of recent multicentre randomised control trials showed no benefit of adjuvant chemotherapy in terms of survival and rates of distant metastases. However, concerns exist regarding the quality of the studies including inadequate staging modalities, out-dated chemotherapeutic regimens and surgical approaches and small sample sizes. It has become evident that not all the patients respond to adjuvant chemotherapy and more personalised approach should be employed when considering the benefits of adjuvant chemotherapy. The present review discusses the strengths and weaknesses of the current evidence-base and suggests improvements for future studies. PMID:26677436

CTA1-DD adjuvant promotes strong immunity against human immunodeficiency virus type 1 envelope glycoproteins following mucosal immunization.

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Sundling, Christopher; Schön, Karin; Mörner, Andreas; Forsell, Mattias N E; Wyatt, Richard T; Thorstensson, Rigmor; Karlsson Hedestam, Gunilla B; Lycke, Nils Y

2008-12-01

Strategies to induce potent and broad antibody responses against the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Env) at both systemic and mucosal sites represent a central goal for HIV-1 vaccine development. Here, we show that the non-toxic CTA1-DD adjuvant promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal (i.n.) immunizations with trimeric or monomeric forms of HIV-1 Env in mice and in non-human primates. Env-specific IgG subclasses in the serum of immunized mice reflected a balanced Th1/Th2 type of response. Strikingly, i.n. immunizations with Env and the CTA1-DD adjuvant induced substantial levels of mucosal anti-Env IgA in bronchial alveolar lavage and also detectable levels in vaginal secretions. By contrast, parenteral immunizations of Env formulated in Ribi did not stimulate mucosal IgA responses, while the two adjuvants induced a similar distribution of Env-specific IgG-subclasses in serum. A single parenteral boost with Env in Ribi adjuvant into mice previously primed i.n. with Env and CTA1-DD, augmented the serum anti-Env IgG levels to similar magnitudes as those observed after three intraperitoneal immunizations with Env in Ribi. The augmenting potency of CTA1-DD was similar to that of LTK63 or CpG oligodeoxynucleotides (ODN). However, in contrast to CpG ODN, the effect of CTA1-DD and LTK63 appeared to be independent of MyD88 and toll-like receptor signalling. This is the first demonstration that CTA1-DD augments specific immune responses also in non-human primates, suggesting that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for humoral and cell-mediated immunity against HIV-1 Env.

Configuration model of partial repairable spares under batch ordering policy based on inventory state

Institute of Scientific and Technical Information of China (English)

Ruan Minzhi; Luo Yi; Li Hua

2014-01-01

Rational planning of spares configuration project is an effective approach to improve equipment availability as well as reduce life cycle cost (LCC). With an analysis of various impacts on support system, the spares demand rate forecast model is constructed. According to systemic analysis method, spares support effectiveness evaluation indicators system is built, and then, initial spares configuration and optimization method is researched. To the issue of discarding and con-sumption for incomplete repairable items, its expected backorders function is approximated by Laplace demand distribution. Combining the (s-1, s) and (R, Q) inventory policy, the spares resup-ply model is established under the batch ordering policy based on inventory state, and the optimi-zation analysis flow for spares configuration is proposed. Through application on shipborne equipment spares configuration, the given scenarios are analyzed under two constraint targets:one is the support effectiveness, and the other is the spares cost. Analysis reveals that the result is consistent with practical regulation;therefore, the model’s correctness, method’s validity as well as optimization project’s rationality are proved to a certain extent.

A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant.

Science.gov (United States)

Jiang, Janina; Liu, Guangchao; Kickhoefer, Valerie A; Rome, Leonard H; Li, Lin-Xi; McSorley, Stephen J; Kelly, Kathleen A

2017-01-19

Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4) cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP) and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG) peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a C. muridarum challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a Chlamydia -vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.

A Protective Vaccine against Chlamydia Genital Infection Using Vault Nanoparticles without an Added Adjuvant

Directory of Open Access Journals (Sweden)

Janina Jiang

2017-01-01

Full Text Available Chlamydia trachomatis genital infection is the most common sexually transmitted bacterial disease, causing a significant burden to females due to reproductive dysfunction. Intensive screening and antibiotic treatment are unable to completely prevent female reproductive dysfunction, thus, efforts have become focused on developing a vaccine. A major impediment is identifying a safe and effective adjuvant which induces cluster of differentiation 4 (CD4 cells with attributes capable of halting genital infection and inflammation. Previously, we described a natural nanocapsule called the vault which was engineered to contain major outer membrane protein (MOMP and was an effective vaccine which significantly reduced early infection and favored development of a cellular immune response in a mouse model. In the current study, we used another chlamydial antigen, a polymorphic membrane protein G-1 (PmpG peptide, to track antigen-specific cells and evaluate, in depth, the vault vaccine for its protective capacity in the absence of an added adjuvant. We found PmpG-vault immunized mice significantly reduced the genital bacterial burden and histopathologic parameters of inflammation following a C. muridarum challenge. Immunization boosted antigen-specific CD4 cells with a multiple cytokine secretion pattern and reduced the number of inflammatory cells in the genital tract making the vault vaccine platform safe and effective for chlamydial genital infection. We conclude that vaccination with a Chlamydia-vault vaccine boosts antigen-specific immunities that are effective at eradicating infection and preventing reproductive tract inflammation.

A Multidisciplinary Orbit-Sparing Treatment Approach That Includes Proton Therapy for Epithelial Tumors of the Orbit and Ocular Adnexa

Energy Technology Data Exchange (ETDEWEB)

Holliday, Emma B. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Esmaeli, Bita [Orbital Oncology and Ophthalmic Plastic Surgery Program, Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Pinckard, Jamie [School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas (United States); Garden, Adam S.; Rosenthal, David I.; Morrison, William H. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kies, Merrill S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gunn, G. Brandon; Fuller, C. David; Phan, Jack; Beadle, Beth M. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Zhu, Xiarong Ronald; Zhang, Xiaodong [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-05-01

Purpose: Postoperative radiation is often indicated in the treatment of malignant epithelial tumors of the orbit and ocular adnexa. We present details of radiation technique and toxicity data after orbit-sparing surgery followed by adjuvant proton radiation therapy. Methods and Materials: Twenty patients underwent orbit-sparing surgery followed by proton therapy for newly diagnosed malignant epithelial tumors of the lacrimal gland (n=7), lacrimal sac/nasolacrimal duct (n=10), or eyelid (n=3). Tumor characteristics, treatment details, and visual outcomes were obtained from medical records. Acute and chronic toxicity were prospectively scored using Common Terminology Criteria for Adverse Events version 4.0. Results: The median radiation dose was 60 Gy(RBE) (relative biological effectiveness; [range 50-70 Gy]); 11 patients received concurrent chemotherapy. Dose to ipsilateral anterior optic structures was reduced in 13 patients by having them gaze away from the target during treatment. At a median follow-up time of 27.1 months (range 2.6-77.2 months), no patient had experienced local recurrence; 1 had regional and 1 had distant recurrence. Three patients developed chronic grade 3 epiphora, and 3 developed grade 3 exposure keratopathy. Four patients experienced a decrease in visual acuity from baseline but maintained vision sufficient to perform all activities of daily living without difficulty. Patients with grade ≥3 chronic ocular toxicity had higher maximum dose to the ipsilateral cornea (median 46.3 Gy[RBE], range 36.6-52.7 Gy[RBE] vs median 37.4 Gy[RBE], range 9.0-47.3 Gy(RBE); P=.017). Conclusions: Orbit-sparing surgery for epithelial tumors of the orbit and ocular adnexa followed by proton therapy successfully achieved disease control and was well tolerated. No patient required orbital exenteration or enucleation. Chronic grade 3 toxicity was associated with high maximum dose to the cornea. An eye-deviation technique can be used to limit the maximum

Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

Science.gov (United States)

Payne, Richard; McDonald, David; Byrne, Scott

2015-10-01

Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice

Science.gov (United States)

Wegmann, Frank; Moghaddam, Amin E.; Schiffner, Torben; Gartlan, Kate H.; Powell, Timothy J.; Russell, Rebecca A.; Baart, Matthijs; Carrow, Emily W.

2015-01-01

The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8+ T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines. PMID:26135973

Nipple- and areola-sparing mastectomy for the treatment of breast cancer.

Science.gov (United States)

Mota, Bruna S; Riera, Rachel; Ricci, Marcos Desidério; Barrett, Jessica; de Castria, Tiago B; Atallah, Álvaro N; Bevilacqua, Jose Luiz B

2016-11-29

The efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of breast cancer are still questionable. It is estimated that the local recurrence rates following nipple-sparing mastectomy are very similar to breast-conserving surgery followed by radiotherapy. To assess the efficacy and safety of nipple-sparing mastectomy and areola-sparing mastectomy for the treatment of ductal carcinoma in situ and invasive breast cancer in women. We searched the Cochrane Breast Cancer Group's Specialized Register, the Cochrane Center Register of Controlled Trials (CENTRAL), MEDLINE (via PubMed), Embase (via OVID) and LILACS (via Biblioteca Virtual em Saúde [BVS]) using the search terms "nipple sparing mastectomy" and "areola-sparing mastectomy". Also, we searched the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials.gov. All searches were conducted on 30th September 2014 and we did not apply any language restrictions. Randomised controlled trials (RCTs) however if there were no RCTs, we expanded our criteria to include non-randomised comparative studies (cohort and case-control studies). Studies evaluated nipple-sparing and areola-sparing mastectomy compared to modified radical mastectomy or skin-sparing mastectomy for the treatment of ductal carcinoma in situ or invasive breast cancer. Two review authors (BS and RR) performed data extraction and resolved disagreements. We performed descriptive analyses and meta-analyses of the data using Review Manager software. We used Cochrane's risk of bias tool to assess studies, and adapted it for non-randomised studies, and we evaluated the quality of the evidence using GRADE criteria. We included 11 cohort studies, evaluating a total of 6502 participants undergoing 7018 procedures: 2529 underwent a nipple-sparing mastectomy (NSM), 818 underwent skin-sparing mastectomy (SSM) and 3671 underwent traditional mastectomy, also known as modified radical

Association of chitosan and aluminium as a new adjuvant strategy for improved vaccination.

Science.gov (United States)

Lebre, F; Bento, D; Ribeiro, J; Colaço, M; Borchard, G; de Lima, M C Pedroso; Borges, O

2017-07-15

The use of particulate adjuvants offers an interesting possibility to enhance and modulate the immune responses elicited by vaccines. Aluminium salts have been extensively used as vaccine adjuvants, but they lack the capacity to induce a strong cellular and mucosal immune response. Taking this into consideration, in this study we designed a new antigen delivery system combining aluminium salts with chitosan. Chitosan-aluminium nanoparticles (CH-Al NPs) exhibited a mean diameter of 280nm and a positive surface charge. The newly developed CH-Al NPs are more stable at physiological environment than classical CH NPs, showing no cytotoxic effects and revealing potential as a delivery system for a wide range of model antigens. In vivo studies showed that mice immunized with hepatitis B surface antigen (HBsAg)-containing CH NPs display high anti-HBsAg IgG titers in the serum, as well as the highest antigen-specific IgG on vaginal washes. Furthermore, in contrast to mice receiving antigen alone, mice immunized with the particulate adjuvant were able to elicit IgG2c antibody titers and exhibited higher antigen-specific IFN-γ levels in splenocytes. In conclusion, we established that CH-Al NPs, combining two immunostimulants to enhance both humoral and cellular immune responses, are a safe and promising system for antigen delivery. Our findings point towards their potential in future vaccination approaches. Copyright © 2017 Elsevier B.V. All rights reserved.

Foveal sparing in stargardt disease

NARCIS (Netherlands)

Huet, R.A.C. van; Bax, N.M.; Westeneng-van Haaften, S.C.; Muhamad, M.; Zonneveld-Vrieling, M.N.; Hoefsloot, L.H.; Cremers, F.P.M.; Boon, C.J.F.; Klevering, B.J.; Hoyng, C.B.

2014-01-01

PURPOSE: To provide a clinical and genetic description of a patient cohort with Stargardt disease (STGD1) with identifiable foveal sparing. METHODS: Patients with retinal atrophy (defined as an absence of autofluorescence) that surrounded the fovea by at least 180 degrees and did not include the

Reframing the land-sparing/land-sharing debate for biodiversity conservation.

Science.gov (United States)

Kremen, Claire

2015-10-01

Conservation biologists are devoting an increasing amount of energy to debating whether land sparing (high-yielding agriculture on a small land footprint) or land sharing (low-yielding, wildlife-friendly agriculture on a larger land footprint) will promote better outcomes for local and global biodiversity. In turn, concerns are mounting about how to feed the world, given increasing demands for food. In this review, I evaluate the land-sparing/land-sharing framework--does the framework stimulate research and policy that can reconcile agricultural land use with biodiversity conservation, or is a revised framing needed? I review (1) the ecological evidence in favor of sparing versus sharing; (2) the evidence from land-use change studies that assesses whether a relationship exists between agricultural intensification and land sparing; and (3) how that relationship may be affected by socioeconomic and political factors. To address the trade-off between biodiversity conservation and food production, I then ask which forms of agricultural intensification can best feed the world now and in the future. On the basis of my review, I suggest that the dichotomy of the land-sparing/land-sharing framework limits the realm of future possibilities to two, largely undesirable, options for conservation. Both large, protected regions and favorable surrounding matrices are needed to promote biodiversity conservation; they work synergistically and are not mutually exclusive. A "both-and" framing of large protected areas surrounded by a wildlife-friendly matrix suggests different research priorities from the "either-or" framing of sparing versus sharing. Furthermore, wildlife-friendly farming methods such as agroecology may be best adapted to provide food for the world's hungry people. © 2015 New York Academy of Sciences.

Early and medium term results of the sleeve valve-sparing procedure for aortic root ectasia.

Science.gov (United States)

Gamba, Amando; Tasca, Giordano; Giannico, Floriana; Lobiati, Elisabetta; Skouse, Douglas; Galanti, Andrea; Martino, Antonello Stefano; Triggiani, Michele

2015-04-01

The aim of this retrospective study was to evaluate our experience of using a simplified aortic valve sleeve procedure to treat aortic root ectasia and aneurysms with or without aortic regurgitation. In experienced hands, 2 aortic valve-sparing procedures, ie, Yacoub and David, have yielded excellent long-term results in the treatment of aortic root aneurysms, with or without aortic regurgitation. However, these techniques are demanding and not widely used. Recently, a new and simplified valve-sparing technique, named "sleeve procedure," has been proposed, and has yielded encouraging early results. Ninety consecutive patients with aortic root aneurysms underwent sleeve procedures from October 2006 to October 2012. Follow-up data (clinical 100% complete and echocardiographic 93% complete) were acquired from our outpatient clinic or from the referring cardiologist. The mean age of the patients was 61.5 ± 12.5 years, 79% were male, 16 (18%) had a bicuspid valve, 3 had Marfan syndrome, and 2 had aortic dissection. Over a mean clinical follow-up of 34 ± 19 months, 2 patients died from noncardiac causes and 1 was reoperated on for the recurrence of aortic regurgitation. On follow-up echocardiography after a mean of 18 ± 9 months, aortic regurgitation was absent/negligible, mild or moderate in 62%, 37%, and 1% of patients, respectively, and the diameters of the annulus, Valsalva sinuses, and sinotubular junction were 27.3 + 2.2, 37.0 + 3.4, and 30.6 + 3.1 mm, respectively. Our encouraging early and medium term results suggest that the sleeve procedure is a safe and effective aortic valve-sparing technique for the treatment of aortic root ectasia and aneurysm. However, longer follow-up is needed in order to draw definitive conclusions. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Critical spare parts ordering decisions using conditional reliability and stochastic lead time

International Nuclear Information System (INIS)

Godoy, David R.; Pascual, Rodrigo; Knights, Peter

2013-01-01

Asset-intensive companies face great pressure to reduce operation costs and increase utilization. This scenario often leads to over-stress on critical equipment and its spare parts associated, affecting availability, reliability, and system performance. As these resources impact considerably on financial and operational structures, the opportunity is given by demand for decision-making methods for the management of spare parts processes. We proposed an ordering decision-aid technique which uses a measurement of spare performance, based on the stress–strength interference theory; which we have called Condition-Based Service Level (CBSL). We focus on Condition Managed Critical Spares (CMS), namely, spares which are expensive, highly reliable, with higher lead times, and are not available in store. As a mitigation measure, CMS are under condition monitoring. The aim of the paper is orienting the decision time for CMS ordering or just continuing the operation. The paper presents a graphic technique which considers a rule for decision based on both condition-based reliability function and a stochastic/fixed lead time. For the stochastic lead time case, results show that technique is effective to determine the time when the system operation is reliable and can withstand the lead time variability, satisfying a desired service level. Additionally, for the constant lead time case, the technique helps to define insurance spares. In conclusion, presented ordering decision rule is useful to asset managers for enhancing the operational continuity affected by spare parts

Geometric factors influencing dosimetric sparing of the parotid glands using IMRT

International Nuclear Information System (INIS)

Hunt, Margie A.; Jackson, Andrew; Narayana, Ashwatha; Lee, Nancy

2006-01-01

Purpose/Objective: To determine the relationship between the parotid volume, parotid-planning target volume (PTV) overlap, and dosimetric sparing of the parotid with intensity-modulated radiation therapy (IMRT). Methods and Materials: Parotid data were collected retrospectively for 51 patients treated with simultaneous boost IMRT. Unresectable patients received 54 or 59.4 Gy to subclinical disease, 70 Gy to gross disease. Patients treated postoperatively received 54, 60, and 66 Gy to low-risk, high-risk, and tumor bed regions. Volume and mean dose of each gland and gland segments outside of and overlapping the PTV were collected. Proximity of each gland to each PTV was recorded. Results: Dosimetric sparing (mean dose ≤26.5 Gy) was achieved in 66 of 71 glands with ≤21% parotid-PTV overlap and 8 of 23 glands with >21% overlap (p = 21%. Median mean dose was 25.9 Gy to glands overlapping PTV 54 or PTV 59 alone and 30.0 Gy to those abutting PTV 7 (p 7 was associated with higher parotid dose, satisfactory sparing was achieved in 24 of 43 ipsilateral glands. Conclusions: Dosimetric sparing of the parotid is feasible when the parotid-PTV overlap is less than approximately 20%. With more overlap, sparing may result in low doses within the overlap region, possibly leading to inadequate PTV coverage. Gland proximity to the high-dose PTV is associated with higher mean dose but does not always preclude dosimetric sparing

Prophylactic Nipple-Sparing Mastectomy and Direct-to-Implant Reconstruction of the Large and Ptotic Breast: Is Preshaping of the Challenging Breast a Key to Success?

Science.gov (United States)

Gunnarsson, Gudjon L; Bille, Camilla; Reitsma, Laurens C; Wamberg, Peter; Thomsen, Jørn Bo

2017-09-01

Nipple-sparing mastectomy with simultaneous hammock technique direct-to-implant reconstruction is increasingly offered to patients opting for risk-reducing mastectomy. Despite this promising method, patients with macromastia and ptotic breasts remain a challenging group to treat satisfactorily and more often end up undergoing a difficult corrective procedure and experience an unacceptably high rate of failed reconstruction. The authors examined whether targeted preshaping mastopexy/reduction could prepare these patients for a successful nipple-sparing mastectomy/direct-to-implant reconstruction. Patients seeking risk-reducing nipple-sparing mastectomy/direct-to-implant reconstruction at the authors' institutions deemed unfit for a one-stage procedure based on their previous experience were offered a targeted two-stage, risk-reducing mastopexy/reduction followed by a delayed secondary nipple-sparing mastectomy and direct-to-implant reconstruction. Patients were followed up at 3 weeks and 6 or 12 months. Forty-four reconstructions were performed in 22 patients aged 43 years (range, 26 to 57 years). All 44 procedures were completed successfully without any failure or nipple-areola complex losses. Patients' median body mass index was 30 kg/m (range, 22 to 44 kg/m). Six patients were smokers and one had hypertension. Two patients underwent reoperation because of hematoma and fat necrosis. The authors' results demonstrate that a targeted preshaping mastopexy/reduction followed by nipple-sparing mastectomy/direct-to-implant reconstruction can be safely planned in women who opt for a risk-reducing mastectomy and can be performed successfully with a 3- to 4-month time span between operations. On the basis of these results and the superior cosmetic outcome, the two-stage approach has become the authors' standard of care in all such settings. Therapeutic, IV.

All-Cause Mortality After Fertility-Sparing Surgery for Stage I Epithelial Ovarian Cancer.

Science.gov (United States)

Melamed, Alexander; Rizzo, Anthony E; Nitecki, Roni; Gockley, Allison A; Bregar, Amy J; Schorge, John O; Del Carmen, Marcela G; Rauh-Hain, J Alejandro

2017-07-01

To compare all-cause mortality between women who underwent fertility-sparing surgery with those who underwent conventional surgery for stage I ovarian cancer. In a cohort study using the National Cancer Database, we identified women younger than 40 years diagnosed with stage IA and unilateral IC epithelial ovarian cancer between 2004 and 2012. Fertility-sparing surgery was defined as conservation of one ovary and the uterus. The primary outcome was time from diagnosis to death. We used propensity score methods to assemble a cohort of women who underwent fertility-sparing or conventional surgery but were otherwise similar on observed covariates and conducted survival analyses using the Kaplan-Meier method and Cox proportional hazard models. We identified 1,726 women with stage IA and unilateral IC epithelial ovarian cancer of whom 825 (47.8%) underwent fertility-sparing surgery. Fertility-sparing surgery was associated with younger age, residence in the northeastern and western United States, and serous or mucinous histology (Pfertility-sparing surgery and 37 deaths among propensity-matched women who underwent conventional surgery after a median follow-up of 63 months. Fertility-sparing surgery was not associated with hazard of death (hazard ratio 0.80, 95% confidence interval [CI] 0.49-1.29, P=.36). The probability of survival 10 years after diagnosis was 88.5% (95% CI 82.4-92.6) in the fertility-sparing group and 88.9% (95% CI 84.9-92.0) in the conventional surgery group. In patients with high-risk features such as clear cell histology, grade 3, or stage IC, 10-year survival was 80.5% (95% CI 68.5-88.3) among women who underwent fertility-sparing surgery and 83.4% (95% 76.0-88.7) among those who had conventional surgery (hazard ratio 0.86, 95% CI 0.49-1.53, P=.61). Compared with conventional surgery, fertility-sparing surgery was not associated with increased risk of death in young women with stage I epithelial ovarian cancer.

Novel Adjuvants and Immunomodulators for Veterinary Vaccines.

Science.gov (United States)

Heegaard, Peter M H; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the vaccine is becoming a reality with our increased understanding of innate and adaptive immune activation. This will allow future vaccines to induce immune reactivity having adequate specificity as well as protective and recallable immune effector mechanisms in appropriate body compartments, including mucosal surfaces. Here we describe these new developments and, when possible, relate new immunological knowledge to the many years of experience with traditional, empirical adjuvants. Finally, some protocols are given for production of emulsion (oil-based) and liposome-based adjuvant/antigen formulations.

Adjuvant chemotherapy and cancer cure

International Nuclear Information System (INIS)

Bertino, J.R.

1983-01-01

The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available

Cultural activities in primary school students' spare time

Directory of Open Access Journals (Sweden)

Mikanović Brane

2014-01-01

Full Text Available Culture is a form of creative expression of a human being through which he reshapes the world, acts on it adding it value and creating new, cultural values. A human being is able to create a product of culture only when he is free and able to express himself. A contemporary man can incorporate various cultural activities into his spare time. They are especially important when they concern children and young people: regardless of whether they are used in institutional settings or in spare time. The authors conducted an empirical research of students' assumptions and beliefs concerning cultural activities in their free time. The sample comprised 233 fifth grade students. The findings show that in their spare time fifth graders: engage in various cultural activities; that students who live in urban areas attend more cultural events; that students have the opportunity to engage in extra-curricular activities in the area of culture - join cultural and artistic groups and associations and engage in various creative pursuits at different levels of participation (as consumers, full participants; and that students' attitudes concerning the influence of parents and teachers on the selection of cultural activities to be pursued do not vary greatly by gender, location or school achievement. Cultural activities do play a significant part in the free time of primary school students. This is why it is important that guidance provided in school and in spare time should be brought in greaer harmony.

Integrated service engineers and spare parts planning in the maintenance logistics

NARCIS (Netherlands)

Al Hanbali, Ahmad; Zijm, Willem H.M.

2016-01-01

We analyze the integrated tactical capacity planning of spare parts supply and workforce allocation in maintenance logistics of advanced equipment. The equipment time-to-failure, spare parts replenishment time, and equipment repair time are random and independent of each other.

Muscle sparing lateral thoracotomy: the standard incision for thoracic procedures

Directory of Open Access Journals (Sweden)

Mihai Dumitrescu

2017-05-01

Full Text Available Lateral thoracotomy is a versatile approach with many variations and is currently the most widely used incision in thoracic surgery. In the current article we are presenting the muscle-sparing lateral thoracotomy in the lateral decubitus position which we consider to be the “standard” for lateral thoracotomies. Indications, surgical technique and pitfalls are described alongside our experience with thoracic drainage. Although there is no consensus regarding the name of this incision, some authors call it “axillary thoracotomy” while others call it a “modified lateral thoracotomy”, they all agree on one aspect – the importance of muscle sparing – which makes it the go-to thoracotomy for both small and large procedures involving the lung. Lateral muscle sparing thoracotomy allows for good exposure of the pulmonary hilum, fissures, apex and diaphragm. The approach is easy and quick to perform while at the same time ensuring faster postoperative recovery by sparing the latissimus dorsi muscle, better cosmetics and lower postoperative pain score when compared to the posterolateral or classical lateral thoracotomies.

Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

International Nuclear Information System (INIS)

Herman, Joseph M.; Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy; Wood, Laura D.; Blackford, Amanda L.; Ellsworth, Susannah; Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana; Hidalgo, Manuel; Donehower, Ross C.; Schulick, Richard D.; Edil, Barish H.; Choti, Michael A.; Hruban, Ralph H.

2013-01-01

Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m 2 twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m 2 on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer

Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Herman, Joseph M., E-mail: jherma15@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Fan, Katherine Y.; Wild, Aaron T.; Hacker-Prietz, Amy [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Wood, Laura D. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Blackford, Amanda L. [Department of Oncology Biostatistics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Ellsworth, Susannah [Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Zheng, Lei; Le, Dung T.; De Jesus-Acosta, Ana [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hidalgo, Manuel [Centro Nacional de Investigaciones Oncologicas, Madrid (Spain); Donehower, Ross C. [Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Schulick, Richard D.; Edil, Barish H. [Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, Colorado (United States); Choti, Michael A. [Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); Hruban, Ralph H. [Department of Pathology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland (United States); and others

2013-07-15

Purpose: Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC. Methods and Materials: Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m{sup 2} twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m{sup 2} on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS). Results: The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively. Conclusion: Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.

SNS Central Helium Liquefier spare Carbon Bed installation and commissioning

Energy Technology Data Exchange (ETDEWEB)

Degraff, Brian D. [ORNL; Howell, Matthew P. [ORNL; Kim, Sang-Ho [ORNL; Neustadt, Thomas S. [ORNL

2017-07-01

The Spallation Neutron Source (SNS) Central Helium Liquefier (CHL) at Oak Ridge National Laboratory (ORNL) has been without major operations downtime since operations were started back in 2006. This system utilizes a vessel filled with activated carbon as the final major component to remove oil vapor from the compressed helium circuit prior to insertion into the system's cryogenic cold box. The need for a spare carbon bed at SNS due to the variability of carbon media lifetime calculation to adsorption efficiency will be discussed. The fabrication, installation and commissioning of this spare carbon vessel will be presented. The novel plan for connecting the spare carbon vessel piping to the existing infrastructure will be presented.

Spare parts sharing with joint optimization of maintenance and inventory policies

DEFF Research Database (Denmark)

Larsen, Christian; Wong, Hartanto Wijaya; Nielsen, Lars Relund

We consider a collaborative arrangement where a number of companies are willing to share expensive spare parts, required for both failure replacement and preventive maintenance purposes. We develop a discrete-time Markov decision model for the joint optimization of maintenance and spare parts...

Multiobjective spare part allocation by means of genetic algorithms and Monte Carlo simulation

International Nuclear Information System (INIS)

Marseguerra, Marzio; Zio, Enrico; Podofillini, Luca

2005-01-01

The management of spare parts is a major concern for several industrial organizations, due to the significant amount of resources invested every year for holding spares inventories. In this paper, we explore the possibility of using genetic algorithms for the task of optimizing the number of spare parts required by a multi-component system. To address the question of how many spares should be kept in inventory for each component kind, the analyst is required to define objective functions with respect to which the optimization is sought. In our work we will look at multiple objectives such as, for example, the maximization of system revenues and the minimization of the total spares volume. The modeling of the system failure, repair and replacement stochastic processes is done by means of Monte Carlo simulation, whose flexibility allows a closer adherence to reality

Inventory Centralization Decision Framework for Spare Parts

DEFF Research Database (Denmark)

Gregersen, Nicklas; Herbert-Hansen, Zaza Nadja Lee

2018-01-01

Within the current literature, there is a lack of a holistic and multidisciplinary approach to managing spare parts and their inventory configuration. This paper addresses this research gap by examining the key contextual factors which influence the degree of inventory centralization and proposes...... a novel holistic theoretical framework, the Inventory Centralization Decision Framework (ICDF), useful for practitioners. Through an extensive review of inventory management literature, six contextual factors influencing the degree of inventory centralization have been identified. Using the ICDF...... practitioners can assess the most advantageous inventory configuration of spare parts. The framework is tested on a large global company which, as a result, today actively uses the ICDF; thus showing its practical applicability....

Modern Vaccines/Adjuvants Formulation—Session 2 (Plenary II)

Science.gov (United States)

Collin, Nicolas

2013-01-01

On the 15–17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies. PMID:23966098

Robotic-assisted transperitoneal nephron-sparing surgery for small renal masses with associated surgical procedures: surgical technique and preliminary experience.

Science.gov (United States)

Ceccarelli, Graziano; Codacci-Pisanelli, Massimo; Patriti, Alberto; Ceribelli, Cecilia; Biancafarina, Alessia; Casciola, Luciano

2013-09-01

Small renal masses (T1a) are commonly diagnosed incidentally and can be treated with nephron-sparing surgery, preserving renal function and obtaining the same oncological results as radical surgery. Bigger lesions (T1b) may be treated in particular situations with a conservative approach too. We present our surgical technique based on robotic assistance for nephron-sparing surgery. We retrospectively analysed our series of 32 consecutive patients (two with 2 tumours and one with 4 bilateral tumours), for a total of 37 robotic nephron-sparing surgery (RNSS) performed between June 2008 and July 2012 by a single surgeon (G.C.). The technique differs depending on tumour site and size. The mean tumour size was 3.6 cm; according to the R.E.N.A.L. Nephrometry Score 9 procedures were considered of low, 14 of moderate and 9 of hight complexity with no conversion in open surgery. Vascular clamping was performed in 22 cases with a mean warm ischemia time of 21.5 min and the mean total procedure time was 149.2 min. Mean estimated blood loss was 187.1 ml. Mean hospital stay was 4.4 days. Histopathological evaluation confirmed 19 cases of clear cell carcinoma (all the multiple tumours were of this nature), 3 chromophobe tumours, 1 collecting duct carcinoma, 5 oncocytomas, 1 leiomyoma, 1 cavernous haemangioma and 2 benign cysts. Associated surgical procedures were performed in 10 cases (4 cholecystectomies, 3 important lyses of peritoneal adhesions, 1 adnexectomy, 1 right hemicolectomy, 1 hepatic resection). The mean follow-up time was 28.1 months ± 12.3 (range 6-54). Intraoperative complications were 3 cases of important bleeding not requiring conversion to open or transfusions. Regarding post-operative complications, there were a bowel occlusion, 1 pleural effusion, 2 pararenal hematoma, 3 asymptomatic DVT (deep vein thrombosis) and 1 transient increase in creatinine level. There was no evidence of tumour recurrence in the follow-up. RNSS is a safe and feasible technique

CpG oligodeoxynucleotides are a potent adjuvant for an inactivated polio vaccine produced from Sabin strains of poliovirus.

Science.gov (United States)

Yang, Chunting; Shi, Huiying; Zhou, Jun; Liang, Yanwen; Xu, Honglin

2009-11-05

Poliovirus transmission is controlled globally through world-wide use of a live attenuated oral polio vaccine (OPV). However, the imminence of global poliovirus eradication calls for a switch to the inactivated polio vaccine (IPV). Given the limited manufacturing capacity and high cost of IPV, this switch is unlikely in most developing and undeveloped countries. Adjuvantation is an effective strategy for antigen sparing. In this study, we evaluated the adjuvanticity of CpG oligodeoxynucleotides (CpG-ODN) for an experimental IPV produced from Sabin strains of poliovirus. Our results showed that CpG-ODN, alone or in combination with alum, can significantly enhance both the humoral and cellular immune responses to IPV in mice, and, consequently, the antigen dose could be reduced substantially. Therefore, our study suggests that the global use of IPV could be facilitated by using CpG-ODN or other feasible adjuvants.

Adjuvant radiation for vulvar carcinoma: improved local control

International Nuclear Information System (INIS)

Faul, Clare M.; Mirmow, Dwight; Huang Qingshon; Gerszten, Kristina; Day, Roger; Jones, Mirka W.

1997-01-01

Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and

Adjuvant single-fraction radiotherapy is safe and effective for intractable keloids

International Nuclear Information System (INIS)

Song, Changhoon; Wu, Honggyun; Chang, Hak; Kim, Il Han; Ha, Sung W.

2014-01-01

The aim of this study was to assess the feasibility and efficacy of high-dose, single-fraction electron beam radiotherapy for therapy-resistant keloids. Before 2010, intractable keloids were treated at our institution with post-operative irradiation of 6-15 Gy in 3-5 fractionations. For convenience and cost effectiveness, we have changed our treatment protocol to high-dose single-fraction radiotherapy. A total of 12 patients with 16 keloid lesions were treated from January 2010 to January 2013 in our department. A 10-Gy dose of electron irradiation was given within 72 h of the surgical excision. The mean follow-up period was 20 months. Treatments were well tolerated, and there was no recurrence in any of the patients. Severe adverse effects were not observed. Surgical excision of the keloid, followed by immediate, single-fraction, high-dose radiotherapy, is both safe and effective in preventing recurrence of therapy-resistant keloids. (author)

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

Science.gov (United States)

Fox, Christopher B; Haensler, Jean

2013-07-01

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Does lipophilicity per se induce adjuvant effects?

DEFF Research Database (Denmark)

Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.

2007-01-01

Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... respiratory patterns were significantly affected in the MP groups. The OVA + Al(OH)3 group had a significantly higher IgG1 and IgE production, as well as higher eosinophil infiltration in the BAL fluid. These studies showed that effects of adjuvants not are necessarily due to their lipophilicity; that is...

Novel Adjuvants and Immunomodulators for Veterinary Vaccines

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers

2016-01-01

Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...

Antibody-antigen-adjuvant conjugates enable co-delivery of antigen and adjuvant to dendritic cells in cis but only have partial targeting specificity.

Directory of Open Access Journals (Sweden)

Martin Kreutz

Full Text Available Antibody-antigen conjugates, which promote antigen-presentation by dendritic cells (DC by means of targeted delivery of antigen to particular DC subsets, represent a powerful vaccination approach. To ensure immunity rather than tolerance induction the co-administration of a suitable adjuvant is paramount. However, co-administration of unlinked adjuvant cannot ensure that all cells targeted by the antibody conjugates are appropriately activated. Furthermore, antigen-presenting cells (APC that do not present the desired antigen are equally strongly activated and could prime undesired responses against self-antigens. We, therefore, were interested in exploring targeted co-delivery of antigen and adjuvant in cis in form of antibody-antigen-adjuvant conjugates for the induction of anti-tumour immunity. In this study, we report on the assembly and characterization of conjugates consisting of DEC205-specific antibody, the model antigen ovalbumin (OVA and CpG oligodeoxynucleotides (ODN. We show that such conjugates are more potent at inducing cytotoxic T lymphocyte (CTL responses than control conjugates mixed with soluble CpG. However, our study also reveals that the nucleic acid moiety of such antibody-antigen-adjuvant conjugates alters their binding and uptake and allows delivery of the antigen and the adjuvant to cells partially independently of DEC205. Nevertheless, antibody-antigen-adjuvant conjugates are superior to antibody-free antigen-adjuvant conjugates in priming CTL responses and efficiently induce anti-tumour immunity in the murine B16 pseudo-metastasis model. A better understanding of the role of the antibody moiety is required to inform future conjugate vaccination strategies for efficient induction of anti-tumour responses.

Homonymous Hemianopia with Macular Sparing: Clinical and ...

African Journals Online (AJOL)

Dr. Osoba

peripheral vision function in the cerebral cortex is located. Sparing ... Key words: brain, magnetic resonance imaging, macula, occipital lobe, vision ... luminance right homonymous hemianopia affecting inferior and superior ... infarction in left.

Towards an understanding of the adjuvant action of aluminium

Science.gov (United States)

Marrack, Philippa; McKee, Amy S.; Munks, Michael W.

2011-01-01

The efficacy of vaccines depends on the presence of an adjuvant in conjunction with the antigen. Of these adjuvants, the ones that contain aluminium, which were first discovered empirically in 1926, are currently the most widely used. However, a detailed understanding of their mechanism of action has only started to be revealed. In this Timeline article, we briefly describe the initial discovery of aluminium adjuvants and discuss historically important advances. We also summarize recent progress in the field and discuss their implications and the remaining questions on how these adjuvants work. PMID:19247370

Macula-Sparing rhegmatogenous retinal detachment: Is emergent surgery necessary?

Directory of Open Access Journals (Sweden)

Sasan Mahmoudi

2016-01-01

Full Text Available The status of the macula is a significant factor in determining final visual outcomes in rhegmatogenous retinal detachment (RRD and should be considered in the timing of surgical repair. Several studies have shown that macula-involving RRDs attain similar visual and anatomic outcomes when surgery is performed within seven days as compared to emergent surgery (within 24 hours. In contrast, surgery prior to macular detachment in macula-sparing RRDs generally yields the best visual outcomes. In the case of macula-sparing RRDs, it is not clear how long the macula may remain attached, therefore, standard practice dictates emergent surgery. Timing of presentation, examination findings, case complexity, co-existing medical conditions, surgeon expertise, and timing and quality of access to operating facilities and staff, however, should all be considered in determining whether a macula-sparing RRD requires immediate intervention or if equivalent visual and possibly better overall outcomes can be achieved with scheduled surgery within an appropriate time frame.

Management of spare parts in the obsolescence of equipment. Experiences of TECNATOM

Energy Technology Data Exchange (ETDEWEB)

Martin Frances, Antonio [Spares Engineering, TECNATOM, Ave. Montes de Oca 1, 28709, Madrid (Spain)

2010-07-01

Since 1957, Tecnatom is giving engineering specialized services to the Electric Power Generation Plants. These activities also extend to other industrial areas like aerospace sector. TECNATOM it's made up of highly qualified specialists with an extensive experience and dedicated spirit and a pool of young people who interact with them to ensure the continuity of the company as a great team. As an important part of our activities, the 'Spares Engineering', complements the reliability and guarantee of a committed company. Nowadays, because of different reasons, there is a growing problematic in the collection of safety equipment and its spares in the NPPs. Tecnatom has set several actions in motion directed to improve the availability of these equipment and spares, by means of life extension of equipment installed, by means of the development of equipment and spares alternatives to the originals, or by means of services in relation with the spare parts. The actions developed until now have provided satisfactory results in technical and economical terms for the Plants. We have developments at present in course, that we hope they will increase this contribution to solve the problems of obsolescence in NPP's. (authors)

Toxicity ranking and toxic mode of action evaluation of commonly used agricultural adjuvants on the basis of bacterial gene expression profiles.

Directory of Open Access Journals (Sweden)

Ingrid Nobels

Full Text Available The omnipresent group of pesticide adjuvants are often referred to as "inert" ingredients, a rather misleading term since consumers associate this term with "safe". The upcoming new EU regulation concerning the introduction of plant protection products on the market (EC1107/2009 includes for the first time the demand for information on the possible negative effects of not only the active ingredients but also the used adjuvants. This new regulation requires basic toxicological information that allows decisions on the use/ban or preference of use of available adjuvants. In this study we obtained toxicological relevant information through a multiple endpoint reporter assay for a broad selection of commonly used adjuvants including several solvents (e.g. isophorone and non-ionic surfactants (e.g. ethoxylated alcohols. The used assay allows the toxicity screening in a mechanistic way, with direct measurement of specific toxicological responses (e.g. oxidative stress, DNA damage, membrane damage and general cell lesions. The results show that the selected solvents are less toxic than the surfactants, suggesting that solvents may have a preference of use, but further research on more compounds is needed to confirm this observation. The gene expression profiles of the selected surfactants reveal that a phenol (ethoxylated tristyrylphenol and an organosilicone surfactant (ethoxylated trisiloxane show little or no inductions at EC(20 concentrations, making them preferred surfactants for use in different applications. The organosilicone surfactant shows little or no toxicity and good adjuvant properties. However, this study also illustrates possible genotoxicity (induction of the bacterial SOS response for several surfactants (POEA, AE, tri-EO, EO FA and EO NP and one solvent (gamma-butyrolactone. Although the number of compounds that were evaluated is rather limited (13, the results show that the used reporter assay is a promising tool to rank commonly

The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro.

Science.gov (United States)

Schuch, Rodrigo Andrade; Oliveira, Thaís Larré; Collares, Thaís Farias; Monte, Leonardo Garcia; Inda, Guilherme Roig; Dellagostin, Odir Antonio; Vendruscolo, Claire Tondo; Moreira, Angelita da Silveira; Hartwig, Daiane Drawanz

2017-01-01

The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3), and assessed the levels of IFN- γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN- γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.

The Use of Xanthan Gum as Vaccine Adjuvant: An Evaluation of Immunostimulatory Potential in BALB/c Mice and Cytotoxicity In Vitro

Directory of Open Access Journals (Sweden)

Rodrigo Andrade Schuch

2017-01-01

Full Text Available The successful production of new, safe, and effective vaccines that generate immunological memory is directly related to adjuvant feature, which is responsible for increasing and/or modulating the immune response. Several compounds display adjuvant activity, including carbohydrates. These compounds play important roles in the immune response, as well as having biocompatible properties in vaccine formulations. One such carbohydrate is xanthan gum, a polysaccharide that is produced by the plant-pathogenic bacterium Xanthomonas spp., which has adjuvant attributes. This study evaluated the immune response induced by xanthan gum associated with ovalbumin in BALB/c mice, which were subcutaneously immunized, in terms of antibody production (IgG1, IgG2a, IgG2b, and IgG3, and assessed the levels of IFN-γ in the splenocyte culture using indirect ELISA. Furthermore, we investigated in vitro cytotoxicity of xanthan in the embryo fibroblasts cell line of the NIH/3T3 mouse by MTT assay and propidium iodide uptake assay. The mice immunized with ovalbumin plus xanthan gum exhibited higher antibody IgG1 responses than control groups. Furthermore, the xanthan polysaccharide was capable of increasing the immunogenicity of antigens by producing IFN-γ and did not exhibit cytotoxicity effects in NIH/3T3 mouse fibroblast cells, considered a promising candidate for vaccine adjuvant.

Oncofertility in patients with stage I epithelial ovarian cancer: fertility-sparing surgery in young women of reproductive age.

Science.gov (United States)

Jiang, Xuan; Yang, Jiaxin; Yu, Mei; Xie, Weimin; Cao, Dongyan; Wu, Ming; Pan, Lingya; Huang, Huifang; You, Yan; Shen, Keng

2017-08-15

Fertility-sparing surgery is indicated for patients with stage I epithelial ovarian cancers. We sought to evaluate the clinical outcomes and oncofertility in a cohort of patients of reproductive age with stage I epithelial ovarian cancer (EOC). Overall, 108 patients of reproductive age (≤ 40 years) diagnosed with stage I EOC who were treated at Peking Union Medical College Hospital between 1999 and 2013 were included in the study. The Kaplan-Meier model and Cox regression analyses were used for the survival analysis. The type of surgery included fertility-sparing surgery (FSS) (48.1%) and radical surgery (RS) (51.9%). After a median follow-up of 83 months, we observed that grade 3 or clear-cell carcinoma was the only independent risk factor for disease-free survival and tumor-specific survival in the multivariate analysis. Patients with grade 3 or clear-cell carcinoma tended to be older than 30 years, have endometriosis, and undergo RS (p Fertility-sparing surgery did not affect disease-free survival or tumor-specific survival among patients of reproductive age with stage I EOC and among high-risk patients with stage IC2-3, grade 3, or clear-cell carcinoma. Thirty-four out of 52 (65.4%) FSS patients attempted to get pregnant. Twenty-eight (82.4%) achieved a successful pregnancy with a full-term delivery. Grade 3 or clear-cell carcinoma was the only independent risk factor for survival of patients of reproductive age with stage I EOC. FSS can be safely performed on patients of reproductive age with grade 1-2, stage I EOC. The safety of FSS for grade 3 and clear-cell carcinoma warrants further investigation.

Production, purification and immunogenicity of recombinant Ebola virus proteins - A comparison of Freund's adjuvant and adjuvant system 03.

Science.gov (United States)

Melén, Krister; Kakkola, Laura; He, Felix; Airenne, Kari; Vapalahti, Olli; Karlberg, Helen; Mirazimi, Ali; Julkunen, Ilkka

2017-04-01

There is an urgent need for Ebola virus (EBOV) proteins, EBOV-specific antibodies and recombinant antigens to be used in diagnostics and as potential vaccine candidates. Our objective was to produce and purify recombinant proteins for immunological assays and for the production of polyclonal EBOV specific antibodies. In addition, a limited comparison of the adjuvant effects of Freund's complete adjuvant (FCA) and adjuvant system 03 (AS03) was carried out. Recombinant EBOV GST-VP24, -VP30, -VP35, -VP40 and -NP were produced in E. coli and purified with affinity chromatography followed by preparative gel electrophoresis. Recombinant EBOV GP-His was produced in Sf9 insect cells and purified by preparative gel electrophoresis. To compare the adjuvant effect of FCA and AS03, 12 rabbits were immunized four times with one of the six recombinant EBOV proteins using FCA or AS03. In addition, three guinea pigs were immunized with EBOV VP24 using FCA. With the exception of sera from two rabbits immunized with GST-VP24, the antisera against all other EBOV proteins showed very high and specific antibody responses after three to four immunizations. The adjuvant effect of AS03 was comparable to that of FCA. The produced antibodies recognized the corresponding EBOV proteins in wild type EBOV-infected cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Immunomodulators as adjuvants for vaccines and antimicrobial therapy.

Science.gov (United States)

Nicholls, Erin F; Madera, Laurence; Hancock, Robert E W

2010-12-01

A highly effective strategy for combating infectious diseases is to enhance host defenses using immunomodulators, either preventatively, through vaccination, or therapeutically. The effectiveness of many vaccines currently in use is due in part to adjuvants, molecules that have little immunogenicity by themselves but which help enhance and appropriately skew the immune response to an antigen. The development of new vaccines necessitates the development of new types of adjuvants to ensure an appropriate immune response. Herein, we review commonly used vaccine adjuvants and discuss promising adjuvant candidates. We also discuss various other immunomodulators (namely cytokines, Toll-like receptor agonists, and host defense peptides) that are, or have potential to be, useful for antimicrobial therapies that exert their effects by boosting host immune responses rather than targeting pathogens directly.

