Sample records for targeted treatment modalities

  1. Treatment of sentence comprehension and production in aphasia: is there cross-modal generalisation?

    PubMed

    Adelt, Anne; Hanne, Sandra; Stadie, Nicole

    2016-09-09

    Exploring generalisation following treatment of language deficits in aphasia can provide insights into the functional relation of the cognitive processing systems involved. In the present study, we first review treatment outcomes of interventions targeting sentence processing deficits and, second report a treatment study examining the occurrence of practice effects and generalisation in sentence comprehension and production. In order to explore the potential linkage between processing systems involved in comprehending and producing sentences, we investigated whether improvements generalise within (i.e., uni-modal generalisation in comprehension or in production) and/or across modalities (i.e., cross-modal generalisation from comprehension to production or vice versa). Two individuals with aphasia displaying co-occurring deficits in sentence comprehension and production were trained on complex, non-canonical sentences in both modalities. Two evidence-based treatment protocols were applied in a crossover intervention study with sequence of treatment phases being randomly allocated. Both participants benefited significantly from treatment, leading to uni-modal generalisation in both comprehension and production. However, cross-modal generalisation did not occur. The magnitude of uni-modal generalisation in sentence production was related to participants' sentence comprehension performance prior to treatment. These findings support the assumption of modality-specific sub-systems for sentence comprehension and production, being linked uni-directionally from comprehension to production.

  2. Evaluation of target coverage and margins adequacy during CyberKnife Lung Optimized Treatment.

    PubMed

    Ricotti, Rosalinda; Seregni, Matteo; Ciardo, Delia; Vigorito, Sabrina; Rondi, Elena; Piperno, Gaia; Ferrari, Annamaria; Zerella, Maria Alessia; Arculeo, Simona; Francia, Claudia Maria; Sibio, Daniela; Cattani, Federica; De Marinis, Filippo; Spaggiari, Lorenzo; Orecchia, Roberto; Riboldi, Marco; Baroni, Guido; Jereczek-Fossa, Barbara Alicja

    2018-04-01

    Evaluation of target coverage and verification of safety margins, in motion management strategies implemented by Lung Optimized Treatment (LOT) module in CyberKnife system. Three fiducial-less motion management strategies provided by LOT can be selected according to tumor visibility in the X ray images acquired during treatment. In 2-view modality the tumor is visible in both X ray images and full motion tracking is performed. In 1-view modality the tumor is visible in a single X ray image, therefore, motion tracking is combined with an internal target volume (ITV)-based margin expansion. In 0-view modality the lesion is not visible, consequently the treatment relies entirely on an ITV-based approach. Data from 30 patients treated in 2-view modality were selected providing information on the three-dimensional tumor motion in correspondence to each X ray image. Treatments in 1-view and 0-view modalities were simulated by processing log files and planning volumes. Planning target volume (PTV) margins were defined according to the tracking modality: end-exhale clinical target volume (CTV) + 3 mm in 2-view and ITV + 5 mm in 0-view. In the 1-view scenario, the ITV encompasses only tumor motion along the non-visible direction. Then, non-uniform ITV to PTV margins were applied: 3 mm and 5 mm in the visible and non-visible direction, respectively. We defined the coverage of each voxel of the CTV as the percentage of X ray images where such voxel was included in the PTV. In 2-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the predicted target position, as recorded in log files. In 1-view modality, coverage was calculated as the intersection between the CTV centred on the imaged target position and the PTV centred on the projected predictor data. In 0-view modality coverage was calculated as the intersection between the CTV centred on the imaged target position and the non

  3. Antibody Drug Conjugates: Application of Quantitative Pharmacology in Modality Design and Target Selection.

    PubMed

    Sadekar, S; Figueroa, I; Tabrizi, M

    2015-07-01

    Antibody drug conjugates (ADCs) are a multi-component modality comprising of an antibody targeting a cell-specific antigen, a potent drug/payload, and a linker that can be processed within cellular compartments to release payload upon internalization. Numerous ADCs are being evaluated in both research and clinical settings within the academic and pharmaceutical industry due to their ability to selectively deliver potent payloads. Hence, there is a clear need to incorporate quantitative approaches during early stages of drug development for effective modality design and target selection. In this review, we describe a quantitative approach and framework for evaluation of the interplay between drug- and systems-dependent properties (i.e., target expression, density, localization, turnover, and affinity) in order to deliver a sufficient amount of a potent payload into the relevant target cells. As discussed, theoretical approaches with particular considerations given to various key properties for the target and modality suggest that delivery of the payload into particular effect cells to be more sensitive to antigen concentrations for targets with slow turnover rates as compared to those with faster internalization rates. Further assessments also suggest that increasing doses beyond the threshold of the target capacity (a function of target internalization and expression) may not impact the maximum amount of payload delivered to the intended effect cells. This article will explore the important application of quantitative sciences in selection of the target and design of ADC modalities.

  4. Differences in Funding Sources of Phase III Oncology Clinical Trials by Treatment Modality and Cancer Type.

    PubMed

    Jairam, Vikram; Yu, James B; Aneja, Sanjay; Wilson, Lynn D; Lloyd, Shane

    2017-06-01

    Given the limited resources available to conduct clinical trials, it is important to understand how trial sponsorship differs among different therapeutic modalities and cancer types and to consider the ramifications of these differences. We searched clinicaltrials.gov for a cross-sectional register of active, phase III, randomized controlled trials (RCTs) studying treatment-related endpoints such as survival and recurrence for the 24 most prevalent malignancies. We classified the RCTs into 7 categories of therapeutic modality: (1) chemotherapy/other cancer-directed drugs, (2) targeted therapy, (3) surgery, (4) radiation therapy (RT), (5) RT with other modalities, (6) multimodality therapy without RT, and (7) other. RCTs were categorized as being funded by one or more of the following groups: (1) government, (2) hospital/university, (3) industry, and (4) other. χ analysis was performed to detect differences in funding source distribution between modalities and cancer types. The percentage of multimodality trials (5%) and radiation RCTs (4%) funded by industry was less than that for chemotherapy (32%, P<0.01) or targeted therapy (48%, P<0.01). Trials studying targeted therapy were less likely to have hospital/university funding than any of the other modalities (P<0.01 in each comparison). Trials of chemotherapy were more likely to be funded by industry if they also studied targeted therapy (P<0.01). RCTs studying targeted therapies are more likely to be funded by industry than trials studying multimodality therapy or radiation. The impact of industry funding versus institutional or governmental sources of funding for cancer research is unclear and requires further study.

  5. Treatment modalities and evaluation models for periodontitis

    PubMed Central

    Tariq, Mohammad; Iqbal, Zeenat; Ali, Javed; Baboota, Sanjula; Talegaonkar, Sushama; Ahmad, Zulfiqar; Sahni, Jasjeet K

    2012-01-01

    Periodontitis is the most common localized dental inflammatory disease related with several pathological conditions like inflammation of gums (gingivitis), degeneration of periodontal ligament, dental cementum and alveolar bone loss. In this perspective, the various preventive and treatment modalities, including oral hygiene, gingival irrigations, mechanical instrumentation, full mouth disinfection, host modulation and antimicrobial therapy, which are used either as adjunctive treatments or as stand-alone therapies in the non-surgical management of periodontal infections, have been discussed. Intra-pocket, sustained release systems have emerged as a novel paradigm for the future research. In this article, special consideration is given to different locally delivered anti-microbial and anti inflammatory medications which are either commercially available or are currently under consideration for Food and Drug Administration (FDA) approval. The various in vitro dissolution models and microbiological strain investigated to impersonate the infected and inflamed periodontal cavity and to predict the in vivo performance of treatment modalities have also been thrashed out. Animal models that have been employed to explore the pathology at the different stages of periodontitis and to evaluate its treatment modalities are enlightened in this proposed review. PMID:23373002

  6. Continuation of Weight Loss Treatment Is Associated with the Number of Self-Selected Treatment Modalities

    ERIC Educational Resources Information Center

    Martin, Corby K.; Drab-Hudson, Danae L.; York-Crowe, Emily; Mayville, Stephen B.; Yu, Ying; Greenway, Frank L.

    2007-01-01

    Behavior therapy is a cornerstone of weight loss treatment and behaviorists help direct patients' treatment. A novel design was used that allowed participants to choose different treatment modalities during behavioral weight loss treatment. The association between the selection of different treatment modalities and program completion was examined…

  7. Equivalence in Dose Fall-Off for Isocentric and Nonisocentric Intracranial Treatment Modalities and Its Impact on Dose Fractionation Schemes

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

    Ma Lijun, E-mail: lijunma@radonc.ucsf.ed; Sahgal, Arjun; Descovich, Martina

    2010-03-01

    Purpose: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. Methods and Materials: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1more » to 30) was studied for the three modalities. Results: The derived model fitted remarkably well for all the cases (R{sup 2} > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. Conclusion: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.« less

  8. "Combo" nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy.

    PubMed

    Kemp, Jessica A; Shim, Min Suk; Heo, Chan Yeong; Kwon, Young Jik

    2016-03-01

    The dynamic and versatile nature of diseases such as cancer has been a pivotal challenge for developing efficient and safe therapies. Cancer treatments using a single therapeutic agent often result in limited clinical outcomes due to tumor heterogeneity and drug resistance. Combination therapies using multiple therapeutic modalities can synergistically elevate anti-cancer activity while lowering doses of each agent, hence, reducing side effects. Co-administration of multiple therapeutic agents requires a delivery platform that can normalize pharmacokinetics and pharmacodynamics of the agents, prolong circulation, selectively accumulate, specifically bind to the target, and enable controlled release in target site. Nanomaterials, such as polymeric nanoparticles, gold nanoparticles/cages/shells, and carbon nanomaterials, have the desired properties, and they can mediate therapeutic effects different from those generated by small molecule drugs (e.g., gene therapy, photothermal therapy, photodynamic therapy, and radiotherapy). This review aims to provide an overview of developing multi-modal therapies using nanomaterials ("combo" nanomedicine) along with the rationale, up-to-date progress, further considerations, and the crucial roles of interdisciplinary approaches. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Treatment modalities of palmoplantar lichen planus: a brief review.