The Protein-Sparing Modified Fast Diet

Directory of Open Access Journals (Sweden)

Marwan Bakhach MD

2016-01-01

Full Text Available Objectives: The protein-sparing modified fast (PSMF is a rigorous way of rapidly losing a large amount of weight. Although adult studies have shown the PSMF to be effective, data in adolescents are lacking. The aim of this study was to determine the efficacy and safety of the PSMF in severely obese adolescents. Methods: 12 subjects who were evaluated in the Obesity Management Program at the Cleveland Clinic from 2011 to 2014 were included. The subjects were initiated on the PSMF after failing other conventional methods of weight loss. Once the goal weight was achieved, subjects were transitioned to the refeeding phase for weight maintenance. Results: Follow-up was scheduled at 3-month (11 patients and 6-month (6 patients intervals. At the 6-month follow-up visit, the average weight loss was 11.19 kg (95% confidence interval = -5.4, -27.8, P = .028, with average of 9.8% from baseline. Fifty percent of subjects had >5% weight loss and 20% had >10% weight loss. Four patients were lost to the follow-up (40%. An improvement was noted in total cholesterol and high-density lipoprotein. Due to a small sample size these results were not statistically significant. Side effects reported by subjects were mild dehydration due to nausea (2 patients, decreased energy (1 patient, and transient labile mood (1 patient. No life-threatening side effects were reported. Conclusion: Our results show that the PSMF diet can be used as an effective and safe method in the outpatient setting for rapid weight loss in adolescents with severe obesity.

House dust extracts contain potent immunological adjuvants

NARCIS (Netherlands)

Beukelman, C.J.; Dijk, H. van; Aerts, P.C.; Rademaker, P.M.; Berrens, L.; Willers, J.M.N.

1987-01-01

A crude aqueous extract of house dust and two house dust subfractions were tested for adjuvant activity in a sensitivity assay performed in mice. Evidence is presented that house dust contains at least two potent immunological adjuvants. One of these, present in both subfractions, was probably

Adjuvant chemotherapy in early breast cancer.

Science.gov (United States)

Ejlertsen, Bent

2016-05-01

of epirubicin and the presence of TOP2A, but not the presence of HER2 aberrations. The results obtained in the 89D trial regarding TOP2A have been reproduced by others, but not consistently. However, a recent individual-patient pooled analysis of five adjuvant trials demonstrated that patients with either TOP2A or centromere 17 aberrations, but not with HER2 amplification, benefit from anthracycline-containing adjuvant chemotherapy. Anthracyclins have additional distinct biological mechanisms; and results from the DBCG 89D suggested that tumours with normal TOP2A were only non-responsive to anthracyclines if they were TIMP1 immunoreactive. The DBCG READ trial (N = 2,015) prospectively included patients without TOP2A-aberrated breast cancers, and its results are awaited for prospective confirmation of the results from the DBCG 89D and the individual-patient pooled analysis. Adjuvant chemotherapy substantially reduces the risk of recurrence and mortality of breast cancer, but is also associated with significant toxicity. However, according to a large cohort study from DBCG, chemotherapy can safely be withheld in one fourth of postmenopausal patients who will be without excess mortality following sufficient adjuvant endocrine therapy for ER positive breast cancer. A prognostic standard mortality rate index (PSI) was constructed using regression coefficients obtained in a multivariate fractional polynomials model, and most accurately identified those who could be spared chemotherapy. In addition to age, tumour size, nodal status, histological type and malignancy grade, the PSI also includes ER level addressed as a continuous variable in the MFP model. In the MFP model, absence of LVI was sufficient to counteract the impact of other risk factors, while that could not be achieved with a categorical multivariate model in a prior study. An evaluation of whether the addition of results from a molecular assay may improve the clinical utility of the PSI is on-going, but when

Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

Energy Technology Data Exchange (ETDEWEB)

Baumann, Brian C. [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Guzzo, Thomas J. [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); He Jiwei [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vaughn, David J.; Keefe, Stephen M. [Department of Medical Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Vapiwala, Neha; Deville, Curtiland; Bekelman, Justin E.; Tucker, Kai [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Hwang, Wei-Ting [Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Malkowicz, S. Bruce [Department of Urology, University of Pennsylvania, Philadelphia, Pennsylvania (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-02-01

Purpose: Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. Methods and Materials: Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. Results: Compared with stage {<=}pT2, stage {>=}pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage {>=}pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage {>=}pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage {>=}pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. Conclusions: Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest

Clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma.

Science.gov (United States)

Hu, Jun; Zhu, Li-rong; Liang, Zhi-qing; Meng, Yuan-guang; Guo, Hong-yan; Qu, Peng-peng; Ma, Cai-ling; Xu, Cong-jian; Yuan, Bi-bo

2011-10-01

To assess the clinical outcomes of fertility-sparing treatments in young patients with epithelial ovarian carcinoma (EOC). A retrospective study of young EOC inpatients (≤40 years old) was performed during January 1994 and December 2010 in eight institutions. Data were analyzed from 94 patients treated with fertility-sparing surgery with a median follow-up time of 58.7 months. As histologic grade increased, overall survival (OS) and disease-free survival (DFS) of patients receiving fertility-sparing surgery declined. Neither staging surgery nor laparoscopy of early stage EOC with conservative surgery had a significant effect on OS or DFS. Normal menstruation recommenced after chemotherapy in 89% of the fertility-sparing group. Seventeen pregnancies among twelve patients were achieved by the end of the follow-ups. Fertility-sparing treatment for patients with EOC Stage I Grade 1 could be cautiously considered for young patients. The surgical procedure and surgical route might not significantly influence the prognosis. Standard chemotherapy is not likely to have an evident impact on ovarian function or fertility in young patients.

Development of the spare parts program at Shearon Harris

International Nuclear Information System (INIS)

Roberts, A.J.

1987-01-01

Throughout construction, testing, and commercial operation of a nuclear power plant, utilities have a need for spare parts and consumables that must meet a wide range of technical and quality assurance (QA) requirements. The applications for which parts and consumables may be used need to be identified prior to procurement to ensure that the design basis of the plant is not compromised. The spare parts program at Shearon Harris nuclear power plant supported the maintenance department with the proper parts when needed for all but 5% of the maintenance work requests

ADAPTIVE OPTICS IMAGING OF FOVEAL SPARING IN GEOGRAPHIC ATROPHY SECONDARY TO AGE-RELATED MACULAR DEGENERATION.

Science.gov (United States)

Querques, Giuseppe; Kamami-Levy, Cynthia; Georges, Anouk; Pedinielli, Alexandre; Capuano, Vittorio; Blanco-Garavito, Rocio; Poulon, Fanny; Souied, Eric H

2016-02-01

To describe adaptive optics (AO) imaging of foveal sparing in geographic atrophy (GA) secondary to age-related macular degeneration. Flood-illumination AO infrared (IR) fundus images were obtained in four consecutive patients with GA using an AO retinal camera (rtx1; Imagine Eyes). Adaptive optics IR images were overlaid with confocal scanning laser ophthalmoscope near-IR autofluorescence images to allow direct correlation of en face AO features with areas of foveal sparing. Adaptive optics appearance of GA and foveal sparing, preservation of functional photoreceptors, and cone densities in areas of foveal sparing were investigated. In 5 eyes of 4 patients (all female; mean age 74.2 ± 11.9 years), a total of 5 images, sized 4° × 4°, of foveal sparing visualized on confocal scanning laser ophthalmoscope near-IR autofluorescence were investigated by AO imaging. En face AO images revealed GA as regions of inhomogeneous hyperreflectivity with irregularly dispersed hyporeflective clumps. By direct comparison with adjacent regions of GA, foveal sparing appeared as well-demarcated areas of reduced reflectivity with less hyporeflective clumps (mean 14.2 vs. 3.2; P = 0.03). Of note, in these areas, en face AO IR images revealed cone photoreceptors as hyperreflective dots over the background reflectivity (mean cone density 3,271 ± 1,109 cones per square millimeter). Microperimetry demonstrated residual function in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence. Adaptive optics allows the appreciation of differences in reflectivity between regions of GA and foveal sparing. Preservation of functional cone photoreceptors was demonstrated on en face AO IR images in areas of foveal sparing detected by confocal scanning laser ophthalmoscope near-IR autofluorescence.

Sistem Pendukung Keputusan Pengalokasian Spare Part

Directory of Open Access Journals (Sweden)

Rita Wiryasaputra

2013-01-01

Full Text Available Abstrak Era informasi yang semakin berkembang mempengaruhi lingkungan bisnis. Pengaruhnya dapat dilihat pada proses pengambilan keputusan. Proses pengambilan keputusan terhadap sejumlah alternatif dan sejumlah tujuan diselesaikan dengan sebuah sistem. Sistem  yang bermodelkan Multi Attribute Decision Making (MADM dan Multi Objective Decision Making (MODM. Model MODM digunakan untuk menyelesaikan perancangan alternatif terbaik dan model MADM digunakan untuk menyelesaikan penyeleksian terhadap beberapa alternatif dalam jumlah yang terbatas. Salah satu pendekatan model MADM adalah TOPSIS (Technique for Order Preference by Similarity to Ideal Solution. Konsep utama TOPSIS adalah alternatif preferensi terbaik memiliki jarak terpendek dari solusi ideal positif dan memiliki jarak terjauh dari solusi ideal negatif. Hasil metode TOPSIS adalah perankingan terhadap sejumlah alternatif. Salah satu masukan dari metode TOPSIS adalah nilai pembobotan kriteria. Nilai pembobotan kriteria dapat diberikan secara langsung oleh pengambil keputusan atau dihitung melalui sebuah metode. Penelitian akan menghitung nilai pembobotan kriteria dengan metode Entropy. Tujuannya adalah untuk memberikan objektifitas pembobotan kriteria. Penelitian mengangkat kasus tentang pengalokasian spare part ke sejumlah store. Alternatif terbaik dengan sumber daya yang terbatas, beberapa tujuan yang saling bertentangan didekati dengan metode Goal programming. Pengambilan keputusan akan lebih terarah karena sistem menghasilkan perankingan store spare part, dan menampilkan  informasi alokasi spare part.   Kata kunci— Sistem Pendukung Keputusan, Entropy, TOPSIS, Goal Programming   Abstract The capabilities of computrized systems facilitate decision support in a number of ways, such as speed computations, increased productivity ,improved data management and others. Decisions are often made by individuals. There may be conflicting objectives even for a  decision maker. The conflicting

Adjuvant solution for pandemic influenza vaccine production.

Science.gov (United States)

Clegg, Christopher H; Roque, Richard; Van Hoeven, Neal; Perrone, Lucy; Baldwin, Susan L; Rininger, Joseph A; Bowen, Richard A; Reed, Steven G

2012-10-23

Extensive preparation is underway to mitigate the next pandemic influenza outbreak. New vaccine technologies intended to supplant egg-based production methods are being developed, with recombinant hemagglutinin (rHA) as the most advanced program for preventing seasonal and avian H5N1 Influenza. Increased efforts are being focused on adjuvants that can broaden vaccine immunogenicity against emerging viruses and maximize vaccine supply on a worldwide scale. Here, we test protection against avian flu by using H5N1-derived rHA and GLA-SE, a two-part adjuvant system containing glucopyranosyl lipid adjuvant (GLA), a formulated synthetic Toll-like receptor 4 agonist, and a stable emulsion (SE) of oil in water, which is similar to the best-in-class adjuvants being developed for pandemic flu. Notably, a single submicrogram dose of rH5 adjuvanted with GLA-SE protects mice and ferrets against a high titer challenge with H5N1 virus. GLA-SE, relative to emulsion alone, accelerated induction of the primary immune response and broadened its durability against heterosubtypic H5N1 virus challenge. Mechanistically, GLA-SE augments protection via induction of a Th1-mediated antibody response. Innate signaling pathways that amplify priming of Th1 CD4 T cells will likely improve vaccine performance against future outbreaks of lethal pandemic flu.

An improved method for forecasting spare parts demand using extreme value theory

NARCIS (Netherlands)

Zhu, S.; Dekker, R.; van Jaarsveld, W.; Renjie, R.W.; Koning, A.J.

2017-01-01

Inventory control for spare parts is essential for many organizations due to the trade-off between preventing high holding cost and stockouts. The lead time demand distribution plays a central role in inventory control. The estimation of this distribution is problematic as the spare part demand is

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Science.gov (United States)

Nolan, Terry; Roy-Ghanta, Sumita; Montellano, May; Weckx, Lily; Ulloa-Gutierrez, Rolando; Lazcano-Ponce, Eduardo; Kerdpanich, Angkool; Safadi, Marco Aurélio Palazzi; Cruz-Valdez, Aurelio; Litao, Sandra; Lim, Fong Seng; de Los Santos, Abiel Mascareñas; Weber, Miguel Angel Rodriguez; Tinoco, Juan-Carlos; Mezerville, Marcela Hernandez-de; Faingezicht, Idis; Kosuwon, Pensri; Lopez, Pio; Borja-Tabora, Charissa; Li, Ping; Durviaux, Serge; Fries, Louis; Dubin, Gary; Breuer, Thomas; Innis, Bruce L.; Vaughn, David W.

2014-01-01

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. PMID:24652494

Comparison of Reconstructive Outcomes in Breast Cancer Patients With Preexisting Subpectoral Implants: Implant-Sparing Mastectomy With Delayed Implant Exchange Versus Immediate Tissue Expander Reconstruction.

Science.gov (United States)

Parabkaharan, Sangeetha; Melody, Megan; Trotta, Rose; Lleshi, Amina; Sun, Weihong; Smith, Paul D; Khakpour, Nazanin; Dayicioglu, Deniz

2016-06-01

Women who have undergone prior augmentation mammoplasty represent a unique subset of breast cancer patients with several options available for breast reconstruction. We performed a single institution review of surgical outcomes of breast reconstruction performed in patients with breast cancer with prior history of subpectoral breast augmentation. Institutional review board-approved retrospective review was conducted among patients with previously mentioned criteria treated at our institution between 2000 and 2014. Reconstructions were grouped into 2 categories as follows: (1) removal of preexisting subpectoral implant during mastectomy with immediate tissue expander placement and (2) implant-sparing mastectomy followed by delayed exchange to a larger implant. We reviewed demographics, tumor features, and reconstruction outcomes of these groups. Fifty-three patients had preexisting subpectoral implants. Of the 63 breast reconstructions performed, 18 (28.6%) had immediate tissue expander placed and 45 (71.4%) had implant-sparing mastectomy followed by delayed implant exchange. The groups were comparable based on age, body mass index, cancer type, tumor grade, TNM stage at presentation, and hormonal receptor status. No significant difference was noted between tumor margins or subsequent recurrence, mastectomy specimen weight, removed implant volume, volume of implant placed during reconstruction, or time from mastectomy to final implant placement. Rates of complications were significantly higher in the tissue expander group compared to the implant-sparing mastectomy group 7 (38.9%) versus 4 (8.9%) (P = 0.005). Implant-sparing mastectomy with delayed implant exchange in patients with preexisting subpectoral implants is safe and has fewer complications compared to tissue expander placement. There was no difference noted in the final volume of implant placed, time interval for final implant placement, or tumor margins.

Preventing Mitochondrial Diseases: Embryo-Sparing Donor-Independent Options.

Science.gov (United States)

Adashi, Eli Y; Cohen, I Glenn

2018-05-01

Mutant mitochondrial DNA gives rise to a broad range of incurable inborn maladies. Prevention may now be possible by replacing the mutation-carrying mitochondria of zygotes or oocytes at risk with donated unaffected counterparts. However, mitochondrial replacement therapy is being held back by theological, ethical, and safety concerns over the loss of human zygotes and the involvement of a donor. These concerns make it plain that the identification, validation, and regulatory adjudication of novel embryo-sparing donor-independent technologies remains a pressing imperative. This Opinion highlights three emerging embryo-sparing donor-independent options that stand to markedly allay theological, ethical, and safety concerns raised by mitochondrial replacement therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

Pancreas-sparing duodenectomy for an obstructive adenocarcinoma of the duodenum

OpenAIRE

Lam, D; Croome, KP; Hernandez-Alejandro, R

2012-01-01

A duodenal adenocarcinoma arising from the junction of the second and third portion of the duodenum, which was resected by pancreas-sparing duodenectomy, is reported. The completely obstructing tumour was circumferential and measured 6.5cm x 3.5cm x 1.0 cm. There was no evidence of pancreas invasion, nor any lymph node metastasis. Pancreas-sparing duodenectomy was performed, with dissection of the pancreaticoduodenal lymph nodes. The proximal duodenum was transected just distal to the ampula ...

The adjuvant potential of synthetic alkylglycerols.

Science.gov (United States)

Acevedo, Reinaldo; Gil, Danay; del Campo, Judith; Bracho, Gustavo; Valdés, Yolanda; Pérez, Oliver

2006-04-12

Alkylglycerols (AGs) have shown immune stimulant and adjuvant activity in many studies, but natural sources are not so accessible and their extraction from them is very complicated. Therefore, a group of chemists at IFAL have synthesized AG analogs. The aim of this work was to evaluate the adjuvant potential of different synthetic AGs. A mix of ovoalbumin (Ova) and AGs increase anti-Ova IgG antibodies production in sera of immunized mice. The predominant subclass was IgG1 although higher levels of IgG2a were observed as the carbon chain length of AGs increased. AGs also induced the production of IL-12 and nitric oxide (NO) in the U937 human histiocyte and J774 mouse macrophage cell lines, respectively. These results indicate that synthetic AGs are effective adjuvants for the standardized antigen, Ova.

A new model for Assessment and Optimization of Number of Spare Transformers and their Locations in Distribution Systems

Directory of Open Access Journals (Sweden)

M Sedaghati

2015-12-01

Full Text Available In this paper, a new model has been presented to determine the number of spare transformers and their locations for distribution stations. The number of spare transformers must be so that they need minimum investment. Furthermore, they must be sufficient for replacing with transformers that have been damaged. For this reason, in this paper a new purpose function has been presented to maximize profit in distribution company’s budgeting and planning. For determining the number of spares that must be available in a stock room, this paper considers the number of spares and transformer’s fault at the same time. The number of spare transformers is determined so that at least one spare transformer will be available for replacing with the failed transformers. This paper considers time required for purchasing or repairing a failed transformer to determine the number of required spare transformers. Furthermore, whatever the number of spare equipment are increased, cost of maintenance will be increased, so an economic comparison must be done between reduced costs from reducing of outage time and increased costs from spare transformers existence.

SOME SIMPLE APPROACHES TO PLANNING THE INVENTORY OF SPARE COMPONENTS OF AN INDUSTRIAL SYSTEM

Directory of Open Access Journals (Sweden)

Alenka Brezavšek

2016-02-01

Full Text Available Two variants of a simple stochastic model for planning the inventory of spare components supporting maintenance of an industrial system are developed. In both variants, the aim is to determine how many spare components are needed at the beginning of a planning interval to fulfil demand for corrective replacements during this interval. Under the first variant, the acceptable probability of spare shortage during the planning interval is chosen as a decision variable while in the second variant, the adequate spare inventory level is assessed taking into account the expected number of component failures within the planning interval. Calculation of the number of spare components needed depends on the form of the probability density function of component failure times. Different statistical density functions that are useful to describe this function are presented. Advantages and disadvantages of using a particular density function in our model are discussed. The applicability of the model is given through illustrative numerical examples.

Aortic valve sparing root surgery for Marfan syndrome.

Science.gov (United States)

Matalanis, George; Perera, Nisal K

2017-11-01

Aortic valve sparing root surgery (AVSRS) is a safe and durable alternative for patients with dilated roots or pure aortic regurgitation (AR), which avoids the risks of anticoagulation or valvular degeneration with prosthetic valves. Notwithstanding the theoretical challenges of greater tissue fragility in Marfan syndrome (MFS), AVSRS has been demonstrated to have equal outcomes in this condition as it does in those without MFS. The benefits of retaining the native aortic valve in this generally younger age group extend beyond those of avoiding the inconvenience and complications of prolonged exposure to anticoagulants and include ease of management for future aortic, cardiac and non-cardiac procedures which are the norm for these patients. The essential principles of AVSRS in MFS do not differ from those for the rest of the population. Successful repair and durable valve function depend on a sound understanding of the close interaction between the structure and function of this exquisitely designed piece of engineering. We are fortunate to have numerous tools in our surgical armamentarium to preserve these valves. It is the purpose of this paper to demystify the complex structure-function interactions of the aortic valve, thereby gaining an intuition for AVSRS. We will also elaborate on specific technical details of established techniques that we have found successful in preserving the normal function of these valves in the long term.

An overview of adjuvants utilized in prophylactic vaccine formulation as immunomodulators.

Science.gov (United States)

Chauhan, Nidhi; Tiwari, Sukirti; Iype, Tessy; Jain, Utkarsh

2017-05-01

Development of efficient and cost effective vaccines have been recognized as the primary concern to improve the overall healthcare in a country. In order to achieve this goal, more improved and powerful adjuvants need to be developed. Lacking in the self-adjuvanting immuno-modulatory constituents, vaccines exhibit lower immunogenicity. Combining potent adjuvants with vaccines is the most appropriate method to enhance the efficacy of the vaccines. Hence, this review is focussed on the most potent adjuvants for the formulation of vaccines. Areas covered: This review focuses on Oil-based emulsions, Mineral compounds, Liposomes, Bacterial products, ISCOMs and most recently used nanomaterials as adjuvants for enhancing the antigenicity of vaccines. Furthermore, this review explains the immunological response elicited by various particles. Moreover, case studies are incorporated providing an in depth analyses of various adjuvant-containing vaccines which are currently used. Expert commentary: Enhanced fundamental knowledge about the adjuvants and their immuno-stimulatory capabilities and delivery mechanisms will facilitate the rational designing of prophylactic vaccines with better efficacy.

A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yi [Yisheng Biopharma. Co., Ltd., Beijing (China); Zhang, Shoufeng [Academy of Military Medical Sciences, Changchun (China); Li, Wei [National Center for Safety Evaluation of Drugs, Beijing (China); Hu, Yuchi; Zhao, Jinyan [Beijing Institute for Drug Control, Beijing (China); Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu [Yisheng Biopharma. Co., Ltd., Beijing (China); Hu, Rongliang, E-mail: ronglianghu@hotmail.com [Academy of Military Medical Sciences, Changchun (China); Shao, Hui, E-mail: hui.shao@yishengbio.com [Yisheng Biopharma. Co., Ltd., Beijing (China); Li, Lietao, E-mail: lietao.li@gmail.com [Yisheng Biopharma. Co., Ltd., Beijing (China)

2016-02-15

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

International Nuclear Information System (INIS)

Zhang, Yi; Zhang, Shoufeng; Li, Wei; Hu, Yuchi; Zhao, Jinyan; Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu; Hu, Rongliang; Shao, Hui; Li, Lietao

2016-01-01

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

Does Smoking History Confer a Higher Risk for Reconstructive Complications in Nipple-Sparing Mastectomy?

Science.gov (United States)

Frey, Jordan D; Alperovich, Michael; Levine, Jamie P; Choi, Mihye; Karp, Nolan S

2017-07-01

History of smoking has been implicated as a risk factor for reconstructive complications in nipple-sparing mastectomy (NSM), however there have been no direct analyses of outcomes in smokers and nonsmokers. All patients undergoing NSM at New York University Langone Medical Center from 2006 to 2014 were identified. Outcomes were compared for those with and without a smoking history and stratified by pack-year smoking history and years-to-quitting (YTQ). A total of 543 nipple-sparing mastectomies were performed from 2006 to 2014 with a total of 49 in patients with a history of smoking. Reconstructive outcomes in NSM between those with and without a smoking history were equivalent. Those with a smoking history were not significantly more likely to have mastectomy flap necrosis (p = 0.6251), partial (p = 0.8564), or complete (p = 0.3365) nipple-areola complex (NAC) necrosis. Likewise, active smokers alone did not have a higher risk of complications compared to nonsmokers or those with smoking history. Comparing nonsmokers and those with a less or greater than 10 pack-year smoking history, those with a > 10 pack-year history had significantly more complete NAC necrosis (p = 0.0114, smoking history or >5 YTQ prior to NSM were equivalent to those without a smoking history. We demonstrate that NSM may be safely offered to those with a smoking history although a > 10 pack-year smoking history or <5 YTQ prior to NSM may impart a higher risk of reconstructive complications, including complete NAC necrosis. © 2017 Wiley Periodicals, Inc.

Environmental adjuvants, apoptosis and the censorship over autoimmunity.

Science.gov (United States)

Rovere-Querini, Patrizia; Manfredi, Angelo A; Sabbadini, Maria Grazia

2005-11-01

Alterations during apoptosis lead to the activation of autoreactive T cells and the production of autoantibodies. This article discusses the pathogenic potential of cells dying in vivo, dissecting the role of signals that favor immune responses (adjuvants) and the influence of genetic backgrounds. Diverse factors determine whether apoptosis leads or not to a self-sustaining, clinically apparent autoimmune disease. The in vivo accumulation of uncleared dying cells per se is not sufficient to cause disease. However, dying cells are antigenic and their complementation with immune adjuvants causes lethal diseases in predisposed lupus-prone animals. At least some adjuvant signals directly target the function and the activation state of antigen presenting cells. Several laboratories are aggressively pursuing the molecular identification of endogenous adjuvants. Sodium monourate and the high mobility group B1 protein (HMGB1) are, among those identified so far, well known to rheumatologists. However, even the complementation of apoptotic cells with potent adjuvant signals fail to cause clinical autoimmunity in most strains: autoantibodies generated are transient, do not undergo to epitope/spreading and do not cause disease. Novel tools for drug development will derive from the molecular identification of the constraints that prevent autoimmunity in normal subjects.

Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8+ TEM and TRM Cell Responses against Herpesvirus Infection and Disease.

Science.gov (United States)

Lopes, Patricia P; Todorov, George; Pham, Thanh T; Nesburn, Anthony B; Bahraoui, Elmostafa; BenMohamed, Lbachir

2018-04-15

There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8 + T cell epitope (HSV-gB 498-505 ) covalently linked with the promiscuous glycoprotein D CD4 + T helper cell epitope (HSV-gD 49-89 ). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8 + T cells (T EM cells) and tissue-resident CD8 + T cells (T RM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections. IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser

Post-nerve-sparing prostatectomy, dose-escalated intensity-modulated radiotherapy: effect on erectile function

International Nuclear Information System (INIS)

Bastasch, Michael D.; Teh, Bin S.; Mai, W.-Y.; Carpenter, L. Steven; Lu, Hsin H.; Chiu, J. Kam; Woo, Shiao Y.; Grant, Walter H.; Miles, Brian J.; Kadmon, Dov; Butler, E. Brian

2002-01-01

Purpose: The advent of widespread prostate-specific antigen screening has resulted in more younger, potent men being diagnosed with early-stage, organ-confined prostate cancer amenable to definitive surgery. Nerve-sparing prostatectomy is a relatively new surgical advance in the treatment of prostate cancer. Very few data exist on the effect of postoperative radiotherapy (RT) on erectile function after nerve-sparing prostatectomy. They are based on conventional techniques using moderate doses of radiation, 45-54 Gy. Intensity-modulated RT (IMRT) is becoming more widespread because it allows dose escalation with increased sparing of the surrounding normal tissue. We investigated the effect of postprostatectomy, high-dose IMRT on patients' erectile function. Methods and Materials: A review of patient records found 51 patients treated between April 1998 and December 2000 with IMRT after unilateral or bilateral nerve-sparing prostatectomy. The pathologic disease stage in these patients was T2 in 47.4% and T3 in 52.6%. Postoperatively, 4 patients received hormonal ablation consisting of one injection of Lupron Depot (30 mg) 2 months before RT. The median age was 65 years (range 46-77) at the time of RT. The prescribed dose was 64 Gy (range 60-66). The mean dose was 69.6 Gy (range 64.0-72.3). Erectile function was assessed before and after RT by questionnaires. Sexual potency was defined as erectile rigidity adequate for vaginal penetration. Results: Of the 51 patients, 18 (35.3%) maintained their potency and 33 (64.7%) became impotent after nerve-sparing prostatectomy. Patients who underwent bilateral nerve-sparing prostatectomy had higher rates of postoperative potency than did those who underwent unilateral nerve-sparing surgery (72.2% vs. 27.8%; p=0.025). The follow-up for the entire group was 19.5 months. All 18 patients (100%) who were potent postoperatively remained potent after RT. The median follow-up for the 18 potent patients was 27.2 months, significantly

Adjuvant Therapy for Gallbladder Carcinoma: The Mayo Clinic Experience

International Nuclear Information System (INIS)

Gold, Douglas G.; Miller, Robert C.; Haddock, Michael G.; Gunderson, Leonard L.; Quevedo, Fernando; Donohue, John H.; Bhatia, Sumita; Nagorney, David M.

2009-01-01

Purpose: To analyze the effect of adjuvant chemoradiotherapy on gallbladder carcinoma. Methods and Materials: We retrospectively reviewed the records from consecutive patients who underwent R0 resection of gallbladder carcinoma between January 1, 1985, and December 31, 2004. Patients had either Stage I (T1-T2N0M0) or Stage II (T3N0M0 or T1-T3N1M0) disease. Patients undergoing adjuvant therapy received 5-fluorouracil chemotherapy concurrently with radiotherapy (median dosage, 50.4 Gy in 28 fractions). Adverse prognostic factors and the effect of adjuvant treatment on overall survival (OS) were evaluated. Results: A total of 73 patients were included in the analysis; of these, 25 received adjuvant chemoradiotherapy. On univariate analysis, no adverse prognostic factors for OS reached statistical significance, but trends were noted for Stage N1 vs. N0 (p = .06), Nx vs. N0 (p = .09), Stage T3 vs. T1-T2 (p = .06), and histologic findings other than adenocarcinoma (p = .13). The median OS for patients receiving adjuvant chemoradiotherapy vs. surgery alone was 4.8 years and 4.2 years, respectively (log-rank test, p = .56). However, a significantly greater percentage of patients receiving adjuvant chemoradiotherapy had Stage II disease (p <.001). In the multivariate Cox model, increasing T and N category and histologic findings other than adenocarcinoma were significant predictors of decreased OS. Additionally, adjuvant chemoradiotherapy was a significant predictor of improved OS after adjusting for these prognostic factors (hazard ratio for death, 0.3; 95% confidence interval, 0.13-0.69; p = .004). Conclusion: After adjusting for the stage parameters and histologic findings, our data suggest that adjuvant chemoradiotherapy might improve OS for patients with gallbladder cancer.

Endovenous Laser Ablation of the Small Saphenous Vein Sparing the Saphenopopliteal Junction

International Nuclear Information System (INIS)

Janne d'Othee, Bertrand; Walker, T. Gregory; Kalva, Sanjeeva P.; Ganguli, Suvranu; Davison, Brian

2010-01-01

To assess outcomes after endovenous laser ablation (EVLA) of the small saphenous vein (SSV). Retrospective review was performed of all consecutive EVLA procedures performed over a 39-month period at three neighboring vein practices for symptomatic, duplex ultrasound-proven incompetence of the SSV. EVLA was performed under ultrasound guidance with an 810- or 980-nm diode laser in continuous mode using the pullback method while sparing the deep, most cephalad segment of the SSV near the saphenopopliteal junction. Follow-up after EVLA included patient symptoms, physical examination, and duplex ultrasound. Pretreatment variables were similar across all three practices. EVLA was performed to treat 67 incompetent SSVs in 63 patients (86% women; mean age and 95% confidence interval, 50 ± 3 years; range, 20-82 years). Average energy delivered was 92 J/cm. Immediate technical success and occlusion of the treated vein at 1-2 weeks was 100%. Imaging follow-up length was 243 ± 65 days (range, 3-893 days). Clinical follow-up (243 ± 66 days) showed symptomatic improvement in 66 (99%) of 67 patients; one patient had recanalization with recurrent reflux by ultrasound (2%). Complications included one case of paresthesias lasting beyond 1 month of follow-up (2%) and three cases of superficial phlebitis (4%), but no deep vein thrombosis, skin burns, or other complications. Although ablation involved only the superficial portion of the SSV and spared its deep segment in the popliteal fossa, SSV occlusion typically extended up to the saphenopopliteal junction or to a gastrocnemial collateral, without popliteal vein involvement. EVLA of the SSV is safe and effective when the saphenopopliteal junction and popliteal fossa are avoided. This approach may help reduce the risk of paresthesias or other complications while maintaining low recanalization rates.

Cognitive Spare Capacity and Speech Communication: A Narrative Overview

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Mary Rudner

2014-01-01

Full Text Available Background noise can make speech communication tiring and cognitively taxing, especially for individuals with hearing impairment. It is now well established that better working memory capacity is associated with better ability to understand speech under adverse conditions as well as better ability to benefit from the advanced signal processing in modern hearing aids. Recent work has shown that although such processing cannot overcome hearing handicap, it can increase cognitive spare capacity, that is, the ability to engage in higher level processing of speech. This paper surveys recent work on cognitive spare capacity and suggests new avenues of investigation.

Optimal provisioning strategies for slow moving spare parts with small lead times

NARCIS (Netherlands)

Teunter, R.H.; Klein Haneveld, W.K.

When an expensive piece of equipment is bought, spare parts can often be bought at a reduced price. A decision must be made about the initial provisioning of spare parts. Furthermore, if at a certain time the stock drops to zero, because a number of failures have occurred, a decision must be made

Model of delivery consolidation of critical spare part : case study of an oil and gas company

Science.gov (United States)

Hartanto, D.; Agustinita, A.

2018-04-01

The availability of spare parts in oil and gas industry is very important to prevent the occurrence of very high opportunity cost, that is the loss caused by exploitation equipment which must stop because of unavailability of the spare part. This is done by providing safety stock with a very high service level that leads to high inventory costs. If the company wants to lower inventory costs, the choices are not to lower the service level but to lower the ordering cost. One of the components of ordering cost is the delivery cost. Exploitation facilities are usually located in remote areas so that the cost of delivery is high. In addition, many spare parts are supplied by the same supplier. Therefore, there is an opportunity to lower the cost of delivery of spare parts by consolidation. In this paper,mixed integer linear programming (MILP) model is developed to plan the procurement of spare parts so that inventory costs which include holding and ordering cost for spare parts can be minimized. The model has been verified and validated. Using this model the company can lower inventory costs of the spare part by 32%.

Hippocampus sparing in whole-brain radiotherapy. A review

International Nuclear Information System (INIS)

Oskan, F.; Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M.

2014-01-01

Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [de

Membrane-bound IL-12 and IL-23 serve as potent mucosal adjuvants when co-presented on whole inactivated influenza vaccines.

Science.gov (United States)

Khan, Tila; Heffron, Connie L; High, Kevin P; Roberts, Paul C

2014-05-03

Potent and safe adjuvants are needed to improve the efficacy of parenteral and mucosal vaccines. Cytokines, chemokines and growth factors have all proven to be effective immunomodulatory adjuvants when administered with a variety of antigens. We have previously evaluated the efficacy of membrane-anchored interleukins (IL) such as IL-2 and IL-4 co-presented as Cytokine-bearing Influenza Vaccines (CYT-IVACs) using a mouse model of influenza challenge. Here, we describe studies evaluating the parenteral and mucosal adjuvanticity of membrane-bound IL-12 and IL-23 CYT-IVACs in young adult mice. Mucosal immunization using IL-12 and IL-23 bearing whole influenza virus vaccine (WIV) was more effective at eliciting virus-specific nasal IgA and reducing viral lung burden following challenge compared to control WIV vaccinated animals. Both IL-12 and IL-23 bearing WIV elicited the highest anti-viral IgA levels in serum and nasal washes. This study highlights for the first time the mucosal adjuvant potential of IL-12 and IL-23 CYT-IVAC formulations in eliciting mucosal immune responses and reducing viral lung burden. The co-presentation of immunomodulators in direct context with viral antigen in whole inactivated viral vaccines may provide a means to significantly lower the dose of vaccine required for protection.

Music as an adjuvant therapy in control of pain and symptoms in hospitalized adults: a systematic review.

Science.gov (United States)

Cole, Linda C; LoBiondo-Wood, Geri

2014-03-01

The objective of this review is to evaluate the evidence regarding the use of music as an adjuvant therapy for pain control in hospitalized adults. The search terms music, music therapy, pain, adults, inpatient, and hospitalized were used to search the Cochrane Library, Cinahl, Medline, Natural Standard, and Scopus databases from January 2005 to March 2011. (A systematic review conducted by the Cochrane Collaboration has extensively covered the time frame from 1966 to 2004.) Seventeen randomized controlled trials met criteria for review and inclusion. Seven of the research studies were conducted with surgical patients, three with medical patients, one with medical-surgical patients, four with intensive care patients, and two with pregnant patients. The combined findings of these studies provide support for the use of music as an adjuvant approach to pain control in hospitalized adults. The use of music is safe, inexpensive, and an independent nursing function that can be easily incorporated into the routine care of patients. Copyright © 2014 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Erlotinib-induced rash spares previously irradiated skin

International Nuclear Information System (INIS)

Lips, Irene M.; Vonk, Ernest J.A.; Koster, Mariska E.Y.; Houwing, Ronald H.

2011-01-01

Erlotinib is an epidermal growth factor receptor inhibitor prescribed to patients with locally advanced or metastasized non-small cell lung carcinoma after failure of at least one earlier chemotherapy treatment. Approximately 75% of the patients treated with erlotinib develop acneiform skin rashes. A patient treated with erlotinib 3 months after finishing concomitant treatment with chemotherapy and radiotherapy for non-small cell lung cancer is presented. Unexpectedly, the part of the skin that had been included in his previously radiotherapy field was completely spared from the erlotinib-induced acneiform skin rash. The exact mechanism of erlotinib-induced rash sparing in previously irradiated skin is unclear. The underlying mechanism of this phenomenon needs to be explored further, because the number of patients being treated with a combination of both therapeutic modalities is increasing. The therapeutic effect of erlotinib in the area of the previously irradiated lesion should be assessed. (orig.)

Stochastic model of forecasting spare parts demand

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Ivan S. Milojević

2012-01-01

hypothesis of the existence of phenomenon change trends, the next step in the methodology of forecasting is the determination of a specific growth curve that describes the regularity of the development in time. These curves of growth are obtained by the analytical representation (expression of dynamic lines. There are two basic stages in the process of expression and they are: - The choice of the type of curve the shape of which corresponds to the character of the dynamic order variation - the determination of the number of values (evaluation of the curve parameters. The most widespread method of forecasting is the trend extrapolation. The basis of the trend extrapolation is the continuing of past trends in the future. The simplicity of the trend extrapolation process, on the one hand, and the absence of other information on the other hand, are the main reasons why the trend extrapolation is used for forecasting. The trend extrapolation is founded on the following assumptions: - The phenomenon development can be presented as an evolutionary trajectory or trend, - General conditions that influenced the trend development in the past will not undergo substantial changes in the future. Spare parts demand forecasting is constantly being done in all warehouses, workshops, and at all levels. Without demand forecasting, neither planning nor decision making can be done. Demand forecasting is the input for determining the level of reserve, size of the order, ordering cycles, etc. The question that arises is the one of the reliability and accuracy of a forecast and its effects. Forecasting 'by feeling' is not to be dismissed if there is nothing better, but in this case, one must be prepared for forecasting failures that cause unnecessary accumulation of certain spare parts, and also a chronic shortage of other spare parts. All this significantly increases costs and does not provide a satisfactory supply of spare parts. The main problem of the application of this model is that each

Predictive markers of safety and immunogenicity of adjuvanted vaccines.

Science.gov (United States)

Mastelic, Beatris; Garçon, Nathalie; Del Giudice, Giuseppe; Golding, Hana; Gruber, Marion; Neels, Pieter; Fritzell, Bernard

2013-11-01

Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

Can sparing of the superficial contralateral parotid lobe reduce xerostomia following radiotherapy for head and neck cancer?

Science.gov (United States)

Nevens, Daan; Nuyts, Sandra

2017-12-01

The purpose of this study is to see whether sparing the superficial contralateral parotid lobe can help limiting xerostomia following radiotherapy for head and neck cancer. 88 patients that were included in two prospective randomized studies were analysed in the current study. Using the dosimetry of both the parotid glands, we divided our patients in four groups. Group 1 includes patients where we were able to reduce the radiation dose below the threshold in order to spare both the ipsilateral and contralateral parotid glands, Group 2 consists of patients where only the contralateral parotid gland could be spared. Group 3 consists of patients where only the contralateral superficial parotid lobe could be spared, while in Group 4 not even the contralateral superficial lobe could be spared. When we compared Group 1 and Group 2, we did not observe a significant difference between both groups in terms of xerostomia scores at 6 or 12 months. When we compared these groups with Group 3, we observed significant differences with more xerostomia in Group 3 where only the contralateral superficial lobe was spared. A significant difference was also observed between Group 3 and Group 4 with more xerostomia in Group 4. Sparing of just one superficial parotid lobe results in less xerostomia when compared to not sparing any lobe of both parotid glands. Advances in knowledge: When sparing of the whole contralateral parotid gland is not possible, delineating both the superficial parotid glands and trying to spare at least one of them can mean a way forward in limiting xerostomia in head and neck cancer patients treated with radiotherapy.

Long-term heart function after adjuvant epirubicin chemotherapy for breast cancer

DEFF Research Database (Denmark)

Appel, Jon M; Zerahn, Bo; Møller, Susanne

2012-01-01

Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment.......Newer studies raise concern that adjuvant anthracycline treatment for breast cancer (BC) causes long-term heart damage. We aimed to examine whether heart failure or impairment could be demonstrated several years after low-dose epirubicin-based adjuvant treatment....

Adjuvant Biological Therapies in Chronic Leg Ulcers

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Natalia Burgos-Alonso

2017-11-01

Full Text Available Current biological treatments for non-healing wounds aim to address the common deviations in healing mechanisms, mainly inflammation, inadequate angiogenesis and reduced synthesis of extracellular matrix. In this context, regenerative medicine strategies, i.e., platelet rich plasmas and mesenchymal stromal cell products, may form part of adjuvant interventions in an integral patient management. We synthesized the clinical experience on ulcer management using these two categories of biological adjuvants. The results of ten controlled trials that are included in this systematic review favor the use of mesenchymal stromal cell based-adjuvants for impaired wound healing, but the number and quality of studies is moderate-low and are complicated by the diversity of biological products. Regarding platelet-derived products, 18 controlled studies investigated their efficacy in chronic wounds in the lower limb, but the heterogeneity of products and protocols hinders clinically meaningful quantitative synthesis. Most patients were diabetic, emphasizing an unmet medical need in this condition. Overall, there is not sufficient evidence to inform routine care, and further clinical research is necessary to realize the full potential of adjuvant regenerative medicine strategies in the management of chronic leg ulcers.

AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5.

Science.gov (United States)

Bracho, Gustavo; Zayas, Caridad; Wang, Lina; Coppel, Ross; Pérez, Oliver; Petrovsky, Nikolai

2009-02-27

Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated. Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline. AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses. Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.

A critical spare part inventory control based on hazard function approach: A case study in a garment company

Science.gov (United States)

Melinda, Intan Dewi; Jauhari, Wakhid Ahmad

2018-02-01

Spare part procurement is a complex issue and requires an accurate analysis. Stock outs of spare part can leads a great impact on production. Therefore, it is necessary to design the inventory control of spare parts that guarantee the availability of spare parts needed for supporting the maintenance activity. This paper studies the inventory policy for sewing machine spare part using hazard function to approximate the demand. Hazard function is the indicator of the effect of ageing on the reliability of the system. It quantifies the risk of failure as the age of the system increases. We use a continuous review policy based on Hadley Within Approach to calculate the optimum inventory level for critical spare parts. There are four spare parts categorized as critical spare parts, which are needle plate, feed dog, rotary and binder attachment. The optimal ordering quantity for needle plate, feed, rotary and binder attachment are 5 units, 17 units, 5 units, and 9 units, respectively and the reorder point are 2 units, 1 unit, 2 units and 1 unit, respectively. Finally, the service level achieved by the proposed policy is in a range of 95.91%-97.93%, which indicates that the inventory level of spare parts can be used to support the required parts in the maintenance activity.

Adjuvant therapy for ampullary carcinomas: The Mayo Clinic experience

International Nuclear Information System (INIS)

Bhatia, Sumita; Miller, Robert C.; Haddock, Michael G.; Donohue, John H.; Krishnan, Sunil

2006-01-01

Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed

Chemokines as Cancer Vaccine Adjuvants

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Agne Petrosiute

2013-10-01

Full Text Available We are witnessing a new era of immune-mediated cancer therapies and vaccine development. As the field of cancer vaccines advances into clinical trials, overcoming low immunogenicity is a limiting step in achieving full success of this therapeutic approach. Recent discoveries in the many biological roles of chemokines in tumor immunology allow their exploitation in enhancing recruitment of antigen presenting cells (APCs and effector cells to appropriate anatomical sites. This knowledge, combined with advances in gene therapy and virology, allows researchers to employ chemokines as potential vaccine adjuvants. This review will focus on recent murine and human studies that use chemokines as therapeutic anti-cancer vaccine adjuvants.

Characterization of a Broadly Reactive Anti-CD40 Agonistic Monoclonal Antibody for Potential Use as an Adjuvant.

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Cameron Martin

Full Text Available Lack of safe and effective adjuvants is a major hindrance to the development of efficacious vaccines. Signaling via CD40 pathway leads to enhanced antigen processing and presentation, nitric oxide expression, pro-inflammatory cytokine expression by antigen presenting cells, and stimulation of B-cells to undergo somatic hypermutation, immunoglobulin class switching, and proliferation. Agonistic anti-CD40 antibodies have shown promising adjuvant qualities in human and mouse vaccine studies. An anti-CD40 monoclonal antibody (mAb, designated 2E4E4, was identified and shown to have strong agonistic effects on primary cells from multiple livestock species. The mAb recognize swine, bovine, caprine, and ovine CD40, and evoked 25-fold or greater proliferation of peripheral blood mononuclear cells (PBMCs from these species relative to cells incubated with an isotype control (p<0.001. In addition, the mAb induced significant nitric oxide (p<0.0001 release by bovine macrophages. Furthermore, the mAb upregulated the expression of MHC-II by PBMCs, and stimulated significant (p<0.0001 IL-1α, IL6, IL-8, and TNF-α expression by PBMCs. These results suggest that the mAb 2E4E4 can target and stimulate cells from multiple livestock species and thus, it is a potential candidate for adjuvant development. This is the first study to report an anti-swine CD40 agonistic mAb that is also broadly reactive against multiple species.

AS03-adjuvanted versus non-adjuvanted inactivated trivalent influenza vaccine against seasonal influenza in elderly people: a phase 3 randomised trial

NARCIS (Netherlands)

McElhaney, J.E.; Beran, J.; Devaster, J.M.; Esen, M.; Launay, O.; Leroux-Roels, G.; Ruiz-Palacios, G.M.; Essen, G.A. van; Caplanusi, A.; Claeys, C.; Durand, C.; Duval, X.; Idrissi, M. El; Falsey, A.R.; Feldman, G.; Frey, S.E.; Galtier, F.; Hwang, S.J.; Innis, B.L.; Kovac, M.; Kremsner, P.; McNeil, S.; Nowakowski, A.; Richardus, J.H.; Trofa, A.; Oostvogels, L.; Verheugt, F.W.; et al.,

2013-01-01

BACKGROUND: We aimed to compare AS03-adjuvanted inactivated trivalent influenza vaccine (TIV) with non-adjuvanted TIV for seasonal influenza prevention in elderly people. METHODS: We did a randomised trial in 15 countries worldwide during the 2008-09 (year 1) and 2009-10 (year 2) influenza seasons.

Matrix-M Adjuvated Seasonal Virosomal Influenza Vaccine Induces Partial Protection in Mice and Ferrets against Avian H5 and H7 Challenge.