    PubMed

    Feily, Amir; Yaghoobi, Reza; Nilforoushzadeh, Mohammad Ali

    2016-12-01

    Palmoplantar lichen planus is a localized and uncommon variant of lichen planus which is mostly resistant to treatment. Our purpose was to discuss all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. A systematic review of the literature was conducted to evaluate evidence regarding all treatment modalities proposed and tested for palmoplantar lichen planus in the literature. Two major databases (PubMed, Google scholar) were searched. The review included all case reports, letters and original articles reporting any treatment for palmoplantar lichen planus but not treatment used in the other type of lichen planus, generalized lichen planus or other type of palmoplantar dermatoses. We have gone over more than 50 articles. There are many drugs that have been used in the treatment of lichen planus and generalized lichen planus but the palmoplantar type is a rare variety of lichen planus. That is why we could not find any clinical trial on the subject and just case reports have been described in this manuscript. In spite of plentiful investigations carried out on lichen planus, there is no treatment modality that has proved to be utterly satisfactory in treatment of palmoplantar lichen planus.

  10. Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

    NASA Technical Reports Server (NTRS)

    Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

    1994-01-01

    Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

  11. A tri-modality image fusion method for target delineation of brain tumors in radiotherapy.

    PubMed

    Guo, Lu; Shen, Shuming; Harris, Eleanor; Wang, Zheng; Jiang, Wei; Guo, Yu; Feng, Yuanming

    2014-01-01

    To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors. A new method of tri-modality image fusion was developed, which can fuse and display all image sets in one panel and one operation. And a feasibility study in gross tumor volume (GTV) delineation using data from three patients with brain tumors was conducted, which included images of simulation CT, MRI, and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) examinations before radiotherapy. Tri-modality image fusion was implemented after image registrations of CT+PET and CT+MRI, and the transparency weight of each modality could be adjusted and set by users. Three radiation oncologists delineated GTVs for all patients using dual-modality (MRI/CT) and tri-modality (MRI/CT/PET) image fusion respectively. Inter-observer variation was assessed by the coefficient of variation (COV), the average distance between surface and centroid (ADSC), and the local standard deviation (SDlocal). Analysis of COV was also performed to evaluate intra-observer volume variation. The inter-observer variation analysis showed that, the mean COV was 0.14(± 0.09) and 0.07(± 0.01) for dual-modality and tri-modality respectively; the standard deviation of ADSC was significantly reduced (p<0.05) with tri-modality; SDlocal averaged over median GTV surface was reduced in patient 2 (from 0.57 cm to 0.39 cm) and patient 3 (from 0.42 cm to 0.36 cm) with the new method. The intra-observer volume variation was also significantly reduced (p = 0.00) with the tri-modality method as compared with using the dual-modality method. With the new tri-modality image fusion method smaller inter- and intra-observer variation in GTV definition for the brain tumors can be achieved, which improves the consistency and accuracy for target delineation in individualized radiotherapy.

  12. Pathogenesis and treatment modalities of localized scleroderma.

    PubMed

    Valančienė, Greta; Jasaitienė, Daiva; Valiukevičienė, Skaidra

    2010-01-01

    Localized scleroderma is a chronic inflammatory disease primarily of the dermis and subcutaneous fat that ultimately leads to a scar-like sclerosis of connective tissue. The disorder manifests as various plaques of different shape and size with signs of skin inflammation, sclerosis, and atrophy. This is a relatively rare inflammatory disease characterized by a chronic course, unknown etiology, and insufficiently clear pathogenesis. Many factors may influence its appearance: trauma, genetic factors, disorders of the immune system or hormone metabolism, viral infections, toxic substances or pharmaceutical agents, neurogenic factors, and Borrelia burgdorferi infection. Various therapeutic modalities are being used for the treatment of localized scleroderma. There is no precise treatment scheme for this disease. A majority of patients can be successfully treated with topical pharmaceutical agents and phototherapy, but some of them with progressive, disseminated, and causing disability localized scleroderma are in need of systemic treatment. The aim of this article is not only to dispute about the clinical and morphological characteristics of localized scleroderma, but also to present the newest generalized data about the possible origin, pathogenesis, and treatment modalities of this disease.

  13. Current and Under Development Treatment Modalities of Psoriasis: A Review.

    PubMed

    Albaghdadi, Abdullah

    2017-01-01

    Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are

  14. Combined-modality treatment of solid tumors using radiotherapy and molecular targeted agents.

    PubMed

    Ma, Brigette B Y; Bristow, Robert G; Kim, John; Siu, Lillian L

    2003-07-15

    Molecular targeted agents have been combined with radiotherapy (RT) in recent clinical trials in an effort to optimize the therapeutic index of RT. The appeal of this strategy lies in their potential target specificity and clinically acceptable toxicity. This article integrates the salient, published research findings into the underlying molecular mechanisms, preclinical efficacy, and clinical applicability of combining RT with molecular targeted agents. These agents include inhibitors of intracellular signal transduction molecules, modulators of apoptosis, inhibitors of cell cycle checkpoints control, antiangiogenic agents, and cyclo-oxygenase-2 inhibitors. Molecular targeted agents can have direct effects on the cytoprotective and cytotoxic pathways implicated in the cellular response to ionizing radiation (IR). These pathways involve cellular proliferation, DNA repair, cell cycle progression, nuclear transcription, tumor angiogenesis, and prostanoid-associated inflammation. These pathways can also converge to alter RT-induced apoptosis, terminal growth arrest, and reproductive cell death. Pharmacologic modulation of these pathways may potentially enhance tumor response to RT though inhibition of tumor repopulation, improvement of tumor oxygenation, redistribution during the cell cycle, and alteration of intrinsic tumor radiosensitivity. Combining RT and molecular targeted agents is a rational approach in the treatment of solid tumors. Translation of this approach from promising preclinical data to clinical trials is actively underway.

  15. Characterizing smoking, cessation services, and quit interest across outpatient substance abuse treatment modalities

    PubMed Central

    McClure, Erin A.; Acquavita, Shauna P.; Dunn, Kelly E.; Stoller, Kenneth B.; Stitzer, Maxine L.

    2013-01-01

    The majority of individuals seeking treatment for substance use disorders are cigarette smokers, yet smoking cessation is rarely addressed during treatment. Conducting a detailed smoking-related characterization of substance abuse treatment patients across treatment modalities may facilitate the development of tailored treatment strategies. This study administered a battery of self-report instruments to compare tobacco use, quit attempts, smoking knowledge and attitudes, program services, and interest in quitting among smoking patients enrolled in opioid replacement therapy (ORT) vs. non-opioid replacement (non-ORT). ORT compared with non-ORT participants smoked more heavily, had greater tobacco dependence, and endorsed greater exposure to smoking cessation services at their treatment programs. Favorable attitudes towards cessation during treatment were found within both groups. These data identify several potential clinical targets, most notably including confidence in abstaining and attitudes toward cessation pharmacotherapies that may be addressed by substance abuse treatment clinics. PMID:23988192

  16. Dosimetric comparison of different treatment modalities for stereotactic radiotherapy.

    PubMed

    Hsu, Shih-Ming; Lai, Yuan-Chun; Jeng, Chien-Chung; Tseng, Chia-Ying

    2017-09-16

    The modalities for performing stereotactic radiotherapy (SRT) on the brain include the cone-based linear accelerator (linac), the flattening filter-free (FFF) volumetric modulated arc therapy (VMAT) linac, and tomotherapy. In this study, the cone-based linac, FFF-VMAT linac, and tomotherapy modalities were evaluated by measuring the differences in doses delivered during brain SRT and experimentally assessing the accuracy of the output radiation doses through clinical measurements. We employed a homemade acrylic dosimetry phantom representing the head, within which a thermoluminescent dosimeter (TLD) and radiochromic EBT3 film were installed. Using the conformity/gradient index (CGI) and Paddick methods, the quality of the doses delivered by the various SRT modalities was evaluated. The quality indicators included the uniformity, conformity, and gradient indices. TLDs and EBT3 films were used to experimentally assess the accuracy of the SRT dose output. The dose homogeneity indices of all the treatment modalities were lower than 1.25. The cone-based linac had the best conformity for all tumors, regardless of the tumor location and size, followed by the FFF-VMAT linac; tomography was the worst-performing treatment modality in this regard. The cone-based linac had the best gradient, regardless of the tumor location and size, whereas the FFF-VMAT linac had a better gradient than tomotherapy for a large tumor diameter (28 mm). The TLD and EBT3 measurements of the dose at the center of tumors indicated that the average difference between the measurements and the calculated dose was generally less than 4%. When the 3% 3-mm gamma passing rate metric was used, the average passing rates of all three treatment modalities exceeded 98%. Regarding the dose, the cone-based linac had the best conformity and steepest dose gradient for tumors of different sizes and distances from the brainstem. The results of this study suggest that SRT should be performed using the cone