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Freek Cox

Full Text Available There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV adjuvated with the saponin-based adjuvant Matrix-M (MM can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

Shoulder complaints after nerve sparing neck dissections

NARCIS (Netherlands)

van Wilgen, CP; Dijkstra, PU; van der Laan, BFAM; Plukker, JTM; Roodenburg, JLN

The purpose of the study was to analyse the prevalence of shoulder complaints after nerve sparing neck dissection at least I year after surgery, and to analyse the influence of radiation therapy on shoulder complaints. Patients were interviewed for shoulder complaints, and patients filled out the

A novel non-toxic combined CTA1-DD and ISCOMS adjuvant vector for effective mucosal immunization against influenza virus.

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Eliasson, Dubravka Grdic; Helgeby, Anja; Schön, Karin; Nygren, Caroline; El-Bakkouri, Karim; Fiers, Walter; Saelens, Xavier; Lövgren, Karin Bengtsson; Nyström, Ida; Lycke, Nils Y

2011-05-23

Here we demonstrate that by using non-toxic fractions of saponin combined with CTA1-DD we can achieve a safe and above all highly efficacious mucosal adjuvant vector. We optimized the construction, tested the requirements for function and evaluated proof-of-concept in an influenza A virus challenge model. We demonstrated that the CTA1-3M2e-DD/ISCOMS vector provided 100% protection against mortality and greatly reduced morbidity in the mouse model. The immunogenicity of the vector was superior to other vaccine formulations using the ISCOM or CTA1-DD adjuvants alone. The versatility of the vector was best exemplified by the many options to insert, incorporate or admix vaccine antigens with the vector. Furthermore, the CTA1-3M2e-DD/ISCOMS could be kept 1 year at 4°C or as a freeze-dried powder without affecting immunogenicity or adjuvanticity of the vector. Strong serum IgG and mucosal IgA responses were elicited and CD4 T cell responses were greatly enhanced after intranasal administration of the combined vector. Together these findings hold promise for the combined vector as a mucosal vaccine against influenza virus infections including pandemic influenza. The CTA1-DD/ISCOMS technology represents a breakthrough in mucosal vaccine vector design which successfully combines immunomodulation and targeting in a safe and stable particulate formation. Copyright © 2011 Elsevier Ltd. All rights reserved.

Development of a minimal saponin vaccine adjuvant based on QS-21

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Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.

2014-07-01

Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.

Psoriasis sparing the polio-affected limb: Is it merely the koebner phenomenon?

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B C Ravikumar

2014-01-01

Full Text Available Psoriasis being a common skin condition, atypical forms and unusual localizations of this disease are quite frequently seen. However, psoriasis sparing a polio-affected limb is extremely rare. We report a case of an adult male, who presented with psoriasis distributed all over the body but with almost complete sparing of the polio-affected left lower limb.

Advax, a Delta Inulin Microparticle, Potentiates In-built Adjuvant Property of Co-administered Vaccines

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Masayuki Hayashi

2017-02-01

Full Text Available Advax, a delta inulin-derived microparticle, has been developed as an adjuvant for several vaccines. However, its immunological characteristics and potential mechanism of action are yet to be elucidated. Here, we show that Advax behaves as a type-2 adjuvant when combined with influenza split vaccine, a T helper (Th2-type antigen, but behaves as a type-1 adjuvant when combined with influenza inactivated whole virion (WV, a Th1-type antigen. In addition, an adjuvant effect was not observed when Advax-adjuvanted WV vaccine was used to immunize toll-like receptor (TLR 7 knockout mice which are unable to respond to RNA contained in WV antigen. Similarly, no adjuvant effect was seen when Advax was combined with endotoxin-free ovalbumin, a neutral Th0-type antigen. An adjuvant effect was also not seen in tumor necrosis factor (TNF-α knockout mice, and the adjuvant effect required the presences of dendritic cells (DCs and phagocytic macrophages. Therefore, unlike other adjuvants, Advax potentiates the intrinsic or in-built adjuvant property of co-administered antigens. Hence, Advax is a unique class of adjuvant which can potentiate the intrinsic adjuvant feature of the vaccine antigens through a yet to be determined mechanism.

Who Benefits From Adjuvant Radiation Therapy for Gastric Cancer? A Meta-Analysis

International Nuclear Information System (INIS)

Ohri, Nitin; Garg, Madhur K.; Aparo, Santiago; Kaubisch, Andreas; Tome, Wolfgang; Kennedy, Timothy J.; Kalnicki, Shalom; Guha, Chandan

2013-01-01

Purpose: Large randomized trials have demonstrated significant survival benefits with the use of adjuvant chemotherapy or chemoradiation therapy for gastric cancer. The importance of adjuvant radiation therapy (RT) remains unclear. We performed an up-to-date meta-analysis of randomized trials testing the use of RT for resectable gastric cancer. Methods and Materials: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant (including neoadjuvant) RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine whether the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, or lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR = 0.78, 95% CI: 0.70-0.86, P<.001) and DFS (HR = 0.71, 95% CI: 0.63-0.80, P<.001). In the 5 studies that tested adjuvant chemoradiation therapy against adjuvant chemotherapy, similar effects were seen for OS (HR = 0.83, 95% CI: 0.67-1.03, P=.087) and DFS (HR = 0.77, 95% CI: 0.91-0.65, P=.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusion: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regard to patient selection and integration with systemic therapy

Subcutaneously Placed Breast Implants after a Skin-Sparing Mastectomy: Do We Always Need ADM?

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Apresh Singla, MBBS, MSc

2017-07-01

Full Text Available Background:. Immediate breast reconstruction is an acceptable treatment option after mastectomy for prophylaxis of early breast cancer. Different options exist for implant placement, incision technique, patient suitability, and institutional experience. This article is a case series exploring the feasibility and outcomes of patients undergoing immediate breast reconstruction using skin-sparing mastectomy without mesh or acellular dermal matrix (ADM and with a vertical inframammary incision. Methods:. A single-institution retrospective analysis was performed for all patients who underwent immediate single-stage reconstruction with subcutaneous silicon implants without ADM between 2009 and 2014 inclusive. Patient, operative and treatment variables were extracted. All patients with viable mastectomy skin flaps intraoperatively and at least 5 mm of subcutaneous tissue were eligible except for patients who were deemed too slim by the senior surgeon preoperatively and thus at risk of implant visibility or skin rippling. Results:. There were 26 patients (bilateral n = 12 and unilateral n = 14 eligible for analysis, with a median long-term follow-up of 51.5 months. The majority of complications were classified as minor affecting 46.2% of the cohort (n = 12. There were 20 episodes of complications overall. The most frequent episodes were contour defects (x = 5, minor seroma (x = 4, and malrotation and minor infection (x = 3. There was 1 episode of capsular contracture. Conclusion:. Skin-sparing mastectomy with immediate subcutaneous silicon implant reconstruction with a vertical incision and without the need for mesh or ADM is an acceptable and safe treatment option. Accurate patient selection and skin flap viability is the key to achieving optimal outcomes with this approach.

Joint Optimization of Preventive Maintenance and Spare Parts Inventory with Appointment Policy

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Jing Cai

2017-01-01

Full Text Available Under the background of the wide application of condition-based maintenance (CBM in maintenance practice, the joint optimization of maintenance and spare parts inventory is becoming a hot research to take full advantage of CBM and reduce the operational cost. In order to avoid both the high inventory level and the shortage of spare parts, an appointment policy of spare parts is first proposed based on the prediction of remaining useful lifetime, and then a corresponding joint optimization model of preventive maintenance and spare parts inventory is established. Due to the complexity of the model, the combination method of genetic algorithm and Monte Carlo is presented to get the optimal maximum inventory level, safety inventory level, potential failure threshold, and appointment threshold to minimize the cost rate. Finally, the proposed model is studied through a case study and compared with both the separate optimization and the joint optimization without appointment policy, and the results show that the proposed model is more effective. In addition, the sensitivity analysis shows that the proposed model is consistent with the actual situation of maintenance practices and inventory management.

MANAGEMENT OF ENDOCRINE DISEASE: Outcome of adrenal sparing surgery in heritable pheochromocytoma.

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Castinetti, F; Taieb, D; Henry, J F; Walz, M; Guerin, C; Brue, T; Conte-Devolx, B; Neumann, H P H; Sebag, F

2016-01-01

The management of hereditary pheochromocytoma has drastically evolved in the last 20 years. Bilateral pheochromocytoma does not increase mortality in MEN2 or von Hippel-Lindau (VHL) mutation carriers who are followed regularly, but these mutations induce major morbidities if total bilateral adrenalectomy is performed. Cortical sparing adrenal surgery may be proposed to avoid definitive adrenal insufficiency. The surgical goal is to leave sufficient cortical tissue to avoid glucocorticoid replacement therapy. This approach was achieved by the progressive experience of minimally invasive surgery via the transperitoneal or retroperitoneal route. Cortical sparing adrenal surgery exhibits management of all patients with MEN2 or VHL hereditary pheochromocytoma. Hereditary pheochromocytoma is a rare disease, and a randomized trial comparing cortical sparing vs classical adrenalectomy is probably not possible. This lack of data most likely explains why cortical sparing surgery has not been adopted in most expert centers that perform at least 20 procedures per year for the treatment of this disease. This review examined recent data to provide insight into the technique, its indications, and the results and subsequent follow-up in the management of patients with hereditary pheochromocytoma with a special emphasis on MEN2. © 2016 European Society of Endocrinology.

Optimization of dose distributions for adjuvant locoregional radiotherapy of gastric cancer by IMRT

International Nuclear Information System (INIS)

Lohr, F.; Dobler, B.; Mai, S.; Hermann, B.; Tiefenbacher, U.; Wieland, P.; Steil, V.; Wenz, F.

2003-01-01

Background and Purpose: Locoregional relapse is a problem frequently encountered with advanced gastric cancer. Data from the randomized Intergroup trial 116 suggest effectiveness of adjuvant radiochemotherapy, albeit with significant toxicity. The potential of intensity-modulated radiotherapy (IMRT) to reduce toxicity by significantly reducing maximum and median doses to organs at risk while still applying sufficient dose to the target volume in the upper abdomen was studied. Patient and Methods: For a typical configuration of target volumes and organs, a step-and-shoot IMRT plan (eight beam orientations), developed as a class solution for treatment of tumors in the upper abdomen (Figures 1 to 3), a conventional plan, a combination of the conventional plan with a kidney-sparing boost plan, and a conventional plan with noncoplanar ap and pa fields for improved kidney sparing were compared with respect to coverage of target volume and dose to organs at risk with a dose of 45 Gy delivered as the median dose to the target volume. Results: When using the conventional three-dimensionally planned box techniques, the right kidney could be kept below tolerance, but median dose to the left kidney amounted to between 14.8 and 26.9 Gy, depending on the plan. IMRT reduced the median dose to the left kidney to 10.5 Gy, while still keeping the dose to the right kidney 90% of prescription dose were delivered to > 90% of target volume with IMRT (Table 1). Conclusion: IMRT has the potential to deliver efficient doses to target volumes in the upper abdomen, while delivering dose to organs at risk in a more advantageous fashion than a conventional technique. For clinical implementation, the possibility of extensive organ motion in the upper abdomen has to be taken into account for treatment planning and patient positioning. The multitude of potential risks related to its application has to be the subject of thorough follow-up and further studies. (orig.)

Adjuvant Chemoradiation Therapy for Pancreatic Adenocarcinoma: Who Really Benefits?

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Merchant, Nipun B; Rymer, Jennifer; Koehler, Elizabeth AS; Ayers, G Daniel; Castellanos, Jason; Kooby, David A; Weber, Sharon H; Cho, Clifford S; Schmidt, C Max; Nakeeb, Atilla; Matos, Jesus M; Scoggins, Charles R; Martin, Robert CG; Kim, Hong Jin; Ahmad, Syed A; Chu, Carrie K; McClaine, Rebecca; Bednarski, Brian K; Staley, Charles A; Sharp, Kenneth; Parikh, Alexander A

2014-01-01

BACKGROUND The role of adjuvant chemoradiation therapy (CRT) in pancreatic cancer remains controversial. The primary aim of this study was to determine if CRT improved survival in patients with resected pancreatic cancer in a large, multiinstitutional cohort of patients. STUDY DESIGN Patients undergoing resection for pancreatic adenocarcinoma from seven academic medical institutions were included. Exclusion criteria included patients with T4 or M1 disease, R2 resection margin, preoperative therapy, chemotherapy alone, or if adjuvant therapy status was unknown. RESULTS There were 747 patients included in the initial evaluation. Primary analysis was performed between patients that had surgery alone (n = 374) and those receiving adjuvant CRT (n = 299). Median followup time was 12.2 months and 14.5 months for survivors. Median overall survival for patients receiving adjuvant CRT was significantly longer than for those undergoing operation alone (20.0 months versus 14.5 months, p = 0.001). On subset and multivariate analysis, adjuvant CRT demonstrated a significant survival advantage only among patients who had lymph node (LN)-positive disease (hazard ratio 0.477, 95% CI 0.357 to 0.638) and not for LN-negative patients (hazard ratio 0.810, 95% CI 0.556 to 1.181). Disease-free survival in patients with LN-negative disease who received adjuvant CRT was significantly worse than in patients who had surgery alone (14.5 months versus 18.6 months, p = 0.034). CONCLUSIONS This large multiinstitutional study emphasizes the importance of analyzing subsets of patients with pancreas adenocarcinoma who have LN metastasis. Benefit of adjuvant CRT is seen only in patients with LN-positive disease, regardless of resection margin status. CRT in patients with LN-negative disease may contribute to reduced disease-free survival. PMID:19476845

Simultaneous determination of three pesticide adjuvant residues in plant-derived agro-products using liquid chromatography-tandem mass spectrometry.

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Li, Hui; Jiang, Zejun; Cao, Xiaolin; Su, Hang; Shao, Hua; Jin, Fen; Abd El-Aty, A M; Wang, Jing

2017-12-15

Herein, an accurate and reliable isotope-labelled internal standard method was developed and validated for simultaneous determination of three polar pesticide adjuvants, namely 2-pyrrolidone, N-methyl-2-pyrrolidone, and N-ethyl-2-pyrrolidone in plant-derived agro-products. Matrices, including apple, cabbage, tomato, cucumber, rice, and wheat were extracted with a modified quick, easy, cheap, effective, rugged, and safe "QuEChERS" method and purified with a new clean-up sorbent (Z-Sep). A hydrophilic interaction liquid chromatography column (HILIC), exhibiting a lipophilic-hydrophilic character, was used to separate the three analytes over 10min using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Matrix effects in various matrices were evaluated and an isotope-labelled internal standard method was employed to compensate for ion enhancement/suppression effects. At three fortification levels (2.0, 5.0, and 20.0μg/kg), the mean recoveries ranged from 78.5 to 112.1% with relative standard deviations (RSDs)determination of the three tested pesticide adjuvant residues in agro-products of plant origin. Copyright © 2017 Elsevier B.V. All rights reserved.

Immune adjuvant activity of the olive, soybean and corn oils

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Ana Claudia Marinho da Silva

2016-08-01

Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.

Long-term outcomes of patients with breast cancer after nipple-sparing mastectomy/skin-sparing mastectomy followed by immediate transverse rectus abdominis musculocutaneous flap reconstruction: Comparison with conventional mastectomy in a single center study.

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Lee, Sae Byul; Lee, Jong Won; Kim, Hee Jeong; Ko, Beom Seok; Son, Byung Ho; Eom, Jin Sup; Lee, Taik Jong; Ahn, Sei-Hyun

2018-05-01

To evaluate the oncological outcomes of patients with breast cancer after nipple-sparing mastectomy (NSM)/skin-sparing mastectomy (SSM), followed by immediate reconstruction, as compared to conventional mastectomy (CM).SSM/NSM has been increasingly used to treat women with breast cancer who wish to preserve the overlying breast skin, but concern exist regarding its oncological safety due to the potential for residual breast tissue. We report our experience performing SSM/NSM for breast cancer treatment compared to CM with a long follow-up period.All consecutive patients who underwent mastectomy for breast cancer at Asan Medical Center between January 1993 and December 2008 were identified by retrospective medical chart review. The patients who underwent NSM/SSM, followed by immediate breast reconstruction with a pedicled transverse rectus abdominis musculocutaneous flap (TRAM), were compared to the patients who underwent CM in terms of breast-cancer specific survival (BCSS) rate, distant metastasis-free survival (DMFS) rate, and local recurrence (LR) rate.During the study period, 6028 patients underwent mastectomy for breast cancer. Of these, 1032 and 4996 underwent NSM/SSM with TRAM and CM, respectively. Their median follow-up durations were 94.4 (range, 8.1-220.2) and 110.8 (range, 6.1-262.0) months, respectively. Their 5 year BCSS rates were 95.4% and 88.1%, respectively (log-rank, P < .001). Their 5 year DMFS rates were 93.0% and 85.6%, respectively (log-rank, P < .001).Relative to CM, NSM/SSM, followed by immediate breast reconstruction, may be a viable and oncologically safe surgical treatment in selected patients with breast cancer.

Learning impairment in honey bees caused by agricultural spray adjuvants.

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Timothy J Ciarlo

Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many

Adjuvant and Definitive Radiotherapy for Adrenocortical Carcinoma

International Nuclear Information System (INIS)

Sabolch, Aaron; Feng, Mary; Griffith, Kent; Hammer, Gary; Doherty, Gerard; Ben-Josef, Edgar

2011-01-01

Purpose: To evaluate the impact of both adjuvant and definitive radiotherapy on local control of adrenocortical carcinoma. Methods and Materials: Outcomes were analyzed from 58 patients with 64 instances of treatment for adrenocortical carcinoma at the University of Michigan's Multidisciplinary Adrenal Cancer Clinic. Thirty-seven of these instances were for primary disease, whereas the remaining 27 were for recurrent disease. Thirty-eight of the treatment regimens involved surgery alone, 10 surgery plus adjuvant radiotherapy, and 16 definitive radiotherapy for unresectable disease. The effects of patient, tumor, and treatment factors were modeled simultaneously using multiple variable Cox proportional hazards regression for associations with local recurrence, distant recurrence, and overall survival. Results: Local failure occurred in 16 of the 38 instances that involved surgery alone, in 2 of the 10 that consisted of surgery plus adjuvant radiotherapy, and in 1 instance of definitive radiotherapy. Lack of radiotherapy use was associated with 4.7 times the risk of local failure compared with treatment regimens that involved radiotherapy (95% confidence interval, 1.2-19.0; p = 0.030). Conclusions: Radiotherapy seems to significantly lower the risk of local recurrence/progression in patients with adrenocortical carcinoma. Adjuvant radiotherapy should be strongly considered after surgical resection.

Effects of processing adjuvants on traditional Chinese herbs

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Lin-Lin Chen

2018-04-01

Full Text Available Processing of Chinese medicines is a pharmaceutical technique that transforms medicinal raw materials into decoction pieces for use in different therapies. Various adjuvants, such as vinegar, wine, honey, and brine, are used in the processing to enhance the efficacy and reduce the toxicity of crude drugs. Proper processing is essential to ensure the quality and safety of traditional Chinese medicines (TCMs. Therefore, sound knowledge of processing principles is crucial to the standardized use of these processing adjuvants and to facilitate the production and clinical use of decoction pieces. Many scientific reports have indicated the synergistic effects of processing mechanisms on the chemistry, pharmacology, and pharmacokinetics of the active ingredients in TCMs. Under certain conditions, adjuvants change the content of active or toxic components in drugs by chemical or physical transformation, increase or decrease drug dissolution, exert their own pharmacological effects, or alter drug pharmacokinetics. This review summarizes various processing methods adopted in the last two decades, and highlights current approaches to identify the effects of processing parameters on TCMs. Keywords: Adjuvant, Processing, Synergism, Traditional Chinese medicine

Benefits of adjuvant chemotherapy in high-grade gliomas.

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DeAngelis, Lisa M

2003-12-01

The current standard of care for patients with high-grade glioma is resection followed by radiotherapy. Adjuvant chemotherapy is not widely accepted because of the low sensitivity of gliomas to traditional antineoplastic agents, the poor penetration of most drugs across the blood-brain barrier, and the significant systemic toxicity associated with current agents. However, nitrosoureas and, subsequently, temozolomide (Temodar [US], Temodal [international]; Schering-Plough Corporation, Kenilworth, NJ), a novel alkylating agent, cross the blood-brain barrier and have activity against gliomas. Nitrosoureas have been studied in phase III trials in the adjuvant setting. In individual trials, chemotherapy did not increase median survival but did increase the proportion of patients surviving >/=18 months by 15%. Only with large meta-analyses did the addition of chemotherapy achieve a statistically significant improvement in median survival. Currently there is no means of identifying which patients will benefit from adjuvant chemotherapy, but nitrosoureas and temozolomide are well tolerated in most patients, justifying the administration of adjuvant chemotherapy to all newly diagnosed patients with malignant glioma.

Impact of shelf life on measured prompt fraction of spare Inconel in-core flux detectors

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Mohindra, VK; Sadeghi, S. [Atomic Energy of Canada Limited, Mississauga, Ontario (Canada); Crouse, B. [Darlington Nuclear Generating Station, Bowmanville, Ontario (Canada)

2008-07-01

Prompt fraction measurements associated with spare self-powered Inconel In-Core Flux Detectors (ICFDs) carried out a few years after installation on Shut Down System number 1 (SDS1) and Reactor Regulating System (RRS) at Darlington Nuclear Generating Station (DNGS), were found to be lower than those of the original detectors. These detectors, spares and originals, were manufactured in the late 80s, however, the former were kept at manufacturer's warehouse and latter were installed in the reactor core within a few years after manufacturing. Although the prompt fractions of the spare detectors were relatively low, the electronic/electrical behavior of the spare detectors was intact. The first batch of the original detectors performed as per the design requirements. Therefore, it is suspected that during shelf life, spare Inconel in-core flux detectors underwent changes that lowered their measured values of prompt fraction, which were taken within a few years after installation in the reactor. Detailed study of detectors' material composition and impurity concentrations revealed no association with the lower prompt fraction measurements. The evaluation of the limited data of the original and spare Inconel ICFDs installed at Darlington showed: 1. The reduction in prompt fraction was roughly proportional to the shelf life of the detectors; and 2. The rate of reduction in prompt fraction during storage was about double the rate of reduction during operation in the reactor. Above observations were based on the data provided by DNGS for a few detectors. The purpose of this paper is two fold, firstly to present the results of the complete study carried out to investigate the cause of relatively low prompt fractions measured on spare SDS1 and RRS Inconel ICFDs at DNGS, and secondly to generate interest/awareness within other CANDU utilities to add to the database of prompt fractions of spare Inconel ICFDs measured after installation. The data will help to improve

Canadian Adjuvant Initiative Workshop, March 26–27, 2013—Ottawa, Canada

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Krishnan, Lakshmi; Twine, Susan; Gerdts, Volker; Barreto, Luis; Richards, James C

2014-01-01

Novel adjuvants hold the promise for developing effective modern subunit vaccines capable of appropriately modulating the immune response against challenging diseases such as those caused by chronic and/or intracellular pathogens and cancer. Over the past decade there has been intensive research into discovering new adjuvants, however, their translation into routine clinical use is lagging. To stimulate discussion and identify opportunities for networking and collaboration among various stakeholders, a Canadian Adjuvant Initiative Workshop was held in Ottawa. Sponsored by the National Research Council Canada, Canadian Institutes of Health Research and the Vaccine Industry Committee, a two day workshop was held that brought together key Canadian and international stakeholders in adjuvant research from industry, academia and government. To discover innovation gaps and unmet needs, the presentations covered a board range of topics in adjuvant development; criteria for selection of lead adjuvant candidates from an industry perspective, discovery research across Canada, bioprocessing needs and challenges, veterinary vaccines, Canadian vaccine trial capabilities, the Canadian regulatory framework and WHO formulation laboratory experience. The workshop concluded with a discussion on the opportunity to create a Canadian Adjuvant Development Network. This report details the key discussion points and steps forward identified for facilitating adjuvant development research in Canada. PMID:24192752

Neural stem cell sparing by linac based intensity modulated stereotactic radiotherapy in intracranial tumors

International Nuclear Information System (INIS)

Oehler, Julia; Brachwitz, Tim; Wendt, Thomas G; Banz, Nico; Walther, Mario; Wiezorek, Tilo

2013-01-01

Neurocognitive decline observed after radiotherapy (RT) for brain tumors in long time survivors is attributed to radiation exposure of the hippocampus and the subventricular zone (SVZ). The potential of sparing capabilities for both structures by optimized intensity modulated stereotactic radiotherapy (IMSRT) is investigated. Brain tumors were irradiated by stereotactic 3D conformal RT or IMSRT using m3 collimator optimized for PTV and for sparing of the conventional OARs (lens, retina, optic nerve, chiasm, cochlea, brain stem and the medulla oblongata). Retrospectively both hippocampi and SVZ were added to the list of OAR and their dose volume histograms were compared to those from two newly generated IMSRT plans using 7 or 14 beamlets (IMSRT-7, IMSRT-14) dedicated for optimized additional sparing of these structures. Conventional OAR constraints were kept constant. Impact of plan complexity and planning target volume (PTV) topography on sparing of both hippocampi and SVZ, conformity index (CI), the homogeneity index (HI) and quality of coverage (QoC) were analyzed. Limits of agreement were used to compare sparing of stem cell niches with either IMSRT-7 or IMSRT-14. The influence of treatment technique related to the topography ratio between PTV and OARs, realized in group A-D, was assessed by a mixed model. In 47 patients CI (p ≤ 0.003) and HI (p < 0.001) improved by IMSRT-7, IMSRT-14, QoC remained stable (p ≥ 0.50) indicating no compromise in radiotherapy. 90% of normal brain was exposed to a significantly higher dose using IMSRT. IMSRT-7 plans resulted in significantly lower biologically effective doses at all four neural stem cell structures, while contralateral neural stem cells are better spared compared to ipsilateral. A further increase of the number of beamlets (IMSRT-14) did not improve sparing significantly, so IMSRT-7 and IMSRT-14 can be used interchangeable. Patients with tumors contacting neither the subventricular zone nor the cortex benefit

Linking the spare parts management with the total costs of ownership: An agenda for future research

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Orlando Duran

2016-12-01

Full Text Available Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC. Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view. Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO. Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

Linking the spare parts management with the total costs of ownership: An agenda for future research

International Nuclear Information System (INIS)

Duran, O.; Roda, I.; Macchi, M.

2016-01-01

Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC). Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view). Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO). Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

Linking the spare parts management with the total costs of ownership: An agenda for future research

Energy Technology Data Exchange (ETDEWEB)

Duran, O.; Roda, I.; Macchi, M.

2016-07-01

Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC). Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view). Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO). Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

Postoperative adjuvant therapy of colorectal carcinoma

International Nuclear Information System (INIS)

Scheithauer, W.

1989-01-01

Evaluating the results of controlled clinical trials, an attempt has been made to summarize the current status of adjuvant therapy in colorectal cancer. Several different adjuvant treatment approaches including immunotherapy, postoperative fibrinolysis, anticoagulation, pre- and postoperative radiotherapy when used as a single modality, have not resulted in any long-term survival benefit. Rather in contrast to previous experiences, recent prospective randomized trials have provided evidence for the efficacy of chemotherapy in the adjuvant treatment of colon and rectal cancer. Whereas its definitive role in the former disease remains somewhat controversial, for rectal cancer, it seems clear that combined modality therapy including polychemotherapy with or without radiation prolongs the disease-free interval, lowers the local recurrence rate, and may improve survival compared to surgery alone. Questions which remain to be answered by future clinical trials are related to the optimal duration and sequence of combined modality, to the role of different radiation sensitizers, and in both colon and rectal cancer, to the choice of the most effective systemtic chemotherapeutic drugs. (orig./MG) [de

Comparison of adjuvants for immune potentiating properties and side effects in mice

NARCIS (Netherlands)

Leenaars, P.P.A.M.; Hendriksen, C.F.M.; Koedam, M.A.; Claassen, I.; Claassen, E.

1995-01-01

Four types of adjuvants were evaluated as alternatives to the use of Freund's complete adjuvant in mice. The adjuvants evaluated included a water-in-oil emulsion (Specol), a microorganism (Lactobacillus), preformed immune-stimulating complexes (ISCOM) containing rabies virus glycoprotein and a

Morphine sparing effect of low dose ketamine during patient ...

African Journals Online (AJOL)

Adele

2003-09-12

Sep 12, 2003 ... KEY WORDS: Ketamine, morphine sparing effect, patient controlled intravenous analgesia. ... Measurements: Morphine consumption, visual analogue pain score (VAPS), pulse ..... Brain Research, 1990; 518: 218-222. 7.

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

Science.gov (United States)

Srivastava, Atul; Gowda, Devegowda Vishakante; Madhunapantula, SubbaRao V; Shinde, Chetan G; Iyer, Meenakshi

2015-04-01

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production. © 2015 APMIS. Published by John Wiley & Sons Ltd.

AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5

Directory of Open Access Journals (Sweden)

Pérez Oliver

2009-02-01

Full Text Available Abstract Background Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP, to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4 and 5 (MSP5, was evaluated. Methods Complete Freund's adjuvant (CFA, which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH, T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline. Results AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses. Conclusion Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.

Adjuvant treatment and outcomes of stage III endometrial carcinoma

International Nuclear Information System (INIS)

Connell, C.; Ludbrook, J.; Davy, M.; Yeoh, E

2003-01-01

Surgery with staging using FIGO (1988) classification is accepted management for stage III endometrial carcinoma. The delivery of adjuvant therapy is controversial and tends to be individualised. Retrospective review of stage III endometrial carcinoma patients who underwent radical surgery at the Royal Adelaide and Queen Elizabeth Hospitals from 1984 to 2003 was carried out. Medical records were reviewed for details of patient characteristics, surgery, histopathology, adjuvant therapy and recurrence/survival. Sixty-six patients with a median age of 69 (37-97), had a median follow-up of 26 months (1-188 ). For all stage III patients, the actuarial 5-year disease-free and overall survivals were 50 and 43% respectively. Thirty-five patients received pelvic +/- paraaortic radiotherapy, 5 whole abdominal radiotherapy, 14 vaginal brachytherapy boost, 10 chemotherapy and 13 adjuvant hormones. Forty-six percent of patients recurred in a median time of 13 months (0-95). For these patients, the sites of first recurrence were pelvis in 27%, pelvis and abdomen in 23%, abdomen alone in 13%, distant alone in 27%, distant and abdominal in 7% and all three sites in 3%. On univariate analysis disease-free survival was impacted by; age, grade, parametrial involvement, number of extrauterine sites, lymphovascular invasion, adjuvant radiotherapy to the pelvis alone and postoperative macroscopic residual disease. Lymphovascular invasion, post-operative residual disease and adjuvant pelvic radiotherapy remained significant on multivariate analysis. These outcomes for stage III endometrial carcinoma are comparable to the current literature. Ongoing research is required to establish the most appropriate adjuvant therapy in these high risk patients

Bladder Cancer Patterns of Pelvic Failure: Implications for Adjuvant Radiation Therapy

International Nuclear Information System (INIS)

Baumann, Brian C.; Guzzo, Thomas J.; He Jiwei; Vaughn, David J.; Keefe, Stephen M.; Vapiwala, Neha; Deville, Curtiland; Bekelman, Justin E.; Tucker, Kai; Hwang, Wei-Ting; Malkowicz, S. Bruce; Christodouleas, John P.

2013-01-01

Purpose: Local-regional failures (LFs) after cystectomy with or without chemotherapy are common in locally advanced disease. Adjuvant radiation therapy (RT) could reduce LFs, but toxicity has discouraged its use. Modern RT techniques with improved normal tissue sparing have rekindled interest but require knowledge of pelvic failure patterns to design treatment volumes. Methods and Materials: Five-year LF rates after radical cystectomy plus pelvic node dissection with or without chemotherapy were determined for 8 pelvic sites among 442 urothelial bladder carcinoma patients. The impact of pathologic stage, margin status, nodal involvement, and extent of node dissection on failure patterns was assessed using competing risk analysis. We calculated the percentage of patients whose sites of LF would have been completely encompassed within various hypothetical clinical target volumes (CTVs) for postoperative radiation. Results: Compared with stage ≤pT2, stage ≥pT3 patients had higher 5-year LF rates in virtually all pelvic sites. Among stage ≥pT3 patients, margin status significantly altered the failure pattern whereas extent of node dissection and nodal positivity did not. In stage ≥pT3 patients with negative margins, failure occurred predominantly in the iliac/obturator nodes and uncommonly in the cystectomy bed and/or presacral nodes. Of these patients in whom failure subsequently occurred, 76% would have had all LF sites encompassed within CTVs covering only the iliac/obturator nodes. In stage ≥pT3 with positive margins, cystectomy bed and/or presacral nodal failures increased significantly. Only 57% of such patients had all LF sites within CTVs limited to the iliac/obturator nodes, but including the cystectomy bed and presacral nodes in the CTV when margins were positive increased the percentage of LFs encompassed to 91%. Conclusions: Patterns of failure within the pelvis are summarized to facilitate design of adjuvant RT protocols. These data suggest that

Adjuvant radiation therapy for bladder cancer: A dosimetric comparison of techniques

Energy Technology Data Exchange (ETDEWEB)

Baumann, Brian C.; Noa, Kate [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Wileyto, E. Paul [Department of Biostatistics and Epidemiology at the University of Pennsylvania, Philadelphia, PA (United States); Bekelman, Justin E. [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Deville, Curtiland [Department of Radiation Oncology and Molecular Radiation Sciences at Johns Hopkins University School of Medicine, Baltimore, MD (United States); Vapiwala, Neha; Kirk, Maura; Both, Stefan; Dolney, Derek; Kassaee, Ali [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States); Christodouleas, John P., E-mail: christojo@uphs.upenn.edu [Department of Radiation Oncology at the University of Pennsylvania, Philadelphia, PA (United States)

2015-01-01

Trials of adjuvant radiation after cystectomy are under development. There are no studies comparing radiation techniques to inform trial design. This study assesses the effect on bowel and rectal dose of 3 different modalities treating 2 proposed alternative clinical target volumes (CTVs). Contours of the bowel, rectum, CTV-pelvic sidewall (common/internal/external iliac and obturator nodes), and CTV-comprehensive (CTV-pelvic sidewall plus cystectomy bed and presacral regions) were drawn on simulation images of 7 post-cystectomy patients. We optimized 3-dimensional conformal radiation (3-D), intensity-modulated radiation (IMRT), and single-field uniform dose (SFUD) scanning proton plans for each CTV. Mixed models regression was used to compare plans for bowel and rectal volumes exposed to 35% (V{sub 35%}), 65% (V{sub 65%}), and 95% (V{sub 95%}) of the prescribed dose. For any given treatment modality, treating the larger CTV-comprehensive volume compared with treating only the CTV-pelvic sidewall nodes significantly increased rectal dose (V{sub 35%} {sub rectum}, V{sub 65%} {sub rectum}, and V{sub 95%} {sub rectum}; p < 0.001 for all comparisons), but it did not produce significant differences in bowel dose (V{sub 95%} {sub bowel}, V{sub 65%} {sub bowel}, or V{sub 35%} {sub bowel}). The 3-D plans, compared with both the IMRT and the SFUD plans, had a significantly greater V{sub 65%} {sub bowel} and V{sub 95%} {sub bowel} for each proposed CTV (p < 0.001 for all comparisons). The effect of treatment modality on rectal dosimetry differed by CTV, but it generally favored the IMRT and the SFUD plans over the 3-D plans. Comparison of the IMRT plan vs the SFUD plan yielded mixed results with no consistent advantage for the SFUD plan over the IMRT plan. Targeting a CTV that spares the cystectomy bed and presacral region may marginally improve rectal toxicity but would not be expected to improve the bowel toxicity associated with any given modality of adjuvant radiation

Cost-utility analysis of adjuvant goserelin (Zoladex and adjuvant chemotherapy in premenopausal women with breast cancer

Directory of Open Access Journals (Sweden)

Cheng Tsui

2012-01-01

Full Text Available Abstract Background Increased health care costs have made it incumbent on health-care facilities and physicians to demonstrate both clinical and cost efficacy when recommending treatments. Though studies have examined the cost-effectiveness of adjuvant goserelin with radiotherapy for locally advanced prostate cancer, few have compared the cost-effectiveness of adjuvant goserelin to adjuvant chemotherapy alone in premenopausal breast cancer. Methods In this retrospective study at one hospital, the records of 152 patients with stage Ia to IIIa ER + breast cancer who received goserelin or chemotherapy were reviewed. Survival analysis was assessed by the Kaplan-Meier method. Patients were interviewed to evaluate their quality of life using the European Organization for Research and Treatment Quality of Life questionnaire (EORTC-QLQ-C30, version 4.0, and to obtain the utility value by the standard gamble (SG and visual scale (VS methods. Total medical cost was assessed from the (National Health Insurance NHI payer's perspective. Results Survival at 11 years was significantly better in the groserelin group (P Conclusions Goserelin therapy results in better survival and higher utility-weighted life-years, and is more cost-effective than TC or TEC chemotherapy.

Land Sparing and Land Sharing Policies in Developing Countries - Drivers and Linkages to Scientific Debates

DEFF Research Database (Denmark)

Mertz, Ole; Mertens, Charlotte Filt

2017-01-01

The need for developing land sparing or land sharing policies for protecting the environment has been a polarized debate in the scientific literature. Some studies show that "spared" landscapes with clearly separated intensive agriculture and pristine forest are better for biodiversity and other...... ecosystem services, whereas others demonstrate the benefits of "shared" mosaic landscapes composed of a mix of forest types, agricultural fields, grassland, and plantations. Increasingly, these scientific views have been depolarized, recognizing that both shared and spared landscapes have a role to play......, depending on the context. However, it is less clear from the literature what drives actual policy-making related to land sparing and land sharing in developing countries and what the outcomes of these policies are. We therefore reviewed the international peer-reviewed literature for evidence of policies...

Adjuvant Treatment for Older Women with Invasive Breast Cancer

Science.gov (United States)

Jolly, Trevor A; Williams, Grant R; Bushan, Sita; Pergolotti, Mackenzi; Nyrop, Kirsten A; Jones, Ellen L; Muss, Hyman B

2016-01-01

Older women experience a large share of breast cancer incidence and death. With the projected rise in the number of older cancer patients, adjuvant chemo-, radiation and endocrine therapy management will become a key component of breast cancer treatment in older women. Many factors influence adjuvant treatment decisions including patient preferences, life expectancy and tumor biology. Geriatric assessment predicts important outcomes, identifies key deficits, and can aid in the decision making process. This review utilizes clinical vignettes to illustrate core principles in adjuvant management of breast cancer in older women and suggests an approach incorporating life expectancy and geriatric assessment. PMID:26767315

CWT and RWT Metrics Measure the Performance of the Army's Logistics Chain for Spare Parts

National Research Council Canada - National Science Library

2003-01-01

.... Maintaining these weapon systems requires that spare parts be available where and when they are needed. Thus, the responsive functioning of the logistics chain for spare parts is critical to keeping equipment ready to operate...

Adjuvants and delivery systems in veterinary vaccinology: current state and future developments

DEFF Research Database (Denmark)

Heegaard, Peter M. H.; Dedieu, Laurence; Johnson, Nicholas

2011-01-01

Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have...

Current adjuvant treatment modalities for gastric cancer: From history to the future

Science.gov (United States)

Kilic, Leyla; Ordu, Cetin; Yildiz, Ibrahim; Sen, Fatma; Keskin, Serkan; Ciftci, Rumeysa; Pilanci, Kezban Nur

2016-01-01

The discrepancy between the surgical technique and the type of adjuvant chemotherapy used in clinical trials and patient outcomes in terms of overall survival rates has led to the generation of different adjuvant treatment protocols in distinct parts of the world. The adjuvant treatment recommendation is generally chemoradiotherapy in the United States, perioperative chemotherapy in the United Kingdom and parts of Europe, and chemotherapy in Asia. These options mainly rely on the United States Intergroup-0116, United Kingdom British Medical Research Council Adjuvant Gastric Infusional Chemotherapy, and the Asian Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer and Capecitabine and Oxaliplatin Adjuvant Study in Stomach Cancer trials. However, the benefits were evident for only certain patients, which were not very homogeneous regarding the type of surgery, chemotherapy regimens, and stage of disease. Whether the dissimilarities in survival are attributable to surgical technique or intrinsic biological differences is a subject of debate. Regardless of the extent of surgery, multimodal therapy may offer modest survival advantage at least for diseases with lymph node involvement. Moreover, in the era of individualized treatment for most of the other cancer types, identification of special subgroups comprising those who will derive more or no benefit from adjuvant therapy merits further investigation. The aim of this review is to reveal the historical evolution and future reflections of adjuvant treatment modalities for resected gastric cancer patients. PMID:27190583

Does adjuvant therapy improve overall survival for stage IA/B pancreatic adenocarcinoma?

Science.gov (United States)

Ostapoff, Katherine T; Gabriel, Emmanuel; Attwood, Kristopher; Kuvshinoff, Boris W; Nurkin, Steven J; Hochwald, Steven N

2017-07-01

Current guidelines recommend adjuvant chemotherapy for resected pancreatic adenocarcinoma (PDAC). However, no studies have addressed its survival benefit for stage I patients as they comprise IA or IB PDAC were identified. Median OS was 60.3 months (mo) for stage IA and 36.9 mo for IB. 45.5% received adjuvant chemotherapy; 19.9% received adjuvant chemoradiation. There was OS benefit for both stage IA/IB patients with adjuvant chemotherapy (HR = 0.73 and 0.76 for IA and IB, respectively, p = 0.002 and IA disease (n = 1,477, 37.8%), age ≥70 (p < 0.001), higher grade (p < 0.001), ≤10 lymph nodes examined (p = 0.008), positive margins (p < 0.001), and receipt of adjuvant chemoradiation (p = 0.002) were associated with worse OS. For stage IB patients (n = 2,432, 62.2%), similar associations were observed with the exception of adjuvant chemoradiation whereby there was no significant association (p = 0.35). Adjuvant chemotherapy was associated with an OS benefit for patients with stage I PDAC; adjuvant chemoradiation was either of no benefit or associated with worse OS. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Some Aspects Of Adjuvant Treatment Of Colorectal Cancer

International Nuclear Information System (INIS)

Hlavata, Z.

2008-01-01

Colorectal cancer is one of the most common cancers in Europe and in North America. Cornerstone of the treatment of localized colorectal cancer is surgical resection followed by chemotherapy or radio-chemotherapy in indicated cases. For patients with Stage III colon cancer recent data have shown efficacy through the combining fluorouracil-based chemotherapy with oxaliplatin into adjuvant treatment program. For patients with Stage II colon cancer, the use of adjuvant chemotherapy remains controversial, but may be appropriate in a subset of individuals at high risk for disease recurrence. Current randomized clinical trials in the adjuvant therapy of colorectal cancer are examining the value of adding agents known to be active in metastatic disease, including those that modify specific molecular targets. (author)

Old and new adjuvants for hepatitis B vaccines.

Science.gov (United States)

Leroux-Roels, Geert

2015-02-01

The safety and immunogenicity profiles of currently available recombinant hepatitis B vaccines are excellent. However, it remains a real challenge to induce protective immunity in the target groups that respond poorly or not at all to conventional vaccines. Ideally, a hepatitis B vaccine can be developed that conveys lifelong protection against infection rapidly after the injection of a single dose. Although this goal is far from being reached, important improvements have been made. Novel vaccine adjuvants have been developed that enhance the immunogenicity of recombinant hepatitis B vaccines while maintaining a good safety profile. The different adjuvants and adjuvant systems that are discussed herein have all been thoroughly evaluated in clinical trials and some have reached or are close to reach the market.

Imaging of hepatic steatosis and fatty sparing

Energy Technology Data Exchange (ETDEWEB)

Karcaaltincaba, Musturay [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)]. E-mail: musturayk@yahoo.com; Akhan, Okan [Department of Radiology, Hacettepe University School of Medicine, Ankara 06100 (Turkey)

2007-01-15

Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing.

Imaging of hepatic steatosis and fatty sparing

International Nuclear Information System (INIS)

Karcaaltincaba, Musturay; Akhan, Okan

2007-01-01

Radiology has gained importance in the non-invasive diagnosis of hepatic steatosis. Ultrasonography is usually the first imaging modality for the evaluation of hepatic steatosis. Unenhanced CT with or without dual kVp measurement and MRI with in and out of phase sequence can allow objective evaluation of hepatic steatosis. However, none of the imaging modalities can differentiate non-alcoholic steatohepatitis/fatty liver disease from simple steatosis. Evaluation of hepatic steatosis is important in donor evaluation before orthotopic liver transplantation and hepatic surgery. Recently, one-stop shop evaluation of potential liver donors has become possible by CT and MRI integrating vascular, parenchymal, volume and steatosis evaluation. Moreover hepatic steatosis (diffuse, multinodular, focal, subcortical, perilesional, intralesional, periportal and perivenular), hypersteatosis and sparing (geographic, nodular and perilesional or peritumoral) can cause diagnostic problems as a pseudotumor particularly in the evaluation of oncology patients. Liver MRI is used as a problem-solving tool in these patients. In this review, we discuss the current role of radiology in diagnosing, quantifying hepatic steatosis and solutions for diagnostic problems associated with fatty infiltration and sparing

Additive manufacturing technology in spare parts supply chain

DEFF Research Database (Denmark)

Li, Yao; Jia, Guozhu; Yang, Cheng

2017-01-01

Additive Manufacturing (AM) technology has the potential to significantly improve supply chain dynamics. The purpose of this paper is to investigate the impact of AM on spare parts supply chain. Three supply chain scenarios are investigated in this paper, namely conventional supply chain...

[Status and suggestions for adjuvant standard for Chinese materia medica processing in China].

Science.gov (United States)

Yang, Chun-Yu; Cao, Hui; Wang, Xiao-Tao; Tu, Jia-Sheng; Qian, Zhong-Zhi; Yu, Zhi-Ling; Shang, Yue; Zhang, Bao-Xian

2017-04-01

In this paper, the status of adjuvant standard for Chinese materia medica processing in the Chinese Pharmacopoeia 2015 edition, the National Specification of Chinese Materia Medica Processing, and the 29 provincial specification of Chinese materia medica was summarized, and the the status including general requirements, specific requirements, and quality standard in the three grade official specifications was collected and analyzed according to the "medicine-adjuvant homology" and "food-adjuvant homology" features of adjuvants. This paper also introduced the research situation of adjuvant standard for Chinese materia medica processing in China; In addition, analyzed and discussed the problems existing in the standard system of adjuvant for Chinese materia medica processing, such as lack of general requirements, low level of standard, inconsistent standard references, and lack of research on the standard, and provided suggestions for the further establishment of the national standards system of adjuvant for Chinese materia medica processing. Copyright© by the Chinese Pharmaceutical Association.

Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

Science.gov (United States)

Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

2016-01-01

Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

Spare-parts and perpetuity of equipment in French PWR plants

International Nuclear Information System (INIS)

Briolat, R.

1993-01-01

Supply of plants with new or repaired parts in strict quality conditions aids maintaining safety in operation and energy availability. Taking into account their expected life-time, a process of perpetuity in partnership with suppliers is necessary to ensure operation for the medium and long term. At EDF, the method involves a classification of mechanical and electrical spare parts in two levels of quality, responding to safety and availability imperatives and current available industrial practices. A diagram is presented to define optimal strategy for each equipment component, which gives choice between spare part storage, longevity agreement with the supplier, or a technology transfer agreement. 1 tab

Postoperative adjuvant chemotherapy in rectal cancer operated for cure.