  17. Molecular targeted therapy for the treatment of gastric cancer.

    PubMed

    Xu, Wenting; Yang, Zhen; Lu, Nonghua

    2016-01-04

    Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

  18. Combined treatment modalities for age related macular degeneration.

    PubMed

    Das, R A; Romano, A; Chiosi, F; Menzione, M; Rinaldi, M

    2011-02-01

    Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of

  19. SU-F-T-27: A Comparative Case Study Among Four Modalities for the Superficial Treatment of Squamous Cell Carcinoma

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

    Ashenafi, M; Koch, N; Peng, J

    Purpose: We performed a comparative planning study among High Dose Rate (HDR) brachytherapy, superficial electrons, Volume Modulated Arc Therapy (VMAT), and Helical IMRT (Tomotherapy) for squamous cell carcinoma of the abdominal wall with consideration for the underlining bowel. Methods: A 69-year old female presented with squamous cell carcinoma protruding 8mm beyond the anterior skin surface of the midabdomen was considered for treatment. The patient had a ventral hernia which resulted in the reduction of the abdominal wall thickness and the adjacent small bowel being the dose limiting structure. Four plans were generated using different treatment modalities: a) an enface electronmore » field (eMC, Eclipse v. 11), b) Tomotherapy (HI-Art II v.5.0.5), c) VMAT (Acuros, Eclipse v. 11), and d) HDR using a Freiburg applicator (Oncentra v. 4.3). The following plan objectives were used for all four plans: for the CTV target, V90% ≥90% (61.8Gy2/2).For the small bowel, D0.1cc < 56.2 Gy2/2 was a hard constraint and expressed as a percentage of the prescription for comparison to demonstrate the dose fall-off achieved among the modalities.For HDR, V200% <0.1cc was an additional constraint. Multiple dosimetric parameters, including those listed above, were compared among the four modalities. Results: The HDR plan showed comparable target coverage compared to the Tomotherapy plan and better coverage compared to the electron plan. Small bowel doses (D0.1cc) were lower in HDR plan compared to Tomotherapy, electron, & VMAT plans (88.8%, 89.6%, 90.9%, & 96.6%). Integral dose to the whole body (V5%) was much higher for HDR, VMAT, and Tomotherapy when compared to electron plan by factors of seven, eight, and ten, respectively. After reviewing all treatment modalities, the physician selected HDR owing to better control of the small bowel dose while maintaining adequate target coverage. Conclusion: This case study demonstrated HDR can successfully treat superficial lesions with

  20. Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research*

    PubMed Central

    Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A.; Cheung, Alfred K.; Brunelli, Steve; Heagerty, Patrick J.; Katz, Ronit; Molnar, Miklos Z.; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

    2015-01-01

    Background The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. Methods This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007–2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Results Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. Conclusions This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. PMID:25883196

  1. Molecular Platform for Design and Synthesis of Targeted Dual-Modality Imaging Probes

    PubMed Central

    2015-01-01

    We report a versatile dendritic structure based platform for construction of targeted dual-modality imaging probes. The platform contains multiple copies of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) branching out from a 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) core. The specific coordination chemistries of the NOTA and DOTA moieties offer specific loading of 68/67Ga3+ and Gd3+, respectively, into a common molecular scaffold. The platform also contains three amino groups which can potentiate targeted dual-modality imaging of PET/MRI or SPECT/MRI (PET: positron emission tomography; SPECT: single photon emission computed tomography; MRI: magnetic resonance imaging) when further functionalized by targeting vectors of interest. To validate this design concept, a bimetallic complex was synthesized with six peripheral Gd-DOTA units and one Ga-NOTA core at the center, whose ion T1 relaxivity per gadolinium atom was measured to be 15.99 mM–1 s–1 at 20 MHz. Further, the bimetallic agent demonstrated its anticipated in vivo stability, tissue distribution, and pharmacokinetic profile when labeled with 67Ga. When conjugated with a model targeting peptide sequence, the trivalent construct was able to visualize tumors in a mouse xenograft model by both PET and MRI via a single dose injection. PMID:25615011

  2. Predictors of treatment with dialysis modalities in observational studies for comparative effectiveness research.

    PubMed

    Kuttykrishnan, Sooraj; Kalantar-Zadeh, Kamyar; Arah, Onyebuchi A; Cheung, Alfred K; Brunelli, Steve; Heagerty, Patrick J; Katz, Ronit; Molnar, Miklos Z; Nissenson, Allen; Ravel, Vanessa; Streja, Elani; Himmelfarb, Jonathan; Mehrotra, Rajnish

    2015-07-01

    The Institute of Medicine has identified the comparative effectiveness of renal replacement therapies as a kidney-related topic among the top 100 national priorities. Given the importance of ensuring internal and external validity, the goal of this study was to identify potential sources of bias in observational studies that compare outcomes with different dialysis modalities. This observational cohort study used data from the electronic medical records of all patients that started maintenance dialysis in the calendar years 2007-2011 and underwent treatment for at least 60 days in any of the 2217 facilities operated by DaVita Inc. Each patient was assigned one of six dialysis modalities for each 91-day period from the date of first dialysis (thrice weekly in-center hemodialysis (HD), peritoneal dialysis (PD), less-frequent HD, home HD, frequent HD and nocturnal in-center HD). Of the 162 644 patients, 18% underwent treatment with a modality other than HD for at least one 91-day period. Except for PD, patients started treatment with alternative modalities after variable lengths of treatment with HD; the time until a change in modality was shortest for less-frequent HD (median time = 6 months) and longest for frequent HD (median time = 15 months). Between 30 and 78% of patients transferred to another dialysis facility prior to change in modality. Finally, there were significant differences in baseline and time-varying clinical characteristics associated with dialysis modality. This analysis identified numerous potential sources of bias in studies of the comparative effectiveness of dialysis modalities. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  3. Cross-modal versus within-modal recall: differences in behavioral and brain responses.

    PubMed

    Butler, Andrew J; James, Karin H

    2011-10-31

    Although human experience is multisensory in nature, previous research has focused predominantly on memory for unisensory as opposed to multisensory information. In this work, we sought to investigate behavioral and neural differences between the cued recall of cross-modal audiovisual associations versus within-modal visual or auditory associations. Participants were presented with cue-target associations comprised of pairs of nonsense objects, pairs of nonsense sounds, objects paired with sounds, and sounds paired with objects. Subsequently, they were required to recall the modality of the target given the cue while behavioral accuracy, reaction time, and blood oxygenation level dependent (BOLD) activation were measured. Successful within-modal recall was associated with modality-specific reactivation in primary perceptual regions, and was more accurate than cross-modal retrieval. When auditory targets were correctly or incorrectly recalled using a cross-modal visual cue, there was re-activation in auditory association cortex, and recall of information from cross-modal associations activated the hippocampus to a greater degree than within-modal associations. Findings support theories that propose an overlap between regions active during perception and memory, and show that behavioral and neural differences exist between within- and cross-modal associations. Overall the current study highlights the importance of the role of multisensory information in memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Current concepts for the combined treatment modality of ionizing radiation with anticancer agents.

    PubMed

    Oehler, Christoph; Dickinson, Daniel J; Broggini-Tenzer, Angela; Hofstetter, Barbara; Hollenstein, Andreas; Riesterer, Oliver; Vuong, Van; Pruschy, Martin

    2007-01-01

    In current applied radiobiology, there exists a tremendous effort in basic and translational research to identify novel treatment modalities combining ionizing radiation with anticancer agents. This is mainly due to the highly improved molecular understanding of intrinsic radioresistance and the profiling of cellular stress responses to irradiation during recent years. Ionizing radiation not only damages DNA but also affects multiple cellular components that induce a multi-layered stress response. The treatment responses can be restricted to the individual cell level but might also be part of an intercellular stress communication network. Both DNA damage-induced signaling (which results in cell cycle arrest and induction of the DNA-repair machinery) and also ionizing radiation-induced signal transduction cascades, which are generated at cellular sites distant from and independent of DNA-damage, represent interesting targets for anticancer treatment modalities to sensitize for ionizing radiation. Due to the lack of molecular knowledge classic radiobiology assembled the cellular and tissue responses into four groups (4 R's of radiotherapy) which describe biological factors influencing the treatment response to fractionated radiotherapy. These classic 4 R's are Repair, Reassortment, Repopulation and Reoxygenation. With the tremendous progress in molecular oncology we now begin to understand theses factors on the molecular level. At the same time this classification may guide modern molecular radiobiologists to identify novel pharmaceuticals and antisignaling agents which can modulate the treatment response to irradiation. In this review we describe current approaches to sensitize tumor cells with novel anticancer agents along the lines of these 4 R's.

  5. Comparative analysis of success of psoriasis treatment with standard therapeutic modalities and balneotherapy.

    PubMed

    Baros, Duka Ninković; Gajanin, Vesna S; Gajanin, Radoslav B; Zrnić, Bogdan

    2014-01-01

    Psoriasis is a chronic, inflammatory, immune-mediated skin disease. In addition to standard therapeutic modalities (antibiotics, cytostatics, phototherapy, photochemotherapy and retinoids), nonstandard methods can be used in the treatment of psoriasis. This includes balneotherapy which is most commonly used in combination with therapeutic resources. The aim of this research was to determine the length of remission of psoriasis in patients treated with standard therapeutic modalities, balneotherapy, and combined treatment (standard therapeutic modalities and balneotherapy). The study analyzed 60 adult patients, of both sexes, with different clinical forms of psoriasis, who were divided into three groups according to the applied therapeutic modalities: the first group (treated with standard therapeutic modalities), the second group (treated with balneotherapy) and the third group (treated with combined therapy-standard methods therapy and balneotherapy). The Psoriasis Area and Severity Index was determined in first, third and sixth week of treatment for all patients. The following laboratory analysis were performed and monitored: C reactive protein, iron with total iron binding capacity, unsaturated iron binding capacity and ferritin, uric acid, rheumatoid factors and antibodies to streptolysin O in the first and sixth week of treatment. The average length of remission in patients treated with standard therapeutic modalities and in those treated with balneotherapy was 1.77 +/- 0.951 months and 1.79 +/- 0.918 months, respectively. There was a statistically significant difference in the duration of remission between the patients treated with combination therapy and patients treated with standard therapeutic modalities (p = 0.019) and balneotherapy (p = 0.032). The best results have been achieved when the combination therapy was administered.