Science.gov (United States)

Petersen, Sune Høirup; Harling, Henrik; Kirkeby, Lene Tschemerinsky; Wille-Jørgensen, Peer; Mocellin, Simone

2012-03-14

Colorectal cancer is one of the most common types of cancer in the Western world. Apart from surgery - which remains the mainstay of treatment for resectable primary tumours - postoperative (i.e., adjuvant) chemotherapy with 5-fluorouracil (5-FU) based regimens is now the standard treatment in Dukes' C (TNM stage III) colon tumours i.e. tumours with metastases in the regional lymph nodes but no distant metastases. In contrast, the evidence for recommendations of adjuvant therapy in rectal cancer is sparse. In Europe it is generally acknowledged that locally advanced rectal tumours receive preoperative (i.e., neoadjuvant) downstaging by radiotherapy (or chemoradiotion), whereas in the US postoperative chemoradiotion is considered the treatment of choice in all Dukes' C rectal cancers. Overall, no universal consensus exists on the adjuvant treatment of surgically resectable rectal carcinoma; moreover, no formal systematic review and meta-analysis has been so far performed on this subject. We undertook a systematic review of the scientific literature from 1975 until March 2011 in order to quantitatively summarize the available evidence regarding the impact of postoperative adjuvant chemotherapy on the survival of patients with surgically resectable rectal cancer. The outcomes of interest were overall survival (OS) and disease-free survival (DFS). CCCG standard search strategy in defined databases with the following supplementary search. 1. Rect* or colorect* - 2. Cancer or carcinom* or adenocarc* or neoplasm* or tumour - 3. Adjuv* - 4. Chemother* - 5. Postoper* Randomised controlled trials (RCT) comparing patients undergoing surgery for rectal cancer who received no adjuvant chemotherapy with those receiving any postoperative chemotherapy regimen. Two authors extracted data and a third author performed an independent search for verification. The main outcome measure was the hazard ratio (HR) between the risk of event between the treatment arm (adjuvant chemotherapy

Opioid-sparing effects of the thoracic interfascial plane blocks: A meta-analysis of randomized controlled trials

Directory of Open Access Journals (Sweden)

Preet Mohinder Singh

2018-01-01

Conclusions: Use of PECS block and its modifications with general anesthesia for breast surgery has significant opioid-sparing effect intraoperatively and during the first 24 h after surgery. It also has higher intraoperative opioid-sparing effect when compared to PVB. During the 1st postoperative day, PVB has slightly more morphine sparing potential that may however be associated with higher complication rates. The present PECS block techniques show marked interstudy variations and need standardization.

Quality of the spare triple-GEM detectors

CERN Document Server

Lenci, Rosario; Paoletti, Emiliano; Pasquali, Luigi; Pinci, Davide; Piscitelli, Carmelo; Poli Lener, Marco; Sciubba, Adalberto; Tskhadadze, Edisher

2017-01-01

Triple-GEM chambers equip the inner region of the M1 muon station. In order to provide spare detectors in case of problems in the operating ones, new chambers have been assembled at the Frascati National Laboratories of the INFN. This note summarizes the results of the quality tests performed at the end of the production procedure.

Optimization Policy of Inventory Spare Parts Stocking and Provisioning

International Nuclear Information System (INIS)

Yun, Tae Sik; Park, Jong Hyuk; Hwang, Eui Youp; Yoo, Sung Soo; Kim, In Hwan

2005-01-01

Spare parts, especially safety related items, being used in Korea Nuclear Power Plants are largely from the United States, Canada, France and the like, meaning the inventory policy, stocking and provision, should be influenced by those countries' nuclear industry situation in a direct or indirect manner. As a result of nuclear industry downturn practices, lots of spare supply corporations have gone broke, which gave immediate signals we have to resolve inventory purchases in need. It is known for that nuclear maintenance spare items are particularly composed of many kinds with small quantities, which makes matters worse to Korea nuclear operation company (KHNP) to purchase them. Hence, Korea nuclear business is trying to change its exinventory purchasing paradigm into innovative schemes it did not have to consider in the past. In order to implement a new stocking policy, it should be kept in mind the factors such as not only how much to stock for a smooth operation but also economic point of view. Even though it has done a lot of studies to optimize the inventory stocking level in an academic curiosity, it is not easy to apply the researches in a real world. Since it is so tough job to anticipate when and how large scale even occurs. Hence, it would be thought that the nuclear inventory should be dealt in a different manner from the general manufacturing industry

Spare parts inventory control under system availability constraints

NARCIS (Netherlands)

Houtum, van G.J.J.A.N.; Kranenburg, A.A.

2015-01-01

This book focuses on the tactical planning level for spare parts management. It describes a series of multi-item inventory models and presents exact and heuristic optimization methods, including greedy heuristics that work well for real, life-sized problems. The intended audience consists of

Use of chemical and biological adjuvants to achieve the optimum application of radiological techniques

International Nuclear Information System (INIS)

Azab, K.S.

2010-01-01

Nowadays, the optimization and attainment of maximum guarantee are representing the real challenge for the nuclear technology exercise. The Adjuvant techniques might be considered one of the available tactics for the developing, reducing risk and facilitating secure clearing of nuclear waste in the field of radiation technology applications. The history describes the belief that an adjuvant is required for immunity because the immune system evolved to respond to dangerous situations such as infections, and the presence of an adjuvant is the mechanism used to identify these situations. In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect. Adjuvants are coming increasingly into focus for vaccine developers since many novel split and subunit vaccines are insufficiently immunogenic on their own. Among the used today are alum (aluminum hydroxide) and Glycosyl ceramides. It is worth mentioning that manufacturers already had produced thousands of different adjuvants, for both industrial and agricultural purposes. Today, the agricultural and horticultural industries are being overwhelmed by adjuvant choices. Complete Freunds adjuvant is the adjuvant used in animal research studies of basic and applied immunology. (author)

Self-Adjuvanting Glycopeptide Conjugate Vaccine against Disseminated Candidiasis

Science.gov (United States)

Xin, Hong; Cartmell, Jonathan; Bailey, Justin J.; Dziadek, Sebastian; Bundle, David R.; Cutler, Jim E.

2012-01-01

Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface β-1, 2–mannotriose [β-(Man)3] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine β-(Man)3-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the β-(Man)3-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified β-(Man)3-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the β-(Man)3-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the β-(Man)3-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a

Outcomes of Aortic Valve-Sparing Operations in Marfan Syndrome.

Science.gov (United States)

David, Tirone E; David, Carolyn M; Manlhiot, Cedric; Colman, Jack; Crean, Andrew M; Bradley, Timothy

2015-09-29

In many cardiac units, aortic valve-sparing operations have become the preferred surgical procedure to treat aortic root aneurysm in patients with Marfan syndrome, based on relatively short-term outcomes. This study examined the long-term outcomes of aortic valve-sparing operations in patients with Marfan syndrome. All patients with Marfan syndrome operated on for aortic root aneurysm from 1988 through 2012 were followed prospectively for a median of 10 years. Follow-up was 100% complete. Time-to-event analyses were calculated using the Kaplan-Meier method with log-rank test for comparisons. A total of 146 patients with Marfan syndrome had aortic valve-sparing operations. Reimplantation of the aortic valve was performed in 121 and remodeling of the aortic root was performed in 25 patients. Mean age was 35.7 ± 11.4 years and two-thirds were men. Nine patients had acute, 2 had chronic type A, and 3 had chronic type B aortic dissections before surgery. There were 1 operative and 6 late deaths, 5 caused by complications of dissections. Mortality rate at 15 years was 6.8 ± 2.9%, higher than the general population matched for age and sex. Five patients required reoperation on the aortic valve: 2 for endocarditis and 3 for aortic insufficiency. Three patients developed severe, 4 moderate, and 3 mild-to-moderate aortic insufficiency. Rate of aortic insufficiency at 15 years was 7.9 ± 3.3%, lower after reimplantation than remodeling. Nine patients developed new distal aortic dissections during follow-up. Rate of dissection at 15 years was 16.5 ± 3.4%. Aortic valve-sparing operations in patients with Marfan syndrome were associated with low rates of valve-related complications in long-term follow-up. Residual and new aortic dissections were the leading cause of death. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

A decision-making framework to integrate maintenance contract conditions with critical spares management

International Nuclear Information System (INIS)

Godoy, David R.; Pascual, Rodrigo; Knights, Peter

2014-01-01

Maintenance outsourcing is a strategic driver for asset intensive industries pursuing to enhance supply chain performance. Spare parts management plays a relevant role in this premise since its significant impact on equipment availability, and hence on business success. Designing critical spares policies might therefore seriously affect maintenance contracts profitability, yet service receivers and external providers traditionally attempt to benefit separately. To coordinate both chain parties, we investigated whether the spare components pool should be managed in-house or contracted out. This paper provides a decision-making framework to efficiently integrate contractual conditions with critical spares stockholding. Using an imperfect maintenance strategy over a finite horizon, the scheme maximizes chain returns whilst evaluating the impact of an additional part to stock. As result, an original joint value – preventive interval and stock level – sets the optimal agreement to profitably allocate the components pool within the service contract. Subsidization bonuses on preventive interventions and pooling costs are also estimated to induce the service provider to adjust its policy when needed. The proposed contractual conditions motivate stakeholders to continuously improve maintenance performance and supply practices, thus obtaining higher joint benefits

Tissue sparing, behavioral recovery, supraspinal axonal sparing/regeneration following sub-acute glial transplantation in a model of spinal cord contusion.

Science.gov (United States)

Barbour, Helen R; Plant, Christine D; Harvey, Alan R; Plant, Giles W

2013-09-27

It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. OEG and SCs transplanted rats showed significant increased locomotion when compared to control injury only in the open field tests (BBB). However, the ladder walk test did not show statistically significant differences between treatment and control groups. Fluorogold retrograde tracing showed a statistically significant increase in the number of supraspinal nuclei projecting into the distal spinal cord in both OEG and SCs transplanted rats. These included the raphe, reticular and vestibular systems. Further pairwise multiple comparison tests also showed a statistically significant increase in raphe projecting neurons in OEG transplanted rats when compared to SCs transplanted animals. Immunohistochemistry of spinal cord sections short term (2 weeks) and long term (4 months) showed differences in host glial activity, migration and proteoglycan deposits between the two cell types. Histochemical staining revealed that the volume of tissue remaining at the lesion site had increased in all OEG and SCs treated groups. Significant tissue sparing was

Survival Following Kidney Sparing Management of Upper Urinary ...

African Journals Online (AJOL)

Survival Following Kidney Sparing Management of Upper Urinary Tract Transitional Cell Carcinoma is Adversely Affected By Prior History of Bladder Cancer. ... The tumor biology rather than the surgical approach dictates prognosis. Patients with higher stage and grade disease may be better served with a more aggressive ...

Activity of glycated chitosan and other adjuvants to PDT vaccines

Science.gov (United States)

Korbelik, Mladen; Banáth, Judit; Čiplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

2015-03-01

Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

Focal sparing around the gallbladder in fatty liver

International Nuclear Information System (INIS)

Chen, Kemin; Hiramatsu, Yoshihiro; Yunoki, Masanori; Hirano, Yoko

1989-01-01

In evaluating fatty liver with CT, the residual normal liver tissues without fat deposits are occasionally detected on CT as high attenuation regions, especially surrounding the gallbladder. This study examined the incidence of this phenomenon in terms of the diagnostic value of CT in fatty liver. Fifty-seven patients with fatty liver were examined with CT. The incidence of focal sparing area was the highest in the gallbladder bed (42/57, 74%), followed by the interlobar fissure or subcapsular area (13, 23%), quadrate lobe (8, 14%), caudate lobe (2, 4%), and right lobe (one, 1.8%). These CT appearances were of spot, band, ring, and the mixed type. In 38 patients, fatty liver was too moderate to be detected without CT attenuation numbers. Among them, 27 patients (71%) had focal sparing area surrounding the gallbladder. This CT appearance seemed to be of significance in preventing the missing of moderate fatty liver. (Namekawa, K)

Characterization of the structure and immunostimulatory activity of a vaccine adjuvant, de-O-acylated lipooligosaccharide.

Directory of Open Access Journals (Sweden)

Ji Eun Han

Full Text Available Lipopolysaccharide (LPS is a major component of the outer membrane of Gram-negative bacteria. LPS elicits strong immunopathological responses during bacterial infection, and the lipid A moiety of LPS is responsible for this immunostimulatory activity. Lipid A exerts its biological activity by sending signals via TLR4 present on immune cells, and TLR4 agonists have been a target for vaccine adjuvant. Previously, we demonstrated an adjuvant activity of deacylated lipooligosaccharide (dLOS to viral and bacterial antigens. In this study, we characterized the chemical structure of dLOS and evaluated its immunostimulatory activity on mouse and human immune cells in comparison with monophosphoryl lipid A (MPL. dLOS consists of the R3-type core, a glucosamine disaccharide with two phosphate groups, and two N-linked acyl groups [corrected], and two N-linked acyl groups. dLOS was similar to MPL in induction of cytokine production in mouse peritoneal macrophages, but was a more potent activator in human monocytes and dendritic cells (DCs. Results of an analysis of allogeneic T cell responses revealed that dLOS induces Th1, Th2, and Th17-type immune responses in a dose-dependent manner. The immunostimulatory activities of dLOS were completely abrogated in TLR4(-/- mice, which confirms its TLR4-dependency. These results suggest that in the presence of the core oligosaccharide, O-linked acyl groups of LPS are dispensable for activating the TLR4 signaling pathway. dLOS did not cause any pathological effects or death at 0.25, 0.5, or 1 mg per kg body weight in mice in the acute toxicity tests. This result suggests that dLOS has a low toxicity. dLOS should be considered for further development as a safe and effective adjuvant for human vaccines.

The effect of several adjuvants on glufosinate effectiveness in Conyza species.

Science.gov (United States)

Fernandez-Cerejido, M C; Bastida, F; Menendez, J

2009-01-01

The effect of several adjuvants on the effectiveness of glufosinate and the role of adherence and contact angle modifications due to the presence of these adjuvants in the spraying solution on the increase in efficacy observed on the broadleaved weeds Conyza albida and Conyza bonariensis has been determined under laboratory controlled conditions. The adjuvants used on the experiment were a mixture of methyl oleate and palmitate (MO/MP), a dodecylbenzene ammonium sulphonate (DBAS), a paraffinic oil (PO), an alkylglycol ester (AGE), and a lecithin + propionic acid + non ionic surfactant based product (LI-700). Dose-response experiments showed that C. albida displayed higher susceptibility to glufosinate than C. bonariensis, no matter the adjuvant tested. However, none of the mixtures increased the herbicide effectiveness on C. atlbida, with LI 700 and PO showing an antagonistic effect on the herbicide efficacy. On C. bonariensis, MO/MP and DBAS showed significant better results than non-amended glufosinate controls, with LI 700 showing again an antagonistic effect. Both adherence and contact angle studies were inconclusive, since adjuvants with best adherence and contact angle values were not the most effective ones. Therefore, other unknown parameters putatively modified by adjuvants such as herbicide penetration should be questioned.

Carotid sparing intensity modulated radiotherapy on early glottic cancer: Preliminary study

Energy Technology Data Exchange (ETDEWEB)

Choi, Hoon Sik; Jeong, Bae Kwon; Jeong, Ho Jin; Song, Jin Ho; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon; Kang, Ki Mun [Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of)

2016-03-15

To compare the dose distribution between carotid sparing intensity modulated radiotherapy (IMRT) and opposed lateral field technique (LAFT), and to determine the effects of carotid sparing IMRT in early glottic cancer patients who have risk factors for atherosclerosis. Ten early glottic cancer patients were treated with carotid sparing IMRT. For each patient, the conventional LAFT plan was developed for comparison. IMRT and LAFT plans were compared in terms of planning target volume (PTV) coverage, conformity index, homogeneity index, and the doses to planning organ at risk volume (PRV) for carotid arteries, spinal cord and pharyngeal constrictor muscle. Recurrence was not observed in any patients during the follow-up period. V95% for PTV showed no significant difference between IMRT and LAFT plans, while V100% was significantly higher in the IMRT plan (95.5% vs. 94.6%, p = 0.005). The homogeneity index (11.6%) and conformity index (1.4) in the IMRT plan were significantly better than those in the LAFT plans (8.5% and 5.1, respectively) (p = 0.005). The median V5Gy (90.0%), V25Gy (13.5%), and V50Gy (0%) for carotid artery PRV in the IMRT plan were significantly lower than those in the LAFT plan (99.1%, 89.0%, and 77.3%, respectively) (p = 0.005). Our study suggests that carotid sparing IMRT can significantly decrease the dose to carotid arteries compared to LAFT, and it would be considered for early glottic cancer patient with high risk of atherosclerosis.

Conserving the birds of Uganda's banana-coffee arc: land sparing and land sharing compared.

Directory of Open Access Journals (Sweden)

Mark F Hulme

Full Text Available Reconciling the aims of feeding an ever more demanding human population and conserving biodiversity is a difficult challenge. Here, we explore potential solutions by assessing whether land sparing (farming for high yield, potentially enabling the protection of non-farmland habitat, land sharing (lower yielding farming with more biodiversity within farmland or a mixed strategy would result in better bird conservation outcomes for a specified level of agricultural production. We surveyed forest and farmland study areas in southern Uganda, measuring the population density of 256 bird species and agricultural yield: food energy and gross income. Parametric non-linear functions relating density to yield were fitted. Species were identified as "winners" (total population size always at least as great with agriculture present as without it or "losers" (total population sometimes or always reduced with agriculture present for a range of targets for total agricultural production. For each target we determined whether each species would be predicted to have a higher total population with land sparing, land sharing or with any intermediate level of sparing at an intermediate yield. We found that most species were expected to have their highest total populations with land sparing, particularly loser species and species with small global range sizes. Hence, more species would benefit from high-yield farming if used as part of a strategy to reduce forest loss than from low-yield farming and land sharing, as has been found in Ghana and India in a previous study. We caution against advocacy for high-yield farming alone as a means to deliver land sparing if it is done without strong protection for natural habitats, other ecosystem services and social welfare. Instead, we suggest that conservationists explore how conservation and agricultural policies can be better integrated to deliver land sparing by, for example, combining land-use planning and agronomic

Trastuzumab-associated cardiac adverse effects in the herceptin adjuvant trial

NARCIS (Netherlands)

Suter, Thomas M.; Procter, Marion; van Veldhuisen, Dirk J.; Muscholl, Michael; Bergh, Jonas; Carlomagno, Chiara; Perren, Timothy; Passalacqua, Rodolfo; Bighin, Claudia; Klijn, Jan G. M.; Ageev, Fail T.; Hitre, Erika; Groetz, Juergen; Iwata, Hiroji; Knap, Malgorzata; Gnant, Michael; Muehlbauer, Susanne; Spence, Alison; Gelber, Richard D.; Piccart-Gebhart, Martine J.

2007-01-01

Purpose The purpose of this analysis was to investigate trastuzumab- associated cardiac adverse effects in breast cancer patients after completion of ( neo) adjuvant chemotherapy with or without radiotherapy. Patients and Methods The Herceptin Adjuvant ( HERA) trial is a three- group, multicenter,

Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

International Nuclear Information System (INIS)

Showalter, Timothy N.; Ohri, Nitin; Teti, Kristopher G.; Foley, Kathleen A.; Keith, Scott W.; Trabulsi, Edouard J.; Lallas, Costas D.; Dicker, Adam P.; Hoffman-Censits, Jean; Pizzi, Laura T.; Gomella, Leonard G.

2012-01-01

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

Physician Beliefs and Practices for Adjuvant and Salvage Radiation Therapy After Prostatectomy

Energy Technology Data Exchange (ETDEWEB)

Showalter, Timothy N., E-mail: timothy.showalter@jeffersonhospital.org [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Ohri, Nitin; Teti, Kristopher G. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Foley, Kathleen A. [Strategic Consulting, Thomson Reuters Healthcare, Cambridge, MA (United States); Keith, Scott W. [Division of Biostatistics, Department of Pharmacology and Experimental Therapeutics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Trabulsi, Edouard J.; Lallas, Costas D. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Dicker, Adam P. [Department of Radiation Oncology, Jefferson Medical College, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Hoffman-Censits, Jean [Department of Medical Oncology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States); Pizzi, Laura T. [School of Pharmacy, Thomas Jefferson University, Philadelphia, PA (United States); Gomella, Leonard G. [Department of Urology, Jefferson Medical College and Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA (United States)

2012-02-01

Purpose: Despite results of randomized trials that support adjuvant radiation therapy (RT) after radical prostatectomy (RP) for prostate cancer with adverse pathologic features (APF), many clinicians favor selective use of salvage RT. This survey was conducted to evaluate the beliefs and practices of radiation oncologists (RO) and urologists (U) regarding RT after RP. Methods and Materials: We designed a Web-based survey of post-RP RT beliefs and policies. Survey invitations were e-mailed to a list of 926 RO and 591 U. APF were defined as extracapsular extension, seminal vesicle invasion, or positive surgical margin. Differences between U and RO in adjuvant RT recommendations were evaluated by comparative statistics. Multivariate analyses were performed to evaluate factors predictive of adjuvant RT recommendation. Results: Analyzable surveys were completed by 218 RO and 92 U (overallresponse rate, 20%). Adjuvant RT was recommended based on APF by 68% of respondents (78% RO, 44% U, p <0.001). U were less likely than RO to agree that adjuvant RT improves survival and/or biochemical control (p < 0.0001). PSA thresholds for salvage RT were higher among U than RO (p < 0.001). Predicted rates of erectile dysfunction due to RT were higher among U than RO (p <0.001). On multivariate analysis, respondent specialty was the only predictor of adjuvant RT recommendations. Conclusions: U are less likely than RO to recommend adjuvant RT. Future research efforts should focus on defining the toxicities of post-RP RT and on identifying the subgroups of patients who will benefit from adjuvant vs. selective salvage RT.

Vaginal brachytherapy alone is sufficient adjuvant treatment of surgical stage I endometrial cancer

International Nuclear Information System (INIS)

Solhjem, Matthew C.; Petersen, Ivy A.; Haddock, Michael G.

2005-01-01

Purpose To determine the efficacy and complications of adjuvant vaginal high-dose-rate brachytherapy alone for patients with Stage I endometrial cancer in whom complete surgical staging had been performed. Methods and Materials Between April 1998 and March 2004, 100 patients with Stage I endometrial cancer underwent surgical staging (total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic ± paraaortic nodal sampling) and postoperative vaginal high-dose-rate brachytherapy at our institution. The total dose was 2100 cGy in three fractions. Results With a median follow-up of 23 months (range 2-62), no pelvic or vaginal recurrences developed. All patients underwent pelvic dissection, and 42% underwent paraaortic nodal dissection. A median of 29.5 pelvic nodes (range 1-67) was removed (84% had >10 pelvic nodes removed). Most patients (73%) had endometrioid (or unspecified) adenocarcinoma, 16% had papillary serous carcinoma, and 11% had other histologic types. The International Federation of Gynecology and Obstetrics stage and grade was Stage IA, grade III in 5; Stage IB, grade I, II, or III in 6, 27, or 20, respectively; and Stage IC, grade I, II, or III in 13, 17, or 10, respectively. The Common Toxicity Criteria (version 2.0) complications were mild (Grade 1-2) and consisted primarily of vaginal mucosal changes, temporary urinary irritation, and temporary diarrhea. Conclusion Adjuvant vaginal high-dose-rate brachytherapy alone may be a safe and effective alternative to pelvic external beam radiotherapy for surgical Stage I endometrial cancer

Connecting inventory control and repair shop control : a differentiated control structure for repairable spare parts

NARCIS (Netherlands)

Driessen, M.A.; Rustenburg, W.D.; Houtum, van G.J.J.A.N.; Wiers, V.C.S.

2014-01-01

This paper presents a control structure for integrating decisions on spare parts inventory control and the control of repair shops for maintenance spare parts. A dierentiated control structure is proposed for the various repair shop types recognized in practice. Decisions functions are mapped and

Valve-sparing aortic root replacement in children: intermediate-term results.

Science.gov (United States)

Patel, Nishant D; Arnaoutakis, George J; George, Timothy J; Allen, Jeremiah G; Alejo, Diane E; Dietz, Harry C; Cameron, Duke E; Vricella, Luca A

2011-03-01

Valve-sparing root replacement (VSRR) is an attractive option for aortic aneurysm in children with low-operative risk, but mid- and late-term results are not yet known. Between 1997 and 2009, 56 children (mean age 11.5 years) underwent VSRR at our institution. Twenty-six (46.4%) had Marfan syndrome and 24 (42.8%) had Loeys-Dietz syndrome. Mean preoperative max sinus diameter was 4.2±0.8 cm (Z-score 7.7±2.9). Five (8.9%) had >2+ aortic insufficiency (AI). Two (3.6%) underwent David I reimplantation with a straight-tube, 12 (21.4%) had a Yacoub remodeling procedure, and 42 (75.0%) had reimplantation using a Valsalva-graft. There were one (1.8%) operative and three (5.4%) late deaths. One patient required reoperation for bleeding and one required late repair of a distal pseudoaneurysm. Mean follow-up was 5.2 years (range 0-12 years). No patients suffered thromboembolic events or had endocarditis. Of the 12 remodeling patients, four (33.3%) developed >2+ AI and required aortic valve repair or replacement. No patient developed >2+ AI after reimplantation. VSRR in children is a safe alternative to aortic root replacement with mechanical or biological prostheses. In this particular group of patients with connective tissue disorders and proclivity toward annular dilation and late AI, reimplantation is superior to remodeling.

Cognitive function after adjuvant treatment for early breast cancer

DEFF Research Database (Denmark)

Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer

2010-01-01

The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged ... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...... themselves as impaired at 6 months. Our results do not support that adjuvant chemotherapy is associated with cognitive side effects in breast cancer patients....

Posterior Pole Sparing Laser Photocoagulation Combined with Intravitreal Bevacizumab Injection in Posterior Retinopathy of Prematurity

Directory of Open Access Journals (Sweden)

Rebecca Kim

2014-01-01

Full Text Available Purpose. To report the results of the posterior pole sparing laser photocoagulation combined with intravitreal bevacizumab injection (IVB in retinopathy of prematurity (ROP. Methods. A retrospective chart review of premature babies with ROP, all of whom received laser photocoagulation with IVB. Eleven eyes of 6 infants with advanced zone I ROP underwent laser ablation sparing posterior pole with concurrent IVB. The results were compared with those of full-laser treatment combined with IVB to 8 eyes of 5 infants with advanced ROP without involvement of the posterior pole. Results. The posterior pole sparing laser with IVB was performed with zone I, stage 3+ ROP at the mean postmenstrual age of 36 weeks and 5 days. The plus sign decreased significantly at postoperative day 1, the neovascular proliferation regressed by postoperative week 1, and the normal vascularization started at postoperative day 32 on the average. Two months after treatment, vascularization of the spared avascular area was completed. There was no macular dragging, tractional retinal detachment, foveal destruction by laser scars, or any other adverse event. No significant anatomical differences were identified from those of full-laser ablation combined with IVB. Conclusions. Posterior pole sparing laser with IVB can give favorable results without destruction of posterior pole retina.

Multi-echelon, multi-indenture spare parts inventory control subject to system availability and budget constraints

International Nuclear Information System (INIS)

Costantino, Francesco; Di Gravio, Giulio; Tronci, Massimo

2013-01-01

Inventory management of spare parts is one of the most critical issues in the aeronautical industry, given the required level of system availability related to the strategic importance and high stocking costs of the components. Even if a large number of spare parts increases warehousing costs, every single shortage have a greater impact: the adoption of best-in-class inventory management techniques becomes crucial. On these considerations, the paper presents an innovative model of spare parts allocation for the Italian Air Force with the aim of minimizing backorders and, at the same time, ensuring an availability of 99% depending on the actual flight plan. The model, solved by a marginal analysis, considers an original configuration of features combining different skills of maintenance centers in a hierarchical multi-echelon, multi-item, multi-indenture structure. A real case is provided in order to analyze the solving method and the results. -- Highlights: •We studied a problem of allocations for spare parts of aeronautical systems. •The model presents different repair capabilities of maintenance centers. •The model fits constraints on budget and on total operational availability. •The model is solved by a marginal analysis with a backorder/price ratio. •A numerical example shows a spare parts allocation with relative considerations

Ketogenic diets as an adjuvant cancer therapy: History and potential mechanism

Science.gov (United States)

Allen, Bryan G.; Bhatia, Sudershan K.; Anderson, Carryn M.; Eichenberger-Gilmore, Julie M.; Sibenaller, Zita A.; Mapuskar, Kranti A.; Schoenfeld, Joshua D.; Buatti, John M.; Spitz, Douglas R.; Fath, Melissa A.

2014-01-01

Cancer cells, relative to normal cells, demonstrate significant alterations in metabolism that are proposed to result in increased steady-state levels of mitochondrial-derived reactive oxygen species (ROS) such as O2•−and H2O2. It has also been proposed that cancer cells increase glucose and hydroperoxide metabolism to compensate for increased levels of ROS. Given this theoretical construct, it is reasonable to propose that forcing cancer cells to use mitochondrial oxidative metabolism by feeding ketogenic diets that are high in fats and low in glucose and other carbohydrates, would selectively cause metabolic oxidative stress in cancer versus normal cells. Increased metabolic oxidative stress in cancer cells would in turn be predicted to selectively sensitize cancer cells to conventional radiation and chemotherapies. This review summarizes the evidence supporting the hypothesis that ketogenic diets may be safely used as an adjuvant therapy to conventional radiation and chemotherapies and discusses the proposed mechanisms by which ketogenic diets may enhance cancer cell therapeutic responses. PMID:25460731

Clinic-radiology findings at limp-sparing surgery of alveolar sarcoma

International Nuclear Information System (INIS)

Tzekov, A.; Penchev, V.; Niagolova, S.; Kovachev, V.

2007-01-01

Soft-tissue sarcomas are a rare and heterogeneous group of tumors. Alveolar soft part sarcoma is a rare sarcoma of an unclear cause. It is representing 0.2-1 percent of soft tissue sarcomas. Unique biologic behaviors of soft-tissue sarcomas features include formation of a reactive zone, intra-compartmental growth, and, rarely, the presence of skip metastases. Although the soft-tissue sarcomas have a unique morphology, biological behavior, and prognosis, they share biological characteristics and are treated in a similar fashion. The concept of limb-sparing surgery, or limb salvage, has gradually evolved over the past 25 years. Prior to this the basic principles of surgical oncology for the extremities consisted solely of determining the correct level at which to perform an amputation. The three stages of a limb-sparing procedure are as follows: tumor resection skeletal reconstruction and soft-tissue coverage and muscle transfers to restore function. Imaging diagnostic is a key step in the limp-sparing surgery of a soft tissue sarcomas at relation of: preoperatively - the diagnosis of lesion, the decision for biopsy, about location of the lesion and what is the safest anatomic route to that location, possibly lung and bone metastases; postoperative - checking the position of the prosthesis, inflammatory, mechanic and oncology complications. (authors)

Raman spectroscopic detection of peripheral nerves towards nerve-sparing surgery

Science.gov (United States)

Minamikawa, Takeo; Harada, Yoshinori; Takamatsu, Tetsuro

2017-02-01

The peripheral nervous system plays an important role in motility, sensory, and autonomic functions of the human body. Preservation of peripheral nerves in surgery, namely nerve-sparing surgery, is now promising technique to avoid functional deficits of the limbs and organs following surgery as an aspect of the improvement of quality of life of patients. Detection of peripheral nerves including myelinated and unmyelinated nerves is required for the nerve-sparing surgery; however, conventional nerve identification scheme is sometimes difficult to identify peripheral nerves due to similarity of shape and color to non-nerve tissues or its limited application to only motor peripheral nerves. To overcome these issues, we proposed a label-free detection technique of peripheral nerves by means of Raman spectroscopy. We found several fingerprints of peripheral myelinated and unmyelinated nerves by employing a modified principal component analysis of typical spectra including myelinated nerve, unmyelinated nerve, and adjacent tissues. We finally realized the sensitivity of 94.2% and the selectivity of 92.0% for peripheral nerves including myelinated and unmyelinated nerves against adjacent tissues. Although further development of an intraoperative Raman spectroscopy system is required for clinical use, our proposed approach will serve as a unique and powerful tool for peripheral nerve detection for nerve-sparing surgery in the future.

Adjuvant Chemotherapy and Trastuzumab Is Safe and Effective in Older Women With Small, Node-Negative, HER2-Positive Early-Stage Breast Cancer.

Science.gov (United States)

Cadoo, Karen A; Morris, Patrick G; Cowell, Elizabeth P; Patil, Sujata; Hudis, Clifford A; McArthur, Heather L

2016-12-01

The benefit of adjuvant trastuzumab with chemotherapy is well established for women with higher risk human epidermal growth factor receptor 2-positive (HER2 + ) breast cancer. However, its role in older patients with smaller, node-negative tumors is less clear. We conducted a retrospective, sequential cohort study of this population to describe the impact of trastuzumab on breast cancer outcomes and cardiac safety. Women ≥ 55 years with ≤ 2 cm, node-negative, HER2 + breast cancer were identified and electronic medical records reviewed. A no-trastuzumab cohort of 116 women diagnosed between January 1, 1999 and May 14, 2004 and a trastuzumab cohort of 128 women diagnosed between May 16, 2006 and December 31, 2010 were identified. Overall survival and distant relapse-free survival were estimated by Kaplan-Meier methods. The median ages of the trastuzumab and no-trastuzumab cohorts were 62 and 64 years, respectively. More patients in the trastuzumab cohort had grade III (P = .001), lymphovascular invasion (P = .001), or estrogen receptor-negative (P cancers. The majority of the trastuzumab cohort received chemotherapy versus one-half of the no-trastuzumab cohort (98% vs. 53%; P women in the trastuzumab cohort and 1 in the no-trastuzumab cohort developed symptomatic heart failure. There were no cardiac-related deaths in either arm. Following adjuvant trastuzumab with chemotherapy, selected older women with small, node-negative, HER2 + breast cancers have excellent disease control. The rate of cardiac events is low. Copyright © 2016 Elsevier Inc. All rights reserved.

Current Status of Nephron-Sparing Surgery (NSS) in the Management of Renal Tumours.

Science.gov (United States)

Venkatramani, Vivek; Swain, Sanjaya; Satyanarayana, Ramgopal; Parekh, Dipen J

2017-06-01

Nephron-sparing surgery has emerged as the surgical treatment of choice for small renal masses over the past two decades, replacing the traditional teaching of radical nephrectomy for renal cell carcinoma. With time, there has been an evolution in the techniques and indications for partial nephrectomy. This review summarizes the current status of nephron-sparing surgery for renal carcinoma and also deals with the future of this procedure.

Factors Affecting Adjuvant Therapy in Stage III Pancreatic Cancer—Analysis of the National Cancer Database

Directory of Open Access Journals (Sweden)

Mridula Krishnan

2017-08-01

Full Text Available Background: Adjuvant therapy after curative resection is associated with survival benefit in stage III pancreatic cancer. We analyzed the factors affecting the outcome of adjuvant therapy in stage III pancreatic cancer and compared overall survival with different modalities of adjuvant treatment. Methods: This is a retrospective study of patients with stage III pancreatic cancer listed in the National Cancer Database (NCDB who were diagnosed between 2004 and 2012. Patients were stratified based on adjuvant therapy they received. Unadjusted Kaplan-Meier and multivariable Cox regression analysis were performed. Results: We analyzed a cohort included 1731 patients who were recipients of adjuvant therapy for stage III pancreatic cancer within the limits of our database. Patients who received adjuvant chemoradiation had the longest postdiagnosis survival time, followed by patients who received adjuvant chemotherapy, and finally patients who received no adjuvant therapy. On multivariate analysis, advancing age and patients with Medicaid had worse survival, whereas Spanish origin and lower Charlson comorbidity score had better survival. Conclusions: Our study is the largest trial using the NCDB addressing the effects of adjuvant therapy specifically in stage III pancreatic cancer. Within the limits of our study, survival benefit with adjuvant therapy was more apparent with longer duration from date of diagnosis.

Land sharing not sparing in the “green economy”

NARCIS (Netherlands)

Dressler, Wolfram; Koning, de Jessica; Montefrio, Marvin; Firn, Jennifer

2016-01-01

In Southeast Asia's green economy, conservation interventions intensify the production of resources as commodities through land sparing activities and zoning in extensively used landscapes. Such initiatives encounter problems where poor resource users diversify livelihoods in multi-functional

Exploring patient experiences of neo-adjuvant chemotherapy for breast cancer.

Science.gov (United States)

Beaver, Kinta; Williamson, Susan; Briggs, Jean

2016-02-01

Neo-adjuvant chemotherapy is recommended for 'inoperable' locally advanced and inflammatory breast cancers. For operable breast cancers, trials indicate no survival differences between chemotherapy given pre or post-surgery. Communicating evidence based information to patients is complex and studies examining patient experiences of neo-adjuvant chemotherapy are lacking. This study aims to explore the experiences of women who received neo-adjuvant chemotherapy for breast cancer. A qualitative approach using in-depth interviews with 20 women who had completed neo-adjuvant chemotherapy for breast cancer. Interview data were analysed using thematic analysis. The sample included a relatively young group of women, with caring responsibilities. Five main themes emerged: coping with the rapid transition from 'well' to 'ill', information needs and decision making, needing support and empathy, impact on family, and creating a new 'normal'. More support was needed towards the end of chemotherapy, when side effects were at their most toxic, and decisions about forthcoming surgery were being made. Some women were referred to psychological services, but usually when a crisis point had been reached. Information and support would have been beneficial at key time points. This information is vital in developing services and interventions to meet the complex needs of these patients and potentially prevent late referral to psychological services. Specialist oncology nurses are able to develop empathetic relationships with patients and have the experience, knowledge and skills to inform and support women experiencing neo-adjuvant chemotherapy. Targeting key time points and maintaining relationship throughout neo-adjuvant chemotherapy would be highly beneficial. Copyright © 2015 Elsevier Ltd. All rights reserved.

Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

Science.gov (United States)

Chung, Ki-Young Y; Kelsen, David

2006-06-01

The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

Adjuvant whole brain radiotherapy: strong emotions decide but rational studies are needed.

Science.gov (United States)

Brown, Paul D; Asher, Anthony L; Farace, Elana

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

Energy Technology Data Exchange (ETDEWEB)

Brown, Paul D. [Department of Radiation Oncology, Mayo Clinic, Rochester, MN (United States)], E-mail: brown.paul@mayo.edu; Asher, Anthony L [Brain and Spinal Cord Tumors Programs, Carolinas Medical Center and Presbyterian Hospital, Charlotte, NC (United States); Farace, Elana [Department of Neurosurgery, Pennsylvania State University, Penn State Milton S. Hershey Medical Center, Hershey, PA (United States)

2008-04-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival.

Adjuvant Whole Brain Radiotherapy: Strong Emotions Decide But Rational Studies Are Needed

International Nuclear Information System (INIS)

Brown, Paul D.; Asher, Anthony L.; Farace, Elana

2008-01-01

Brain metastases are common in cancer patients and cause considerable morbidity and mortality. For patients with limited disease and good performance status, treatment typically involves a combination of focal measures (e.g., surgical resection or radiosurgery) for the radiographically apparent disease, followed by adjuvant whole brain radiotherapy (WBRT) to treat subclinical disease. Because of concerns regarding the toxicity of WBRT, especially neurocognitive deterioration, many have advocated withholding adjuvant WBRT. Recently published studies have shed more light on the efficacy of adjuvant WBRT and the neurocognitive effects of WBRT. However, the inclusion of neurocognitive and quality-of-life data in clinical trials are still required to better define the role of adjuvant WBRT. Currently, two Phase III trials are underway, one in Europe and one in North America, that will determine the effect of adjuvant WBRT on patients' quality of life, neurocognitive function, and survival

Initial Spare Parts of the A400M Aircraft

Science.gov (United States)

2012-03-08

inventory. Therefore, a balance has to be sought between inventory cost and customer service ( Heizer & Render , 2010:500-501). Nevertheless, spare part... Heizer , Jay H. and Barry Render . Principles of Operations Management. Boston: Pearson Education, 2011. Heuninckx, Baudouin. “Availability

Engineering of an Inhalable DDA/TDB Liposomal Adjuvant

DEFF Research Database (Denmark)

Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle

2013-01-01

The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....

Ordering decision-making methods on spare parts for a new aircraft fleet based on a two-sample prediction

International Nuclear Information System (INIS)

Yongquan, Sun; Xi, Chen; He, Ren; Yingchao, Jin; Quanwu, Liu

2016-01-01

Ordering decision-making on spare parts is crucial in maximizing aircraft utilization and minimizing total operating cost. Extensive researches on spare parts inventory management and optimal allocation could be found based on the amount of historical operation data or condition-monitoring data. However, it is challengeable to make an ordering decision on spare parts under the case of establishment of a fleet by introducing new aircraft with little historical data. In this paper, spare parts supporting policy and ordering decision-making policy for new aircraft fleet are analyzed firstly. Then two-sample predictions for a Weibull distribution and a Weibull process are incorporated into forecast of the first failure time and failure number during certain time period using Bayesian and classical method respectively, according to which the ordering time and ordering quantity for spare parts are identified. Finally, a case study is presented to illustrate the methods of identifying the ordering time and ordering number of engine-driven pumps through forecasting the failure time and failure number, followed by a discussion on the impact of various fleet sizes on prediction results. This method has the potential to decide the ordering time and quantity of spare parts when a new aircraft fleet is established. - Highlights: • A modeling framework of ordering spare parts for a new fleet is proposed. • Models for ordering time and number are established based on two-sample prediction. • The computation of future failure time is simplified using Newtonian binomial law. • Comparison of the first failure time PDFs is used to identify process parameters. • Identification methods for spare parts are validated by Engine Driven Pump case study.

Aluminium based adjuvants and their effects on mitochondria and lysosomes of phagocytosing cells.

Science.gov (United States)

Ohlsson, Lars; Exley, Christopher; Darabi, Anna; Sandén, Emma; Siesjö, Peter; Eriksson, Håkan

2013-11-01

Aluminium oxyhydroxide, Al(OH)3 is one of few compounds approved as an adjuvant in human vaccines. However, the mechanism behind its immune stimulating properties is still poorly understood. In vitro co-culture of an aluminium adjuvant and the human monocytic cell line THP-1 resulted in reduced cell proliferation. Inhibition occurred at concentrations of adjuvant several times lower than would be found at the injection site using a vaccine formulation containing an aluminium adjuvant. Based on evaluation of the mitochondrial membrane potential, THP-1 cells showed no mitochondrial rupture after co-culture with the aluminium adjuvant, instead an increase in mitochondrial activity was seen. The THP-1 cells are phagocytosing cells and after co-culture with the aluminium adjuvant the phagosomal pathway was obstructed. Primary or early phagosomes mature into phagolysosomes with an internal pH of 4.5 - 5 and carry a wide variety of hydrolysing enzymes. Co-culture with the aluminium adjuvant yielded a reduced level of acidic vesicles and cathepsin L activity, a proteolytic enzyme of the phagolysosomes, was almost completely inhibited. THP-1 cells are an appropriate in vitro model in order to investigate the mechanism behind the induction of a phagocytosing antigen presenting cell into an inflammatory cell by aluminium adjuvants. Much information will be gained by investigating the phagosomal pathway and what occurs inside the phagosomes and to elucidate the ultimate fate of phagocytosed aluminium particles. © 2013.

Defense Acquisitions: Prices of Marine Corps Spare Parts Have Increased

National Research Council Canada - National Science Library

2000-01-01

...) examine spare part prices to determine whether these were increasing at a rate faster than inflation and the extent to which surcharges, suppliers' prices, and other factors contributed to price increases...

Xerostomia and its predictors following parotid-sparing irradiation of head-and-neck cancer

International Nuclear Information System (INIS)

Eisbruch, Avraham; Kim, Hyungjin M.; Terrell, Jeffrey E.; Marsh, Lon H.C.; Dawson, Laura A.; Ship, Jonathan A.

2001-01-01

Purpose: To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy (RT) for head-and-neck cancer, and to find the patient and therapy-related factors that affect its severity. Patients and Methods: From March 1994 through January 2000, 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT (IMRT) aiming to spare the major salivary glands. Before RT and periodically through 2 years after the completion of RT, salivary flow rates from each of the major salivary glands were selectively measured. At the same time intervals, each patient completed an 8-item self-reported xerostomia-specific questionnaire (XQ). To gain a relative measure of the effect of RT on the minor salivary glands, whose output could not be measured, the surfaces of the oral cavity (extending to include the surface of the base of tongue) were outlined in the planning CT scans. The mean doses to the new organ ('oral cavity') were recorded. Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison. Factors predicting the XQ scores were analyzed using a random-effects model. Results: The XQ was found to be reliable and valid in measuring patient-reported xerostomia. The spared salivary glands which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT, and the spared glands in the unilateral RT group, which had received very low doses, demonstrated increased salivary production beyond their pre-RT levels. The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups. The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group, but the difference narrowed at 2 years. The major salivary gland flow rates had only a weak correlation with the xerostomia scores. Factors found to be

Evaluation of the safety and adjuvant effect of a detoxified listeriolysin O mutant on the humoral response to dengue virus antigens.

Science.gov (United States)

Hernández-Flores, K G; Calderón-Garcidueñas, A L; Mellado-Sánchez, G; Ruiz-Ramos, R; Sánchez-Vargas, L A; Thomas-Dupont, P; Izaguirre-Hernández, I Y; Téllez-Sosa, J; Martínez-Barnetche, J; Wood, L; Paterson, Y; Cedillo-Barrón, L; López-Franco, O; Vivanco-Cid, H

2017-04-01

Listeriolysin O (LLO) has been proposed as a potential carrier or adjuvant molecule in the vaccination field. However, the cytotoxic and pro-apoptotic effects of LLO are the major limitations for this purpose. Here, we have performed a preclinical safety evaluation and characterized a new potential adjuvant application for a non-cytolytic LLO mutant (dtLLO) to enhance and modulate the immune response against the envelope (E) protein from dengue virus. In addition, we have studied the adjuvant effects of dtLLO on human immune cells and the role of membrane cholesterol for the binding and proinflammatory property of the toxoid. Our in-vivo results in the murine model confirmed that dtLLO is a safer molecule than wild-type LLO (wtLLO), with a significantly increased survival rate for mice challenged with dtLLO compared with mice challenged with wtLLO (P < 0·001). Histopathological analysis showed non-toxic effects in key target organs such as brain, heart, liver, spleen, kidney and lung after challenge with dtLLO. In vitro, dtLLO retained the capacity of binding to plasma membrane cholesterol on the surface of murine and human immune cells. Immunization of 6-8-week-old female BALB/c mice with a combination of dtLLO mixed with E protein elicited a robust specific humoral response with isotype diversification of immunoglobulin (Ig)G antibodies (IgG1 and IgG2a). Finally, we demonstrated that cholesterol and lipid raft integrity are required to induce a proinflammatory response by human cells. Taken together, these findings support a potential use of the dtLLO mutant as a safe and effective adjuvant molecule in vaccination. © 2016 British Society for Immunology.

Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

Science.gov (United States)

Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

2012-07-20

Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

Physical exercise during adjuvant chemotherapy

NARCIS (Netherlands)

van Waart, H.

2017-01-01

This thesis evaluates the effect of physical exercise during chemotherapy. In chapter two the study design, rationale and methods of the Physical exercise during Adjuvant Chemotherapy Study (PACES) are described. Chapter three presents the effects of the randomized controlled trial evaluating a

Spare part management of an electricity distribution network

Energy Technology Data Exchange (ETDEWEB)

Lauronen, J.

1998-07-01

Electricity distribution companies are required to improve their operational cost effectiveness. The storage systems of the companies have traditionally been based on the 'adequate' number of stores with plenty of different components. Therefore, they are potential objects for cost reduction. The effective operation of spare part management of an electricity distribution network requires that the spare components can be delivered at the fault site quickly in order to avoid excessive outage costs. In a fault situation the stores form a net structure. Currently the rural electricity distribution companies lack suitable methods for designing a spare part storage system. This thesis presents a suitable method for the designing problem. The models assume that faults of a distribution network are stochastic. Therefore, they are best suited for component types installed in large quantities. Improved methods for defining the outage, material and total costs for perpetual order quantity and periodic order-up-to-level storage control systems are described. The method for determining the control parameters of the stores is also presented and ways for finding the necessary initial parameter values are introduced. The developed method is tested in Haemeen Saehko Oy (HSOY). The results of the calculations are given. The key findings are: Small differences in the designing results can increase costs remarkably. For example, in HSOY too low stock levels can result in even eight folds higher outage costs than in the proper design. The best number of stores is not the same for all component types. For example, in HSOY the best number of stores is seven for the 50 kVA transformers and one for the 315 kVA transformers in a summer. If the stock levels are increased the protection against the demand variations is the better the shorter the duration of the review period and/or the replenishment lead time is. (orig.)

Spare part management of an electricity distribution network

Energy Technology Data Exchange (ETDEWEB)

Lauronen, J

1998-07-01

Electricity distribution companies are required to improve their operational cost effectiveness. The storage systems of the companies have traditionally been based on the 'adequate' number of stores with plenty of different components. Therefore, they are potential objects for cost reduction. The effective operation of spare part management of an electricity distribution network requires that the spare components can be delivered at the fault site quickly in order to avoid excessive outage costs. In a fault situation the stores form a net structure. Currently the rural electricity distribution companies lack suitable methods for designing a spare part storage system. This thesis presents a suitable method for the designing problem. The models assume that faults of a distribution network are stochastic. Therefore, they are best suited for component types installed in large quantities. Improved methods for defining the outage, material and total costs for perpetual order quantity and periodic order-up-to-level storage control systems are described. The method for determining the control parameters of the stores is also presented and ways for finding the necessary initial parameter values are introduced. The developed method is tested in Haemeen Saehko Oy (HSOY). The results of the calculations are given. The key findings are: Small differences in the designing results can increase costs remarkably. For example, in HSOY too low stock levels can result in even eight folds higher outage costs than in the proper design. The best number of stores is not the same for all component types. For example, in HSOY the best number of stores is seven for the 50 kVA transformers and one for the 315 kVA transformers in a summer. If the stock levels are increased the protection against the demand variations is the better the shorter the duration of the review period and/or the replenishment lead time is. (orig.)

The Impact of Skin-Sparing Mastectomy With Immediate Reconstruction in Patients With Stage III Breast Cancer Treated With Neoadjuvant Chemotherapy and Postmastectomy Radiation

International Nuclear Information System (INIS)

Prabhu, Roshan; Godette, Karen; Carlson, Grant; Losken, Albert; Gabram, Sheryl; Fasola, Carolina; O’Regan, Ruth; Zelnak, Amelia; Torres, Mylin

2012-01-01

Purpose: The safety and efficacy of skin-sparing mastectomy (SSM) with immediate reconstruction (IR) in patients with locally advanced breast cancer are unclear. The purpose of this study is to compare the outcomes of women with noninflammatory Stage III SSM with IR vs. non–SSM-treated women who underwent neoadjuvant chemotherapy and adjuvant radiation therapy (XRT). Methods and Materials: Between October 1997 and March 2010, 100 consecutive patients (40 SSM with IR vs. 60 non-SSM) with Stage III breast cancer received anthracycline- and/or taxane-based neoadjuvant chemotherapy, mastectomy, and adjuvant XRT. Clinical stage (SSM with IR vs. for non-SSM) was IIIA (75% vs. 67%), IIIB (8% vs. 18%), and IIIC (8% vs. 8%). Tumors greater than 5 cm were found in 74% vs. 69%; 97% of patients in both groups were clinically node positive; and 8% vs. 18% had T4b disease. Results: The time from initial biopsy to XRT was prolonged for SSM–IR patients (274 vs. 254 days, p = 0.04), and there was a trend toward XRT delay of more than 8 weeks (52% vs. 31%, p = 0.07) after surgery. The rate of complications requiring surgical intervention was higher in the SSM–IR group (37.5% vs. 5%, p < 0.001). The 2-year actuarial locoregional control, breast cancer–specific survival, and overall survival rates for SSM with IR vs. non-SSM were 94.7% vs. 97.4%, 91.5% vs. 86.3%, and 87.4% vs. 84.8%, respectively (p = not significant). Conclusions: In our small study with limited follow-up, SSM with IR prolonged overall cancer treatment time and trended toward delaying XRT but did not impair oncologic outcomes. Complication rates were significantly higher in this group. Longer follow-up is needed.

Adjuvant Chemoradiation Therapy After Pancreaticoduodenectomy in Elderly Patients With Pancreatic Adenocarcinoma

International Nuclear Information System (INIS)

Horowitz, David P.; Hsu, Charles C.; Wang Jingya; Makary, Martin A.; Winter, Jordan M.; Robinson, Ray; Schulick, Richard D.; Cameron, John L.; Pawlik, Timothy M.; Herman, Joseph M.

2011-01-01

Purpose: To evaluate the efficacy of adjuvant chemoradiation therapy (CRT) for pancreatic adenocarcinoma patients ≥75 years of age. Methods: The study group of 655 patients underwent pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma at the Johns Hopkins Hospital over a 12-year period (8/30/1993 to 2/28/2005). Demographic characteristics, comorbidities, intraoperative data, pathology data, and patient outcomes were collected and analyzed by adjuvant treatment status and age ≥75 years. Cox proportional hazards analysis determined clinical predictors of mortality and morbidity. Results: We identified 166 of 655 (25.3%) patients were ≥75 years of age and 489 of 655 patients (74.7%) were <75 years of age. Forty-nine patients in the elderly group (29.5%) received adjuvant CRT. For elderly patients, node-positive metastases (p = 0.008), poor/anaplastic differentiation (p = 0.012), and undergoing a total pancreatectomy (p = 0.010) predicted poor survival. The 2-year survival for elderly patients receiving adjuvant therapy was improved compared with surgery alone (49.0% vs. 31.6%, p = 0.013); however, 5-year survival was similar (11.7% vs. 19.8%, respectively, p = 0.310). After adjusting for major confounders, adjuvant therapy in elderly patients had a protective effect with respect to 2-year survival (relative risk [RR] 0.58, p = 0.044), but not 5-year survival (RR 0.80, p = 0.258). Among the nonelderly, CRT was significantly associated with 2-year survival (RR 0.60, p < 0.001) and 5-year survival (RR 0.69, p < 0.001), after adjusting for confounders. Conclusions: Adjuvant therapy after PD is significantly associated with increased 2-year but not 5-year survival in elderly patients. Additional studies are needed to select which elderly patients are likely to benefit from adjuvant CRT.

Role of adjuvant radiotherapy in granulosa cell tumors of the ovary.

Science.gov (United States)

Hauspy, Jan; Beiner, Mario E; Harley, Ian; Rosen, Barry; Murphy, Joan; Chapman, William; Le, Lisa W; Fyles, Anthony; Levin, Wilfred

2011-03-01

To review the role of adjuvant radiotherapy (RT) in the outcome and recurrence patterns of granulosa cell tumors (GCTs) of the ovary. The records of all patients with GCTs referred to the Princess Margaret Hospital University Health Network between 1961 and 2006 were retrospectively reviewed. The patient, tumor, and treatment factors were assessed by univariate and multivariate analyses using disease-free survival (DFS) as the endpoint. A total of 103 patients with histologically confirmed GCTs were included in the present study. The mean duration of follow-up was 100 months (range, 1-399). Of the 103 patients, 31 received adjuvant RT. A total of 39 patients developed tumor recurrence. The tumor size, incidence of intraoperative rupture, and presence of concurrent endometrial cancer were not significant risk factors for DFS. The median DFS was 251 months for patients who underwent adjuvant RT compared with 112 months for patients who did not (p=.02). On multivariate analysis, adjuvant RT remained a significant prognostic factor for DFS (p=.004). Of the 103 patients, 12 had died and 44 were lost to follow-up. Ovarian GCTs can be indolent, with patients achieving long-term survival. In our series, adjuvant RT resulted in a significantly longer DFS. Ideally, randomized trials with long-term follow-up are needed to define the role of adjuvant RT for ovarian GCTs. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

Science.gov (United States)

Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

2018-06-22

Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

Science.gov (United States)

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemotherapy (i.e., limited survival benefit with considerable toxicity) requires a careful assessment of expected risks and benefits for individual patients. Treatment choices vary widely based on the different geographic areas, with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States. In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses. The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery; the same Authors also showed that disease-free survival may be used as a surrogate end-point for overall survival. We finally discuss future research issues such as the need of economic evaluations, development of prognostic or predictive biomarkers, and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment. PMID:24782604

Novel adjuvants & delivery vehicles for vaccines development: a road ahead.

Science.gov (United States)

Mohan, Teena; Verma, Priyanka; Rao, D Nageswara

2013-11-01

The pure recombinant and synthetic antigens used in modern day vaccines are generally less immunogenic than older style live/attenuated and killed whole organism vaccines. One can improve the quality of vaccine production by incorporating immunomodulators or adjuvants with modified delivery vehicles viz. liposomes, immune stimulating complexes (ISCOMs), micro/nanospheres apart from alum, being used as gold standard. Adjuvants are used to augment the effect of a vaccine by stimulating the immune system to respond to the vaccine, more vigorously, and thus providing increased immunity to a particular disease. Adjuvants accomplish this task by mimicking specific sets of evolutionary conserved molecules which include lipopolysaccharides (LPS), components of bacterial cell wall, endocytosed nucleic acids such as dsRNA, ssDNA and unmethylated CpG dinucleotide containing DNA. This review provides information on various vaccine adjuvants and delivery vehicles being developed to date. From literature, it seems that the humoral immune responses have been observed for most adjuvants and delivery platforms while viral-vector, ISCOMs and Montanides have shown cytotoxic T-cell response in the clinical trials. MF59 and MPL® have elicited Th1 responses, and virus-like particles (VLPs), non-degradable nanoparticle and liposomes have also generated cellular immunity. Such vaccine components have also been evaluated for alternative routes of administration with clinical success reported for intranasal delivery of viral-vectors and proteosomes and oral delivery of VLP vaccines.

Adjuvant therapy for gastric cancer: what have we learned since INT0116?

Science.gov (United States)

Jácome, Alexandre A; Sankarankutty, Ajith K; dos Santos, José Sebastião

2015-04-07

Gastric cancer is one of the main cancer-related causes of death worldwide. The curative treatment of gastric cancer consists of tumor resection and lymphadenectomy. However, surgical treatment alone is associated with high recurrence rates. Adjuvant treatment strategies have been studied over the last decades, but there have been controversial results from the initial studies. The pivotal INT0116 study demonstrated that the use of adjuvant chemoradiotherapy with 5-fluorouracil increases relapse-free and overall survival, and it has been adopted across the Western world. The high toxicity of radiochemotherapy and suboptimal surgical treatment employed, with fewer than 10% of the patients submitted to D2 lymphadenectomy, were the main study limitations. Since its publication, other adjuvant treatment modalities have been studied, and radiochemotherapy is being refined to improve its efficacy and safety. A multimodal approach has been demonstrated to significantly increase relapse-free and overall survival, and it can be offered in the form of perioperative chemotherapy, adjuvant chemoradiotherapy or adjuvant chemotherapy, regardless of the extent of lymphadenectomy. The objective of the present review is to report the major advances obtained in the last decades in the adjuvant treatment of gastric cancer as well as the perspectives of treatment based on recent knowledge of the molecular biology of the disease.

Cardiac monitoring during adjuvant trastuzumab therapy: Guideline adherence in clinical practice

NARCIS (Netherlands)

Visser, Annemiek; van de Ven, Eline M. W.; Ruczynski, Larissa I. A.; Blaisse, Reinoud J. B.; van Halteren, Henk K.; Aben, Katja; van Laarhoven, Hanneke W. M.

2016-01-01

Cardiotoxicity is an important adverse effect of adjuvant breast cancer treatment with trastuzumab and three monthly left ventricular ejection fraction (LVEF) monitoring is considered mandatory. The purpose of this study was to gain insight into LVEF monitoring during adjuvant trastuzumab treatment

UHV testing of spare straight section chambers of Indus-2

International Nuclear Information System (INIS)

Tiwari, S.K.; Ratnakala, K.C.; Sridhar, R.; Bhange, N.J.; Netram; Shukla, S.K.

2015-01-01

The vacuum system of Synchrotron Radiation Source, Indus-2, in RRCAT has been functioning up to the mark, continuously for last 10 years. To continue the same trouble-free functioning, it was planned to procure spares for all critical vacuum components, test for UHV performance and keep ready for installation, in case of requirement. As a part of this planning, fifteen chambers made of Aluminium alloy (6063 T6), procured as spare straight section chambers for Indus-2, and were tested for UHV performance. They were tested in batches of 2 or 3 chambers, depending upon their length, and the similar testing-procedure was followed. This paper narrates the tests carried out, and the results obtained. Ultimate vacuum in the range (2 to 9) x 10 -10 mbar was achieved. (author)

Optimal repairable spare-parts procurement policy under total business volume discount environment

International Nuclear Information System (INIS)

Pascual, Rodrigo; Santelices, Gabriel; Lüer-Villagra, Armin; Vera, Jorge; Cawley, Alejandro Mac

2017-01-01

In asset intensive fields, where components are expensive and high system availability is required, spare parts procurement is often a critical issue. To gain competitiveness and market share is common for vendors to offer Total Business Volume Discounts (TBVD). Accordingly, companies must define the procurement and stocking policy of their spare parts in order to reduce procurement costs and increase asset availability. In response to those needs, this work presents an optimization model that maximizes the availability of the equipment under a TBVD environment, subject to a budget constraint. The model uses a single-echelon structure where parts can be repaired. It determines the optimal number of repairable spare parts to be stocked, giving emphasis on asset availability, procurement costs and service levels as the main decision criteria. A heuristic procedure that achieves high quality solutions in a fast and time-consistent way was implemented to improve the time required to obtain the model solution. Results show that using an optimal procurement policy of spare parts and accounting for TBVD produces better overall results and yields a better availability performance. - Highlights: • We propose a model for procurement of repairable components in single-echelon and business volume discount environments. • We used a mathematical model to develop a competitive heuristic that provides high quality solutions in very short times. • Our model places emphasis on using system availability, procurement costs and service levels as leading decision criteria. • The model can be used as an engine for a multi-criteria Decision Support System.

Randomized trial of adjuvant ovarian suppression in 926 premenopausal patients with early breast cancer treated with adjuvant chemotherapy.

Science.gov (United States)

Arriagada, R; Lê, M G; Spielmann, M; Mauriac, L; Bonneterre, J; Namer, M; Delozier, T; Hill, C; Tursz, T

2005-03-01

The aim of this multicenter trial was to evaluate the role of ovarian suppression in patients with early breast cancer previously treated with local surgery and adjuvant chemotherapy. Nine hundred and twenty-six premenopausal patients with completely resected breast cancer and either axillary node involvement or histological grade 2 or 3 tumors were randomized after surgery to adjuvant chemotherapy alone (control arm) or adjuvant chemotherapy plus ovarian suppression (ovarian suppression arm). Ovarian suppression was obtained by either radiation-induced ovarian ablation or triptorelin for 3 years. The analyses were performed with Cox models stratified by center. Median follow-up was 9.5 years. Mean age was 43 years. Ninety per cent of patients had histologically proven positive axillary nodes, 63% positive hormonal receptors and 77% had received an anthracycline-based chemotherapy regimen. Ovarian suppression was by radiation-induced ovarian ablation (45% of patients) or with triptorelin (48%). At the time of randomization, all patients had regular menses or their follicle-stimulating hormone and estradiol levels indicated a premenopausal status. The 10-year disease-free survival rates were 49% [95% confidence interval (CI) 44% to 54%] in both arms (P = 0.51). The 10-year overall survival rates were 66% (95% CI 61% to 70%) for the ovarian suppression arm and 68% (95% CI 63% to 73%) for the control arm (P = 0.19). There were no variations in the treatment effect according to age, hormonal receptor status or ovarian suppression modality. However, in patients suppression significantly decreased the risk of recurrence (P = 0.01). The results of this trial, after at least 10 years of follow-up, do not favor the use of ovarian suppression after adjuvant chemotherapy. The potential beneficial effect in younger women with hormono-dependent tumors should be further assessed.

Image-guided biopsy in patients with suspected ovarian carcinoma: a safe and effective technique?

International Nuclear Information System (INIS)

Griffin, Nyree; Grant, Lee A.; Freeman, Susan J.; Berman, Laurence H.; Sala, Evis; Jimenez-Linan, Mercedes; Earl, Helena; Ahmed, Ahmed Ashour; Crawford, Robin; Brenton, James

2009-01-01

In patients with suspected advanced ovarian carcinoma, a precise histological diagnosis is required before commencing neo-adjuvant chemotherapy. This study aims to determine the diagnostic accuracy and complication rate of percutaneous biopsies performed under ultrasound or computed tomography guidance. Between 2002 to 2007, 60 consecutive image-guided percutaneous biopsies were performed in patients with suspected ovarian cancer. The following variables were recorded: tissue biopsied, imaging technique, experience of operator, biopsy needle gauge, number of passes, complications, and final histology. Forty-seven patients had omental biopsies, 12 pelvic mass biopsies, and 1 para-aortic lymph node biopsy. Thirty-five biopsies were performed under ultrasound, 25 under computed tomography guidance. Biopsy needle gauges ranged from 14-20 swg with two to five passes for each patient. There were no complications. Histology was obtained in 52 (87%) patients. Percutaneous image-guided biopsy of peritoneal disease or pelvic mass is safe with high diagnostic accuracy. The large-gauge biopsy needle is as safe as the small gauge needle, but has the added value of obtaining tissue samples for immunohistochemistry and genomic studies. (orig.)

Management of Pediatric Myxopapillary Ependymoma: The Role of Adjuvant Radiation

Energy Technology Data Exchange (ETDEWEB)

Agbahiwe, Harold C.; Wharam, Moody [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Batra, Sachin [Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Cohen, Kenneth [Division of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Terezakis, Stephanie A., E-mail: sterezak@jhmi.edu [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States)

2013-02-01

Introduction: Myxopapillary ependymoma (MPE) is a rare tumor in children. The primary treatment is gross total resection (GTR), with no clearly defined role for adjuvant radiation therapy (RT). Published reports, however, suggest that children with MPE present with a more aggressive disease course. The goal of this study was to assess the role of adjuvant RT in pediatric patients with MPE. Methods: Sixteen patients with MPE seen at Johns Hopkins Hospital (JHH) between November 1984 and December 2010 were retrospectively reviewed. Fifteen of the patients were evaluable with a mean age of 16.8 years (range, 12-21 years). Kaplan-Meier curves and descriptive statistics were used for analysis. Results: All patients received surgery as the initial treatment modality. Surgery consisted of either a GTR or a subtotal resection (STR). The median dose of adjuvant RT was 50.4 Gy (range, 45-54 Gy). All patients receiving RT were treated at the involved site. After a median follow-up of 7.2 years (range, 0.75-26.4 years), all patients were alive with stable disease. Local control at 5 and 10 years was 62.5% and 30%, respectively, for surgery alone versus 100% at both time points for surgery and adjuvant RT. Fifty percent of the patients receiving surgery alone had local failure. All patients receiving STR alone had local failure compared to 33% of patients receiving GTR alone. One patient in the surgery and adjuvant RT group developed a distant site of recurrence 1 year from diagnosis. No late toxicity was reported at last follow-up, and neurologic symptoms either improved or remained stable following surgery with or without RT. Conclusions: Adjuvant RT improved local control compared to surgery alone and should be considered after surgical resection in pediatric patients with MPE.

[Critical analysis of reference studies on aluminium-based adjuvants toxicokinetics].

Science.gov (United States)

Masson, J-D; Crépeaux, G; Authier, F-J; Exley, C; Gherardi, R K

2017-07-01

We reviewed the three reference toxicokinetic studies commonly used to suggest innocuity of aluminum (Al)-based adjuvants. A single experimental study was carried out using isotopic 26 Al (Flarend et al., 1997). This study ignored adjuvant cell capture. It was conducted over a short period of time (28 days) and used only two rabbits per adjuvant. At the endpoint, Al retention was 78% for aluminum phosphate and 94% for aluminum hydroxide, both results being incompatible with quick elimination of vaccine-derived Al in urines. Tissue distribution analysis omitted three important retention sites: the injected muscle, the draining lymph node and bone. Two theoretical studies have evaluated the potential risk of vaccine Al in infants, by reference to the oral Minimal Risk Level (MRL) extrapolated from animal studies. Keith et al., 2002 used a too high MRL (2mg/kg/d), an erroneous model of 100% immediate absorption of vaccine Al, and did not consider renal and blood-brain barrier immaturity. Mitkus et al. (2011) only considered absorbed Al, with erroneous calculations of absorption duration. They ignored particulate Al captured by immune cells, which play a role in systemic diffusion and the neuro-inflammatory potential of the adjuvant. MRL they used was both inappropriate (oral Al vs injected adjuvant) and far too high (1mg/kg/d) with regard to experimental studies of Al-induced memory and behavioral changes. Both paucity and serious weaknesses of these studies strongly suggest that novel experimental studies of Al adjuvants toxicokinetics should be performed on the long-term, including post-natal and adult exposures, to ensure innocuity and restore population confidence in Al-containing vaccines. Copyright © 2017 Académie Nationale de Pharmacie. All rights reserved.

Extended Adjuvant Therapy for Breast Cancer

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An NCI Cancer Currents blog on findings from a recent clinical trial which showed that extending adjuvant therapy with an aromatase inhibitor can have important benefits for some women with early-stage cancer.

Safe sex

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... sex; Sexually transmitted - safe sex; GC - safe sex; Gonorrhea - safe sex; Herpes - safe sex; HIV - safe sex; ... contact. STIs include: Chlamydia Genital herpes Genital warts Gonorrhea Hepatitis HIV HPV Syphilis STIs are also called ...

Adjuvant chemotherapy in soft tissue sarcomas…Conflicts, consensus, and controversies

Directory of Open Access Journals (Sweden)

Jyoti Bajpai

2016-01-01

Full Text Available Soft tissue sarcomas (STSs are an uncommon and diverse group of more than 50 mesenchymal malignancies. Each of these histologic subtypes represents a unique disease with distinct biologic behavior and varying sensitivity to chemotherapy. The judicious use of adjuvant/neoadjuvant chemotherapy along with surgery and radiation in the treatment of localized STS has a role in improving patient outcomes by decreasing local and distant recurrences. There is evidence that the use of adjuvant chemotherapy to a mixed cohort of chemo sensitive and insensitive sarcoma subtypes results in limited benefit. Therefore, it is of paramount importance to identify the subpopulation with high metastatic potential and to identify effective histology-specific treatment options to these patients. Present perspective, will focus on the rationale for adjuvant chemotherapy in sarcoma, with emphasis on the histology driven chemotherapy. It will outline key therapeutic opportunities and hurdles in adjuvant medical treatment of sarcoma, focusing on specific subtypes that are on the verge of new breakthroughs, as well as those in which promise has not lived up to expectations.

Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

International Nuclear Information System (INIS)

Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

1996-01-01

Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

Feasibility of MRI-guided Focused Ultrasound as Organ-Sparing Treatment for Testicular Cancer

Science.gov (United States)

Staruch, Robert; Curiel, Laura; Chopra, Rajiv; Hynynen, Kullervo

2009-04-01

High cure rates for testicular cancer have prompted interest in organ-sparing surgery for patients with bilateral disease or single testis. Focused ultrasound (FUS) ablation could offer a noninvasive approach to organ-sparing surgery. The objective of this study was to determine the feasibility of using MR thermometry to guide organ-sparing focused ultrasound surgery in the testis. The testes of anesthetized rabbits were sonicated in several discrete locations using a single-element focused transducer operating at 2.787MHz. Focal heating was visualized with MR thermometry, using a measured PRF thermal coefficient of -0.0089±0.0003 ppm/° C. Sonications at 3.5-14 acoustic watts applied for 30 seconds produced maximum temperature elevations of 10-80° C, with coagulation verified by histology. Coagulation of precise volumes in the testicle is feasible with MRI-guided focused ultrasound. Variability in peak temperature for given sonication parameters suggests the need for online temperature feedback control.

Spare parts management for nuclear research reactors [Paper No.: I-14

International Nuclear Information System (INIS)

Kini, M.P.

1981-01-01

Most of the equipment installed at CIRUS and other reactors are imported units. CIRUS reactor is 20 years old and with present problems for obtaining spare parts for this equipment, indigenous effort in procurement has become imperative. In the absence of specifications and drawings for most of the components, the task of indigenous procurement has become quite demanding. The efforts put by Reactor Operations Division of the Bhabha Atomic Research Centre, Bombay in locating local manufacturers who are willing to fabricate in small quantities of spare parts to specifications and the difficulties involved is the theme of this paper. The paper also covers the efforts on equipment replacement, its success and failures. (author)

Analysis of aortic root surgery with composite mechanical aortic valve conduit and valve-sparing reconstruction.

Science.gov (United States)

Dias, Ricardo Ribeiro; Mejia, Omar Asdrubal Vilca; Fiorelli, Alfredo Inácio; Pomerantzeff, Pablo Maria Alberto; Dias, Altamiro Ribeiro; Mady, Charles; Stolf, Noedir Antonio Groppo

2010-01-01

Comparative analysis of early and late results of aortic root reconstruction with aortic valve sparing operations and the composite mechanical valve conduit replacement. From November 2002 to September 2009, 164 consecutive patients with mean age 54 ± 15 years, 115 male, underwent the aortic root reconstruction (125 mechanical valve conduit replacements and 39 valve sparing operations). Sixteen percent of patients had Marfan syndrome and 4.3% had bicuspid aortic valve. One hundred and forty-four patients (88%) were followed for a mean period of 41.1 ± 20.8 months. The hospital mortality was 4.9%, 5.6% in operations with valved conduits and 2.6% in the valve sparing procedures (P valve sparing operations, respectively (95% CI = 70% - 95%, P = 0.001), (95% CI = 82% - 95% P = 0.03) and (95% CI = 81% - 95%, P = 0.03). Multivariate analysis showed that creatinine greater than 1.4 mg/dl, Cabrol operation and renal dialysis were predictors of mortality, respectively, with occurrence chance of 6 (95% CI = 1.8 - 19.5, P = 0.003), 12 (95% CI = 3 - 49.7, P = 0.0004) and 16 (95% CI = 3.6 - 71.3, P = 0.0002). The aortic root reconstruction has a low early and late mortality, high survival free of complications and low need for reoperation. During the late follow-up, valve sparing aortic root reconstructions presented fewer incidences of bleeding, thromboembolic events and endocarditis.

Optimized lens-sparing treatment of retinoblastoma with electron beams

NARCIS (Netherlands)

Steenbakkers, RJHM; Altschuler, MD; DAngio, GJ; Goldwein, JW; Kassaee, A

1997-01-01

Purpose: The ideal lens-sparing radiotherapy technique for retinoblastoma calls for 100% dose to the entire retina including the ora serrata and zero dose to the lens, Published techniques, most of which use photons, have not accomplished this ideal treatment. We describe here a technique that

Service differentiation in spare parts supply through dedicated stocks

NARCIS (Netherlands)

Alvarez, Elisa; van der Heijden, Matthijs C.; Zijm, Willem H.M.

2012-01-01

We investigate keeping dedicated stocks at customer sites in addition to stock kept at some central location as a tool for applying service differentiation in spare parts supply. We study the resulting two-echelon system in a multi-item setting, both under backordering and under emergency shipments

Nephron-sparing surgery for bilateral Wilms' tumours: A single ...

African Journals Online (AJOL)

All three with unfavourable histology are alive. Four of the five metachronous presentations are alive, as are eight of 12 patients with synchronous bilateral tumours who presented since 2000. Conclusions: Appropriate chemotherapy and nephron-sparing surgery can achieve good results with preservation of adequate renal ...

Recombinant interleukin 6 with M cell-targeting moiety produced in Lactococcus lactis IL1403 as a potent mucosal adjuvant for peroral immunization.

Science.gov (United States)

Li, Hui-Shan; Piao, Da-Chuan; Jiang, Tao; Bok, Jin-Duck; Cho, Chong-Su; Lee, Yoon-Seok; Kang, Sang-Kee; Choi, Yun-Jaie

2015-04-15

Development and application of safe and effective mucosal adjuvants are important to improve immunization efficiency in oral vaccine. Here, we report a novel mucosal adjuvant, IL-6-CKS9, a recombinant cytokine generated by conjugating an M cell-targeting peptide (CKS9) with c-terminus of the murine interleukin 6 (IL-6), which facilitated enhancement of mucosal immune response. Lactococcus lactis IL1403, a food-grade strain of lactic acid bacteria (LAB) which is widely used in dairy industry, was used as a host cell to express and secrete the IL-6-CKS9 for a mucosal vaccine adjuvant. The recombinant L. lactis IL1403 secreting IL-6-CKS9 was orally administered with a model antigen protein, M-BmpB (Brachyspira membrane protein B conjugated with CKS9), to BALB/c mice for mucosal immunization. ELISA analyses showed consistent enhancement tendencies in induction of anti-M-BmpB antibody levels both with mucosal (IgA) and systemic (IgG) immune responses in IL-6-CKS9-LAB treated group compared with other groups tested by conducting two separated mice immunization assays. In addition, we characterized that the oral administration of model protein antigen with live LAB producing IL-6-CKS9 could induce both Th1 and Th2 type immune responses by analysis of the specific anti-BmpB IgG1 and IgG2a isotypes in the sera and also investigated possible oral tolerance in our vaccine strategy. Collectively, our results showed successful production and secretion of recombinant murine IL-6 with M cell-targeting moiety (IL-6-CKS9) from L. lactis IL1403 and demonstrated the live recombinant LAB producing IL-6-CKS9 could have a potential to be used as an efficient adjuvant for peroral vaccination. Copyright © 2015 Elsevier Ltd. All rights reserved.

Three-Dimensional Non-Coplanar Conformal Radiotherapy Yields Better Results Than Traditional Beam Arrangements for Adjuvant Treatment of Gastric Cancer

International Nuclear Information System (INIS)

Soyfer, Viacheslav; Corn, Benjamin W.; Melamud, Alex B.S.; Alani, Shlomi; Tempelhof, Haim; Agai, Reuben; Shmueli, Anat; Figer, Arie; Kovner, Felix

2007-01-01

Purpose: The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. Methods and Materials: A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field 'box' was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. Results: The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Conclusion: Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical

Three-dimensional non-coplanar conformal radiotherapy yields better results than traditional beam arrangements for adjuvant treatment of gastric cancer.

Science.gov (United States)

Soyfer, Viacheslav; Corn, Benjamin W; Melamud, Alex; Alani, Shlomi; Tempelhof, Haim; Agai, Reuben; Shmueli, Anat; Figer, Arie; Kovner, Felix

2007-10-01

The current standard of adjuvant treatment for gastric cancer after curative resection is concurrent administration of radiotherapy and 5-fluorouracil-based chemotherapy. The radiation fields are often arranged as anterioposterior-posteroanterior opposed parallel fields with general recommendations for sparing at least two-thirds of one kidney. We investigated whether a better radiation distribution would be achievable with three-dimensional conformal approaches compared with the classic anterioposterior-posteroanterior fields. A total of 19 patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a non-coplanar four-field arrangement. In each case, parallel planning using an anterioposterior-posteroanterior arrangement and a four-field "box" was performed, and the generated plans were subsequently compared for coverage of target volumes and doses to irradiated organs next to the tumor bed. A separate analysis was performed for kidneys exposed to greater and lower doses in each patient. The mean radiation dose and percentage of kidney volume receiving a dose >20 Gy were registered. Statistical analysis was performed using the two-tailed t test. The clinical target volume was adequately covered in all three plans. In the greater-dose kidney group, all the differences were statistically significant with a benefit for the three-dimensional plan. In the lower-dose kidney group, the differences in the mean radiation dose did not reach the level of statistical significance, and the differences in the kidney volume receiving a dose >20 Gy showed a statistically significant benefit for the three-dimensional plan. Non-coplanar three-dimensional-based conformal planning for postoperative radiotherapy for gastric cancer provided the best results regarding kidney and spinal cord exposure with adequate clinical target volume coverage. This technique was readily implemented in clinical practice.

Effects of adjuvants on IgG subclasses elicited by virus-like Particles

Directory of Open Access Journals (Sweden)

Visciano Maria Luisa

2012-01-01

Full Text Available Abstract Background Virus-Like Particles (VLPs represent an efficient strategy to present and deliver conformational antigens to the immune system, inducing both arms of the adaptive immune response. Moreover, their particulate structure surrounded by cell membrane provides an adjuvanted effect to VLP-based immunizations. In the present study, the elicitation of different patterns of IgG subclasses by VLPs, administered in CpG ODN1826 or poly(I:C adjuvants, has been evaluated in an animal model. Results Adjuvanted VLPs elicited a higher titer of total specific IgG compared to VLPs alone. Furthermore, while VLPs alone induced a balanced TH2 pattern, VLPs formulated with either adjuvant elicited a TH1-biased IgG subclasses (IgG2a and IgG3, with poly(I:C more potent than CpG ODN1826. Conclusions The results confirmed that adjuvants efficiently improve antigen immunogenicity and represent a suitable strategy to skew the adaptive immune response toward the differentiation of the desired T helper subset, also using VLPs as antigen.

Enhancement of human immunodeficiency virus type 1-DNA vaccine potency through incorporation of T-helper 1 molecular adjuvants.

Science.gov (United States)

Calarota, Sandra A; Weiner, David B

2004-06-01

It is clear that the development of a safe and effective vaccine for human immunodeficiency virus type 1 (HIV-1) remains a crucial goal for controlling the acquired immunodeficiency syndrome epidemic. At present, it is not clear what arm of the immune response correlates with protection from HIV-1 infection or disease. Therefore, a strong cellular and humoral immune response will likely be needed to control this infection. Among different vaccine alternatives, DNA vaccines appeared more than a decade ago, demonstrating important qualities of inducing both humoral and cellular immune responses in animal models. However, after several years and various clinical studies in humans, supporting the safety of the HIV-DNA vaccine strategies, it has become clear that their potency should be improved. One way to modulate and enhance the immune responses induced by a DNA vaccine is by including genetic adjuvants such as cytokines, chemokines, or T-cell costimulatory molecules as part of the vaccine itself. Particularly, vaccine immunogenicity can be modulated by factors that attract professional antigen-presenting cells, provide additional costimulation, or enhance the uptake of plasmid DNA. This review focuses on developments in the coadministration of molecular adjuvants for the enhancement of HIV-1 DNA-vaccine potency.

Low GDP Solution and Glucose-Sparing Strategies for Peritoneal Dialysis.

Science.gov (United States)

Szeto, Cheuk Chun; Johnson, David W

2017-01-01

Long-term exposure to a high glucose concentration in conventional peritoneal dialysis (PD) solution has a number of direct and indirect (via glucose degradation products [GDP]) detrimental effects on the peritoneal membrane, as well as systemic metabolism. Glucose- or GDP-sparing strategies often are hypothesized to confer clinical benefits to PD patients. Icodextrin (glucose polymer) solution improves peritoneal ultrafiltration and reduces the risk of fluid overload, but these beneficial effects are probably the result of better fluid removal rather than being glucose sparing. Although frequently used for glucose sparing, the role of amino acid-based solution in this regard has not been tested thoroughly. When glucose-free solutions are used in a combination regimen, published studies showed that glycemic control was improved significantly in diabetic PD patients, and there probably are beneficial effects on peritoneal function. However, the long-term effects of glucose-free solutions, used either alone or as a combination regimen, require further studies. On the other hand, neutral pH-low GDP fluids have been shown convincingly to preserve residual renal function and urine volume. The cost effectiveness of these solutions supports the regular use of neutral pH-low GDP solutions. Nevertheless, further studies are required to determine whether neutral pH-low GDP solutions exert beneficial effects on patient-level outcomes, such as peritonitis, technique survival, and patient survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathological confirmation of nerve-sparing types performed during robot-assisted radical prostatectomy (RARP).

Science.gov (United States)

Ko, Woo Jin; Hruby, Gregory W; Turk, Andrew T; Landman, Jaime; Badani, Ketan K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Incremental nerve-sparing techniques (NSTs) improve postoperative erectile function after robot-assisted radical prostatectomy (RARP). However, there are no studies to date that histologically confirm the surgeon intended NST. Thus, in the present study, we histologically confirmed that the surgeon performed the nerve preservation as his intended NSTs during RARP. Also, we found that there was more variability in fascia width outcome on the left side compared with the right. Therefore, when performing nerve preservation on the surgeon's non-dominant side, we need to pay more close attention. To confirm that the surgeon achieved true intended histological nerve sparing during robot-assisted radical prostatectomy (RARP) by studying RP specimens. To aid the novice robotic surgeon to develop the skills of RARP. Between June 2008 and May 2009, 122 consecutive patients underwent RARP by a single surgeon (K.K.B.). The degree of nerve sparing (wide resection [WR], interfascial nerve sparing [ITE-NS], intrafascial nerve sparing [ITR-NS]) on both sides was recorded. The posterior sectors of RP specimens from distal, mid, and proximal parts were evaluated. Fascia width (FW) of each position in RP specimens were compared across nerve-sparing types (NSTs). FW was recorded at 15 ° intervals (3-9 o'clock position), measured as the distance between the outermost prostate gland and surgical margin. The slides were reviewed by an experienced uropathologist who was 'blinded' to the NST. In all, 93 men were included. The overall mean (sd) FW was the greatest in the order of WR, ITE-NS, and ITR-NS, at 2.42 (1.62), 1.71 (1.40) and 1.16 (1.08) mm, respectively (P ITE-NS, bilateral ITE-NS, ITE-NS/WR, and bilateral WR, respectively. To further validate and confirm these preliminary findings, additional studies involving multicentre cohorts would be required. The surgeon intended dissection and FW correlate, with ITR

Hippocampal sparing radiotherapy for pediatric medulloblastoma: impact of treatment margins and treatment technique.

Science.gov (United States)

Brodin, N Patrik; Munck af Rosenschöld, Per; Blomstrand, Malin; Kiil-Berthlesen, Anne; Hollensen, Christian; Vogelius, Ivan R; Lannering, Birgitta; Bentzen, Søren M; Björk-Eriksson, Thomas

2014-04-01

We investigated how varying the treatment margin and applying hippocampal sparing and proton therapy impact the risk of neurocognitive impairment in pediatric medulloblastoma patients compared with current standard 3D conformal radiotherapy. We included 17 pediatric medulloblastoma patients to represent the variability in tumor location relative to the hippocampal region. Treatment plans were generated using 3D conformal radiotherapy, hippocampal sparing intensity-modulated radiotherapy, and spot-scanned proton therapy, using 3 different treatment margins for the conformal tumor boost. Neurocognitive impairment risk was estimated based on dose-response models from pediatric CNS malignancy survivors and compared among different margins and treatment techniques. Mean hippocampal dose and corresponding risk of cognitive impairment were decreased with decreasing treatment margins (P < .05). The largest risk reduction, however, was seen when applying hippocampal sparing proton therapy-the estimated risk of impaired task efficiency (95% confidence interval) was 92% (66%-98%), 81% (51%-95%), and 50% (30%-70%) for 3D conformal radiotherapy, intensity-modulated radiotherapy, and proton therapy, respectively, for the smallest boost margin and 98% (78%-100%), 90% (60%-98%), and 70% (39%-90%) if boosting the whole posterior fossa. Also, the distance between the closest point of the planning target volume and the center of the hippocampus can be used to predict mean hippocampal dose for a given treatment technique. We estimate a considerable clinical benefit of hippocampal sparing radiotherapy. In choosing treatment margins, the tradeoff between margin size and risk of neurocognitive impairment quantified here should be considered.

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer.

Science.gov (United States)

Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-05-20

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a "high-risk situation" (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12%); 77 of all T4 patients received postoperative chemotherapy (33%). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (pbenefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients.

Melatonin and Fertoprotective Adjuvants: Prevention against Premature Ovarian Failure during Chemotherapy.

Science.gov (United States)

Jang, Hoon; Hong, Kwonho; Choi, Youngsok

2017-06-07

Premature ovarian failure is one of the side effects of chemotherapy in pre-menopausal cancer patients. Preservation of fertility has become increasingly important in improving the quality of life of completely recovered cancer patients. Among the possible strategies for preserving fertility such as ovarian tissue cryopreservation, co-treatment with a pharmacological adjuvant is highly effective and poses less of a burden on the human body. Melatonin is generally produced in various tissues and acts as a universally acting antioxidant in cells. Melatonin is now more widely used in various biological processes including treating insomnia and an adjuvant during chemotherapy. In this review, we summarize the information indicating that melatonin may be useful for reducing and preventing premature ovarian failure in chemotherapy-treated female patients. We also mention that many adjuvants other than melatonin are developed and used to inhibit chemotherapy-induced infertility. This information will give us novel insights on the clinical use of melatonin and other agents as fertoprotective adjuvants for female cancer patients.

The spares provisioning problem with parts inventory

OpenAIRE

Abboud, Nadim E.

1990-01-01

In this research, we consider the spares provisioning problem, where a finite population of homogeneous machines are being deployed to meet a constant demand. While a machine is operating, it could become inoperable due to the failure of a critical built-in part in the machine. Before repairs on the machine can be initiated, however, a replacement part must be obtained. If a replacement part is available from stock, the machine is immediately transferred to the repair subsystem...

Adjuvant Activity of Sargassum pallidum Polysaccharides against Combined Newcastle Disease, Infectious Bronchitis and Avian Influenza Inactivated Vaccines

Directory of Open Access Journals (Sweden)

Li-Jie Li

2012-11-01

Full Text Available This study evaluates the effects of Sargassum pallidum polysaccharides (SPP on the immune responses in a chicken model. The adjuvanticity of Sargassum pallidum polysaccharides in Newcastle disease (ND, infectious bronchitis (IB and avian influenza (AI was investigated by examining the antibody titers and lymphocyte proliferation following immunization in chickens. The chickens were administrated combined ND, IB and AI inactivated vaccines containing SPP at 10, 30 and 50 mg/mL, using an oil adjuvant vaccine as a control. The ND, IB and AI antibody titers and the lymphocyte proliferation were enhanced at 30 mg/mL SPP. In conclusion, an appropriate dose of SPP may be a safe and efficacious immune stimulator candidate that is suitable for vaccines to produce early and persistent prophylaxis.

Effect of different adjuvant formulations on the immunogenicity and protective effect of a live Mycoplasma hyopneumoniae vaccine after intramuscular inoculation.

Science.gov (United States)

Xiong, Qiyan; Wei, Yanna; Xie, Haidong; Feng, Zhixin; Gan, Yuan; Wang, Chunlai; Liu, Maojun; Bai, Fangfang; Xie, Fang; Shao, Guoqing

2014-06-05

Mycoplasma hyopneumoniae (M. hyopneumoniae) vaccine strain 168 is an intrapulmonically injected attenuated live vaccine that is available in the Chinese market. The aim of this study was to develop suitable adjuvants for this live vaccine to provide effective protection after intramuscular inoculation. Several adjuvant components were screened to assess their toxicity for the live vaccine, and various adjuvant formulations were then designed and prepared. Vaccines supplemented with these adjuvants were used to immunize mice intramuscularly to assess the capacity of the adjuvants to induce a specific immune response. The screened formulations were then evaluated in pigs. Seven of the eight adjuvant components did not affect the viability of the live vaccine, and seven different adjuvant formulations were then designed. In mice, the ISCOM-matrix adjuvant and the levamisole-chitosan mixture adjuvant significantly enhanced serum IgG responses against M. hyopneumoniae, while lymphocyte proliferation was enhanced by the ISCOM-matrix adjuvant, the carbomer-astragalus polysaccharide mixture adjuvant and an oil-in-water emulsion adjuvant. These four adjuvants were evaluated in pigs. Enhancement of specific lymphocyte proliferation responses was observed in the groups vaccinated with the ISCOM-matrix adjuvant and the carbomer-astragalus polysaccharide mixture adjuvant. Significant enhancement of serum IgG antibody production was observed before challenge in pigs vaccinated with the carbomer-astragalus polysaccharide mixture adjuvant and the levamisole-chitosan mixture adjuvant, while after challenge, all of the animals that received vaccines containing adjuvants had higher antibody concentrations against M. hyopneumoniae than unvaccinated animals. Animals inoculated with a vaccine containing the ISCOM-matrix adjuvant (median score 3.57) or the carbomer-astragalus polysaccharide mixture adjuvant (median score 5.28) had reduced lesion scores compared to unvaccinated animals

Intensity modulated radiotherapy (IMRT) combined with concurrent but not adjuvant chemotherapy in primary nasopharyngeal cancer – a retrospective single center analysis

International Nuclear Information System (INIS)

Saleh-Ebrahimi, Ladan; Zwicker, Felix; Muenter, Marc W; Bischof, Marc; Lindel, Katja; Debus, Juergen; Huber, Peter E; Roeder, Falk

2013-01-01

We report our experience in 49 consecutive patients with nasopharyngeal carcinoma who were treated by Intensity-modulated radiation therapy (IMRT) combined with simultaneous but not adjuvant chemotherapy (CHT). The medical records of 49 patients with histologically proven primary nasopharygeal carcinoma treated with IMRT and concurrent platin-based CHT (predominantly cisplatin weekly) were retrospectively reviewed. The majority of patients showed advanced clinical stages (stage III/IV:72%) with undifferentiated histology (82%). IMRT was performed in step-and-shoot technique using an integrated boost concept in 84%. In this concept, the boost volume covered the primary tumor and involved nodes with doses of 66–70.4 Gy (single dose 2.2 Gy). Uninvolved regional nodal areas were covered with doses of 54–59.4 Gy (median single dose 1.8 Gy). At least one parotid gland was spared. None of the patients received adjuvant CHT. The median follow-up for the entire cohort was 48 months. Radiation therapy was completed without interruption in all patients and 76% of the patients received at least 80% of the scheduled CHT. Four local recurrences have been observed, transferring into 1-, 3-, and 5-year Local Control (LC) rates of 98%, 90% and 90%. One patient developed an isolated regional nodal recurrence, resulting in 1-, 3-, and 5-year Regional Control (RC) rates of 98%. All locoregional failures were located inside the radiation fields. Distant metastases were found in six patients, transferring into 1-, 3, and 5-year Distant Control (DC) rates of 92%, 86% and 86%. Progression free survival (PFS) rates after 1, 3 and 5 years were 86%, 70% and 69% and 1-, 3- and 5-year Overall Survival (OS) rates were 96%, 82% and 79%. Acute toxicity ≥ grade III mainly consisted of dysphagia (32%), leukopenia (24%), stomatitis (16%), infection (8%) and nausea (8%). Severe late toxicity (grade III) was documented in 18% of the patients, mainly as xerostomia (10%). Concurrent chemoradiation

A single - item replacement decision model for repairable spare ...

African Journals Online (AJOL)

In this paper, we present an analytical method for determining spare parts replacement over an infinite planning horizon. (The objective is to minimize the total system cost). We develop an exact and simple method for determining the time for equipment replacement or making decision about when to replace equipments, ...

Designing CAF-adjuvanted dry powder vaccines: spray drying preserves the adjuvant activity of CAF01.