  6. Targeting the Hippo Pathway Is a New Potential Therapeutic Modality for Malignant Mesothelioma.

    PubMed

    Sekido, Yoshitaka

    2018-03-22

    Malignant mesothelioma (MM) constitutes a very aggressive tumor that arises from the pleural or peritoneal cavities and is highly refractory to conventional therapies. Several key genetic alterations are associated with the development and progression of MM including mutations of the CDKN2A/ARF , NF2 , and BAP1 tumor-suppressor genes. Notably, activating oncogene mutations are very rare; thus, it is difficult to develop effective inhibitors to treat MM. The NF2 gene encodes merlin, a protein that regulates multiple cell-signaling cascades including the Hippo pathway. MMs also exhibit inactivation of Hippo pathway components including LATS1/2, strongly suggesting that merlin-Hippo pathway dysregulation plays a key role in the development and progression of MM. Furthermore, Hippo pathway inactivation has been shown to result in constitutive activation of the YAP1/TAZ transcriptional coactivators, thereby conferring malignant phenotypes to mesothelial cells. Critical YAP1/TAZ target genes, including prooncogenic CCDN1 and CTGF , have also been shown to enhance the malignant phenotypes of MM cells. Together, these data indicate the Hippo pathway as a therapeutic target for the treatment of MM, and support the development of new strategies to effectively target the activation status of YAP1/TAZ as a promising therapeutic modality for this formidable disease.

  7. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    PubMed Central

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

  8. Different treatment modalities of fusiform basilar trunk aneurysm: study on computational hemodynamics.

    PubMed

    Wu, Chen; Xu, Bai-Nan; Sun, Zheng-Hui; Wang, Fu-Yu; Liu, Lei; Zhang, Xiao-Jun; Zhou, Ding-Biao

    2012-01-01

    Unclippable fusiform basilar trunk aneurysm is a formidable condition for surgical treatment. The aim of this study was to establish a computational model and to investigate the hemodynamic characteristics in a fusiform basilar trunk aneurysm. The three-dimensional digital model of a fusiform basilar trunk aneurysm was constructed using MIMICS, ANSYS and CFX software. Different hemodynamic modalities and border conditions were assigned to the model. Thirty points were selected randomly on the wall and within the aneurysm. Wall total pressure (WTP), wall shear stress (WSS), and blood flow velocity of each point were calculated and hemodynamic status was compared between different modalities. The quantitative average values of the 30 points on the wall and within the aneurysm were obtained by computational calculation point by point. The velocity and WSS in modalities A and B were different from those of the remaining 5 modalities; and the WTP in modalities A, E and F were higher than those of the remaining 4 modalities. The digital model of a fusiform basilar artery aneurysm is feasible and reliable. This model could provide some important information to clinical treatment options.

  9. Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma.

    PubMed

    Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

    2015-02-28

    To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P<0.001) and objective tumor response (P=0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P=0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P<0.001). Multivariate analysis identified tumor stage (P<0.001) and tumor type (P=0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P<0.001), surgical treatment (P=0.009), and multi-modal treatment (P=0.002) were identified as independent post-treatment prognostic factors. TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC.

  10. Outcome of transarterial chemoembolization-based multi-modal treatment in patients with unresectable hepatocellular carcinoma

    PubMed Central

    Song, Do Seon; Nam, Soon Woo; Bae, Si Hyun; Kim, Jin Dong; Jang, Jeong Won; Song, Myeong Jun; Lee, Sung Won; Kim, Hee Yeon; Lee, Young Joon; Chun, Ho Jong; You, Young Kyoung; Choi, Jong Young; Yoon, Seung Kew

    2015-01-01

    AIM: To investigate the efficacy and safety of transarterial chemoembolization (TACE)-based multimodal treatment in patients with large hepatocellular carcinoma (HCC). METHODS: A total of 146 consecutive patients were included in the analysis, and their medical records and radiological data were reviewed retrospectively. RESULTS: In total, 119 patients received TACE-based multi-modal treatments, and the remaining 27 received conservative management. Overall survival (P < 0.001) and objective tumor response (P = 0.003) were significantly better in the treatment group than in the conservative group. After subgroup analysis, survival benefits were observed not only in the multi-modal treatment group compared with the TACE-only group (P = 0.002) but also in the surgical treatment group compared with the loco-regional treatment-only group (P < 0.001). Multivariate analysis identified tumor stage (P < 0.001) and tumor type (P = 0.009) as two independent pre-treatment factors for survival. After adjusting for significant pre-treatment prognostic factors, objective response (P < 0.001), surgical treatment (P = 0.009), and multi-modal treatment (P = 0.002) were identified as independent post-treatment prognostic factors. CONCLUSION: TACE-based multi-modal treatments were safe and more beneficial than conservative management. Salvage surgery after successful downstaging resulted in long-term survival in patients with large, unresectable HCC. PMID:25741147

  11. [Physical treatment modalities for chronic leg ulcers].

    PubMed

    Dissemond, J

    2010-05-01

    An increasing numbers of physical treatment options are available for chronic leg ulcer. In this review article, compression therapy, therapeutic ultrasound, negative pressure therapy, extracorporeal shock wave therapy, electrostimulation therapy, electromagnetic therapy, photodynamic therapy, water-filtered infrared-A-radiation and hydrotherapy are discussed in terms of their practical applications and the underlying evidence. With the exception of compression therapy for most of these treatments, good scientific data are not available. However this is a widespread problem in the treatment of chronic wounds. Nevertheless, several of the described methods such as negative pressure therapy represent one of the gold standards in practical treatment of patients with chronic leg ulcers. Although the use of physical treatment modalities may improve healing in patients with chronic leg ulcers, the diagnosis and treatment of the underlying causes are essential for long-lasting success.

  12. Social networking sites: an adjunctive treatment modality for psychological problems.

    PubMed

    Menon, Indu S; Sharma, Manoj Kumar; Chandra, Prabha S; Thennarasu, K

    2014-07-01

    Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. It has implications for developing social networking based adjunctive treatment modality for psychological problems.

  13. Effectiveness of Psychotherapy in Personality Disorders Not Otherwise Specified: A Comparison of Different Treatment Modalities.

    PubMed

    Horn, Eva K; Bartak, Anna; Meerman, Anke M M A; Rossum, Bert V; Ziegler, Uli M; Thunnissen, Moniek; Soons, Mirjam; Andrea, Helene; Hamers, Elisabeth F M; Emmelkamp, Paul M G; Stijnen, Theo; Busschbach, Jan J V; Verheul, Roel

    2015-01-01

    Although personality disorder not otherwise specified (PDNOS) is highly prevalent and associated with a high burden of disease, only a few treatment studies in this patient group exist. This study is the first to investigate the effectiveness of different modalities of psychotherapy in patients with PDNOS, i.e., short-term (up to 6 months) and long-term (more than 6 months) outpatient, day hospital, and inpatient psychotherapy. A total of 205 patients with PDNOS were assigned to one of six treatment modalities. Effectiveness was assessed over 60 months after baseline. The primary outcome measure was symptom severity, and the secondary outcome measures included psychosocial functioning and quality of life. The study design was quasi-experimental, and the multiple propensity score was used to control for initial differences between treatment groups. All treatment modalities showed positive outcomes, especially in terms of improvements of symptom severity and social role functioning. At 12-month follow-up, after adjustment for initial differences between the treatment groups, short-term outpatient psychotherapy and short-term inpatient psychotherapy showed most improvement and generally outperformed the other modalities concerning symptom severity. At 60 months after baseline, effectiveness remained but observed differences between modalities mostly diminished. Patients with PDNOS benefit from psychotherapy both at short-term and long-term follow-up. Short-term outpatient psychotherapy and short-term inpatient psychotherapy seem to be superior to the other treatment modalities at 12-month follow-up. At 60-month follow-up, treatments showed mostly comparable effectiveness. The effectiveness of different modalities of psychotherapy in patients with PDNOS (i.e., short-term vs long-term; outpatient versus day hospital versus inpatient psychotherapy) has not yet been compared. Different modalities of psychotherapy are effective for patients with PDNOS, and positive

  14. Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy.

    PubMed

    Tang, Xiang-Jun; Sun, Xu-Yong; Huang, Kuan-Ming; Zhang, Li; Yang, Zhuo-Shun; Zou, Dan-Dan; Wang, Bin; Warnock, Garth L; Dai, Long-Jun; Luo, Jie

    2015-12-29

    Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events. As an extension of this impactful modality, CAR-T cell-derived exosomes may substitute CAR-T cells to act as ultimate attackers, thereby overcoming some limitations. Exosomes retain most characteristics of parent cells and play an essential role in intercellular communications via transmitting their cargo to recipient cells. The application of CAR-T cell-derived exosomes will make this cell-based therapy more clinically controllable as it also provides a cell-free platform to diversify anticancer mediators, which responds effectively to the complexity and volatility of cancer. It is believed that the appropriate application of both cellular and exosomal platforms will make this effective treatment more practicable.

  15. Dissociable identity- and modality-specific neural representations as revealed by cross-modal nonspatial inhibition of return.

    PubMed

    Chi, Yukai; Yue, Zhenzhu; Liu, Yupin; Mo, Lei; Chen, Qi

    2014-08-01

    There are ongoing debates on whether object concepts are coded as supramodal identity-based or modality-specific representations in the human brain. In this fMRI study, we adopted a cross-modal "prime-neutral cue-target" semantic priming paradigm, in which the prime-target relationship was manipulated along both the identity and the modality dimensions. The prime and the target could refer to either the same or different semantic identities, and could be delivered via either the same or different sensory modalities. By calculating the main effects and interactions of this 2 (identity cue validity: "Identity_Cued" vs. "Identity_Uncued") × 2 (modality cue validity: "Modality_Cued" vs. "Modality_Uncued") factorial design, we aimed at dissociating three neural networks involved in creating novel identity-specific representations independent of sensory modality, in creating modality-specific representations independent of semantic identity, and in evaluating changes of an object along both the identity and the modality dimensions, respectively. Our results suggested that bilateral lateral occipital cortex was involved in creating a new supramodal semantic representation irrespective of the input modality, left dorsal premotor cortex, and left intraparietal sulcus were involved in creating a new modality-specific representation irrespective of its semantic identity, and bilateral superior temporal sulcus was involved in creating a representation when the identity and modality properties were both cued or both uncued. In addition, right inferior frontal gyrus showed enhanced neural activity only when both the identity and the modality of the target were new, indicating its functional role in novelty detection. Copyright © 2014 Wiley Periodicals, Inc.

  16. Social Networking Sites: An Adjunctive Treatment Modality for Psychological Problems

    PubMed Central

    Menon, Indu S.; Sharma, Manoj Kumar; Chandra, Prabha S.; Thennarasu, K.

    2014-01-01

    Background: Social networking is seen as a way to enhance social support and feeling of well-being. The present work explores the potentials of social networking sites as an adjunctive treatment modality for initiating treatment contact as well as for managing psychological problems. Materials and Methods: Interview schedule, Facebook intensity questionnaire were administered on 28 subjects with a combination of 18 males and 10 females. They were taken from the in-patient and out-patient psychiatry setting of the hospital. Results: Facebook was the most popular sites and used to seek emotional support on the basis of the frequent updates of emotional content that users put in their profile; reconciliations, escape from the problems or to manage the loneliness; getting information about illness and its treatment and interaction with experts and also manifested as problematic use. Conclusions: It has implications for developing social networking based adjunctive treatment modality for psychological problems. PMID:25035548

  17. Effectiveness and Cost-effectiveness of Four Treatment Modalities for Substance Disorders: A Propensity Score Analysis

    PubMed Central

    Mojtabai, Ramin; Graff Zivin, Joshua

    2003-01-01

    Objective To assess the effectiveness and cost-effectiveness of four treatment modalities for substance abuse. Data Sources The study used data from the Services Research Outcomes Study (SROS), a survey of 3,047 clients in a random sample of 99 drug treatment facilities across the United States. Detailed sociodemographic, substance use, and clinical data were abstracted from treatment records. Substance abuse outcome and treatment history following discharge from index facilities were assessed using a comprehensive interview with 1,799 of these individuals five years after discharge. Treatment success was defined in two ways: as abstinence and as any reduction in substance use. Study Design Effectiveness and cost-effectiveness of four modalities were compared: inpatient, residential, outpatient detox/methadone, and outpatient drug-free. Clients were stratified based on propensity scores and analyses were conducted within these strata. Sensitivity analyses examined the impact of future substance abuse treatment on effectiveness and cost-effectiveness estimates. Principal Findings Treatment of substance disorders appears to be cost-effective compared to other health interventions. The cost per successfully treated abstinent case in the least costly modality, the outpatient drug-free programs, was $6,300 (95 percent confidence intervals: $5,200–$7,900) in 1990 dollars. There were only minor differences between various modalities of treatment with regard to effectiveness. However, modalities varied considerably with regard to cost-effectiveness. Outpatient drug-free programs were the most cost-effective. There was little evidence that relative effectiveness or cost-effectiveness of programs varied according to factors that were associated with selection into different programs. Conclusions Substance disorders can be treated most cost-effectively in outpatient drug-free settings. Savings from transitioning to the most cost-effective treatment modality may free

  18. Combined modality treatment of aromatherapy, footsoak, and reflexology relieves fatigue in patients with cancer.

    PubMed

    Kohara, Hiroyuki; Miyauchi, Takako; Suehiro, Yoko; Ueoka, Hiroshi; Takeyama, Hiroyasu; Morita, Tatsuya

    2004-12-01

    Fatigue is one of the most distressful symptoms experienced by patients with advanced cancer. Aromatherapy, footsoak, and reflexology are popular health care modality treatments in Japan, however, the effectiveness of each treatment for cancer-related fatigue has not been fully established. To investigate the effectiveness of combined modality treatment consisting of aromatherapy, footsoak, and reflexology against fatigue, an open study was performed in 20 terminally ill patients with cancer. After a patch test was performed, patients received aromatherapy that was accompanied with footsoak in warm water containing lavender essential oil for 3 minutes, followed by reflexology treatment with jojoba oil containing lavender for 10 min. Fatigue was evaluated using the Cancer Fatigue Scale (CFS) before, 1 hour after, and 4 hours after treatment. Total CFS scores improved significantly after this treatment (from 25.6 +/- 11.0 to 18.1 +/- 10.0, p < 0.001). Among three CFS subscales, physical and cognitive subscale scores were reduced significantly (11.3 +/- 6.1 to 6.7 +/- 6.1, p < 0.001; 4.5 +/- 3.2 to 2.4 +/- 2.4, p < 0.001). No adverse effects were experienced. Because all patients desired to continue this treatment, they received treatment eight times on average. Combined modality treatment consisting of aromatherapy, footsoak, and reflexology appears to be effective for alleviating fatigue in terminally ill cancer patients. To confirm safety and effectiveness of this combined modality treatment, further investigation including randomized treatment assignment is warranted.

  19. A modal radar cross section of thin-wire targets via the singularity expansion method

    NASA Technical Reports Server (NTRS)

    Richards, M. A.; Shumpert, T. H.; Riggs, L. S.

    1992-01-01

    A modal radar cross section (RCS) of arbitrary wire scatterers is constructed in terms of SEM parameters. Numerical results are presented for both straight and L-shaped wire targets and are compared to computations performed in the frequency domain using the method of moments.

  20. SU-E-T-410: Evaluation of Treatment Modalities for Stereotactic Lung Radiation Therapy: A Phantom Study

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

    Mohatt, D; Malhotra, H

    Purpose: To evaluate and verify the accuracy of alternative treatment modalities for stereotactic lung therapy with end-to-end testing. We compared three dimensional conformal therapy (3DCRT), dynamic conformal arc therapy (DCAT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) treatment using 6 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photons. Methods: A QUASAR respiratory motion phantom was utilized with custom ion chamber and gafchromatic EBT2 film inserts. The phantom contained a low density lung medium with a cylindrical polystyrene tumor (35 cc). Pseudo representative structures for various organs at risk (OAR) were created. Allmore » treatment plans were created using Eclipse ver. 11 using the same image and structure sets, and delivered via Varian TrueBeam STx linear accelerator equipped with high definition MLC. Evaluation of plan quality followed ROTG 0813 criterion for conformity index (CI100%), high dose spillage, D2cm, and R50%. Results: All treatment plans met the OAR dose constraints per protocol and could be delivered without any beam hold offs or other interlocks and hence were deemed clinically safe. For equivalent beam energies, target conformity was improved for all modalities when switching to FFF mode. Treatment efficiency increased for VMAT FFF by a factor of 3–4 over IMRT, and up to factor of 7 when compared to 3DCRT. Pass rates were > 97% for all treatment using gamma criteria of 3%, 3mm. Absolute dose at iso-center was verified with ion chamber, and found to be within 2% of the treatment planning system. Conclusion: The higher dose rate associated with FFF not only reduces delivery times, but in most cases enhances plan quality. The one modality with succeeding best results for all RTOG criterions was VMAT 6 MV FFF. This end-to-end testing provides necessary confidence in the entire dose delivery chain for lung SBRT patients.« less

  1. Comparison of various treatment modalities for acute tinnitus.

    PubMed

    Shim, Hyun Joon; Song, Seong Jun; Choi, A Young; Hyung Lee, Rae; Yoon, Sang Won

    2011-12-01

    Because in most cases the development of tinnitus is triggered by cochlear damage, there exists the opportunity to eliminate tinnitus while the cochlear lesion is still reversible. Therefore, we evaluated the therapeutic effects of various treatment modalities on acute subjective idiopathic tinnitus (SIT) and investigated prognostic factors affecting the treatment outcome. Prospective, controlled, double-blind trial. A total 107 patients who underwent treatment for unilateral SIT that had developed within the previous 3 months completed the study. The patients were randomly assigned into three groups according to the treatment modality: group I (n = 32), alprazolam orally for 3 months; group II (n = 35), as for group I plus four intratympanic dexamethasone (ITD) injections; and group III (n = 40), as for group II plus four intravenous injections of lipo-prostaglandin E(1) . The improvement rate of group II (75.8%) was significantly higher than that of group I (40.3%; P < .05), and there was no significant difference in the improvement rate of group III (50.0%) compared with groups I and II (P > .05). The cure rates of group II (25.8%) and group III (20.0%) were significantly higher than that of group I (9.8%; P < .05). There was a significant correlation between the cure rate and duration of symptoms. The results of the present study indicate that ITD injection plus alprazolam medication is the best treatment choice for acute SIT within 3 months of development. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  2. Assessing Instructional Modalities: Individualized Treatment Effects for Personalized Learning

    ERIC Educational Resources Information Center

    Beemer, Joshua; Spoon, Kelly; Fan, Juanjuan; Stronach, Jeanne; Frazee, James P.; Bohonak, Andrew J.; Levine, Richard A.