Science.gov (United States)

Ingvarsson, Pall Thor; Schmidt, Signe Tandrup; Christensen, Dennis; Larsen, Niels Bent; Hinrichs, Wouter Leonardus Joseph; Andersen, Peter; Rantanen, Jukka; Nielsen, Hanne Mørck; Yang, Mingshi; Foged, Camilla

2013-05-10

Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassy matrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations. Copyright © 2013 Elsevier B.V. All rights reserved.

The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: a systematic review

International Nuclear Information System (INIS)

Smyth, Lloyd M; Knight, Kellie A; Aarons, Yolanda K; Wasiak, Jason

2015-01-01

Despite technical advancements in breast radiation therapy, cardiac structures are still subject to significant levels of irradiation. As the use of adjuvant radiation therapy after breast-conserving surgery continues to improve survival for early breast cancer patients, the associated radiation-induced cardiac toxicities become increasingly relevant. Our primary aim was to evaluate the cardiac-sparing benefits of the deep inspiration breath-hold (DIBH) technique. An electronic literature search of the PubMed database from 1966 to July 2014 was used to identify articles published in English relating to the dosimetric benefits of DIBH. Studies comparing the mean heart dose of DIBH and free breathing treatment plans for left breast cancer patients were eligible to be included in the review. Studies evaluating the reproducibility and stability of the DIBH technique were also reviewed. Ten studies provided data on the benefits of DIBH during left breast irradiation. From these studies, DIBH reduced the mean heart dose by up to 3.4 Gy when compared to a free breathing approach. Four studies reported that the DIBH technique was stable and reproducible on a daily basis. According to current estimates of the excess cardiac toxicity associated with radiation therapy, a 3.4 Gy reduction in mean heart dose is equivalent to a 13.6% reduction in the projected increase in risk of heart disease. DIBH is a reproducible and stable technique for left breast irradiation showing significant promise in reducing the late cardiac toxicities associated with radiation therapy

The cardiac dose-sparing benefits of deep inspiration breath-hold in left breast irradiation: a systematic review

Energy Technology Data Exchange (ETDEWEB)

Smyth, Lloyd M, E-mail: lloyd.smyth@epworth.org.au [Epworth Radiation Oncology, Level 4, The Epworth Centre, Richmond, Victoria (Australia); Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, School of Biomedical Sciences, Nursing and Health Sciences, Monash University, Clayton, Victoria (Australia); Knight, Kellie A [Department of Medical Imaging and Radiation Sciences, Faculty of Medicine, School of Biomedical Sciences, Nursing and Health Sciences, Monash University, Clayton, Victoria (Australia); Aarons, Yolanda K; Wasiak, Jason [Epworth Radiation Oncology, Level 4, The Epworth Centre, Richmond, Victoria (Australia)

2015-03-15

Despite technical advancements in breast radiation therapy, cardiac structures are still subject to significant levels of irradiation. As the use of adjuvant radiation therapy after breast-conserving surgery continues to improve survival for early breast cancer patients, the associated radiation-induced cardiac toxicities become increasingly relevant. Our primary aim was to evaluate the cardiac-sparing benefits of the deep inspiration breath-hold (DIBH) technique. An electronic literature search of the PubMed database from 1966 to July 2014 was used to identify articles published in English relating to the dosimetric benefits of DIBH. Studies comparing the mean heart dose of DIBH and free breathing treatment plans for left breast cancer patients were eligible to be included in the review. Studies evaluating the reproducibility and stability of the DIBH technique were also reviewed. Ten studies provided data on the benefits of DIBH during left breast irradiation. From these studies, DIBH reduced the mean heart dose by up to 3.4 Gy when compared to a free breathing approach. Four studies reported that the DIBH technique was stable and reproducible on a daily basis. According to current estimates of the excess cardiac toxicity associated with radiation therapy, a 3.4 Gy reduction in mean heart dose is equivalent to a 13.6% reduction in the projected increase in risk of heart disease. DIBH is a reproducible and stable technique for left breast irradiation showing significant promise in reducing the late cardiac toxicities associated with radiation therapy.

Protein Sparing Effects of Lipids in The Practical Diets of ...

African Journals Online (AJOL)

ABSTRACT: A feeding trial was conducted to establish the protein sparing effects of various lipid sources in ... reported to utilize vegetable oil that is high in omega 6 .... origin up to 15 % without any negative effects on ..... Committee on Animal.

Inventory-transportation integrated optimization for maintenance spare parts of high-speed trains

Science.gov (United States)

Wang, Jiaxi; Wang, Huasheng; Wang, Zhongkai; Li, Jian; Lin, Ruixi; Xiao, Jie; Wu, Jianping

2017-01-01

This paper presents a 0–1 programming model aimed at obtaining the optimal inventory policy and transportation mode for maintenance spare parts of high-speed trains. To obtain the model parameters for occasionally-replaced spare parts, a demand estimation method based on the maintenance strategies of China’s high-speed railway system is proposed. In addition, we analyse the shortage time using PERT, and then calculate the unit time shortage cost from the viewpoint of train operation revenue. Finally, a real-world case study from Shanghai Depot is conducted to demonstrate our method. Computational results offer an effective and efficient decision support for inventory managers. PMID:28472097

Joint optimization of preventive maintenance and spare parts inventory for an optimal production plan with consideration of CO_2 emission

International Nuclear Information System (INIS)

Ba, Kader; Dellagi, Sofiene; Rezg, Nidhal; Erray, Walid

2016-01-01

This article presents a joint optimization of spare parts inventory and preventive maintenance. While minimizing CO_2 emissions, this approach is based on an optimal production plan achieved thanks to the HMMS model. The process which is studied in this paper only manufactures one type of product. The purpose of the paper is to determine for a random demand over a given period, a cost-effective production plan and a maintenance policy which integrates a spare parts strategy in accordance with environmental requirements and regulations. Our green spare parts management can be defined as a set of actions that are applied in order to decrease the spare parts footprint in its lifetime (Ba et al., 2015) [1]. Indeed, we take into account the spare parts characteristics (new or used) which will be used during maintenance actions (preventive or corrective) to preserve the environment. Consequently, we set up analytical models based on the effect of the production rate on the system deterioration so as to substantially cut the maintenance costs, production costs and CO_2 emissions. To evaluate the performance of our models, we give some illustrative examples. - Highlights: • Establishment of an optimal production plan for a manufacturing process. • Cost-effective maintenance strategy with a green spare parts strategy. • Possibility to choose between used and new spare parts to execute maintenance action.

Radiation therapy for retinoblastoma: comparison of results with lens-sparing versus lateral beam techniques

International Nuclear Information System (INIS)

McCormick, B.; Ellsworth, R.; Abramson, D.; Haik, B.; Tome, M.; Grabowski, E.; LoSasso, T.

1988-01-01

From 1979 through 1986, 170 children were seen at our institution diagnosed with retinoblastoma. Sixty-six of the children with involvement of 121 eyes, were referred for definitive external beam radiation to one or both eyes. During the study period, two distinct radiation techniques were used. From 1980 through mid-1984, a lens-sparing technique included an anterior electron beam with a contact lens mounted lead shield, combined with a lateral field, was used. Since mid-1984, a modified lateral beam technique has been used, mixing lateral electrons and superior and inferior lateral oblique split beam wedged photons. Doses prescribed were similar for both techniques, ranging from 3,850 to 5,000 cGy in 4 to 5 weeks. The lens-sparing and the modified lateral techniques are compared for local control. For eyes with Group I through III disease, the lens-sparing technique resulted in local control in 33% of the eyes treated, where the modified lateral technique controlled 83% of the eyes treated (p = .006). Mean time to relapse was identical in both groups, that is 24 and 26 months respectively. Most relapses were successfully treated with further local therapy, including laser or cryosurgery, or 60Co plaques. Five eyes required enucleation following initial treatment with the lens-sparing technique, but none thus far with the lateral beam technique. For eyes with Group IV and V disease, no significant differences were found between the two techniques in terms of local control or eventual need for enucleation. With a mean follow-up time of 33 months for the entire group, the 4-year survival is 93%. Two of the 4 deaths are due to second primary tumor, and all 4 have occurred in the lens-sparing group. Because follow-up time is more limited in the lateral beam group, this is not statistically significant and direct survival comparisons are premature

Vaccine Adjuvant Incorporation Strategy Dictates Peptide Amphiphile Micelle Immunostimulatory Capacity.

Science.gov (United States)

Zhang, Rui; Kramer, Jake S; Smith, Josiah D; Allen, Brittany N; Leeper, Caitlin N; Li, Xiaolei; Morton, Logan D; Gallazzi, Fabio; Ulery, Bret D

2018-06-01

Current vaccine research has shifted from traditional vaccines (i.e., whole-killed or live-attenuated) to subunit vaccines (i.e., protein, peptide, or DNA) as the latter is much safer due to delivering only the bioactive components necessary to produce a desirable immune response. Unfortunately, subunit vaccines are very weak immunogens requiring delivery vehicles and the addition of immunostimulatory molecules termed adjuvants to convey protective immunity. An interesting type of delivery vehicle is peptide amphiphile micelles (PAMs), unique biomaterials where the vaccine is part of the nanomaterial itself. Due to the modularity of PAMs, they can be readily modified to deliver both vaccine antigens and adjuvants within a singular construct. Through the co-delivery of a model antigenic epitope (Ovalbumin 319-340 -OVA BT ) and a known molecular adjuvant (e.g., 2,3-dipalmitoyl-S-glyceryl cysteine-Pam 2 C), greater insight into the mechanisms by which PAMs can exert immunostimulatory effects was gained. It was found that specific combinations of antigen and adjuvant can significantly alter vaccine immunogenicity both in vitro and in vivo. These results inform fundamental design rules that can be leveraged to fabricate optimal PAM-based vaccine formulations for future disease-specific applications. Graphical Abstract.

Information system design of inventory control spare parts maintenance (valuation class 5000) (case study: plant kw)

Science.gov (United States)

Fitriana, Rina; Moengin, Parwadi; Riana, Mega

2016-02-01

Plat KW hadn't using optimal inventory level planning yet and hadn't have an information system that well computerized. The research objective is to be able to design an information system related inventory control of spare parts maintenance. The study focused on five types of spare parts with the highest application rate during February 2013- March 2015 and included in the classification of fast on FSN analysis Grinding stones Cut 4". Cable Tie 15". Welding RB 26-32MM. Ring Plat ½" and Ring Plate 5/8 ". Inventory calculation used Economic Order Quantity (EOQ). Safety Stock (SS) and Reorder Point (ROP) methods. System analysis conducted using the framework PIECES with the proposed inventory control system. the performance of the plant KW relating to the supply of spare parts maintenance needs can be more efficient as well as problems at the company can be answered and can perform inventory cost savings amounting Rp.267.066. A computerized information system of inventory control spare parts maintenance provides a menu that can be accessed by each departments as the user needed.

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity.

Science.gov (United States)

Martins, Karen A O; Cooper, Christopher L; Stronsky, Sabrina M; Norris, Sarah L W; Kwilas, Steven A; Steffens, Jesse T; Benko, Jacqueline G; van Tongeren, Sean A; Bavari, Sina

2016-01-01

Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP) as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol), MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh) cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

Influence of various forms of dialyzable leukocyte extracts on rat adjuvant arthritis

International Nuclear Information System (INIS)

Stancikova, Maria; Rovensky, Jozef; Blazickova, Stanislava; Pekarek, J.; Cech, Karel

1994-01-01

Adjuvant-induced arthritis in rats is a chronic inflammatory disease, widely as an animal model for rheumatoid arthritis. In our study the effect of various fractions of dialyzable leukocyte extract (DLE): DLE I-molecular weight below 10 kDa (commercial preparation), DLE II-molecular weight below 5 kDa (suppressor fraction), DLE III-molecular weight 5-10 kDa on rat adjuvant-induced arthritis was studied. The adjuvant arthritic (AA) rats were treated with DLE fractions i.p. in solutions containing an active substance isolated from 12.5 x 10 6 and 6.25 x 10 6 leukocytes from day 1 (adjuvant injected) through day 18, every second day (total 9 times). Various markers in inflammation, immune function and joint destruction were evaluated: hind paw volume, serum hyaluronic acid, serum albumin and biopterin in urine. All these markers showed a significant improvement after using fraction DLE II in comparison with AA controls. Fractions DLE I and DLE III influenced only some markers of inflammation and immune function. Our results demonstrated a therapeutical effect of fraction DLE II on rat adjuvant-induced arthritis. (author). 22 refs, 2 figs, 2 tabs

Spare parts management for nuclear power generation facilities

Science.gov (United States)

Scala, Natalie Michele

With deregulation, utilities in the power sector face a much more urgent imperative to emphasize cost efficiencies as compared to the days of regulation. One major opportunity for cost savings is through reductions in spare parts inventories. Most utilities are accustomed to carrying large volumes of expensive, relatively slow-moving parts because of a high degree of risk-averseness. This attitude towards risk is rooted in the days of regulation. Under regulation, companies recovered capital inventory costs by incorporating them into the base rate charged to their customers. In a deregulated environment, cost recovery is no longer guaranteed. Companies must therefore reexamine their risk profile and develop policies for spare parts inventory that are appropriate for a competitive business environment. This research studies the spare parts inventory management problem in the context of electric utilities, with a focus on nuclear power. It addresses three issues related to this problem: criticality, risk, and policy. With respect to criticality and risk, a methodology is presented that incorporates the use of influence diagrams and the Analytic Hierarchy Process (AHP). A new method is developed for group aggregation in the AHP when Saaty and Vargas' (2007) dispersion test fails and decision makers are unwilling or unable to revise their judgments. With respect to policy, a quantitative model that ranks the importance of keeping a part in inventory and recommends a corresponding stocking policy through the use of numerical simulation is developed. This methodology and its corresponding models will enable utilities that have transitioned from a regulated to a deregulated environment become more competitive in their operations while maintaining safety and reliability standards. Furthermore, the methodology developed is general enough so that other utility plants, especially those in the nuclear sector, will be able to use this approach. In addition to regulated

A joint spare part and maintenance inspection optimisation model using the Delay-Time concept

International Nuclear Information System (INIS)

Wang Wenbin

2011-01-01

Spare parts and maintenance are closely related logistics activities where maintenance generates the need for spare parts. When preventive maintenance is present, it may need more spare parts at one time because of the planned preventive maintenance activities. This paper considers the joint optimisation of three decision variables, e.g., the ordering quantity, ordering interval and inspection interval. The model is constructed using the well-known Delay-Time concept where the failure process is divided into a two-stage process. The objective function is the long run expected cost per unit time in terms of the three decision variables to be optimised. Here we use a block-based inspection policy where all components are inspected at the same time regardless of the ages of the components. This creates a situation that the time to failure since the immediate previous inspection is random and has to be modelled by a distribution. This time is called the forward time and a limiting but closed form of such distribution is obtained. We develop an algorithm for the optimal solution of the decision process using a combination of analytical and enumeration approaches. The model is demonstrated by a numerical example. - Highlights: → Joint optimisation of maintenance and spare part inventory. → The use of the Delay-Time concept. → Block-based inspection. → Fixed order interval but variable order quantity.

Valve-sparing and valve-replacing techniques for aortic root replacement in patients with Marfan syndrome: Analysis of early outcome.

Science.gov (United States)

Volguina, Irina V; Miller, D Craig; LeMaire, Scott A; Palmero, Laura C; Wang, Xing Li; Connolly, Heidi M; Sundt, Thoralf M; Bavaria, Joseph E; Dietz, Harry C; Milewicz, Dianna M; Coselli, Joseph S

2009-05-01

A prospective, international registry study was initiated to provide contemporary comparative data on short-term clinical outcomes after aortic valve-sparing and aortic valve-replacing root operations in patients with Marfan syndrome. The purpose of this initial report is to describe the study design and to compare early outcomes in the first 151 enrolled patients. We assessed 30-day outcomes in 151 patients who met strict Ghent diagnostic criteria for Marfan syndrome and underwent aortic root replacement with either valve-replacing (n = 46) or valve-sparing techniques (n = 105) at one of 18 participating centers. In the valve replacement group, a mechanical composite valve graft was used in 39 (85%) patients and a bioprosthetic valve in 7 (15%). In the valve-sparing group, David V procedures were performed in 57 (54%) patients, David I in 38 (36%), David IV in 8 (8%), Florida sleeve in 1 (1%), and Yacoub remodeling in 1 (1%). No in-hospital or 30-day deaths occurred. Despite longer crossclamp and cardiopulmonary bypass times in the valve-sparing group, there were no significant between-group differences in postoperative complications. Thirty-day valve-related complications occurred in 2 (4%) patients undergoing valve replacement and in 3 (3%) undergoing valve-sparing procedures (P = .6). The analysis of early outcomes revealed that valve-sparing techniques were the most common approach to root replacement in patients with Marfan syndrome in these centers. The complexity of valve-sparing root replacement did not translate into any demonstrable adverse early outcomes. Subsequent analysis will compare the 3-year durability of these two surgical approaches.

Joint optimisation of spare part inventory, maintenance frequency and repair capacity for k-out-of-N systems

NARCIS (Netherlands)

de Smidt-Destombes, Karin S.; van der Heijden, Matthijs C.; van Harten, Aart

2009-01-01

To achieve a high system availability at minimal costs, relevant decisions include the choice of preventive maintenance frequency, spare part inventory levels and spare part repair capacity. We develop heuristics for the joint optimisation of these variables for (a) a single k-out-of-N system under

Adjuvants and the vaccine response to the DS-Cav1-stabilized fusion glycoprotein of respiratory syncytial virus.

Directory of Open Access Journals (Sweden)

Mallika Sastry

Full Text Available Appropriate adjuvant selection may be essential to optimize the potency and to tailor the immune response of subunit vaccines. To induce protective responses against respiratory syncytial virus (RSV-a highly prevalent childhood pathogen without a licensed vaccine-we previously engineered a pre-fusion-stabilized trimeric RSV F (pre-F "DS-Cav1" immunogen, which induced high titer RSV-neutralizing antibodies, in mice and non-human primates, when formulated with adjuvants Poly (I:C and Poly (IC:LC, respectively. To assess the impact of different adjuvants, here we formulated RSV F DS-Cav1 with multiple adjuvants and assessed immune responses. Very high RSV-neutralizing antibody responses (19,006 EC50 were observed in naïve mice immunized with 2 doses of DS-Cav1 adjuvanted with Sigma adjuvant system (SAS, an oil-in-water adjuvant, plus Carbopol; high responses (3658-7108 were observed with DS-Cav1 adjuvanted with Alum, SAS alone, Adjuplex, Poly (I:C and Poly (IC:LC; and moderate responses (1251-2129 were observed with DS-Cav1 adjuvanted with the TLR4 agonist MPLA, Alum plus MPLA or AddaVax. In contrast, DS-Cav1 without adjuvant induced low-level responses (6. A balanced IgG1 and IgG2a (Th2/Th1 immune response was elicited in most of the high to very high response groups (all but Alum and Adjuplex. We also tested the immune response induced by DS-Cav1 in elderly mice with pre-existing DS-Cav1 immunity; we observed that DS-Cav1 adjuvanted with SAS plus Carbopol boosted the response 2-3-fold, whereas DS-Cav1 adjuvanted with alum boosted the response 5-fold. Finally, we tested whether a mixture of ISA 71 VG and Carbopol would enhanced the antibody response in DS-Cav1 immunized calves. While pre-F-stabilized bovine RSV F induced very high titers in mice when adjuvanted with SAS plus Carbopol, the addition of Carbopol to ISA 71 VG did not enhance immune responses in calves. The vaccine response to pre-F-stabilized RSV F is augmented by adjuvant, but the

Nephron sparing surgery (NSS) for unilateral wilms tumor (UWT): the SIOP 2001 experience.

Science.gov (United States)

Wilde, Jim C H; Aronson, Daniel C; Sznajder, Beata; Van Tinteren, Harm; Powis, Mark; Okoye, Bruce; Cecchetto, Giovanni; Audry, Georges; Fuchs, Jörg; Schweinitz, Dietrich Von; Heij, Hugo; Graf, Norbert; Bergeron, Christophe; Pritchard-Jones, Kathy; Van Den Heuvel-Eibrink, Marry; Carli, Modesto; Oldenburger, Foppe; Sandstedt, Bengt; De Kraker, Jan; Godzinski, Jan

2014-12-01

Total nephrectomy (TN) remains the standard treatment of unilateral Wilms tumors (uWT). The SIOP WT-2001 protocol allowed Nephron Sparing Surgery (NSS) for polar or peripherally non-infiltrating tumors. Inventory of the current SIOP NSS-experience. 2,800 patients with a unilateral, localized or metastatic and an unequivocal surgical technique recorded were included. All had neo-adjuvant chemotherapy and delayed surgery. In 91 (3%) NSS was performed and in 2709 TN. Data was retrieved from the SIOP WT 2001 database. NSS group contained 65% stage I tumours and the TN group 48%. Tumor volume (at diagnosis and surgery) was significantly smaller in the NSS group. Within stage III, after NSS, 7/12 (58%) had positive margins (M +), 5 with tumor negative lymph nodes (LN-). After TN, 355/712 (55%) had M + , 182 were LN-. Treatment of M+ in the NSS group resulted in two conversions to TN (one combined with radiotherapy), three patients had radiotherapy only and in two patients local therapy, if given, was not recorded. After NSS, four recurrences occurred. For localized disease the 5-year overall (OS) and event free survival (EFS) in NSS group was 100 and 94.8 (95% CI:89.9-99.9), respectively, while OS and EFS in the TN group were 94.4 (95% CI: 93.2-95.5, log-rank test P = 0.06) and 86.5 (95% CI:85.0-88.1, log-rank test P = 0.06), respectively. NSS was only performed in 3% of patients with uWT. Despite excellent survival with few relapses, the gain of nephrons needs to be weighed against the risk to induce stage III with intensified therapy. © 2014 Wiley Periodicals, Inc.

Gamma ray sterilization of delta inulin adjuvant particles (Advax™) makes minor, partly reversible structural changes without affecting adjuvant activity

Science.gov (United States)

Cooper, P. D.; Barclay, T. G.; Ginic-Markovic, M.; Petrovsky, N.

2014-01-01

We earlier identified a developmental series of seven isoforms/polymorphs of microparticulate inulin by comparing non-covalent bonding strengths. Their pharmaceutical utility lies in modulation of cellular immunity, exploited as vaccine adjuvants (Advax™) especially for delta inulin (DI). As such particles cannot be sterilized by filtration we explore the effect of 60Co gamma radiation (GR) on inulin isoforms, particularly DI. Its adjuvant activity and overt physical properties were unaffected by normal GR sterilizing doses (up to 25 kGy). Heating irradiated isoform suspensions near their critical dissolution temperature revealed increased solubility deduced to reflect a single lethal event in one component of a multi-component structure. Local oxidative effects of GR on DI were not found. The observed DI loss was almost halved by re-annealing at the critical temperature: surviving inulin chains apparently reassemble into smaller amounts of the original type of structure. Colorimetric tetrazolium assay revealed increases in reducing activity after GR of raw inulin powder, which yielded DI with normal physical properties but only 25% normal recovery yet 4× normal reducing ability, implying final retention of some GR-changed inulin chains. These findings suggest minimal inulin chain cleavage and confirm that GR may be a viable strategy for terminal sterilization of microparticulate inulin adjuvants. PMID:24342245

Benefit of Adjuvant Chemotherapy After Curative Resection of Lung Metastasis in Colorectal Cancer.

Science.gov (United States)

Park, Hyung Soon; Jung, Minkyu; Shin, Sang Joon; Heo, Su Jin; Kim, Chang Gon; Lee, Min Goo; Beom, Seung Hoon; Lee, Chang Young; Lee, Jin Gu; Kim, Dae Joon; Ahn, Joong Bae

2016-03-01

The survival benefit of adjuvant chemotherapy after colorectal cancer (CRC) lung metastasectomy is uncertain. We enrolled 221 CRC patients who underwent pulmonary metastasectomy between October 2002 and July 2013, including those with previous liver metastasis that had been curatively resected. Disease-free survival (DFS) and overall survival (OS) were calculated from the day of lung metastasectomy. Among all patients, 176 (79.6%) received adjuvant chemotherapy after lung metastasectomy. Median follow-up was 34.7 months from the time of lung metastasectomy [95% confidence interval (95% CI), 7.4-90.9 months]. Patients treated with adjuvant chemotherapy had longer DFS compared with surgery alone (median 32.7 vs 11.2 months respectively, P = 0.076). Multivariate analysis revealed previous liver metastasis, preoperative carcinoembryonic antigen ≥5 ng/mL, disease-free interval chemotherapy as independent risk factors for recurrence. Low-risk patients who had 0-1 risk factors received a significant survival benefit from adjuvant chemotherapy [hazard ratio (HR) 0.54; 95% CI 0.32-0.91, P = 0.020]; however, high-risk patients with ≥2 risk factors did not (HR 1.02; 95% CI 0.48-2.14, P = 0.964). Patients treated with adjuvant chemotherapy showed no OS benefit compared with patients who received surgery alone (median 89.6 vs 86.8 months respectively, P = 0.833). CRC patients received lung metastasectomy could have a DFS benefit from adjuvant chemotherapy, especially in low-risk patients. Larger, prospective studies are needed to evaluate the role of adjuvant chemotherapy after CRC lung metastasectomy.

Sparingly Solvating Electrolytes for High Energy Density Lithium-Sulfur Batteries

Energy Technology Data Exchange (ETDEWEB)

Cheng, Lei; Curtiss, Larry A.; Zavadil, Kevin R.; Gewirth, Andrew A.; Shao, Yuyan; Gallagher, Kevin

2016-07-11

Moving to lighter and less expensive battery chemistries compared to lithium-ion requires the control of energy storage mechanisms based on chemical transformations rather than intercalation. Lithium sulfur (Li/S) has tremendous theoretical specific energy, but contemporary approaches to control this solution-mediated, precipitation-dissolution chemistry requires using large excesses of electrolyte to fully solubilize the polysulfide intermediate. Achieving reversible electrochemistry under lean electrolyte operation is the only path for Li/S to move beyond niche applications to potentially transformational performance. An emerging topic for Li/S research is the use of sparingly solvating electrolytes and the creation of design rules for discovering new electrolyte systems that fundamentally decouple electrolyte volume from reaction mechanism. This perspective presents an outlook for sparingly solvating electrolytes as the key path forward for longer-lived, high-energy density Li/S batteries including an overview of this promising new concept and some strategies for accomplishing it.

Valve-sparing aortic root replacement in Loeys-Dietz syndrome.

Science.gov (United States)

Patel, Nishant D; Arnaoutakis, George J; George, Timothy J; Allen, Jeremiah G; Alejo, Diane E; Dietz, Harry C; Cameron, Duke E; Vricella, Luca A

2011-08-01

Loeys-Dietz syndrome (LDS) is a recently recognized aggressive aortic disorder characterized by root aneurysm, arterial tortuosity, hypertelorism, and bifid uvula or cleft palate. The results of prophylactic root replacement using valve-sparing procedures (valve-sparing root replacement [VSRR]) in patients with LDS is not known. We reviewed all patients with clinical and genetic (transforming growth factor-β receptor mutations) evidence of LDS who underwent VSRR at our institution. Echocardiographic and clinical data were obtained from hospital and follow-up clinic records. From 2002 to 2009, 31 patients with a firm diagnosis of LDS underwent VSRR for aortic root aneurysm. Mean age was 15 years, and 24 (77%) were children. One (3%) patient had a bicuspid aortic valve. Preoperative sinus diameter was 3.9±0.8 cm (z score 7.0±2.9) and 2 (6%) had greater than 2+ aortic insufficiency. Thirty patients (97%) underwent reimplantation procedures using a Valsalva graft. There were no operative deaths. Mean follow-up was 3.6 years (range, 0 to 7 years). One patient required late repair of a pseudoaneurysm at the distal aortic anastomosis, and 1 had a conversion to a David reimplantation procedure after a Florida sleeve operation. No patient suffered thromboembolism or endocarditis, and 1 (3%) patient experienced greater than 2+ late aortic insufficiency. No patient required late aortic valve repair or replacement. Loeys-Dietz syndrome is an aggressive aortic aneurysm syndrome that can be addressed by prophylactic aortic root replacement with low operative risk. Valve-sparing procedures have encouraging early and midterm results, similar to those in Marfan syndrome, and are an attractive option for young patients. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

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Ivana Škrnjug

Full Text Available The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Cyclic GMP-AMP displays mucosal adjuvant activity in mice.

Science.gov (United States)

Škrnjug, Ivana; Guzmán, Carlos Alberto; Rueckert, Christine; Ruecker, Christine

2014-01-01

The recently discovered mammalian enzyme cyclic GMP-AMP synthase produces cyclic GMP-AMP (cGAMP) after being activated by pathogen-derived cytosolic double stranded DNA. The product can stimulate STING-dependent interferon type I signaling. Here, we explore the efficacy of cGAMP as a mucosal adjuvant in mice. We show that cGAMP can enhance the adaptive immune response to the model antigen ovalbumin. It promotes antigen specific IgG and a balanced Th1/Th2 lymphocyte response in immunized mice. A characteristic of the cGAMP-induced immune response is the slightly reduced induction of interleukin-17 as a hallmark of Th17 activity--a distinct feature that is not observed with other cyclic di-nucleotide adjuvants. We further characterize the innate immune stimulation activity in vitro on murine bone marrow-derived dendritic cells and human dendritic cells. The observed results suggest the consideration of cGAMP as a candidate mucosal adjuvant for human vaccines.

Adjuvant chemotherapy compliance is not superior after thoracoscopic lobectomy

DEFF Research Database (Denmark)

Licht, Peter B; Schytte, Tine; Jakobsen, Erik

2014-01-01

BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single-institution, ......BACKGROUND: It is generally assumed that patient compliance with adjuvant chemotherapy is superior after video-assisted thoracoscopic surgery compared with open lobectomy for non-small cell lung cancer (NSCLC). The level of evidence for this assumption, however, is limited to single...... adjuvant chemotherapy and 121 (38.7%) completed all four cycles. Ordinal logistic regression revealed that chemotherapy compliance (none, partial, and full chemotherapy) was significantly reduced by the patient's age (p....02). No significant difference between video-assisted thoracoscopic surgery and thoracotomy was seen regarding chemotherapy compliance (p=0.17), number of chemotherapy cycles (p=0.60), or time from surgery to chemotherapy (p = 0.41). CONCLUSIONS: Complete national data do not support the widespread assumption...

Radical prostatectomy, sparing of the seminal vesicles, and painful orgasm.

Science.gov (United States)

Mogorovich, Andrea; Nilsson, Andreas E; Tyritzis, Stavros I; Carlsson, Stefan; Jonsson, Martin; Haendler, Leif; Nyberg, Tommy; Steineck, Gunnar; Wiklund, N Peter

2013-05-01

Erectile dysfunction has been widely investigated as the major factor responsible for sexual bother in patients after radical prostatectomy (RP); painful orgasm (PO) is one element of this bother, but little is known about its prevalence and its effects on sexual health. This study aims to investigate the prevalence of PO and to identify potential risk factors. A total of 1,411 consecutive patients underwent open (radical retropubic prostatectomy) or robot-assisted laparoscopic RP between 2002 and 2006. The patients were asked to complete a study-specific questionnaire. Of a total of 145 questions, 5 dealt with the orgasmic characteristics. The questionnaire was also administered to a comparison group of 442 persons, matched for age and area of residency. The response rate was 91% (1,288 patients). A total of 143 (11%) patients reported PO. Among the 834 men being able to have an orgasm, the prevalence was 18% vs. 6% in the comparison group (relative risk [RR] 2.8, 95% confidence interval [CI] 1.7-4.5). When analyzed as independent variables, bilateral seminal vesicle (SV)-sparing approach (RR 2.33, 95% CI 1.0-5.3, P = 0.045) and age <60 years were significantly related to the presence of PO (95% CI 0.5-0.9, P = 0.019). After adjustment for age, bilateral SV-sparing still remained a significant predictor for occurrence of PO. We found that PO occurs significantly more often in patients undergoing bilateral SV-sparing RP when compared with age-matched comparison population. © 2013 International Society for Sexual Medicine.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer

International Nuclear Information System (INIS)

Borstlap, W. A. A.; Tanis, P. J.; Koedam, T. W. A.; Marijnen, C. A. M.; Cunningham, C.

2016-01-01

Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5–20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion

Comparison of quadriceps-sparing minimally invasive and medial parapatellar total knee arthroplasty: A 2-year follow-up study

Directory of Open Access Journals (Sweden)

Hongsen Chiang

2012-12-01

Conclusions: Patients undergoing quadriceps-sparing and standard medial parapatellar TKA had comparable outcomes for quadriceps muscle strength, hamstring–quadriceps balance, and knee function; however, the quadriceps-sparing TKA was more time consuming surgically and resulted in a less accurate prosthesis position.

Feasibility of Performing Total Skin-Sparing Mastectomy in Patients With Prior Circumareolar Mastopexy or Reduction Mammoplasty Incisions.

Science.gov (United States)

Vaughn, Carolyn J; Peled, Anne Warren; Esserman, Laura J; Foster, Robert D

2013-06-19

Total skin-sparing mastectomy (TSSM) techniques with preservation of the nipple-areolar complex (NAC) skin are becoming increasingly popular due to improved cosmesis without compromise in oncologic safety. However, these techniques are not routinely offered to patients who have undergone previous breast surgery involving circumareolar incisions due to concern for NAC viability. We reviewed the outcomes of TSSM in 11 patients who underwent 21 TSSM procedures at our institution between 2008 and 2011. All patients had undergone previous breast surgery including reduction mammaplasty (7 breasts), mastopexy (4 breasts), augmentation (3 breasts), and combined mastopexy-augmentation (7 breasts). Incisions from previous breast surgery included circumareolar (11 cases) and Wise pattern (10 cases) incisions. All patients underwent TSSM through an inframammary incision followed by immediate tissue expander reconstruction and subsequent implant exchange. Patient demographics, previous breast surgery details, tumor and treatment characteristics, and postoperative complications were reviewed. Mean patient age was 43 years (range, 35-53 years) and mean body mass index was 24 kg/m (range, 19-32 kg/m). Mean follow-up was 10.2 months (range, 3-20 months).Indications for TSSM included prophylactic risk reduction in 10 cases, in situ cancer in 2 cases, and invasive cancer in 9 cases. Mean time from previous breast surgery to mastectomy was 6.9 years (range, 6 months-26 years). Major complications requiring operative reintervention included 1 (4.8%) case of cellulitis requiring expander removal and 2 (9.5%) cases of wound breakdown requiring operative closure. There were no complications involving the NAC. Total skin-sparing mastectomy with immediate reconstruction can safely be performed in patients who have undergone previous breast surgery involving circumareolar incisions. Our preferred technique in this group of patients is to perform TSSM through an inframammary incision with 2

Modern Vaccines/Adjuvants Formulation--Session 2 (Plenary II): May 15-17, 2013--Lausanne, Switzerland.

Science.gov (United States)

Collin, Nicolas

2013-09-01

On the 15-17th May 2013, the Fourth International Conference on Modern Vaccines/Adjuvants Formulation was organized in Lausanne, Switzerland, and gathered stakeholders from academics and from the industry to discuss several challenges, advances and promises in the field of vaccine adjuvants. Plenary session 2 of the meeting was composed of four different presentations covering: (1) the recent set-up of an adjuvant technology transfer and training platform in Switzerland, (2) the proposition to revisit existing paradigms of modern vaccinology, (3) the properties of polyethyleneimine as potential new vaccine adjuvant, and (4) the progresses in the design of HIV vaccine candidates able to induce broadly neutralizing antibodies.

Assessment of side effects induced by injection of different adjuvant/antigen combinations in rabbits and mice

NARCIS (Netherlands)

Leenaars, P.P.A.M.; Koedam, M.A.; Wester, P.W.; Baumans, V.; Claassen, E.; Hendriksen, C.F.M.

1998-01-01

We evaluated the side effects induced by injection of Freund's adjuvant (FA) and alternative adjuvants combined with different antigens. Rabbits and mice were injected subcutaneously, intramuscularly (rabbits) and intraperitoneally (mice) with different adjuvants (FA, Specol, RIBI, TiterMax,

Adjuvant-enhanced CD4 T Cell Responses are Critical to Durable Vaccine Immunity

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Karen A.O. Martins

2016-01-01

Full Text Available Protein-based vaccines offer a safer alternative to live-attenuated or inactivated vaccines but have limited immunogenicity. The identification of adjuvants that augment immunogenicity, specifically in a manner that is durable and antigen-specific, is therefore critical for advanced development. In this study, we use the filovirus virus-like particle (VLP as a model protein-based vaccine in order to evaluate the impact of four candidate vaccine adjuvants on enhancing long term protection from Ebola virus challenge. Adjuvants tested include poly-ICLC (Hiltonol, MPLA, CpG 2395, and alhydrogel. We compared and contrasted antibody responses, neutralizing antibody responses, effector T cell responses, and T follicular helper (Tfh cell frequencies with each adjuvant's impact on durable protection. We demonstrate that in this system, the most effective adjuvant elicits a Th1-skewed antibody response and strong CD4 T cell responses, including an increase in Tfh frequency. Using immune-deficient animals and adoptive transfer of serum and cells from vaccinated animals into naïve animals, we further demonstrate that serum and CD4 T cells play a critical role in conferring protection within effective vaccination regimens. These studies inform on the requirements of long term immune protection, which can potentially be used to guide screening of clinical-grade adjuvants for vaccine clinical development.

ANALISIS KLASIFIKASI PERSEDIAAN SUKU CADANG MENGGUNAKAN MUSIC-3D VIEW OF SPARES (Studi Kasus Perusahaan Farmasi di PT. XYZ

Directory of Open Access Journals (Sweden)

Yuli Dwi Astanti

2015-04-01

Full Text Available PT. XYZ is a pharmaceutical company that manufactures both pharmaceuticals and herbal medicinal chemistry. The drug is a vital necessity to society, therefore, the drug production process must be maintained so that its performance can be met drug availability. One way to maintain smooth production process is to maintain engine performance. An engine production facility that is vital and requires periodic maintenance or at any time in case of damage. Each performed maintenance or repairs due to damage, an engine needs replacement parts for the machine to run as before. To support the maintenance activities, PT. XYZ has a warehouse used to store spare parts. During this time, parts storage system in PT. XYZ is not based on consideration of the appropriate classification of its characteristics, but each part has different characteristics, both in terms of price, suppliers, materials, usage, and so on. Due to the large number of stocks and the importance of spare parts, the supply system must be considered in order not to cause any harm to the company. The present study will attempt to analyze the system parts inventory in the warehouse by using MUSIC-3D View of Spares. MUSIC-3D View of spares in the analysis using a 3-dimensional approach that values consumption, availability and critically. The third dimension is represented by the three approaches, namely System ABC, VED, and SDE. Based on the results of the analysis of MUSIC-3D Views of Spares in mind that parts each having a different classification, so it requires a different treatment according to their classification.   Keywords : spare parts, supplies, MUSIC-3D View of Spares

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

Science.gov (United States)

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Interferon alpha for the adjuvant treatment of cutaneous melanoma.

Science.gov (United States)

Mocellin, Simone; Lens, Marko B; Pasquali, Sandro; Pilati, Pierluigi; Chiarion Sileni, Vanna

2013-06-18

Interferon alpha is the only agent approved for the postoperative adjuvant treatment of high-risk cutaneous melanoma. However, the survival advantage associated with this treatment is unclear, especially in terms of overall survival. Thus, adjuvant interferon is not universally considered a gold standard treatment by all oncologists. To assess the disease-free survival and overall survival effects of interferon alpha as adjuvant treatment for people with high-risk cutaneous melanoma. We searched the following databases up to August 2012: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library (2012, issue 8), MEDLINE (from 2005), EMBASE (from 2010), AMED (from 1985), and LILACS (from 1982). We also searched trials databases in 2011, and proceedings of the ASCO annual meeting from 2000 to 2011. We checked the reference lists of selected articles for further references to relevant trials. We included only randomised controlled trials (RCTs) comparing interferon alpha to observation (or any other treatment) for the postoperative (adjuvant) treatment of patients with high-risk skin melanoma, that is, people with regional lymph node metastasis (American Joint Committee on Cancer (AJCC) TNM (tumour, lymph node, metastasis) stage III) undergoing radical lymph node dissection, or people without nodal disease but with primary tumour thickness greater than 1 mm (AJCC TNM stage II). Two authors extracted data, and a third author independently verified the extracted data. The main outcome measure was the hazard ratio (HR), which is the ratio of the risk of the event occurring in the treatment arm (adjuvant interferon) compared to the control arm (no adjuvant interferon). The survival data were either entered directly into Review Manager (RevMan) or extrapolated from Kaplan-Meier plots and then entered into RevMan. Based on the presence of between-study heterogeneity, we applied a fixed-effect or random-effects model for calculating the pooled estimates

Valve-sparing operation for aortic root aneurysm in patients with Marfan syndrome.

Science.gov (United States)

Wang, R; Ma, W G; Tian, L X; Sun, L Z; Chang, Q

2010-03-01

We report our experience with aortic valve-sparing procedures in patients with Marfan syndrome and aortic root aneurysm. Between August 2003 and July 2007, we performed aortic valve-sparing procedures in 20 patients with aortic root aneurysm resulting from Marfan syndrome. Mean age was 28 +/- 10 years (range, 10 to 57 years), and there were 9 females and 11 males. A reimplantation technique was used in 9 cases, a remodeling technique in 8 and a patch technique in 3 cases. Additional procedures included total aorta replacement in 1 patient, and aortic arch replacement plus stented elephant trunk in 2 patients. The mean follow-up time was 46 +/- 16 months (range, 17 to 64 months). No in-hospital or late death occurred. Reexploration for bleeding was required in one case on postoperative day 1. No valve-related complications occurred during the follow-up period. At the end of follow-up, trivial or no aortic regurgitation was demonstrated in 14 patients, mild in 4 patients, moderate in 1 and severe in 1. Two patients with moderate and severe aortic regurgitation required reoperation. The early and mid-term results of the valve-sparing operations were favorable, and the durability of the preserved valve should encourage use of this technique in patients with Marfan syndrome.

Skull base meningioma. Surgical and adjuvant treatment with clinical and PET evaluation

International Nuclear Information System (INIS)

Gudjonsson, O.

2001-01-01

The treatment strategy for skull base meningiomas remains a controversial issue. Because of the proximity of these tumours to critical neurovascular structures, the risk for vascular damage and new cranial neuropathies postoperatively is significant. To avoid unacceptable neurological deficits the surgical treatment strategy includes different surgical approaches and a subtotal removal of these tumours in some cases. However, because the rate of recurrence and progression is significant in these patients, a demand for adjuvant treatment and better prognostic methods is called for so that treatment and follow-up can be tailored to each patient. Accordingly, we have chosen to evaluate general outcome and facial nerve function after translabyrinthine and transcochlear approaches for cerebellopontine angle (CPA) meningiomas. Furthermore, we have evaluated two adjuvant treatments, namely, irradiation by high-energy proton beams and medical treatment with interferon-alpha as well as evaluation of the treatment effect with 11 C-L-methionine PET. In addition, we have evaluated a new PET tracer ( 76 Br-BrdU) for 'in vivo' determination of the growth potential of intracranial tumours. Conclusion: The translabyrinthine and transcochlear approaches are apparently safe surgical procedures in the treatment of CPA meningiomas. Proton beam therapy is technically feasible as suggested by the fact that only minimal side effects were observed. Moreover, none of the meningiomas treated have shown progression during a 36-month follow-up. Our results indicate that IFN-alpha can be an effective oncostatic treatment for certain patients with meningiomas. The 11 C-L-methionine PET method might be used as a complement to CT or MRI in the evaluation of the effect of proton beam and IFN-alpha treatment in meningiomas. The present attempt failed to demonstrate that the PET tracer 76 Br-BrdU could be used for the non-invasive characterisation of growth potential in brain, tumours

Skull base meningioma. Surgical and adjuvant treatment with clinical and PET evaluation

Energy Technology Data Exchange (ETDEWEB)

Gudjonsson, O

2001-05-01

The treatment strategy for skull base meningiomas remains a controversial issue. Because of the proximity of these tumours to critical neurovascular structures, the risk for vascular damage and new cranial neuropathies postoperatively is significant. To avoid unacceptable neurological deficits the surgical treatment strategy includes different surgical approaches and a subtotal removal of these tumours in some cases. However, because the rate of recurrence and progression is significant in these patients, a demand for adjuvant treatment and better prognostic methods is called for so that treatment and follow-up can be tailored to each patient. Accordingly, we have chosen to evaluate general outcome and facial nerve function after translabyrinthine and transcochlear approaches for cerebellopontine angle (CPA) meningiomas. Furthermore, we have evaluated two adjuvant treatments, namely, irradiation by high-energy proton beams and medical treatment with interferon-alpha as well as evaluation of the treatment effect with {sup 11}C-L-methionine PET. In addition, we have evaluated a new PET tracer ({sup 76}Br-BrdU) for 'in vivo' determination of the growth potential of intracranial tumours. Conclusion: The translabyrinthine and transcochlear approaches are apparently safe surgical procedures in the treatment of CPA meningiomas. Proton beam therapy is technically feasible as suggested by the fact that only minimal side effects were observed. Moreover, none of the meningiomas treated have shown progression during a 36-month follow-up. Our results indicate that IFN-alpha can be an effective oncostatic treatment for certain patients with meningiomas. The {sup 11}C-L-methionine PET method might be used as a complement to CT or MRI in the evaluation of the effect of proton beam and IFN-alpha treatment in meningiomas. The present attempt failed to demonstrate that the PET tracer {sup 76}Br-BrdU could be used for the non-invasive characterisation of growth potential in

Role of adjuvant postoperative external beam radiotherapy for well differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jeanny; Wu, Hong Gyun; Youn, Yeo Kyu; Lee, Kyu Eun; Kim, Kwang Hyun; Park, Do Joon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

2013-09-15

To analyze the outcome of adjuvant postoperative external beam radiotherapy (EBRT) in well-differentiated thyroid cancer (WDTC). We identified 84 patients treated with EBRT for WDTC from February 1981 to December 2010. Among them, we analyzed 39 patients who received EBRT after initial radical surgery. Twenty-four females and 15 males were included. The median age was 49 years (range, 16 to 72 years). There were 34 papillary thyroid carcinomas and 5 follicular thyroid carcinomas. Most patients showed pathologic T3/T4 stage (54%/26%). Ten patients (25.6%) had gross residual tumors. Five patients (12.8%) had tumor cells at the margin. The median EBRT dose and fraction size were 62.6 Gy and 1.8 to 2.0 Gy, respectively. The median follow-up was 73 months (range, 21 to 372 months). The five-year overall survival (OS) and locoregional recurrence free survival (LRFS) were 97.4% and 86.9%, respectively. Locoregional failures occurred in 5 and all failure sites were the neck node area. In univariate analysis, OS was significantly influenced by invasion of the trachea (p = 0.016) or esophagus (p = 0.006). LRFS was significantly decreased by male (p = 0.020), gross residuum after resection (p = 0.002), close or positive tumor at surgical margin involvement (p = 0.044), and tracheal invasion (p = 0.040). No significant prognostic factor was identified in the multivariate analysis. No patient experienced the Radiation Therapy Oncology Group grade 3 or more toxicity. Our locoregional control rate of 87.2% is comparable to historical controls with surgery alone, even though our study had a large proportion of advanced stage. Adjuvant EBRT may an effective and safe treatment option in patients with WDTC.

Autoimmune/inflammatory syndrome induced by adjuvants (Shoenfeld's syndrome) - An update.

Science.gov (United States)

Watad, A; Quaresma, M; Brown, S; Cohen Tervaert, J W; Rodríguez-Pint, I; Cervera, R; Perricone, C; Shoenfeld, Y

2017-06-01

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) has been widely described in many studies conducted thus far. The syndrome incorporates five immune-mediated conditions, all associated with previous exposure to various agents such as vaccines, silicone implants and several others. The emergence of ASIA syndrome is associated with individual genetic predisposition, for instance those carrying HLA-DRB1*01 or HLA-DRB4 and results from exposure to external or endogenous factors triggering autoimmunity. Such factors have been demonstrated as able to induce autoimmunity in both animal models and humans via a variety of proposed mechanisms. In recent years, physicians have become more aware of the existence of ASIA syndrome and the relationship between adjuvants exposure and autoimmunity and more cases are being reported. Accordingly, we have created a registry that includes at present more than 300 ASIA syndrome cases that have been reported by different physicians worldwide, describing various autoimmune conditions induced by diverse adjuvants. In this review, we have summarized the updated literature on ASIA syndrome and the knowledge accumulated since 2013 in order to elucidate the association between the exposure to various adjuvant agents and its possible clinical manifestations. Furthermore, we especially referred to the relationship between ASIA syndrome and systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS).

Accounting for adjuvant-induced artifacts in the characterization of vaccine formulations by polyacrylamide gel electrophoresis.

Science.gov (United States)

Jakob, Virginie; Brunner, Livia; Barnier-Quer, Christophe; Blust, Molly; Collin, Nicolas; Carter, Lauren; Carter, Darrick; Rausch, Kelly M; Fox, Christopher B

2017-04-01

Several vaccine adjuvants comprise complex nano- or micro-particle formulations, such as oil-in-water emulsions. In order to characterize interactions and compatibility of oil-in-water emulsion adjuvants with protein antigens in vaccines, effective protein characterization methods that can accommodate potential interference from high concentrations of lipid-based particles are needed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a standard protein characterization technique which is affected by the presence of adjuvants such as oil-in-water emulsions. In this article, we investigate variations in SDS-PAGE methods that result in a reduction of adjuvant-induced staining artifacts. We have investigated whether the SDS method or the adjuvant composition were the reason for these artifacts and succeeded in reducing the artifacts with a modified sample preparation and different staining procedures. The best results were obtained by using gold staining or silver staining instead of a Coomassie Blue staining procedure. Moreover, the replacement of the dilution buffer (20% SDS to disrupt emulsion) by alternative detergents such as Tween® 80 and Triton® X-100 removed adjuvant-induced streaking artifacts at the top of the gel. These methods may be useful for improving characterization approaches of antigen-adjuvant mixtures by SDS-PAGE.

Adjuvant radiotherapy for stage I endometrial cancer.

Science.gov (United States)

Kong, A; Johnson, N; Cornes, P; Simera, I; Collingwood, M; Williams, C; Kitchener, H

2007-04-18

The role of adjuvant radiotherapy (both pelvic external beam radiotherapy and vaginal intracavity brachytherapy) in stage I endometrial cancer following total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO) remains unclear. To assess the efficacy of adjuvant radiotherapy following surgery for stage I endometrial cancer. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CancerLit, Physician Data Query (PDQ) of National Cancer Institute. Handsearching was also carried out where appropriate. Randomised controlled trials (RCTs) which compared adjuvant radiotherapy versus no radiotherapy following surgery for patients with stage I endometrial cancer were included. Quality of the studies was assessed and data collected using a predefined data collection form. The primary endpoint was overall survival. Secondary endpoints were locoregional recurrence, distant recurrence and endometrial cancer death. Data on quality of life (QOL) and morbidity were also collected. A meta-analysis on included trials was performed using the Cochrane Collaboration Review Manager Software 4.2. The meta-analysis was performed on four trials (1770 patients). The addition of pelvic external beam radiotherapy to surgery reduced locoregional recurrence, a relative risk (RR) of 0.28 (95% confidence interval (CI) 0.17 to 0.44, p ASTEC; Lukka) are awaited. External beam radiotherapy carries a risk of toxicity and should be avoided in stage 1 endometrial cancer patients with no high risk factors.

Adjuvant chemotherapy for gastric cancer: Current evidence and future challenges

OpenAIRE

Miceli, Rosalba; Tomasello, Gianluca; Bregni, Giacomo; Di Bartolomeo, Maria; Pietrantonio, Filippo

2014-01-01

Gastric cancer still represents one of the major causes of cancer mortality worldwide. Patients survival is mainly related to stage, with a high proportion of patients with metastatic disease at presentation. Thus, the cure rate largely depend upon surgical resection. Despite the additional, albeit small, benefit of adjuvant chemotherapy has been clearly demonstrated, no general consensus has been reached on the best treatment option. Moreover, the narrow therapeutic index of adjuvant chemoth...

Safety and efficacy of E coli enterotoxin adjuvant for urease-based rectal immunization against Helicobacter pylori.

Science.gov (United States)

Sougioultzis, Stavros; Lee, Cynthia K; Alsahli, Mazen; Banerjee, Subhas; Cadoz, Michel; Schrader, Robert; Guy, Bruno; Bedford, Philip; Monath, Thomas P; Kelly, Ciaran P; Michetti, Pierre

2002-12-13

Low dose E. coli heat-labile enterotoxin (LT), delivered orally or enterically, has been used as an adjuvant for Helicobacter pylori (H. pylori) urease in healthy adults. In this study we aim to test the safety and adjuvant efficacy of LT delivered rectally together with recombinant H. pylori urease. Eighteen healthy adults without present or past H. pylori infection were enrolled in a double blind, randomized, ascending dose study to receive either urease (60 mg), or urease (60 mg) + LT (5 or 25 microg). The immunization preparation was administered per rectum on days 0, 14 and 28. Serum, stool and saliva anti-urease and anti-LT IgG and IgA antibodies (Abs) were measured and urease-specific and LT-specific antigen secreting cells (ASCs) were counted in peripheral blood at baseline and 7 (ASC counts) or 14 days (antibody levels) after each dosing. Peripheral blood lymphoproliferation assays were also performed at baseline and at the end of the study. Rectally delivered urease and LT were well tolerated. Among the 12 subjects assigned to urease+LT, 2 (16.7%) developed anti-urease IgG Abs, 1 (8.3%) developed anti-urease IgA Abs, and 3 (25%) showed urease-specific IgA(+) ASCs. Immune responses to LT were more vigorous, especially in subjects exposed to 5 microg LT. In the urease+ 5 microg LT group, anti-LT IgG and IgA Abs developed in 60 and 80% of the subjects, respectively, while LT-specific IgG(+) and IgA(+) ASCs were detected in all subjects. The magnitude of the anti-LT response was much higher than the response to urease. No IgA anti-urease or anti-LT Abs were detected in stool or saliva and lymphocyte proliferative responses to urease were unsatisfactory. In conclusion, rectal delivery of 5 microg LT is safe and induces vigorous systemic anti-LT immune responses. Further studies are needed to determine if LT can be an effective adjuvant for rectally delivered antigens.

A Pilot Trial of Jawarish Amla as Adjuvant to Anti-Tubercular Treatment Drugs for Control of Adverse Reactions in DOTS Regime in Pulmonary TB.

Science.gov (United States)

Sherwani, Arish Mohammad Khan; Zulkifle, Mohammad; Rehmatulla

2012-01-01

One of the greatest challenges of health care systems at the dawn of the 21st century is tuberculosis (TB). Drug resistant strains of TB are becoming a global public health risk. These strains commonly appear due to faulty therapies. Patients frequently stop treatment due to the toxicity of anti-tubercular treatment (ATT) drugs. Amla (Emblica officinalis) is a well-known Unani single drug. Jawarish amla is a Unani compound formulation which is commonly used to administer amla. This study tested the efficacy of Jawarish amla as an adjuvant to ATT drugs in reducing their side effects. Half of forty eligible pulmonary tuberculosis patients were randomly assigned to Test (Group B) and the other half to Control (Group A). Six grams of Jawarish amla twice daily was administered to the test group, and the same dosage of placebo was administered to control group along with directly observed treatment, short course chemotherapy (DOTS) for 60 days. Fisher exact test and paired t-test were applied for efficacy evaluation. Grading of symptoms was done to assess the toxicity of ATT and outcome of the adjuvant. Significant improvements were observed in almost all subjective and objective parameters. The exceptions were serum creatine and serum uric acid, which showed non-significant slight elevations within normal limits. Jawarish amla was ascertained to be safe and effective adjuvant of DOTS in combating the adverse effects of ATT drugs.

Cost Comparison of B-1B Non-Mission-Capable Drivers Using Finite Source Queueing with Spares

Science.gov (United States)

2012-09-06

COMPARISON OF B-1B NON-MISSION-CAPABLE DRIVERS USING FINITE SOURCE QUEUEING WITH SPARES GRADUATE RESEARCH PAPER Presented to the Faculty...step into the lineup making large-number approximations unusable. Instead, a finite source queueing model including spares is incorporated...were reported as flying time accrued since last occurrence. Service time was given in both start-stop format and MX man-hours utilized. Service time was

The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors

International Nuclear Information System (INIS)

Goy, Barry W.; Lee, Steve P.; Eilber, Frederick; Dorey, Fred; Eckardt, Jeffrey; Fu, Y.-S.; Juillard, Guy J.F.; Selch, Michael T.

1996-01-01

Purpose/Objective: Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly proven the indications for adjuvant radiotherapy in treating resectable desmoid tumors. Materials and Methods: A retrospective analysis was performed on 61 patients with resectable desmoid tumors who were treated at our institution from 1965 to 1992. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five were treated with surgery alone, while 11 received surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. Results: Univariate analysis of 56 patients with unifocal disease revealed that female gender (p=0.025) and positive margins (p=0.032) predicted for local recurrence. Multivariate analysis revealed that only positive margins (p=0.003) independently predicted for local recurrence. Only 3 of 22 patients had local recurrences with clear margins, with a 6 year actuarial local control of 85%. We analyzed 34 patients with positive margins by univariate analysis, and only adjuvant radiotherapy predicted for improved local control (p=0.031). Multivariate analysis of these 34 patients revealed that adjuvant radiotherapy independently predicted for local control (p=0.012), and patients with recurrent disease had a slightly higher risk of local recurrence (p=0.083). The 6 year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32%(±12%) with surgery alone, and 78%(±14%) with surgery plus adjuvant radiotherapy (p=0.019). None of the patients who received radiotherapy for unifocal disease developed serious complications, or a secondary malignancy. Conclusions: Adjuvant radiotherapy is indicated in the treatment of patients with resectable

Forging a potent vaccine adjuvant: CpG ODN/cationic peptide nanorings.

Science.gov (United States)

Gungor, Bilgi; Yagci, Fuat Cem; Gursel, Ihsan; Gursel, Mayda

Type I interferon inducers may potentially be engineered to function as antiviral and anticancer agents, or alternatively, vaccine adjuvants, all of which may have clinical applications. We recently described a simple strategy to convert a Toll-like receptor 9 (TLR9) agonist devoid of interferon α (IFNα) stimulating activity into a robust Type I interferon inducer with potent vaccine adjuvant activity.

A prenatally detected adrenal cyst treated by adrenal-sparing surgery

African Journals Online (AJOL)

A neonatal case of left adrenal cyst detected in utero and successfully treated by adrenal-sparing surgery is presented and discussed with review of the literature. Incidentally discovered prenatal adrenal masses present a diagnostic dilemma. Benign and malignant conditions can present as a fetal suprarenal mass. There is ...

Natural and synthetic saponin adjuvant QS-21 for vaccines against cancer

Science.gov (United States)

Ragupathi, Govind; Gardner, Jeffrey R; Livingston, Philip O; Gin, David Y

2013-01-01

One of the most widely used and potent immunological adjuvants is a mixture of soluble triterpene glycosides purified from the soap bark tree (Quillaja saponaria). Despite challenges in production, quality control, stability and toxicity, the QS-21 fraction from this extract has exhibited exceptional adjuvant properties for a range of antigens. It possesses an ability to augment clinically significant antibody and T-cell responses to vaccine antigens against a variety of infectious diseases, degenerative disorders and cancers. The recent synthesis of active molecules of QS-21 has provided a robust method to produce this leading vaccine adjuvant in high purity as well as to produce novel synthetic QS-21 congeners designed to induce increased immune responsiveness and decreased toxicity. PMID:21506644

Combined-modality treatment in advanced oral squamous cell carcinoma. Primary surgery followed by adjuvant concomitant radiochemotherapy

International Nuclear Information System (INIS)

Kreppel, Matthias; Dreiseidler, Timo; Zoeller, Joachim E.; Scheer, Martin; Drebber, Uta; Eich, Hans-Theodor; Mueller, Rolf-Peter

2011-01-01

The efficacy of adjuvant radiochemotherapy (RCT) in patients with advanced stage head and neck carcinoma has been proven in prospective randomized trials. However, these trials focused on different head and neck sites. Specific analyses for treatment effects in squamous cell carcinoma of the oral cavity (OSCC) are missing. We evaluated our experiences with adjuvant concomitant RCT in advanced OSCC to compare the results with other treatment schemes using adjuvant RCT. A total of 183 patients with OSCC of UICC stages II-IVb were reviewed retrospectively. All patients were treated with radical surgery followed by adjuvant, conventional fractionated concomitant RCT using carboplatin. Overall survival was plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Univariate analysis showed a significant impact of T, N, and UICC stage, histopathologic grading, surgical margins, extracapsular spread (ECS), and lymphangiosis carcinomatosa on overall survival (Table 3). Patients with stage IVa had a higher 5-year overall survival rate (42.8%) than patients with stage IVb (25.0%) (Figure 1). The differences were significant in multivariate analysis (p = 0.033) (Table 4). Adjuvant concomitant RCT is an effective treatment in patients with advanced stage OSCC. However, it remains unclear, which patients should be treated with adjuvant RCT. For patients with stage IVb, adjuvant RCT yields poor results. Prospective randomized trials are needed to confirm which patients should be treated with adjuvant RCT. (orig.)

Systematic Review of Studies Reporting Positive Surgical Margins After Bladder Neck Sparing Radical Prostatectomy.

Science.gov (United States)

Bellangino, Mariangela; Verrill, Clare; Leslie, Tom; Bell, Richard W; Hamdy, Freddie C; Lamb, Alastair D

2017-11-07

Bladder neck preservation (BNP) during radical prostatectomy (RP) has been proposed as a method to improve early recovery of urinary continence after radical prostatectomy. However, there is concern over a possible increase in the risk of positive surgical margins and prostate cancer recurrence rate. A recent systematic review and meta-analysis reported improved early recovery and overall long-term urinary continence without compromising oncologic control. The aim of our study was to perform a critical review of the literature to assess the impact on bladder neck and base margins after bladder neck sparing radical prostatectomy. We carried out a systematic review of the literature using Pubmed, Scopus and Cochrane library databases in May 2017 using medical subject headings and free-text protocol according to PRISMA guidelines. We used the following search terms: bladder neck preservation, prostate cancer, radical prostatectomy and surgical margins. Studies focusing on positive surgical margins (PSM) in bladder neck sparing RP pertinent to the objective of this review were included. Overall, we found 15 relevant studies reporting overall and site-specific positive surgical margins rate after bladder neck sparing radical prostatectomy. This included two RCTs, seven prospective comparative studies, two retrospective comparative studies and four case series. All studies were published between 1993 and 2015 with sample sizes ranging between 50 and 1067. Surgical approaches included open, laparoscopic and robot-assisted radical prostatectomy. The overall and base-specific PSM rates ranged between 7-36% and 0-16.3%, respectively. Mean base PSM was 4.9% in those patients where bladder neck sparing was performed, but only 1.85% in those without sparing. Bladder neck preservation during radical prostatectomy may increase base-positive margins. Further studies are needed to better investigate the impact of this technique on oncological outcomes. A future paradigm could

Nomogram for Predicting the Benefit of Adjuvant Chemoradiotherapy for Resected Gallbladder Cancer

Science.gov (United States)

Wang, Samuel J.; Lemieux, Andrew; Kalpathy-Cramer, Jayashree; Ord, Celine B.; Walker, Gary V.; Fuller, C. David; Kim, Jong-Sung; Thomas, Charles R.

2011-01-01

Purpose Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. Methods Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) –Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. Results A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser–based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. Conclusion A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT. PMID:22067404

Deterministic and heuristic models of forecasting spare parts demand

Directory of Open Access Journals (Sweden)

Ivan S. Milojević

2012-04-01

Full Text Available Knowing the demand of spare parts is the basis for successful spare parts inventory management. Inventory management has two aspects. The first one is operational management: acting according to certain models and making decisions in specific situations which could not have been foreseen or have not been encompassed by models. The second aspect is optimization of the model parameters by means of inventory management. Supply items demand (asset demand is the expression of customers' needs in units in the desired time and it is one of the most important parameters in the inventory management. The basic task of the supply system is demand fulfillment. In practice, demand is expressed through requisition or request. Given the conditions in which inventory management is considered, demand can be: - deterministic or stochastic, - stationary or nonstationary, - continuous or discrete, - satisfied or unsatisfied. The application of the maintenance concept is determined by the technological level of development of the assets being maintained. For example, it is hard to imagine that the concept of self-maintenance can be applied to assets developed and put into use 50 or 60 years ago. Even less complex concepts cannot be applied to those vehicles that only have indicators of engine temperature - those that react only when the engine is overheated. This means that the maintenance concepts that can be applied are the traditional preventive maintenance and the corrective maintenance. In order to be applied in a real system, modeling and simulation methods require a completely regulated system and that is not the case with this spare parts supply system. Therefore, this method, which also enables the model development, cannot be applied. Deterministic models of forecasting are almost exclusively related to the concept of preventive maintenance. Maintenance procedures are planned in advance, in accordance with exploitation and time resources. Since the timing

Benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer

International Nuclear Information System (INIS)

Teufel, Andreas; Gerken, Michael; Hartl, Janine; Itzel, Timo; Fichtner-Feigl, Stefan; Stroszczynski, Christian; Schlitt, Hans Jürgen; Hofstädter, Ferdinand; Klinkhammer-Schalke, Monika

2015-01-01

Colorectal cancer is the third most common cancer and a major cause of morbidity and mortality worldwide. Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection. Adjuvant therapy was not shown to be beneficial in patients with UICC stage II colon cancer. However, there is an ongoing discussion as to whether adjuvant chemotherapy may be beneficial for a subgroup of UICC II patients in a “high-risk situation” (such as T4). We investigated a Bavarian population-based (2.1 million inhabitants) cohort of 1937 patients with UICC II CRC treated between 2002 and 2012 in regard of the benefit of adjuvant chemotherapy for large (T4) tumors. Patients older than 80 years of age were excluded. Of 1937 patients, 240 had a T4 tumor (12 %); 77 of all T4 patients received postoperative chemotherapy (33 %). Kaplan-Meier analysis and Cox regression models were used for survival analyses. Patients with a T4 tumor who received postoperative chemotherapy had a highly significant survival benefit in respect of overall survival (p < 0.001) and recurrence-free survival (p = 0.008). However, no difference was observed between oxaliplatin-containing and non-oxaliplatin-containing treatment regimens. G2 and G3 tumors were found to particularly benefit from adjuvant treatment. Chemotherapy, age at diagnosis, and tumor grading remained independent risk factors in the multivariate cox regression analysis. Our retrospective study demonstrated the significant benefit of adjuvant chemotherapy in the T4 subgroup of patients with UICC II colon cancer. Our data suggest that adjuvant chemotherapy should be seriously considered in these patients. The online version of this article (doi:10.1186/s12885-015-1404-9) contains supplementary material, which is available to authorized users

Timing of adjuvant chemotherapy and its relation to survival among patients with stage III colon cancer.

Science.gov (United States)

Bos, A C R K; van Erning, F N; van Gestel, Y R B M; Creemers, G J M; Punt, C J A; van Oijen, M G H; Lemmens, V E P P

2015-11-01

Currently available data suggest that delaying the start of adjuvant chemotherapy in colon cancer patients has a detrimental effect on survival. We analysed which factors impact on the timing of adjuvant chemotherapy and evaluated the influence on overall survival (OS). Stage III colon cancer patients who underwent resection and received adjuvant chemotherapy between 2008 and 2013 were selected from the Netherlands Cancer Registry. Timing of adjuvant chemotherapy was subdivided into: ⩽ 4, 5-6, 7-8, 9-10, 11-12 and 13-16 weeks post-surgery. Multivariable regressions were performed to assess the influence of several factors on the probability of starting treatment within 8 weeks post-surgery and to evaluate the association of timing of adjuvant chemotherapy with 5-year OS. 6620 patients received adjuvant chemotherapy, 14% commenced after 8 weeks. Factors associated with starting treatment after 8 weeks were older age (Odds ratio (OR) 65-74 versus colon cancer patients within 8 weeks post-surgery. Copyright © 2015 Elsevier Ltd. All rights reserved.

Antinociceptive effect of chlorphenesin carbamate in adjuvant arthritic rats.

Science.gov (United States)

Okuyama, S; Aihara, H

1987-02-01

The antinociceptive effect of chlorphenesin carbamate (CPC) and mephenesin were examined in adjuvant arthritic rats. In the behavioral study, CPC (100-400 mg/kg, p.o.) but not mephenesin (100-400 mg/kg, p.o.) had a dose-dependent antinociceptive effect, determined using the flexion test. In the electrophysiological study, CPC (25-50 mg/kg, i.v.) but not mephenesin (50 mg/kg, i.v.) depressed the evoked neuronal responses of nociceptive neurons in the ventrobasal thalamus (VB), while the evoked responses of non-nociceptive neurons were not depressed by either CPC (50 mg/kg, i.v.) or mephenesin (50 mg/kg, i.v.). The spontaneous firings of the VB nociceptive neurons were depressed by both CPC (50 mg/kg, i.v.) and mephenesin (50 mg/kg, i.v.). However, mephenesin (50 mg/kg, i.v.) but not CPC (50 mg/kg, i.v.) also depressed the spontaneous firings of the mesencephalic reticular formation (RF), in these adjuvant arthritic rats. These results indicate that CPC but not mephenesin, has an antinociceptive action in adjuvant arthritic rats.

Tocotrienols are good adjuvants for developing cancer vaccines

International Nuclear Information System (INIS)

Abdul Hafid, Sitti Rahma; Radhakrishnan, Ammu Kutty; Nesaretnam, Kalanithi

2010-01-01

Dendritic cells (DCs) have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. In this study we have used tocotrienol-rich fraction (TRF), a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF) and DC pulsed with tumour lysate from 4T1 cells (DC+TL). Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF) while two groups of animal which were supplemented daily with carrier oil (control) and with TRF (TRF). After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF) injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF) compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8) and natural killer cells (NK) were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy

Recurrence in Region of Spared Parotid Gland After Definitive Intensity-Modulated Radiotherapy for Head and Neck Cancer

International Nuclear Information System (INIS)

Cannon, Donald M.; Lee, Nancy Y.

2008-01-01

Purpose: To discuss the implications of three examples of periparotid recurrence after definitive intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods and Materials: We present 3 patients with HNC who underwent definitive IMRT with concurrent chemotherapy and later had treatment failure in or near a spared parotid gland. Two patients had bilateral multilevel nodal disease, and all had Level II nodal disease ipsilateral to the site of recurrence. The patients were treated using dose-painting IMRT with a dose of 70 Gy to the gross tumor volume and 59.4 Gy or 54 Gy to the high-risk or low-risk clinical tumor volume, respectively. The parotid glands were spared bilaterally. The patients had not undergone any surgical treatment for HNC before radiotherapy. Results: All patients had treatment failure in the region of a spared parotid gland. Failure in the 2 patients with bilateral multilevel nodal involvement occurred in the periparotid lymph nodes. The third patient developed a dermal metastasis near the tail of a spared parotid gland. On pretreatment imaging, the 2 patients with nodal failure had small nonspecific periparotid nodules that showed no hypermetabolic activity on positron emission tomography. Conclusion: For HNC patients receiving definitive IMRT, nonspecific positron emission tomography-negative periparotid nodules on pretreatment imaging should raise the index of suspicion for subclinical disease in the presence of multilevel or Level II nodal metastases. Additional evaluation of such nodules might be indicated before sparing the ipsilateral parotid gland

Adjuvant endocrine and chemotherapy for early breast cancer

International Nuclear Information System (INIS)

Henderson, I. Craig

1996-01-01

Objective: Present the results of the 1995 World Overview which will be held in Oxford England two weeks before ASTRO. Discuss the interpretation and application of these results. Review current research topics on the use of adjuvant endocrine and chemotherapy for early breast cancer. The survival benefits from adjuvant chemotherapy in premenopausal women and adjuvant tamoxifen in postmenopausal women are well established. Each will reduce the annual odds of death by about 25% resulting in a 10 year survival difference of 8-10%. By the time of this presentation, the results of the 1995 Adjuvant Therapy Overview should be with 10+ years of follow-up, and if possible these will be summarized. Current efforts to improve on previous results are focused on the following areas: Optimal chemotherapy dose. Decreasing dose will compromise patient survival. It is not as certain that increasing dose will have as much impact in improving survival. The NSABP was unable to demonstrate an improvement in survival by modestly increasing the dose of cyclophosphamide alone. However, recent results of a Canadian study of CEF (cyclophosphamide, epidoxorubicin, and 5-fluorouracil) and an Intergroup trial of an intense 16 week polychemotherapy program keep alive the possibility that dose escalation is still a very important question. An NSABP trial evaluating even greater cyclophosphamide dose escalation, an Intergroup evaluation of different doxorubicin doses, and two Intergroup trials evaluating very high dose chemotherapy and bone marrow transplantation should provide definitive evidence regarding the importance of dose. Drug sequence. A study from Milan suggests that initial treatment with single agent doxorubicin followed by CMF will be superior to alternating doxorubicin and CMF. This has not been confirmed yet, and the reason for increased benefit from such a sequence is not entirely clear. This concept is being explored further in an Intergroup trial comparing four cycles of

Laryngeal Muscles Are Spared in the Dystrophin Deficient "mdx" Mouse

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Thomas, Lisa B.; Joseph, Gayle L.; Adkins, Tracey D.; Andrade, Francisco H.; Stemple, Joseph C.

2008-01-01

Purpose: "Duchenne muscular dystrophy (DMD)" is caused by the loss of the cytoskeletal protein, dystrophin. The disease leads to severe and progressive skeletal muscle wasting. Interestingly, the disease spares some muscles. The purpose of the study was to determine the effects of dystrophin deficiency on 2 intrinsic laryngeal muscles, the…

Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

International Nuclear Information System (INIS)

Hendlisz, Alain; Maetens, Marion; Borbath, Ivan; Dresse, Damien; Houbiers, Ghislain; Fried, Michael; Awada, Ahmad; Piccart, Martine; Laethem, Jean-Luc Van; Flamen, Patrick; Golfinopoulos, Vassilis; Deleporte, Amelie; Paesmans, Marianne; Mansy, Hazem El; Garcia, Camilo; Peeters, Marc; Annemans, Lieven; Vandeputte, Caroline

2013-01-01

Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available. Identifying which patients are unlikely to respond to adjuvant chemotherapy from among those who are eligible for such treatment would be a major step towards treatment personalization. It would spare such patients from unnecessary toxicities and would improve the allocation of societal healthcare resources. PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer. The study’s primary objective is to examine the ability of PET/CT-assessed tumor FDG uptake after one course of preoperative chemotherapy to predict the outcome of adjuvant therapy, as measured by 3-year disease-free survival. Secondary objectives are to examine the predictive value of changes in PET/CT-assessed tumor FDG uptake on overall survival, to define the best cut-off value of FDG uptake for predicting treatment outcome, and to analyse the cost-effectiveness of such preoperative chemo-sensitivity testing. At study planning, exploratory translational research objectives were 1) to assess the predictive value of circulating tumor cells for disease-free survival, 2) to examine the predictive value of single nucleotide polymorphisms for disease-free survival with respect to genes related either to

Critical structure sparing in stereotactic ablative radiotherapy for central lung lesions: helical tomotherapy vs. volumetric modulated arc therapy.

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Alexander Chi

Full Text Available BACKGROUND: Helical tomotherapy (HT and volumetric modulated arc therapy (VMAT are both advanced techniques of delivering intensity-modulated radiotherapy (IMRT. Here, we conduct a study to compare HT and partial-arc VMAT in their ability to spare organs at risk (OARs when stereotactic ablative radiotherapy (SABR is delivered to treat centrally located early stage non-small-cell lung cancer or lung metastases. METHODS: 12 patients with centrally located lung lesions were randomly chosen. HT, 2 & 8 arc (Smart Arc, Pinnacle v9.0 plans were generated to deliver 70 Gy in 10 fractions to the planning target volume (PTV. Target and OAR dose parameters were compared. Each technique's ability to meet dose constraints was further investigated. RESULTS: HT and VMAT plans generated essentially equivalent PTV coverage and dose conformality indices, while a trend for improved dose homogeneity by increasing from 2 to 8 arcs was observed with VMAT. Increasing the number of arcs with VMAT also led to some improvement in OAR sparing. After normalizing to OAR dose constraints, HT was found to be superior to 2 or 8-arc VMAT for optimal OAR sparing (meeting all the dose constraints (p = 0.0004. All dose constraints were met in HT plans. Increasing from 2 to 8 arcs could not help achieve optimal OAR sparing for 4 patients. 2/4 of them had 3 immediately adjacent structures. CONCLUSION: HT appears to be superior to VMAT in OAR sparing mainly in cases which require conformal dose avoidance of multiple immediately adjacent OARs. For such cases, increasing the number of arcs in VMAT cannot significantly improve OAR sparing.

Prognostic significance of adjuvant radiation therapy in adenocarcinoma of the cecum

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Hosseini, Sare; Bananzadeh, Ali Mohammad; Mohammadianpanah, Mohammad; Salek, Roham; Taghizadeh-Kermani, Ali

2018-01-01

Purpose Local recurrence is a common failure pattern in adenocarcinoma of the cecum. This study aimed to investigate the potential role of adjuvant radiation therapy on oncologic outcomes of patients with adenocarcinoma of the cecum. Materials and Methods This retrospective study was carried out at three large tertiary university hospitals. We analyzed the characteristics, prognostic factors, and survival of 162 patients with adenocarcinoma of the cecum that were treated and followed up between 2000 and 2013. All the patients had undergone a right hemicolectomy and received chemotherapy with (n = 48) or without (n = 114) adjuvant radiation therapy. Results The subjects were 65 females and 97 males with a median age of 56 years (range, 17 to 90 years) at diagnosis. The 5-year local control (LC), disease free survival (DFS), and overall survival (OS) rates were 72.7%, 57.2%, and 62.6% respectively. In a multivariate analysis, age, tumor stage, node stage, and adjuvant radiation therapy were determined to be independent prognostic factors. Age more than 55 years (hazard ratio [HR] = 1.0; 95% confidence interval [CI], 0.06–0.32; p = 0.003], T4 stage (HR = 6.8; 95% CI, 3.07–15.36; p < 0.001), node positive disease (HR = 4.2; 95% CI, 1.94–9.13; p < 0.001), and the absence of adjuvant radiation therapy (HR = 3.0; 95% CI, 1.39–6.46; p = 0.005) had a negative influence on OS. Conclusion Adjuvant radiation therapy significantly improves DFS and OS in patients with adenocarcinoma of the cecum. PMID:29506326

The identification of plant lectins with mucosal adjuvant activity

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Lavelle, E C; Grant, G; Pusztai, A; Pfüller, U; O'hagan, D T

2001-01-01

To date, the most potent mucosal vaccine adjuvants to be identified have been bacterial toxins. The present data demonstrate that the type 2 ribosome-inactivating protein (type 2 RIP), mistletoe lectin I (ML-I) is a strong mucosal adjuvant of plant origin. A number of plant lectins were investigated as intranasal (i.n.) coadjuvants for a bystander protein, ovalbumin (OVA). As a positive control, a potent mucosal adjuvant, cholera toxin (CT), was used. Co-administration of ML-I or CT with OVA stimulated high titres of OVA-specific serum immunoglobulin G (IgG) in addition to OVA-specific IgA in mucosal secretions. CT and ML-I were also strongly immunogenic, inducing high titres of specific serum IgG and specific IgA at mucosal sites. None of the other plant lectins investigated significantly boosted the response to co-administered OVA. Immunization with phytohaemagglutinin (PHA) plus OVA elicited a lectin-specific response but did not stimulate an enhanced response to OVA compared with the antigen alone. Intranasal delivery of tomato lectin (LEA) elicited a strong lectin-specific systemic and mucosal antibody response but only weakly potentiated the response to co-delivered OVA. In contrast, administration of wheatgerm agglutinin (WGA) or Ulex europaeus lectin 1 (UEA-I) with OVA stimulated a serum IgG response to OVA while the lectin-specific responses (particularly for WGA) were relatively low. Thus, there was not a direct correlation between immunogenicity and adjuvanticity although the strongest adjuvants (CT, ML-I) were also highly immunogenic. PMID:11168640

ERVA - AREVAs Alternative Way for Spare Parts Management

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Hoppe, H.

2014-07-01

The availability of equipment and systems in power plants throughout the life of the plant is a key challenge for plant operators. Therefore, the management of spare parts during the entire life cycle of a plant is of particular importance. In order to maintain the functionality of the equipment without retrofit or re-design it is important to have original parts available for use or to ensure there is adequate stock available for the future. (Author)

Comparing organic farming and land sparing: optimizing yield and butterfly populations at a landscape scale.

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Hodgson, Jenny A; Kunin, William E; Thomas, Chris D; Benton, Tim G; Gabriel, Doreen

2010-11-01

Organic farming aims to be wildlife-friendly, but it may not benefit wildlife overall if much greater areas are needed to produce a given quantity of food. We measured the density and species richness of butterflies on organic farms, conventional farms and grassland nature reserves in 16 landscapes. Organic farms supported a higher density of butterflies than conventional farms, but a lower density than reserves. Using our data, we predict the optimal land-use strategy to maintain yield whilst maximizing butterfly abundance under different scenarios. Farming conventionally and sparing land as nature reserves is better for butterflies when the organic yield per hectare falls below 87% of conventional yield. However, if the spared land is simply extra field margins, organic farming is optimal whenever organic yields are over 35% of conventional yields. The optimal balance of land sparing and wildlife-friendly farming to maintain production and biodiversity will differ between landscapes. © 2010 Blackwell Publishing Ltd/CNRS.

Sparing of descending axons rescues interneuron plasticity in the lumbar cord to allow adaptive learning after thoracic spinal cord injury

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Christopher Nelson Hansen

2016-03-01

Full Text Available This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI. Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX. This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI. To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm. In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days or late (42 days after midthoracic SCI in a rodent model. Early after SCI or TX at 7d, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between

Oncoplastic breast surgery does not delay the onset of adjuvant chemotherapy

DEFF Research Database (Denmark)

Klit, Anders; Tvedskov, Tove Filtenborg; Kroman, Niels

2017-01-01

BACKGROUND: Only a few studies of limited size have examined whether oncoplastic breast surgery delays the onset of adjuvant chemotherapy as compared to conventional breast surgery. We investigated whether oncoplastic breast surgery causes a delay in the onset of adjuvant chemotherapy in comparison...... to lumpectomy and mastectomy. MATERIAL AND METHODS: The study is a population-based cohort study. Within the nationwide registry of the Danish Breast Cancer Group (DBCG), we identified 1798 patients who received adjuvant chemotherapy following mastectomy, lumpectomy or oncoplastic breast surgery for early...... and unilateral invasive breast cancer. Women treated with neoadjuvant chemotherapy were excluded. RESULTS: We found no significant difference between the three groups (mastectomy, lumpectomy, oncoplastic breast surgery) in the time from biopsy to surgery (mean time 17.9, 17.0 and 18.3 days, respectively...

Acquisition Pricing and Inventory Decisions on Dual-Source Spare-Part System with Final Production and Remanufacturing

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Yancong Zhou

2016-01-01

Full Text Available The life spans of durable goods are longer than their warranty periods. To satisfy the service demand of spare parts and keep the market competition advantage, enterprises have to maintain the longer inventory planning of spare parts. However, how to obtain a valid number of spare parts is difficult for those enterprises. In this paper, we consider a spare-part inventory problem, where the inventory can be replenished by two ways including the final production order and the remanufacturing way. Especially for the remanufacturing way, we consider the acquisition management problem of used products concerning an acquisition pricing decision. In a multiperiod setting, we formulate the problem into a dynamic optimization problem, where the system decisions include the final production order and acquisition price of used products at each period. By stochastic dynamic programming, we obtain the optimal policy of the acquisition pricing at each period and give the optimal policy structure of the optimization problem at the first period. Then, a recursion algorithm is designed to calculate the optimal decisions and the critical points in the policy. Finally, the numerical analyses show the effects of demand information and customer’s sensitive degree on the related decisions and the optimal cost.

Impact of adjuvant chemotherapy for gliomatosis cerebri

International Nuclear Information System (INIS)

Kong, Doo-Sik; Nam, Do-Hyun; Kim, Sung Tae; Lee, Jung-Il; Suh, Yeon-Lim; Lim, Do Hoon; Kim, Won Seog; Kwon, Ki-Hoon; Park, Kwan; Kim, Jong Hyun

2010-01-01

Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC

Skin-Sparing Radiation Using Intensity-Modulated Radiotherapy After Conservative Surgery in Early-Stage Breast Cancer: A Planning Study

International Nuclear Information System (INIS)

Saibishkumar, Elantholi P.; MacKenzie, Marc A.; Severin, Diane; Mihai, Alina; Hanson, John M.Sc.; Daly, Helene; Fallone, Gino; Parliament, Matthew B.; Abdulkarim, Bassam S.

2008-01-01

Purpose: To evaluate the feasibility of skin-sparing by configuring it as an organ-at-risk (OAR) while delivering whole-breast intensity-modulated radiotherapy (IMRT) in early breast cancer. Methods and Materials: Archival computed tomography scan images of 14 left-sided early-breast tumor patients who had undergone lumpectomy were selected for this study. Skin was contoured as a 4- to 5-mm strip extending from the patient outline to anterior margin of the breast planning target volume (PTV). Two IMRT plans were generated by the helical tomotherapy approach to deliver 50 Gy in 25 fractions to the breast alone: one with skin dose constraints (skin-sparing plan) and the other without (non-skin-sparing plan). Comparison of the plans was done using a two-sided paired Student t test. Results: The mean skin dose and volume of skin receiving 50 Gy were significantly less with the skin-sparing plan compared with non-skin-sparing plan (42.3 Gy vs. 47.7 Gy and 12.2% vs. 57.8% respectively; p < 0.001). The reduction in skin dose was confirmed by TLD measurements in anthropomorphic phantom using the same plans. Dose-volume analyses for other OARs were similar in both plans. Conclusions: By configuring the skin as an OAR, it is possible to achieve skin dose reduction while delivering whole-breast IMRT without compromising dose profiles to PTV and OARs

Split-field vs extended-field intensity-modulated radiation therapy plans for oropharyngeal cancer: Which spares the larynx? Which spares the thyroid?

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Yu, Yao; Chen, Josephine [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Leary, Celeste I. [Department of Radiation Medicine, Oregon Health Sciences University, Portland, OR (United States); Shugard, Erin [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Yom, Sue S., E-mail: yoms@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA (United States); Department of Otolaryngology—Head and Neck Surgery, University of California, San Francisco, San Francisco, CA (United States)

2016-07-01

Radiation of the low neck can be accomplished using split-field intensity-modulated radiation therapy (sf-IMRT) or extended-field intensity-modulated radiation therapy (ef-IMRT). We evaluated the effect of these treatment choices on target coverage and thyroid and larynx doses. Using data from 14 patients with cancers of the oropharynx, we compared the following 3 strategies for radiating the low neck: (1) extended-field IMRT, (2) traditional split-field IMRT with an initial cord-junction block to 40 Gy, followed by a full-cord block to 50 Gy, and (3) split-field IMRT with a full-cord block to 50 Gy. Patients were planned using each of these 3 techniques. To facilitate comparison, extended-field plans were normalized to deliver 50 Gy to 95% of the neck volume. Target coverage was assessed using the dose to 95% of the neck volume (D{sub 95}). Mean thyroid and larynx doses were computed. Extended-field IMRT was used as the reference arm; the mean larynx dose was 25.7 ± 7.4 Gy, and the mean thyroid dose was 28.6 ± 2.4 Gy. Split-field IMRT with 2-step blocking reduced laryngeal dose (mean larynx dose 15.2 ± 5.1 Gy) at the cost of a moderate reduction in target coverage (D{sub 95} 41.4 ± 14 Gy) and much higher thyroid dose (mean thyroid dose 44.7 ± 3.7 Gy). Split-field IMRT with initial full-cord block resulted in greater laryngeal sparing (mean larynx dose 14.2 ± 5.1 Gy) and only a moderately higher thyroid dose (mean thyroid dose 31 ± 8 Gy) but resulted in a significant reduction in target coverage (D{sub 95} 34.4 ± 15 Gy). Extended-field IMRT comprehensively covers the low neck and achieves acceptable thyroid and laryngeal sparing. Split-field IMRT with a full-cord block reduces laryngeal doses to less than 20 Gy and spares the thyroid, at the cost of substantially reduced coverage of the low neck. Traditional 2-step split-field IMRT similarly reduces the laryngeal dose but also reduces low-neck coverage and delivers very high doses to the thyroid.

Neoadjuvant chemoradiation (modified Eilber protocol) versus adjuvant radiotherapy in the treatment of extremity soft tissue sarcoma

International Nuclear Information System (INIS)

Lehane, Chris; Parasyn, Andrew; Ho, Frederick; Thompson, Stephen R.; Smee, Robert; Links, David; Crowe, Phil; Lewis, Craig; Friedlander, Michael; Williams, Janet

2016-01-01

Local control for extremity soft tissue sarcomas (STS) requires surgery combined with radiotherapy, usually given pre-operatively or post-operatively. The modified Eilber protocol, a neoadjuvant chemoradiation regimen, has been reported with excellent local control rates. This retrospective single-centre study compared outcomes for patients treated with the modified Eilber protocol with those treated with standard adjuvant radiotherapy. Twenty-nine patients were treated with modified Eilber protocol. Thirty-four patients received adjuvant radiotherapy. Three patients (10%) in the Eilber group and five patients (15%) in the Adjuvant group developed local recurrence (P = 0.87). Major acute wound complications were noted in four patients in each group (P = 0.55). One patient (3.4%) in the Eilber group developed Grade 3 or 4 late toxicities after 1 year compared with nine patients (27%) in the Adjuvant group (P = 0.02). Patients with a diagnosis of extremity STS were retrospectively reviewed from the Prince of Wales Hospital Sarcoma Database from 1995 to 2012. Sixty-three patients underwent curative surgery with either neoadjuvant Eilber chemoradiotherapy (Eilber) or adjuvant radiotherapy (Adjuvant). Neoadjuvant chemoradiation (Eilber protocol) provided similar rates of local control when compared with adjuvant radiotherapy. Acute wound complication rates were similar but there was less severe late toxicity in the Eilber group.

Factors influencing bowel sparing in intensity modulated whole pelvic radiotherapy for gynaecological malignancies

International Nuclear Information System (INIS)

Georg, Petra; Georg, Dietmar; Hillbrand, Martin; Kirisits, Christian; Poetter, Richard

2006-01-01

Background and purpose: To evaluate the influence of uterus and bladder size on large and small bowel sparing with intensity modulated whole pelvic radiotherapy (IM-WPRT) in gynecologic patients. Patients and methods: Twenty patients were selected; 10 women with cervical cancer treated with definitive radiotherapy (group 'DEF') and 10 endometrial cancer patients treated postoperatively (group 'POST'). Bladder, rectal wall, small (SB) and large bowel (LB) were delineated as organs at risk. A conformal four field technique and a seven field IMRT plan (prescription dose 50.4 Gy) were compared in terms of DVH and various target parameters. Results: At doses between 40 and 50.4 Gy statistically significant improvements (P<0.05) were observed for IM-WPRT for irradiated volume of rectal wall and bladder. In both patient groups, with IMRT the average irradiated volume of SB was reduced by a factor of 6 at 50.4 Gy. This ratio was 2 for LB. In the DEF group the effect of SB-sparing with IMRT correlated with bladder size (correlation coefficient 0.70) while it did not correlate in the postoperative group. The effect of LB-sparing decreased with increasing bladder size in both groups but the impact of IMRT was larger for postoperative patients. Conclusions: IMRT significantly reduced the absolute volume of rectal wall, bladder and bowel irradiated at the prescribed dose level in gynaecologic patients. Main differences between POST and DEF patients receiving IM-WPRT were absolute volumes of LB irradiated to doses between 35 and 50 Gy, suggesting an impact of intact uterus on LB volume in the pelvis. POST patients seem to benefit most from elective nodal IMRT. Bladder filling is an important co-factor influencing the benefit of IMRT with respect to OAR sparing

Hippocampal-Sparing Whole-Brain Radiotherapy: A 'How-To' Technique Using Helical Tomotherapy and Linear Accelerator-Based Intensity-Modulated Radiotherapy

International Nuclear Information System (INIS)

Gondi, Vinai; Tolakanahalli, Ranjini; Mehta, Minesh P.; Tewatia, Dinesh; Rowley, Howard; Kuo, John S.; Khuntia, Deepak; Tome, Wolfgang A.

2010-01-01

Purpose: Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Methods and Materials: Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. Results: On average, the hippocampal avoidance volume was 3.3 cm 3 , occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy 2 using helical tomotherapy and by 81% to 0.73 Gy 2 using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Conclusion: Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

Adjuvant therapy for locally advanced renal cell cancer: A systematic review with meta-analysis

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Lima Carmen SP

2011-03-01

Full Text Available Abstract Background Many adjuvant trials have been undertaken in an attempt to reduce the risk of recurrence among patients who undergo surgical resection for locally advanced renal cancer. However, no clear benefit has been identified to date. This systematic review was conducted to examine the exact role of adjuvant therapy in renal cancer setting. Methods Randomized controlled trials were searched comparing adjuvant therapy (chemotherapy, vaccine, immunotherapy, biochemotherapy versus no active treatment after surgery among renal cell cancer patients. Outcomes were overall survival (OS, disease-free survival (DFS, and severe toxicities. Risk ratios (RR, hazard ratios (HR and 95% confidence intervals were calculated using a fixed-effects meta-analysis. Heterogeneity was measured by I2. Different strategies of adjuvant treatment were evaluated separately. Results Ten studies (2,609 patients were included. Adjuvant therapy provided no benefits in terms of OS (HR 1.07; 95%CI 0.89 to 1.28; P = 0.48 I2 = 0% or DFS (HR 1.03; 95%CI 0.87 to 1.21; P = 0.77 I2 = 15% when compared to no treatment. No subgroup analysis (immunotherapy, vaccines, biochemotherapy and hormone therapy had relevant results. Toxicity evaluation depicted a significantly higher frequency of serious adverse events in the adjuvant group. Conclusions This analysis provided no support for the hypothesis that the agents studied provide any clinical benefit for renal cancer patients although they increase the risk of toxic effects. Randomized trials are underway to test targeted therapies, which might open a new therapeutic frontier. Until these trials yield results, no adjuvant therapy can be recommended for patients who undergo surgical resection for renal cell cancer.

Intrafascial nerve-sparing endoscopic extraperitoneal radical prostatectomy.