    2018-01-01

    Estimating the efficacy of different instructional modalities, techniques, and interventions is challenging because teaching style covaries with instructor, and the typical student only takes a course once. We introduce the individualized treatment effect (ITE) from analyses of personalized medicine as a means to quantify individual student…

  3. Nonpharmacological, somatic treatments of depression: electroconvulsive therapy and novel brain stimulation modalities

    PubMed Central

    Eitan, Renana; Lerer, Bernard

    2006-01-01

    Until recently, a review of nonpharmacological, somatic treatments of psychiatric disorders would have included only electroconvulsive therapy (ECT). This situation is now changing very substantially Although ECT remains the only modality in widespread clinical use, several new techniques are under investigation. Their principal indication in the psychiatric context is the treatment of major depression, but other applications are also being studied. All the novel treatments involve brain stimulation, which is achieved by different technological methods. The treatment closest to the threshold of clinical acceptability is transcranial magnetic stimulation (TMS). Although TMS is safe and relatively easy to administer, its efficacy has still to be definitively established. Other modalities, at various stages of research development, include magnetic seizure therapy (MST), deep brain stimulation (DBS), and vagus nerve stimulation (VNS). We briefly review the development and technical aspects of these treatments, their potential role in the treatment of major depression, adverse effects, and putative mechanism of action. As the only one of these treatment modalities that is in widespread clinical use, more extended consideration is given to ECT. Although more than half a century has elapsed since ECT was first introduced, it remains the most effective treatment for major depression, with efficacy in patients refractory to antidepressant drugs and an acceptable safety profile. Although they hold considerable promise, the novel brain stimulation techniques reviewed here will be need to be further developed before they achieve clinical acceptability. PMID:16889109

  4. Orthodontic Treatment Timing and Modalities in Anterior Open Bite: Case Series Study

    PubMed Central

    Al Hamadi, Wisam; Saleh, Fayez; Kaddouha, Mohamad

    2017-01-01

    Objective: The purpose of this study was to present early and adult cases of anterior open bite that were treated efficiently using different treatment approaches and mechanics. Materials and Methods: Five patients of different age groups (from 7 to 27 years), suffering from a clear Anterior open bite deformity, were properly diagnosed and relevant treatment modality for each was selected. Results: Positive overbite was efficiently achieved for all patients. Conclusion: Patient compliance is a key factor in using removable habit breakers. However, fixed palatal crib gave the same results but in shorter time. Anterior open bite of skeletal components should be thoroughly evaluated before selecting camouflage or orthognathic surgery treatment modality. PMID:29299074

  5. Physician perceptions of the value of physical modalities in the treatment of musculoskeletal disease.

    PubMed

    Rush, P J; Shore, A

    1994-06-01

    We randomly surveyed 100 specialists in rehabilitation medicine and 100 rheumatologists concerning their perceptions of the value of 11 different physical modalities--cold, active and passive exercise, interferential current, laser, magnetotherapy, microwave, shortwave diathermy, traction, ultrasound and transcutaneous nerve stimulation in the treatment of seven different musculoskeletal conditions--acute arthritis, joint contracture, neck pain, back pain, tendinitis, reflex sympathetic dystrophy and frozen shoulder. There were significant differences in the perceived benefits of modalities which varied by modality and condition. Overall, rehabilitation medicine specialists regarded modalities to be helpful more often than rheumatologists (P < 0.001).

  6. Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system

    NASA Astrophysics Data System (ADS)

    Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E.; Wemple, Charles A.; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; DeNardo, Gerald

    2005-03-01

    The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4—2%, MCNP—10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of

  7. Photoacoustic/ultrasound dual-modality contrast agent and its application to thermotherapy.

    PubMed

    Wang, Yu-Hsin; Liao, Ai-Ho; Chen, Jui-Hao; Wang, Churng-Ren Chris; Li, Pai-Chi

    2012-04-01

    This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.

  8. A Comparison of Therapeutic Factors in Two Group Treatment Modalities: Verbal and Art Therapy.

    ERIC Educational Resources Information Center

    Shechtman, Zipora; Perl-Dekel, Ofra

    2000-01-01

    Compares therapeutic factors in verbal and art group psychotherapy in a psychiatric day-treatment clinic in Israel. Results only partly support the differences between modalities, but do reveal significant differences between participants with only a few interactions between participants and modalities. All therapeutic factors appear in both…

  9. Missing Modality Transfer Learning via Latent Low-Rank Constraint.

    PubMed

    Ding, Zhengming; Shao, Ming; Fu, Yun

    2015-11-01

    Transfer learning is usually exploited to leverage previously well-learned source domain for evaluating the unknown target domain; however, it may fail if no target data are available in the training stage. This problem arises when the data are multi-modal. For example, the target domain is in one modality, while the source domain is in another. To overcome this, we first borrow an auxiliary database with complete modalities, then consider knowledge transfer across databases and across modalities within databases simultaneously in a unified framework. The contributions are threefold: 1) a latent factor is introduced to uncover the underlying structure of the missing modality from the known data; 2) transfer learning in two directions allows the data alignment between both modalities and databases, giving rise to a very promising recovery; and 3) an efficient solution with theoretical guarantees to the proposed latent low-rank transfer learning algorithm. Comprehensive experiments on multi-modal knowledge transfer with missing target modality verify that our method can successfully inherit knowledge from both auxiliary database and source modality, and therefore significantly improve the recognition performance even when test modality is inaccessible in the training stage.

  10. Light and laser treatment modalities for disseminated superficial actinic porokeratosis: a systematic review.

    PubMed

    Aird, Gregory A; Sitenga, Jenna L; Nguyen, Austin Huy; Vaudreuil, Adam; Huerter, Christopher J

    2017-05-01

    Treatment of disseminated superficial actinic porokeratosis (DSAP) is poorly standardized. The present review seeks to comprehensively discuss the potential for laser and light modalities in the treatment of DSAP. A systematic review of light and laser treatment modalities was conducted to include 26 cases of patients with DSAP. Systematic review resulted in 14 articles to be included. Photodynamic therapy (PDT) overall was the least successful treatment modality, with clinical improvement seen in a minority of patients (MAL-PDT: N = 9 patients, 33.3% showed improvement; ALA-PDT: N = 3 patients, 0% improvement; hypericin-PDT: N = 2 patients, 0% improvement) after numerous post-procedural side effects of hyperpigmentation, inflammation, erythema, and discomfort. Overall, in the available reports, PDT demonstrates poor outcomes with greater incidence of side effects. The response rates of DSAP lesions treated with lasers were as follows: (Q-switched ruby lasers: N = 2, 100%; CO 2 laser: N = 1, 100%; PDT and CO 2 combination therapy: N = 2, 0-50%; erbium and neodymium YAG lasers: N = 2, 100%; fractional 1927-nm thulium fiber lasers: N = 2, 100%; Grenz rays: N = 1, 100%; and fractional photothermolysis: N = 2, 100%). The side effects of laser therapy were minimal and included mild erythema, slight hyperpigmentation, and moderate edema. Laser therapy is a promising treatment option for DSAP with an excellent side effect profile. However, higher power studies are required to determine optimal guidelines for laser treatment of DSAP.

  11. Rapid fabrication of carbon quantum dots as multifunctional nanovehicles for dual-modal targeted imaging and chemotherapy.

    PubMed

    Chiu, Sheng-Hui; Gedda, Gangaraju; Girma, Wubshet Mekonnen; Chen, Jem-Kun; Ling, Yong-Chien; Ghule, Anil V; Ou, Keng-Liang; Chang, Jia-Yaw

    2016-12-01

    Herein, we synthesized an S, N, and Gd tri-element doped magnetofluorescent carbon quantum dots (GdNS@CQDs) within 10min by using a one-pot microwave method. Our results showed that these magnetofluorescent GdNS@CQDs have excellent fluorescent and magnetic properties. Moreover, GdNS@CQDs exhibited high stability at physiological conditions and ionic strength. These magnetofluorescent GdNS@CQDs were conjugated with a folic acid, denoted as FA-GdNS@CQDs, for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of FA-GdNS@CQDs. FA-GdNS@CQDs enhanced the MR response as compared to that for commercial Gd-DTPA. The targeting capabilities of FA-GdNS@CQDs were confirmed in HeLa and HepG2 cells using in vitro fluorescence and MR dual modality imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the FA-GdNS@CQDs forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. Importantly, the prepared FA-GdNS@CQDs-DOX showed a high quantity of doxorubicin loading capacity (about 80%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the FA-GdNS@CQDs were observed by confocal laser scanning microscopy. We also successfully demonstrated in vivo fluorescence bio imaging of the FA-GdNS@CQDs, using zebrafish as an animal model. In this manuscript, we reported a facial, rapid, and environmental friendly method to fabricate hetero atoms including gadolinium, nitrogen, and sulfur doped multi-functional magnetofluorescent carbon quantum dots (GdNS@CQDs) nanocomposite. These multifunctional GdNS@CQDs were conjugated with a folic acid for targeting dual modal fluorescence/magnetic resonance imaging. Additionally, an anticancer drug, doxorubicin, was incorporated into the nanocomposite forming FA-GdNS@CQDs-DOX, which enables targeted drug delivery. We have developed GdNS@CQDs with integrated functions for simultaneous in

  12. An overview of clinical and experimental treatment modalities for port wine stains

    PubMed Central

    Chen, Jennifer K.; Ghasri, Pedram; Aguilar, Guillermo; van Drooge, Anne Margreet; Wolkerstorfer, Albert; Kelly, Kristen M.; Heger, Michal

    2014-01-01

    Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy. PMID:22305042

  13. Physical modalities in the treatment of neurological dysfunction.

    PubMed

    Galea, Mary P

    2012-06-01

    This chapter presents modalities of physical therapy used in optimizing sensorimotor recovery from nervous system injury. A brief historical perspective, rationale, indications for application, and evidence of effectiveness of various physical treatment modalities is provided. Many of the facilitatory and inhibitory techniques used in the past are no longer used, as they were based on an understanding of recovery after nervous system injury that is now outdated. There has been a paradigm shift in the management of people with neurological dysfunction. In particular there has been a reduction in focus on the positive features or the upper motor neuron syndrome, such as spasticity, and an increasing emphasis on active, task-related practice of functional tasks. Physical therapy for people with neurological disorders has undergone a paradigm shift as a result of new knowledge about motor control, skill acquisition, and recovery of function after injury. Future research should address new applications of electrical stimulation and whole body vibration as well as the optimal dosage and timing of interventions. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Trismus following different treatment modalities for head and neck cancer: a systematic review of subjective measures.