Science.gov (United States)

Stolzenburg, Jens-Uwe; Rabenalt, Robert; Do, Minh; Schwalenberg, Thilo; Winkler, Mathias; Dietel, Anja; Liatsikos, Evangelos

2008-05-01

Based on our recently published anatomic studies, we present the most recent refinement of the endoscopic extraperitoneal radical prostatectomy (EERPE), the intrafascial nerve-sparing EERPE (nsEERPE). As part of the intrafascial technique, the dissection plane is directly on the prostatic capsule, freeing the prostate laterally from its thin surrounding fascia that contains small vessels and nerves. The technique enables puboprostatic ligament preservation, leaving intact endopelvic fascia, periprostatic fascia, and neurovascular bundles. The operation was performed in 150 patients with indications for nerve-sparing procedure. The mean operative time was 131 min (range: 50-210 min) and the mean catheterization time was 5.9 d (range: 4-20 d). Twelve months postoperatively, 94.3% of the patients were continent (no need for pads), 4.6% had minimal stress incontinence, and one patient required >2 pads/d. At the 12-mo follow-up, the potency rates (erections sufficient for intercourse with or without the use of phosphodiesterase 5 [PDE5] inhibitors) of the patients who underwent bilateral intrafascial nsEERPE were 89.7% (age: 44-55 yr), 81.1% (age: 56-65 yr), and 61.9% (age: >65 yr). Positive surgical margins in pT2 and pT3 tumors were 4.5% and 29.4%, respectively. The intrafascial nsEERPE enables the dissection of the prostate with limited trauma to the surrounding fascias and the enclosed neurovascular bundles. We propose that the preserved neurovascular bundles with intrafascial nsEERPE are more viable. The results advocate this proposition.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial.

Science.gov (United States)

Piccart-Gebhart, Martine; Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I; McCullough, Ann E; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W; Wolff, Antonio C; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D; Perez, Edith A

2016-04-01

Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2-positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2-positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. © 2015 by American Society of Clinical Oncology.

Adjuvant Chemotherapy Improves the Probability of Freedom From Recurrence in Patients With Resected Stage IB Lung Adenocarcinoma.

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Hung, Jung-Jyh; Wu, Yu-Chung; Chou, Teh-Ying; Jeng, Wen-Juei; Yeh, Yi-Chen; Hsu, Wen-Hu

2016-04-01

The benefit of adjuvant chemotherapy remains controversial for patients with stage IB non-small-cell lung cancer (NSCLC). This study investigated the effect of adjuvant chemotherapy and the predictors of benefit from adjuvant chemotherapy in patients with stage IB lung adenocarcinoma. A total of 243 patients with completely resected pathologic stage IB lung adenocarcinoma were included in the study. Predictors of the benefits of improved overall survival (OS) or probability of freedom from recurrence (FFR) from platinum-based adjuvant chemotherapy in patients with resected stage IB lung adenocarcinoma were investigated. Among the 243 patients, 70 (28.8%) had received platinum-based doublet adjuvant chemotherapy. A micropapillary/solid-predominant pattern (versus an acinar/papillary-predominant pattern) was a significantly worse prognostic factor for probability of FFR (p = 0.033). Although adjuvant chemotherapy (versus surgical intervention alone) was not a significant prognostic factor for OS (p = 0.303), it was a significant prognostic factor for a better probability of FFR (p = 0.029) on multivariate analysis. In propensity-score-matched pairs, there was no significant difference in OS between patients who received adjuvant chemotherapy and those who did not (p = 0.386). Patients who received adjuvant chemotherapy had a significantly better probability of FFR than those who did not (p = 0.043). For patients with a predominantly micropapillary/solid pattern, adjuvant chemotherapy (p = 0.033) was a significant prognostic factor for a better probability of FFR on multivariate analysis. Adjuvant chemotherapy is a favorable prognostic factor for the probability of FFR in patients with stage IB lung adenocarcinoma, particularly in those with a micropapillary/solid-predominant pattern. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

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Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

1993-04-01

In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

Further studies on the H-2 linked dependence of the adjuvant action of Brucella abortus

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Oth, D.; Sabolovic, D.

1978-01-01

The B 19S strain of Brucella abortus has been found to act as an adjuvant to the anti-sheep red blood cell (SRBC) reaction in some congenic strains of mice but not in others. If the recipient was H-2sup(b), there was no adjuvant effect (B 19S); neither was there (thymus-dependent) anti-B 19S reaction as measured by thymocyte activation and change of electrophoretic mobility. In contrast, there was a thymus-independent anti-B 19S reaction (production of haemagglutinins) as good in the H-2sup(b) mice as in the others. Experiments with T cell deprived mice showed that the adjuvant action of B 19S was thymus-dependent. As the anti-SRBC reaction without adjuvant was also thymus-dependent, it was difficult to distinguish anti-SRBC and anti-B reactions from the adjuvant action of B 19S on the anti-SRBC reaction. Several explanations are possible, all involving H-2 (Isup(r)) controlled thymus dependent mechanisms. (author)

CpG-DNA enhancement the immune elicited as adjuvant of foot- and- mouth disease vaccine

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Morshedi, A.

2010-01-01

Full Text Available In the present study the effect of the locally produced genetic adjuvant of ginea pig specific CpG-motif-containing oligodeoxynucleotide (CpG-ODN in an inactivated FMD virus vaccine was evaluated. Boosting the ginea pigs with FMD vaccine along with CpG-ODN adjuvant produced relatively higher ratio (5-fold of FMDV-specific IgG2a / IgG1 than those vaccinated in the absence of CpG-ODN. The neutralizing antibody (NA titer induced by FMD vaccine along with CpG-ODN adjuvant was significantly higher (8-fold than NA titer induced by the classical FMD vaccine in Alum adjuvant. The titer of NA and virus clearance from serum was consistently and significantly higher in animals primed with FMD vaccine and boosted by CpG-ODN than the classical FMD vaccine. The results of this study showed the potential of CpG-ODN as a genetic adjuvant to FMD vaccine in the development of Th1 responses.

Age Disparities in the Use of Steroid-sparing Therapy for Inflammatory Bowel Disease.

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Govani, Shail M; Wiitala, Wyndy L; Stidham, Ryan W; Saini, Sameer D; Hou, Jason K; Feagins, Linda A; Sussman, Jeremy B; Higgins, Peter D R; Waljee, Akbar K

2016-08-01

Corticosteroids are effective rescue therapies for patients with inflammatory bowel disease (IBD), but have significant side effects, which may be amplified in the growing population of elderly patients with IBD. We aimed to compare the use of steroids and steroid-sparing therapies (immunomodulators and biologics) and rates of complications among elderly (≥65) and younger patients in a national cohort of veterans with IBD. We used national Veterans Health Administrative data to conduct a retrospective study of veterans with IBD between 2002 and 2010. Medications and the incidence of complications were obtained from the Veterans Health Administrative Decision Support Systems. Multivariate logistic regression accounting for facility-level clustering was used to identify predictors of use of steroid-sparing medications. We identified 30,456 veterans with IBD. Of these, 94% were men and 40% were more than 65, and 32% were given steroids. Elderly veterans were less likely to receive steroids (23.8% versus 38.3%, P fracture rates increased in the elderly patients with IBD, whereas increases in venous thromboembolism and infections after starting steroids affected both age groups. Elderly veterans are less likely to receive steroids and steroid-sparing medications than younger veterans; elderly patients exposed to steroids were more likely to have fractures than the younger population.

Relationship between plasma analytes and SPARE-AD defined brain atrophy patterns in ADNI.

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Jon B Toledo

Full Text Available Different inflammatory and metabolic pathways have been associated with Alzheimeŕs disease (AD. However, only recently multi-analyte panels to study a large number of molecules in well characterized cohorts have been made available. These panels could help identify molecules that point to the affected pathways. We studied the relationship between a panel of plasma biomarkers (Human DiscoveryMAP and presence of AD-like brain atrophy patterns defined by a previously published index (SPARE-AD at baseline in subjects of the ADNI cohort. 818 subjects had MRI-derived SPARE-AD scores, of these subjects 69% had plasma biomarkers and 51% had CSF tau and Aβ measurements. Significant analyte-SPARE-AD and analytes correlations were studied in adjusted models. Plasma cortisol and chromogranin A showed a significant association that did not remain significant in the CSF signature adjusted model. Plasma macrophage inhibitory protein-1α and insulin-like growth factor binding protein 2 showed a significant association with brain atrophy in the adjusted model. Cortisol levels showed an inverse association with tests measuring processing speed. Our results indicate that stress and insulin responses and cytokines associated with recruitment of inflammatory cells in MCI-AD are associated with its characteristic AD-like brain atrophy pattern and correlate with clinical changes or CSF biomarkers.

Adjuvant Therapy: Treatment to Keep Cancer from Returning

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... significant side effects, and these treatments don't benefit everyone. Types of cancer treatment that are used as adjuvant therapy include: Chemotherapy. Chemotherapy uses drugs to kill cancer cells throughout ...

Adjuvant chemotherapy for endometrial cancer after hysterectomy

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Johnson, Nick; Bryant, Andrew; Miles, Tracie; Hogberg, Thomas; Cornes, Paul

2014-01-01

Background Endometrial adenocarcinoma (womb cancer) is a malignant growth of the lining (endometrium) of the womb (uterus). It is distinct from sarcomas (tumours of the uterine muscle). Survival depends the risk of microscopic metastases after surgery. Adjuvant (postoperative) chemotherapy improves survival from some other adenocarcinomas, and there is evidence that endometrial cancer is sensitive to cytotoxic therapy. This systematic review examines the effect of chemotherapy on survival after hysterectomy for endometrial cancer. Objectives To assess efficacy of adjuvant (postoperative) chemotherapy for endometrial cancer. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2010, Issue 3), MEDLINE and EMBASE up to August 2010, registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. Selection criteria Randomised controlled trials (RCTs) comparing adjuvant chemotherapy with any other adjuvant treatment or no other treatment. Data collection and analysis We used a random-effects meta-analysis to assess hazard ratios (HR) for overall and progression-free survival and risk ratios (RR) to compare death rates and site of initial relapse. Main results Five RCTs compared no additional treatment with additional chemotherapy after hysterectomy and radiotherapy. Four trials compared platinum based combination chemotherapy directly with radiotherapy. Indiscriminate pooling of survival data from 2197 women shows a significant overall survival advantage from adjuvant chemotherapy (RR (95% CI) = 0.88 (0.79 to 0.99)). Sensitivity analysis focused on trials of modern platinum based chemotherapy regimens and found the relative risk of death to be 0.85 ((0.76 to 0.96); number needed to treat for an additional beneficial outcome (NNT) = 25; absolute risk reduction = 4% (1% to 8%)). The HR for overall survival is 0.74 (0.64 to 0.89), significantly

A STUDY ON ADJUVANT HEAD CORING IN PATIENTS UNDERGOING LONGITUDINAL PANCREATICOJEJUNOSTOMY AND ITS AID IN PAIN REDUCTION IN CHRONIC PANCREATITIS

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Sudhansu Sekhar Mohanty

2016-07-01

operative time is increased if an adjuvant head coring was done with LPJ. The head coring is a safe procedure as both groups had comparable complication rates. But pain relief was better when an adjuvant head coring was done. Hence the surgery gives better results even if the operative time is prolonged a bit.

Adjuvant radiotherapy after radical prostatectomy: A failure of marketing-based medicine?

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Shakespeare, Thomas P.

2016-01-01

Adjuvant radiotherapy for high-risk patients after radical prostatectomy has been shown to reduce local and metastatic failure, improve overall survival and improve quality of life (QOL). The evidence, based on three randomised studies and a meta-analysis, is so compelling that the national and internatioanl professional bodies, representing urologists and radiation oncologist alike, recommend that high-risk patients be offered immediate adjuvant radiotherapy. Despite this being the standard of care, few patients fo on to recive it. This paper looks at the possibilities of why this is so, highlighting that it could possibly be related to poor marketing, communication and delivery of health information to patients and professional alike. It concludes that we need a more coordinated way to increase utilisation of the gold standard adjuvant radiotherapy post-radical prostatectomy, perhaps learning some valuable lessons from the business community.

Parenteral adjuvant potential of recombinant B subunit of Escherichia coli heat-labile enterotoxin

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Carlos Eduardo Pouey da Cunha

Full Text Available BACKGROUND The B subunit of Escherichia coli heat-labile enterotoxin (LTB is a potent mucosal immune adjuvant. However, there is little information about LTB's potential as a parenteral adjuvant. OBJECTIVES We aimed at evaluating and better understanding rLTB's potential as a parenteral adjuvant using the fused R1 repeat of Mycoplasma hyopneumoniae P97 adhesin as an antigen to characterise the humoral immune response induced by this construct and comparing it to that generated when aluminium hydroxide is used as adjuvant instead. METHODS BALB/c mice were immunised intraperitoneally with either rLTBR1 or recombinant R1 adsorbed onto aluminium hydroxide. The levels of systemic anti-rR1 antibodies (total Ig, IgG1, IgG2a, and IgA were assessed by enzyme-linked immunosorbent assay (ELISA. The ratio of IgG1 and IgG2a was used to characterise a Th1, Th2, or mixed Th1/Th2 immune response. FINDINGS Western blot confirmed rR1, either alone or fused to LTB, remained antigenic; anti-cholera toxin ELISA confirmed that LTB retained its activity when expressed in a heterologous system. Mice immunised with the rLTBR1 fusion protein produced approximately twice as much anti-rR1 immunoglobulins as mice vaccinated with rR1 adsorbed onto aluminium hydroxide. Animals vaccinated with either rLTBR1 or rR1 adsorbed onto aluminium hydroxide presented a mixed Th1/Th2 immune response. We speculate this might be a result of rR1 immune modulation rather than adjuvant modulation. Mice immunised with rLTBR1 produced approximately 1.5-fold more serum IgA than animals immunised with rR1 and aluminium hydroxide. MAIN CONCLUSIONS The results suggest that rLTB is a more powerful parenteral adjuvant than aluminium hydroxide when administered intraperitoneally as it induced higher antibody titres. Therefore, we recommend that rLTB be considered an alternative adjuvant, even if different administration routes are employed.

Adjuvant irradiation improves the outcome of patients with rectal cancer following local excision

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Chakravarti, Arnab; Willett, Christopher G.; Shellito, Paul; Kaufman, Donald; Daley, William J.

1997-01-01

PURPOSE: the long-term outcomes of patients undergoing local excision with or without pelvic irradiation were examined to define the role of adjuvant irradiation following local excision of T1 and T2 rectal cancers. METHODS: From January 1966 to January 1997, 114 patients underwent local excision for rectal cancer. Fifty-nine patients underwent local excision alone, and 55 patients received adjuvant pelvic irradiation (45 Gy to 65.8 Gy)+/-concurrent 5-fluorouracil chemotherapy. Outcome was assessed by treatment, stage, and pathologic features of tumor grade and lymphatic/venous vessel involvement. RESULTS: Of the 114 patients treated by local excision, 90 had T1/T2 tumors. The 5-year actuarial local control (LC) and recurrence-free survival (RFS) of these 90 patients are shown (with numbers of patients at risk at 5 years) in the table below. The 5-year actuarial local control and recurrence-free survival (RFS) for T1/T2 patients treated by local excision alone was 85% and 77%, respectively. The corresponding values for patients undergoing local excision and adjuvant irradiation alone were 88% and 78%, respectively. All 20 patients treated by adjuvant chemoradiation achieved 5-year actuarial local control and had a recurrence-free survival of 88%. The improved outcomes in the adjuvant radiation group become more impressive when the higher T stage distribution of this group is considered. Fifty-five percent of the group receiving adjuvant radiation were stage T2 compared to only 14% of patients treated by local excision alone. Subgroup analysis was performed on those features recognized as poor prognostic factors including poorly differentiated histology and lymphatic vascular invasion. Patients in the local excision alone group with one or more adverse pathologic features had reduced rates of local control compared to those with the absence of such features (38% vs. 91%, respectively, p=0.02). In comparison, the 5 patients with poor prognostic features treated by

Effect of adjuvants on responses to skin immunization by microneedles coated with influenza subunit vaccine.

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William C Weldon

Full Text Available Recent studies have demonstrated the effectiveness of vaccine delivery to the skin by vaccine-coated microneedles; however there is little information on the effects of adjuvants using this approach for vaccination. Here we investigate the use of TLR ligands as adjuvants with skin-based delivery of influenza subunit vaccine. BALB/c mice received 1 µg of monovalent H1N1 subunit vaccine alone or with 1 µg of imiquimod or poly(I:C individually or in combination via coated microneedle patches inserted into the skin. Poly(I:C adjuvanted subunit influenza vaccine induced similar antigen-specific immune responses compared to vaccine alone when delivered to the skin by microneedles. However, imiquimod-adjuvanted vaccine elicited higher levels of serum IgG2a antibodies and increased hemagglutination inhibition titers compared to vaccine alone, suggesting enhanced induction of functional antibodies. In addition, imiquimod-adjuvanted vaccine induced a robust IFN-γ cellular response. These responses correlated with improved protection compared to influenza subunit vaccine alone, as well as reduced viral replication and production of pro-inflammatory cytokines in the lungs. The finding that microneedle delivery of imiquimod with influenza subunit vaccine induces improved immune responses compared to vaccine alone supports the use of TLR7 ligands as adjuvants for skin-based influenza vaccines.

The role of adjuvant radiotherapy in the treatment of resectable desmoid tumors

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Goy, Barry W.; Lee, Steve P.; Eilber, Frederick; Dorey, Fred; Eckardt, Jeffrey; Fu, Yao-Shi; Juillard, Guy J. F.; Selch, Michael T.

1997-01-01

Purpose: Desmoid tumors have a high propensity for local recurrence with surgical resection. There are many reports describing good responses of desmoid tumors to irradiation, but none have clearly established the indications for adjuvant radiotherapy in treating resectable desmoid tumors. Methods and Materials: A retrospective analysis was performed on 61 patients with resectable desmoid tumor(s) who were treated at our institution from 1965 to February of 1992. Five patients had multifocal disease and are analyzed separately. Fifty-six patients had unifocal disease, of which 34 had positive surgical margins. Forty-five of the 56 patients with unifocal disease were treated with surgery alone, while 11 were treated with surgery plus adjuvant radiotherapy. Median follow-up was 6 years. Local control was measured from the last day of treatment, and all cases were reviewed by our Department of Pathology. Results: Multivariate analysis of the 56 patients with unifocal disease revealed that positive margins independently predicted for local recurrence (p ≤ 0.01). Only 3 of 22 patients with clear margins experienced a local recurrence, with a 6-year actuarial local control of 85%. Multivariate analysis of the 34 patients with positive margins revealed that adjuvant radiotherapy independently predicted for improved local control (p 0.01), and patients with recurrent disease had a slightly higher risk of local recurrence (p = 0.08). The 6-year actuarial local control determined by Kaplan-Meier for patients with unifocal disease and positive margins was 32% (±12%) with surgery alone, and 78% (±14%) with surgery plus adjuvant radiotherapy (p = 0.02). Subgroup analysis of the patients with positive margins and recurrent disease revealed that those treated with surgery alone had a 6-year actuarial local control of 0% vs. 80% for those treated with surgery plus radiotherapy (p ≤ 0.01). Patients with positive margins and primary disease had a trend towards improved local

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

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Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

2015-01-01

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

Analysis of adjuvant treatment with chemoradiation in gastric cancer

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Fallas Solis, Elias

2008-01-01

The Hospital San Juan de Dios has analyzed the benefit of patients with gastric cancer who undergo surgery after receiving adjuvant chemoradiation. A retrospective study was performed reviewing records of patients during the period 1 January 2001 to December 31, 2005. These patients have been discharged with a diagnosis of gastric cancer and have received a complete resection with curative gastric malignancy and adjuvant chemoradiation according to the protocol established by Dr. MacDonald. In the study 0116. 743 patients were discharged to Hospital San Juan de Dios, 1 in 20 has been possible to diagnose gastric cancer at early stages for a total of 28 patients. The results obtained were compared at the Hospital San Juan de Dios with those published by Dr. MacDonald. The over-life of 3 years in the chemoradiation group in Hospital San Juan de Dios has been of 42.9% and 50% in the study MacDonald. The group that has not received adjuvant the over-life in the same period has been of 20 % in HSJD and 41% in the study MacDonald, being lower percentage of patients with this over-life, but greater range of difference. [es

76 FR 12719 - Safe Schools/Healthy Students Program; Office of Safe and Drug-Free Schools; Safe Schools/Healthy...

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2011-03-08

... DEPARTMENT OF EDUCATION Safe Schools/Healthy Students Program; Office of Safe and Drug- Free Schools; Safe Schools/Healthy Students Program; Catalog of Federal Domestic Assistance (CFDA) Numbers: 84... priorities, requirements, and definitions under the Safe Schools/Healthy Students (SS/HS) program. Since...

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

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Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

ERCC1 as a biomarker for bladder cancer patients likely to benefit from adjuvant chemotherapy

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Sun, Jong-Mu; Choi, Han Yong; Lim, Ho Yeong; Sung, Ji-Youn; Park, Se Hoon; Kwon, Ghee Young; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Jo, Jisuk

2012-01-01

The role of adjuvant chemotherapy and the value of molecular biomarkers in bladder cancer have not been determined. We aimed to assess the predictive and prognostic values of excision repair cross-complementation 1 (ERCC1) in identifying appropriate patients who may potentially benefit from adjuvant chemotherapy for bladder cancer. A retrospective analysis was performed on 93 patients with completely resected transitional cell carcinoma of the bladder. ERCC1 expression was assessed by immunohistochemistry. ERCC1 expression was analyzed in 57 patients treated with adjuvant gemcitabine plus cisplatin chemotherapy and 36 who were not treated. Among 93 patients, ERCC1 expression was positive in 54 (58.1%) and negative in 39 (41.9%). ERCC1 positivity was significantly associated with longer survival (adjusted hazard ratio for death, 0.12, 95% confidence interval [CI] 0.014-0.99; P = 0.049) in the group without adjuvant chemotherapy while ERCC1 positivity was associated with shorter survival among patients who have received adjuvant chemotherapy (adjusted hazard ratio for death, 2.64; 95% CI 1.01-6.85; P = 0.047). Therefore, clinical benefit from adjuvant chemotherapy was associated with ERCC1 negativity as measured by overall survival (test for interaction, P = 0.034) and by disease-free survival (test for interaction, P = 0.20). Among patients with completely resected transitional cell carcinoma of the bladder, those with ERCC1-negative tumors seemed to benefit more from adjuvant gemcitabine plus cisplatin chemotherapy than those with ERCC1-positive tumors. Future prospective, randomized studies are warranted to confirm our findings

Adjuvant-Mediated Epitope Specificity and Enhanced Neutralizing Activity of Antibodies Targeting Dengue Virus Envelope Protein

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Denicar Lina Nascimento Fabris Maeda

2017-09-01

Full Text Available The heat-labile toxins (LT produced by enterotoxigenic Escherichia coli display adjuvant effects to coadministered antigens, leading to enhanced production of serum antibodies. Despite extensive knowledge of the adjuvant properties of LT derivatives, including in vitro-generated non-toxic mutant forms, little is known about the capacity of these adjuvants to modulate the epitope specificity of antibodies directed against antigens. This study characterizes the role of LT and its non-toxic B subunit (LTB in the modulation of antibody responses to a coadministered antigen, the dengue virus (DENV envelope glycoprotein domain III (EDIII, which binds to surface receptors and mediates virus entry into host cells. In contrast to non-adjuvanted or alum-adjuvanted formulations, antibodies induced in mice immunized with LT or LTB showed enhanced virus-neutralization effects that were not ascribed to a subclass shift or antigen affinity. Nonetheless, immunosignature analyses revealed that purified LT-adjuvanted EDIII-specific antibodies display distinct epitope-binding patterns with regard to antibodies raised in mice immunized with EDIII or the alum-adjuvanted vaccine. Notably, the analyses led to the identification of a specific EDIII epitope located in the EF to FG loop, which is involved in the entry of DENV into eukaryotic cells. The present results demonstrate that LT and LTB modulate the epitope specificity of antibodies generated after immunization with coadministered antigens that, in the case of EDIII, was associated with the induction of neutralizing antibody responses. These results open perspectives for the more rational development of vaccines with enhanced protective effects against DENV infections.

Outcomes of curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma of long bone.

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Kim, Wanlim; Han, Ilkyu; Kim, Eo Jin; Kang, Seungcheol; Kim, Han-Soo

2015-06-01

Low-grade chondrosarcoma of long bones can be treated successfully with extended intralesional curettage using adjuvants. However, there is no study reporting the use of anhydrous alcohol as an adjuvant in the treatment of low-grade chondrosarcoma. We asked (1) whether intralesional curettage and anhydrous alcohol adjuvant for low-grade chondrosarcoma is associated with good oncologic outcomes; and we report (2) the complications of the procedure. Thirty-six patients (13 men, 23 women) with a mean age of 46 years (range, 18-67 years) were treated for low-grade chondrosarcoma and followed up for a median of 62 months (range, 24-169 months). After intralesional curettage, and additional burring, anhydrous alcohol was used as an adjuvant therapy. At the time of last follow-up, there were no local recurrences or distant metastases. Six patients developed complications: 4 postoperative fractures (11%), 1 intra-articular loose body (3%) and 1 postoperative joint stiffness (3%). Anhydrous alcohol is a reasonable adjuvant for the curettage of low-grade chondrosarcoma of long bones. A long-term follow-up study is necessary, considering the slow biological progression of low-grade chondrosarcoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Rare presentation of a testicular angiofibroma treated with testis sparing surgery.

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Leone, Luca; Fulvi, Paola; Sbrollini, Giulia; Filosa, Alessandra; Caraceni, Enrico; Marronaro, Angelo; Galosi, Andrea B

2016-12-30

Testicular benign tumors are very rare (< 5%). Testicular Angiofibroma (AF) is one of those, however the gold standard of treatment and follow-up is still unclear. A 47 years-old man with only one functioning testis was referred to our clinic for a palpable right testicular mass and atrophic contralateral testis. Patient underwent testis-sparing surgery with inguinal approach and intraoperative frozen sections examination with diagnosis of AF. Final histology confirmed AF. Post-operative follow-up was uneventful. Clinical and ultrasonographic follow-up was negative after 8 months. We report a conservative surgery in a patient with AF of the solitary testis. AF is a benign para-testicular fibrous neoplasm that could be misinterpreted as malignant tumor and treated with orchiectomy. Testis-sparing surgery is recommended in this case with intraoperative pathological examination. The excision of the mass is enough but in front of a possible recurrence a long follow-up is advisable.

Rare presentation of a testicular angiofibroma treated with testis sparing surgery

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Luca Leone

2016-12-01

Full Text Available Introduction: Testicular benign tumors are very rare (< 5%. Testicular Angiofibroma (AF is one of those, however the gold standard of treatment and follow-up is still unclear. Case report: A 47 years-old man with only one functioning testis was referred to our clinic for a palpable right testicular mass and atrophic contralateral testis. Patient underwent testis-sparing surgery with inguinal approach and intraoperative frozen sections examination with diagnosis of AF. Final histology confirmed AF. Post-operative follow-up was uneventful. Clinical and ultrasonographic follow-up was negative after 8 months. Conclusion: We report a conservative surgery in a patient with AF of the solitary testis. AF is a benign para-testicular fibrous neoplasm that could be misinterpreted as malignant tumor and treated with orchiectomy. Testis-sparing surgery is recommended in this case with intraoperative pathological examination. The excision of the mass is enough but in front of a possible recurrence a long follow-up is advisable.

Efficacy of l-ornithine-l-aspartate as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy

International Nuclear Information System (INIS)

Abid, S.; Jafri, W.; Mumtaz, K.; Islam, M.; Abbas, Z.

2011-01-01

To evaluate the efficacy of L-ornithine-L-aspartate (LOLA) as an adjuvant therapy in cirrhotic patients with hepatic encephalopathy (HE). Study Design: Randomized placebo controlled study. Place and Duration of Study: The Aga Khan University Hospital, Karachi in the year 2003-2004. Methodology: Patients with HE were randomized to receive LOLA or placebo medicine as an adjuvant to treatment of HE. Number connection test-A (NCT-A), ammonia level, clinical grade of HE and duration of hospitalization were assessed. Results: Out of 120 patients, there were 62 males with mean age of 57 +- 11 years. Improvement in HE was higher (n=40, 66.7%) in LOLA group as compared to the placebo group (n=28, 46.7%, p=0.027). In patients with grade I or less encephalopathy, improvement was seen in 6 (35.3%) and 3 (20%) patients in LOLA and placebo groups respectively (p=0.667). Patients with HE grade II and above showed improvement in 34 (79.1%) and 25 (55.6%) cases in LOLA and placebo group respectively (p=0.019). On multivariate analysis patients with HE of grade II and above showed prothrombin time, creatinine level and use of LOLA influencing the outcome. Duration of hospitalization was 93.6 +- 25.7 hours and 135.2 +- 103.5 hours in LOLA and placebo groups respectively (p=0.025). No side effects were observed in either groups. Conclusion: In cirrhotic patients with advanced hepatic encephalopathy treatment with LOLA was safe and associated with relatively rapid improvement and shorter hospital stay. (author)

Cattle ranching intensification in Brazil can reduce global greenhouse gas emissions by sparing land from deforestation.

Science.gov (United States)

Cohn, Avery S; Mosnier, Aline; Havlík, Petr; Valin, Hugo; Herrero, Mario; Schmid, Erwin; O'Hare, Michael; Obersteiner, Michael

2014-05-20

This study examines whether policies to encourage cattle ranching intensification in Brazil can abate global greenhouse gas (GHG) emissions by sparing land from deforestation. We use an economic model of global land use to investigate, from 2010 to 2030, the global agricultural outcomes, land use changes, and GHG abatement resulting from two potential Brazilian policies: a tax on cattle from conventional pasture and a subsidy for cattle from semi-intensive pasture. We find that under either policy, Brazil could achieve considerable sparing of forests and abatement of GHGs, in line with its national policy targets. The land spared, particularly under the tax, is far less than proportional to the productivity increased. However, the tax, despite prompting less adoption of semi-intensive ranching, delivers slightly more forest sparing and GHG abatement than the subsidy. This difference is explained by increased deforestation associated with increased beef consumption under the subsidy and reduced deforestation associated with reduced beef consumption under the tax. Complementary policies to directly limit deforestation could help limit these effects. GHG abatement from either the tax or subsidy appears inexpensive but, over time, the tax would become cheaper than the subsidy. A revenue-neutral combination of the policies could be an element of a sustainable development strategy for Brazil and other emerging economies seeking to balance agricultural development and forest protection.

Nipple-sparing mastectomy with immediate implant reconstruction: cosmetic outcomes and technical refinements.

Science.gov (United States)

Salgarello, Marzia; Visconti, Giuseppe; Barone-Adesi, Liliana

2010-11-01

Nipple-sparing mastectomy is gaining widespread popularity, as it could allow improved aesthetic outcome without increasing oncologic risk. To investigate the reconstructive issues experienced with immediate implant reconstruction, the authors reviewed the cosmetic outcomes of their series. The authors retrospectively analyzed the data on 33 cases of nipple-sparing mastectomy for both cancer and prophylaxis with immediate implant reconstruction using the submusculo-subfascial pocket. Cosmetic evaluation methods were clinical and photography-based assessments and a patient-satisfaction survey. The average follow-up period was 26.8 months. No nipple-areola complex cancer involvement was registered. The reconstructive outcomes ranged from good to excellent in 83 percent of the cases. Patients' satisfaction was high to very high, except in one patient who experienced total nipple-areola complex loss (one breast, 2.4 percent). Overall, early minor complications were registered in four breasts (9.5 percent) and late minor complications in five cases (12 percent). The authors' series suggest that nipple-sparing mastectomy is an option for carefully selected and screened patients. Larger studies with longer follow-up are needed, however. On the whole, the immediate one-stage implant reconstruction with hyperprojected anatomical gel implants represents a valid option. The skin incision algorithm proposed, which is based on the breast size, shape, and previous scars, might aid in the decision-making process to achieve satisfying results using this procedure. The radial approaches represent a good compromise between the oncologic and reconstructive procedures.

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial

Science.gov (United States)

Holmes, Eileen; Baselga, José; de Azambuja, Evandro; Dueck, Amylou C.; Viale, Giuseppe; Zujewski, Jo Anne; Goldhirsch, Aron; Armour, Alison; Pritchard, Kathleen I.; McCullough, Ann E.; Dolci, Stella; McFadden, Eleanor; Holmes, Andrew P.; Tonghua, Liu; Eidtmann, Holger; Dinh, Phuong; Di Cosimo, Serena; Harbeck, Nadia; Tjulandin, Sergei; Im, Young-Hyuck; Huang, Chiun-Sheng; Diéras, Véronique; Hillman, David W.; Wolff, Antonio C.; Jackisch, Christian; Lang, Istvan; Untch, Michael; Smith, Ian; Boyle, Frances; Xu, Binghe; Gomez, Henry; Suter, Thomas; Gelber, Richard D.; Perez, Edith A.

2016-01-01

Background Lapatinib (L) plus trastuzumab (T) improves outcomes for metastatic human epidermal growth factor 2–positive breast cancer and increases the pathologic complete response in the neoadjuvant setting, but their role as adjuvant therapy remains uncertain. Methods In the Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization trial, patients with centrally confirmed human epidermal growth factor 2–positive early breast cancer were randomly assigned to 1 year of adjuvant therapy with T, L, their sequence (T→L), or their combination (L+T). The primary end point was disease-free survival (DFS), with 850 events required for 80% power to detect a hazard ratio (HR) of 0.8 for L+T versus T. Results Between June 2007 and July 2011, 8,381 patients were enrolled. In 2011, due to futility to demonstrate noninferiority of L versus T, the L arm was closed, and patients free of disease were offered adjuvant T. A protocol modification required P ≤ .025 for the two remaining pairwise comparisons. At a protocol-specified analysis with a median follow-up of 4.5 years, a 16% reduction in the DFS hazard rate was observed with L+T compared with T (555 DFS events; HR, 0.84; 97.5% CI, 0.70 to 1.02; P = .048), and a 4% reduction was observed with T→L compared with T (HR, 0.96; 97.5% CI, 0.80 to 1.15; P = .61). L-treated patients experienced more diarrhea, cutaneous rash, and hepatic toxicity compared with T-treated patients. The incidence of cardiac toxicity was low in all treatment arms. Conclusion Adjuvant treatment that includes L did not significantly improve DFS compared with T alone and added toxicity. One year of adjuvant T remains standard of care. PMID:26598744

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

International Nuclear Information System (INIS)

Morganti, Alessio G.; Falconi, Massimo; Stiphout, Ruud G.P.M. van; Mattiucci, Gian-Carlo; Alfieri, Sergio; Calvo, Felipe A.; Dubois, Jean-Bernard; Fastner, Gerd; Herman, Joseph M.; Maidment, Bert W.; Miller, Robert C.; Regine, William F.; Reni, Michele; Sharma, Navesh K.; Ippolito, Edy

2014-01-01

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT

Multi-institutional Pooled Analysis on Adjuvant Chemoradiation in Pancreatic Cancer

Energy Technology Data Exchange (ETDEWEB)

Morganti, Alessio G. [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Unit of Radiotherapy, Unit of General Oncology, Fondazione Giovanni Paolo II, Campobasso (Italy); Falconi, Massimo [Department of Surgery, University of Verona, Verona (Italy); Stiphout, Ruud G.P.M. van [Department of Radiation Oncology (MAASTRO), GROW, University Medical Centre Maastricht (Netherlands); Mattiucci, Gian-Carlo, E-mail: gcmattiucci@rm.unicatt.it [Department of Radiotherapy, Università Cattolica S. Cuore, Rome (Italy); Alfieri, Sergio [Department of Surgery, Università Cattolica S. Cuore, Rome (Italy); Calvo, Felipe A. [Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid (Spain); Dubois, Jean-Bernard [Département de Radiothérapie, CRLC, Montpellier Cedex (France); Fastner, Gerd [Department of Radiotherapy, PMU, Salzburg (Austria); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Maidment, Bert W. [Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Reni, Michele [Department of Oncology, S. Raffaele Scientific Institute, Milan (Italy); Sharma, Navesh K. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland (United States); Ippolito, Edy [Department of Radiation Oncology, University Campus Biomedico, Roma (Italy); and others

2014-11-15

Purpose: To determine the impact of chemoradiation therapy (CRT) on overall survival (OS) after resection of pancreatic adenocarcinoma. Methods and Materials: A multicenter retrospective review of 955 consecutive patients who underwent complete resection with macroscopically negative margins (R0-1) for invasive carcinoma (T1-4; N0-1; M0) of the pancreas was performed. Exclusion criteria included metastatic or unresectable disease at surgery, macroscopic residual disease (R2), treatment with intraoperative radiation therapy (IORT), and a histological diagnosis of no ductal carcinoma, or postoperative death (within 60 days of surgery). In all, 623 patients received postoperative radiation therapy (RT), 575 patients received concurrent chemotherapy (CT), and 462 patients received adjuvant CT. Results: Median follow-up was 21.0 months. Median OS after adjuvant CRT was 39.9 versus 24.8 months after no adjuvant CRT (P<.001) and 27.8 months after CT alone (P<.001). Five-year OS was 41.2% versus 24.8% with and without postoperative CRT, respectively. The positive impact of CRT was confirmed by multivariate analysis (hazard ratio [HR] = 0.72; confidence interval [CI], 0.60-0.87; P=.001). Adverse prognostic factors identified by multivariate analysis included the following: R1 resection (HR = 1.17; CI = 1.07-1.28; P<.001), higher pT stage (HR = 1.23; CI = 1.11-1.37; P<.001), positive lymph nodes (HR = 1.27; CI = 1.15-1.41; P<.001), and tumor diameter >20 mm (HR = 1.14; CI = 1.05-1.23; P=.002). Multivariate analysis also showed a better prognosis in patients treated in centers with >10 pancreatic resections per year (HR = 0.87; CI = 0.78-0.97; P=.014) Conclusion: This study represents the largest comparative study on adjuvant therapy in patients after resection of carcinoma of the pancreas. Overall survival was better in patients who received adjuvant CRT.

Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine.

Science.gov (United States)

Even-Or, Orli; Samira, Sarit; Rochlin, Eli; Balasingam, Shobana; Mann, Alex J; Lambkin-Williams, Rob; Spira, Jack; Goldwaser, Itzhak; Ellis, Ronald; Barenholz, Yechezkel

2010-09-07

We optimized the immunogenicity of adjuvanted seasonal influenza vaccine based on commercial split influenza virus as an antigen (hemagglutinin = HA) and on a novel polycationic liposome as a potent adjuvant and efficient antigen carrier (CCS/C-HA vaccine). The vaccine was characterized physicochemically, and the mechanism of action of CCS/C as antigen carrier and adjuvant was studied. The optimized CCS/C-HA split virus vaccine, when administered intramuscularly (i.m.), is significantly more immunogenic in mice, rats and ferrets than split virus HA vaccine alone, and it provides for protective immunity in ferrets and mice against live virus challenge that exceeds the degree of efficacy of the split virus vaccine. Similar adjuvant effects of optimized CCS/C are also observed in mice for H1N1 swine influenza antigen. The CCS/C-HA vaccine enhances immune responses via the Th1 and Th2 pathways, and it increases both the humoral responses and the production of IL-2 and IFN-γ but not of the pro-inflammatory factor TNFα. In mice, levels of CD4(+) and CD8(+) T-cells and of MHC II and CD40 co-stimulatory molecules are also elevated. Structure-function relationship studies of the CCS molecule as an adjuvant/carrier show that replacing the saturated palmitoyl acyl chain with the mono-unsaturated oleoyl (C18:1) chain affects neither size distribution and zeta potential nor immune responses in mice. However, replacing the polyalkylamine head group spermine (having two secondary amines) with spermidine (having only one secondary amine) reduces the enhancement of the immune response by ∼ 50%, while polyalkylamines by themselves are ineffective in improving the immunogenicity over the commercial HA vaccine. This highlights the importance of the particulate nature of the carrier and the polyalkylamine secondary amines in the enhancement of the immune responses against seasonal influenza. Altogether, our results suggest that the CCS/C polycationic liposomes combine the

Elucidating the mechanisms of protein antigen adsorption to the CAF/NAF liposomal vaccine adjuvant systems

DEFF Research Database (Denmark)

Hamborg, Mette; Rose, Fabrice; Jorgensen, Lene

2014-01-01

is generally known about how antigens and adjuvants interact at the molecular level. The aim of this study was to elucidate the mechanisms of interactions between the equally sized, but oppositely charged model protein antigens α-lactalbumin and lysozyme, and i) the clinically tested cationic liposomal...... antigens are presented to antigen-presenting cells, and may play an important role for the efficacy of the vaccine-induced immune response. These studies thus exemplify the importance of characterizing the molecular interactions between the vaccine antigen and adjuvant along with immunogenicity......The reverse vaccinology approach has recently resulted in the identification of promising protein antigens, which in combination with appropriate adjuvants can stimulate customized, protective immune responses. Although antigen adsorption to adjuvants influences vaccine efficacy and safety, little...

Inventory management of spare parts in an energy company

Energy Technology Data Exchange (ETDEWEB)

Guajardo, Mario; Roennqvist, Mikael; Halvorsen, Ann Mari; Kallevik, Svein Inge

2012-06-15

We address a problem of inventory management of spare parts in the context of a large energy company, producer of oil and gas. Spare parts are critical for assuring operational conditions in offshore platforms. About 200,000 different items are held in several inventory plants. The inventory system implemented at the company corresponds to a min-max system. The control parameters are decided based mainly on the expert judgment of the planners. Also, though the inventory plants can in practice be supplied from each other, the inventory planning is performed separately by the plant planners. This is because of different ownership structures where the studied company has the operative responsibility. The company is pursuing a system in which all planners conform to the same inventory management approach and evaluation, as well as being more cost efficient. Our work focuses on supporting this goal. We apply methods to decide the inventory control parameters for this system under a service level constraint. The methodology we use distinguishes unit-size and lot-size demand cases. We perform computational experiments to find control parameters for a sample of items. After the control parameters are found, we use them to explore the impact of risk pooling among the plants and inaccuracy arising from duplicate item codes.(Author)

Adjuvant therapy in renal cell carcinoma: does higher risk for recurrence improve the chance for success?

Science.gov (United States)

Figlin, R A; Leibovich, B C; Stewart, G D; Negrier, S

2018-02-01

The success of targeted therapies, including inhibitors of the vascular endothelial growth factor pathway or the mammalian target of rapamycin, in the treatment of metastatic renal cell carcinoma led to interest in testing their efficacy in the adjuvant setting. Results from the first trials are now available, with other studies due to report imminently. This review provides an overview of adjuvant targeted therapy in renal cell carcinoma, including interpretation of currently available conflicting data and future direction of research. We discuss the key differences between the completed targeted therapy adjuvant trials, and highlight the importance of accurately identifying patients who are likely to benefit from adjuvant treatment. We also consider reasons why blinded independent radiology review and treatment dose may prove critical for adjuvant treatment success. The implications of using disease-free survival as a surrogate end point for overall survival from the patient perspective and measurement of health benefit have recently been brought into focus and are discussed. Finally, we discuss how the ongoing adjuvant trials with targeted therapies and checkpoint inhibitors may improve our understanding and ability to prevent tumor recurrence after nephrectomy in the future.

Probability and Confidence Trade-space (PACT) Evaluation: Accounting for Uncertainty in Sparing Assessments

Science.gov (United States)

Anderson, Leif; Box, Neil; Carter, Katrina; DiFilippo, Denise; Harrington, Sean; Jackson, David; Lutomski, Michael

2012-01-01

There are two general shortcomings to the current annual sparing assessment: 1. The vehicle functions are currently assessed according to confidence targets, which can be misleading- overly conservative or optimistic. 2. The current confidence levels are arbitrarily determined and do not account for epistemic uncertainty (lack of knowledge) in the ORU failure rate. There are two major categories of uncertainty that impact Sparing Assessment: (a) Aleatory Uncertainty: Natural variability in distribution of actual failures around an Mean Time Between Failure (MTBF) (b) Epistemic Uncertainty : Lack of knowledge about the true value of an Orbital Replacement Unit's (ORU) MTBF We propose an approach to revise confidence targets and account for both categories of uncertainty, an approach we call Probability and Confidence Trade-space (PACT) evaluation.

Tocotrienols are good adjuvants for developing cancer vaccines

Directory of Open Access Journals (Sweden)

Radhakrishnan Ammu

2010-01-01

Full Text Available Abstract Background Dendritic cells (DCs have the potential for cancer immunotherapy due to their ability to process and present antigens to T-cells and also in stimulating immune responses. However, DC-based vaccines have only exhibited minimal effectiveness against established tumours in mice and humans. The use of appropriate adjuvant enhances the efficacy of DC based cancer vaccines in treating tumours. Methods In this study we have used tocotrienol-rich fraction (TRF, a non-toxic natural compound, as an adjuvant to enhance the effectiveness of DC vaccines in treating mouse mammary cancers. In the mouse model, six-week-old female BALB/c mice were injected subcutaneously with DC and supplemented with oral TRF daily (DC+TRF and DC pulsed with tumour lysate from 4T1 cells (DC+TL. Experimental mice were also injected with DC pulsed with tumour lysate and supplemented daily with oral TRF (DC+TL+TRF while two groups of animal which were supplemented daily with carrier oil (control and with TRF (TRF. After three times vaccination, mice were inoculated with 4T1 cells in the mammary breast pad to induce tumour. Results Our study showed that TRF in combination with DC pulsed with tumour lysate (DC+TL+TRF injected subcutaneously significantly inhibited the growth of 4T1 mammary tumour cells as compared to control group. Analysis of cytokines production from murine splenocytes showed significant increased productions of IFN-γ and IL-12 in experimental mice (DC+TL+TRF compared to control, mice injected with DC without TRF, mice injected with DC pulsed with tumour lysate and mice supplemented with TRF alone. Higher numbers of cytotoxic T cells (CD8 and natural killer cells (NK were observed in the peripheral blood of TRF adjuvanted DC pulsed tumour lysate mice. Conclusion Our study show that TRF has the potential to be an adjuvant to augment DC based immunotherapy.

Retroperitoneal liposarcoma; The role of adjuvant radiation therapy and the prognostic factors

Energy Technology Data Exchange (ETDEWEB)

Lee, Hong Seok; Yu, Jeong Il; Lim, Do Hoon; Kim, Sung Joo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

2016-09-15

To evaluate the benefit of adjuvant radiation therapy (RT) for retroperitoneal liposarcoma (RPLS) following gross tumor removal. We reviewed 77 patients with primary RPLS surgically treated between January 2000 and December 2013. Cases with gross residual disease were excluded. Tumor grade was evaluated according to the French Federation of Cancer Centers Sarcoma Group (FNCLCC) system. Adjuvant RT was delivered to 32 patients (42%) using external beam RT alone. Median follow-up time was 36 months (range, 5 to 169). Among 77 patients, 33 (43%) presented with well-differentiated, 31 (40%) with de-differentiated, 8 (10%) with myxoid/round and 4 (5%) with pleomorphic morphology. The RT group included less well-differentiated subtype than surgery group (28% vs. 53%). During follow up, 34 patients (44%) showed local recurrence. Local recurrence rate was lower in the RT group (38%) compared to the surgery group (49%). The 3-year local control rate (LC) was 55.6%, and the 3-year overall survival (OS) was 82.1%. Tumor histology and FNCLCC grade were significantly associated with local recurrence. There was no statistical significance of adding adjuvant RT in LC (p = 0.312). However, patients with tumor histology other than well-differentiated subtype showed marginally decreased local recurrence rate after adjuvant RT (3-year LC, RT 43.9% vs. no RT 35.3%; p = 0.087). RPLS patients receiving RT experienced less local recurrence. We suggest that the addition of adjuvant RT may be related to improvement of LCs, especially in patients with non-favorable histologic subtypes.

Silica nanoparticles as the adjuvant for the immunisation of mice using hepatitis B core virus-like particles.

Directory of Open Access Journals (Sweden)

Dace Skrastina

Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.

Saponin-based adjuvants induce cross-presentation in dendritic cells by intracellular lipid body formation