    PubMed

    Loh, Sook Y; Mcleod, Robert W J; Elhassan, Hassan A

    2017-07-01

    The aim of this review was to compare systematically the subjective measure of trismus between different interventions to treat head and neck cancer, particularly those of the oropharynx. Using The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) Guidelines, Six databases were searched for the text using various terms which include "oropharyngeal/head and neck cancer", "trismus/mouth opening" and the various treatment modalities. Included in the review were clinical studies (> or =10 patients). Three observers independently assessed the papers identified. Among the six studies reviewed, five showed a significantly worst outcome with regard to the quality-of-life questionnaire scores for a radiotherapy or surgery and radiotherapy (RT) ± chemotherapy or chemoradiotherapy when compared to surgery alone. Only one study showed no significant difference between surgery alone and other treatment modalities. Subjective quality-of-life measures are a concurrent part of modern surgical practice. Although subjective measures were utilised to measure post operative trismus successfully, there was no consensus as to which treatment modality had overall better outcomes, with conflicting studies in keeping with the current debate in this field. Larger and higher quality studies are needed to compare all three treatment modalities.

  15. MO-B-BRC-00: Prostate HDR Treatment Planning - Considering Different Imaging Modalities

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

    NONE

    2016-06-15

    Brachytherapy has proven to be an effective treatment option for prostate cancer. Initially, prostate brachytherapy was delivered through permanently implanted low dose rate (LDR) radioactive sources; however, high dose rate (HDR) temporary brachytherapy for prostate cancer is gaining popularity. Needle insertion during prostate brachytherapy is most commonly performed under ultrasound (U/S) guidance; however, treatment planning may be performed utilizing several imaging modalities either in an intra- or post-operative setting. During intra-operative prostate HDR, the needles are imaged during implantation, and planning may be performed in real time. At present, the most common imaging modality utilized for intra-operative prostate HDR ismore » U/S. Alternatively, in the post-operative setting, following needle implantation, patients may be simulated with computed tomography (CT) or magnetic resonance imaging (MRI). Each imaging modality and workflow provides its share of benefits and limitations. Prostate HDR has been adopted in a number of cancer centers across the nation. In this educational session, we will explore the role of U/S, CT, and MRI in HDR prostate brachytherapy. Example workflows and operational details will be shared, and we will discuss how to establish a prostate HDR program in a clinical setting. Learning Objectives: Review prostate HDR techniques based on the imaging modality Discuss the challenges and pitfalls introduced by the three imagebased options for prostate HDR brachytherapy Review the QA process and learn about the development of clinical workflows for these imaging options at different institutions.« less

  16. An overview of clinical and experimental treatment modalities for port wine stains.

    PubMed

    Chen, Jennifer K; Ghasri, Pedram; Aguilar, Guillermo; van Drooge, Anne Margreet; Wolkerstorfer, Albert; Kelly, Kristen M; Heger, Michal

    2012-08-01

    Port wine stains (PWS) are the most common vascular malformation of the skin, occurring in 0.3% to 0.5% of the population. Noninvasive laser irradiation with flashlamp-pumped pulsed dye lasers (selective photothermolysis) currently comprises the gold standard treatment of PWS; however, the majority of PWS fail to clear completely after selective photothermolysis. In this review, the clinically used PWS treatment modalities (pulsed dye lasers, alexandrite lasers, neodymium:yttrium-aluminum-garnet lasers, and intense pulsed light) and techniques (combination approaches, multiple passes, and epidermal cooling) are discussed. Retrospective analysis of clinical studies published between 1990 and 2011 was performed to determine therapeutic efficacies for each clinically used modality/technique. In addition, factors that have resulted in the high degree of therapeutic recalcitrance are identified, and emerging experimental treatment strategies are addressed, including the use of photodynamic therapy, immunomodulators, angiogenesis inhibitors, hypobaric pressure, and site-specific pharmaco-laser therapy. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  17. Axillary hyperhidrosis: A review of the extent of the problem and treatment modalities.

    PubMed

    Singh, Sanjay; Davis, Harriet; Wilson, Paul

    2015-10-01

    The purpose of this review is to summarize the extent of the problem of axillary hyperhidrosis and treatment modalities available. The benefits and disadvantages of various treatments are reflected on with the hope of providing a starting point to investigate new ways of treating hyperhidrosis. A literature search was conducted using various databases and search criteria. Current treatments include aluminium chloride antiperspirants, iontophoresis, botox injections and endoscopic thoracic sympathectomy. Botox therapy is usually the most effective treatment, without surgery or unpleasant side effects. However it has to be administered by a skilled clinician and involves around 20 injections to treat axillary hyperhidrosis. Other ways of giving Botox are being developed, the most promising one being the use of microneedles which are able to penetrate the skin and deliver drugs to the target area of the dermis without causing pain. In comparison to the temporary effects of microneedles, laser and microwave therapies are also assessed as they offer the hope of permanent relief from hyperhidrosis. There is a considerable dearth in the literature on the management of axillary hyperhidrosis. Further study in larger populations with longer follow up times is critical to access the long term effects of treatment. Microneedles could be the future treatment of choice with the potential to deliver drugs in a safe and pain free way. Copyright © 2015 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  18. The effectiveness of psychosocial modalities in the treatment of alcohol problems in adults: a review of the evidence.

    PubMed

    Martin, Garth W; Rehm, Jürgen

    2012-06-01

    Our objectives were to review the effectiveness of psychosocial modalities in the treatment of alcohol use disorders and problems, and to examine the impact of therapists on treatment outcome, the evidence on best practices for comorbid conditions, and the evidence on treatment matching. We based our review on published systematic reviews of this topic after 2000. There is strong evidence that some, but not all, psychosocial treatments are effective in treating alcohol problems. Those with the strongest empirical support are motivational enhancement therapy, various cognitive-behavioural interventions, and brief interventions. Meta-analyses for several of these modalities suggest typical effect sizes in the low-to-moderate range. When these modalities have been compared with one another in well-designed clinical trials, they have been shown to be of comparable effectiveness. There is little basis on which to recommend one of these modalities over another but good reason to select from among them.

  19. Non-invasive different modalities of treatment for temporomandibular disorders: review of literature

    PubMed Central

    2018-01-01

    Temporomandibular disorders (TMDs) are diseases that affect the temporomandibular joint and supporting structures. The goal of treatment for TMDs is elimination or reduction of pain and return to normal temporomandibular joint function. Initial treatment for TMDs is non-invasive and conservative, not surgical. Oral and maxillofacial surgeons should fully understand and actively care about non-invasive treatments for TMDs. The purpose of this study is to review the validity and outcomes of non-invasive and surgical treatment modalities for TMDs. PMID:29732308

  20. A geriatrician's guide to the use of the physical modalities in the treatment of pain and dysfunction.

    PubMed

    Perret, Danielle Marie; Rim, Josephine; Cristian, Adrian

    2006-05-01

    The use of the physical modalities in the treatment of musculoskeletal conditions has a long and rich history. This article explores the various physical modalities and their indications, precautions, and contraindications, especially in their applied use in pain management. It also highlights the role of the physical modalities as agents for the management of pain in the geriatric population.

  1. Non-pharmacological treatment options for refractory epilepsy: an overview of human treatment modalities and their potential utility in dogs.

    PubMed

    Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie

    2014-03-01

    Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. The small molecule survivin inhibitor YM155 may be an effective treatment modality for colon cancer through increasing apoptosis

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

    Li, Wan Lu, E-mail: lvvlchina@msn.cn; Lee, Mi-Ra, E-mail: mira1125@yonsei.ac.kr; Cho, Mee-Yon, E-mail: meeyon@yonsei.ac.kr

    Survivin has a known beneficial role in the survival of both cancer cells and normal cells. Therapies targeting survivin have been proposed as an alternative treatment modality for various tumors; however, finding the proper indication for this toxic therapy is critical for reducing unavoidable side effects. We recently observed that high survivin expression in CD133{sup +} cells is related to chemoresistance in Caco-2 colon cancer cells. However, the effect of survivin-targeted therapy on CD133{sup +} colon cancer is unknown. In this study, we investigated the roles of CD133 and survivin expression in colon cancer biology in vitro and comparatively analyzed themore » anticancer effects of survivin inhibitor on CD133{sup +} cells (ctrl-siRNA group) and small interfering RNA (siRNA)-induced CD133{sup −} cells (CD133-siRNA group) obtained from a single colon cancer cell line. CD133 knockdown via siRNA transfection did not change the tumorigenicity of cells, although in vitro survivin expression levels in CD133{sup +} cells were higher than those in siRNA-induced CD133{sup −} cells. The transfection procedure seemed to induce survivin expression. Notably, a significant number of CD133{sup −} cells (33.8%) was found in the cell colonies of the CD133-siRNA group. In the cell proliferation assay after treatment, YM155 and a combination of YM155 and 5-fluorouracil (5-FU) proved to be far more effective than 5-FU alone. A significantly increased level of apoptosis was observed with increasing doses of YM155 in all groups. However, significant differences in therapeutic effect and apoptosis among the mock, ctrl-siRNA, and CD133-siRNA groups were not detected. Survivin inhibitor is an effective treatment modality for colon cancer; however, the role of CD133 and the use of survivin expression as a biomarker for this targeted therapy must be verified.« less

  3. TU-FG-201-03: Automatic Pre-Delivery Verification Using Statistical Analysis of Consistencies in Treatment Plan Parameters by the Treatment Site and Modality

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

    Liu, S; Wu, Y; Chang, X

    Purpose: A novel computer software system, namely APDV (Automatic Pre-Delivery Verification), has been developed for verifying patient treatment plan parameters right prior to treatment deliveries in order to automatically detect and prevent catastrophic errors. Methods: APDV is designed to continuously monitor new DICOM plan files on the TMS computer at the treatment console. When new plans to be delivered are detected, APDV checks the consistencies of plan parameters and high-level plan statistics using underlying rules and statistical properties based on given treatment site, technique and modality. These rules were quantitatively derived by retrospectively analyzing all the EBRT treatment plans ofmore » the past 8 years at authors’ institution. Therapists and physicists will be notified with a warning message displayed on the TMS computer if any critical errors are detected, and check results, confirmation, together with dismissal actions will be saved into database for further review. Results: APDV was implemented as a stand-alone program using C# to ensure required real time performance. Mean values and standard deviations were quantitatively derived for various plan parameters including MLC usage, MU/cGy radio, beam SSD, beam weighting, and the beam gantry angles (only for lateral targets) per treatment site, technique and modality. 2D-based rules of combined MU/cGy ratio and averaged SSD values were also derived using joint probabilities of confidence error ellipses. The statistics of these major treatment plan parameters quantitatively evaluate the consistency of any treatment plans which facilitates automatic APDV checking procedures. Conclusion: APDV could be useful in detecting and preventing catastrophic errors immediately before treatment deliveries. Future plan including automatic patient identify and patient setup checks after patient daily images are acquired by the machine and become available on the TMS computer. This project is supported by

  4. Helium ions for radiotherapy? Physical and biological verifications of a novel treatment modality

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

    Krämer, Michael, E-mail: m.kraemer@gsi.de; Scifoni, Emanuele; Schuy, Christoph

    Purpose: Modern facilities for actively scanned ion beam radiotherapy allow in principle the use of helium beams, which could present specific advantages, especially for pediatric tumors. In order to assess the potential use of these beams for radiotherapy, i.e., to create realistic treatment plans, the authors set up a dedicated {sup 4}He beam model, providing base data for their treatment planning system TRiP98, and they have reported that in this work together with its physical and biological validations. Methods: A semiempirical beam model for the physical depth dose deposition and the production of nuclear fragments was developed and introduced inmore » TRiP98. For the biological effect calculations the last version of the local effect model was used. The model predictions were experimentally verified at the HIT facility. The primary beam attenuation and the characteristics of secondary charged particles at various depth in water were investigated using {sup 4}He ion beams of 200 MeV/u. The nuclear charge of secondary fragments was identified using a ΔE/E telescope. 3D absorbed dose distributions were measured with pin point ionization chambers and the biological dosimetry experiments were realized irradiating a Chinese hamster ovary cells stack arranged in an extended target. Results: The few experimental data available on basic physical processes are reproduced by their beam model. The experimental verification of absorbed dose distributions in extended target volumes yields an overall agreement, with a slight underestimation of the lateral spread. Cell survival along a 4 cm extended target is reproduced with remarkable accuracy. Conclusions: The authors presented a simple simulation model for therapeutical {sup 4}He beams which they introduced in TRiP98, and which is validated experimentally by means of physical and biological dosimetries. Thus, it is now possible to perform detailed treatment planning studies with {sup 4}He beams, either exclusively or

  5. Opinions about Treatment Modalities among Patients Involuntarily Committed to a Forensic Psychiatric Hospital in Finland

    ERIC Educational Resources Information Center

    Repo-Tiihonen, Eila; Vuorio, Osmo; Koivisto, Hanna; Paavola, Paula; Hakola, Panu

    2004-01-01

    Patient satisfaction studies concerning various treatment modalities are few among involuntary forensic psychiatric treatment. They indicate general satisfaction with medication, interactive treatment and occupational therapy but dissatisfaction with lack of privacy, insufficiently explained rules and inadequately explained reasons of seclusion.…

  6. Advances in diagnostic and treatment modalities for intracranial tumors.

    PubMed

    Dickinson, P J

    2014-01-01

    Intracranial neoplasia is a common clinical condition in domestic companion animals, particularly in dogs. Application of advances in standard diagnostic and therapeutic modalities together with a broad interest in the development of novel translational therapeutic strategies in dogs has resulted in clinically relevant improvements in outcome for many canine patients. This review highlights the status of current diagnostic and therapeutic approaches to intracranial neoplasia and areas of novel treatment currently in development. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  7. Cross-modal links among vision, audition, and touch in complex environments.

    PubMed

    Ferris, Thomas K; Sarter, Nadine B

    2008-02-01

    This study sought to determine whether performance effects of cross-modal spatial links that were observed in earlier laboratory studies scale to more complex environments and need to be considered in multimodal interface design. It also revisits the unresolved issue of cross-modal cuing asymmetries. Previous laboratory studies employing simple cues, tasks, and/or targets have demonstrated that the efficiency of processing visual, auditory, and tactile stimuli is affected by the modality, lateralization, and timing of surrounding cues. Very few studies have investigated these cross-modal constraints in the context of more complex environments to determine whether they scale and how complexity affects the nature of cross-modal cuing asymmetries. Amicroworld simulation of battlefield operations with a complex task set and meaningful visual, auditory, and tactile stimuli was used to investigate cuing effects for all cross-modal pairings. Significant asymmetric performance effects of cross-modal spatial links were observed. Auditory cues shortened response latencies for collocated visual targets but visual cues did not do the same for collocated auditory targets. Responses to contralateral (rather than ipsilateral) targets were faster for tactually cued auditory targets and each visual-tactile cue-target combination, suggesting an inhibition-of-return effect. The spatial relationships between multimodal cues and targets significantly affect target response times in complex environments. The performance effects of cross-modal links and the observed cross-modal cuing asymmetries need to be examined in more detail and considered in future interface design. The findings from this study have implications for the design of multimodal and adaptive interfaces and for supporting attention management in complex, data-rich domains.

  8. Choice of treatment modalities was not influenced by pain, severity or co-morbidity in patients with knee osteoarthritis.

    PubMed

    Jamtvedt, Gro; Dahm, Kristin Thuve; Holm, Inger; Odegaard-Jensen, Jan; Flottorp, Signe

    2010-03-01

    Patients with knee osteoarthritis (OA) are commonly treated by physiotherapists in primary care. The physiotherapists use different treatment modalities. In a previous study, we identified variation in the use of transcutaneous electrical nerve stimulation (TENS), low level laser or acupuncture, massage and weight reduction advice for patients with knee OA. The purpose of this study was to examine factors that might explain variation in treatment modalities for patients with knee OA. Practising physiotherapists prospectively collected data for one patient with knee osteoarthritis each through 12 treatment sessions.We chose to examine factors that might explain variation in the choice of treatment modalities supported by high or moderate quality evidence, and modalities which were frequently used but which were not supported by evidence from systematic reviews. Experienced clinicians proposed factors that they thought might explain the variation in the choice of these specific treatments. We used these factors in explanatory analyses. Using TENS, low level laser or acupuncture was significantly associated with having searched databases to help answer clinical questions in the last six months (odds ratio [OR] = 1.93, 95% confidence interval [CI] = 1.08-3.42). Not having Internet access at work and using more than four treatment modalities were significant determinants for giving massage (OR = 0.36, 95% CI = 0.19-0.68 and OR = 8.92, 95% CI = 4.37-18.21, respectively). Being a female therapist significantly increased the odds for providing weight reduction advice (OR = 3.60, 95% CI = 1.12-11.57). No patient characteristics, such as age, pain or co-morbidity, were significantly associated with variation in practice. Factors related to patient characteristics, such as pain severity and co-morbidity, did not seem to explain variation in treatment modalities for patients with knee OA. Variation was associated with the following factors: physiotherapists having Internet

  9. Non-ablative fractional resurfacing in combination with topical tretinoin cream as a field treatment modality for multiple actinic keratosis: a pilot study and a review of other field treatment modalities.

    PubMed

    Prens, Sebastiaan P; de Vries, Karin; Neumann, H A Martino; Prens, Errol P

    2013-06-01

    Actinic keratoses (AK) are premalignant lesions occurring mainly in sun-damaged skin. Current topical treatment options for AK and photo-damaged skin such as liquid nitrogen and electrosurgery are not suitable for field treatment. Otherwise, therapies suitable for field treatment bring along considerable patient discomfort. Non-ablative fractional resurfacing has emerged as a logical treatment option especially for field treatment of AK. To evaluate the clinical efficacy of fractional laser therapy for clearing AK and improving skin quality. To compare patient friendliness of the "fractional" therapy with those reported for other field treatment modalities. Ten patients with Fitzpatrick skin type I to III with multiple AK and extensive sun-damaged skin, received 5-10 sessions with a 4-week interval using a 1550 nm Erbium-Glass Fractionated laser (Sellas, Korea). Four weeks and 24 weeks after the last treatment the clinical results were evaluated by an independent physician. The mean degree of improvement, in terms of reduction in the number of AK and improvement of skin texture, was 54% on a 4 point PGA scale, and persisted for approximately 6 months. The biggest advantage of fractional laser treatment, besides the eradication of AK and a clear rejuvenation effect, is the absence of "downtime". Fractional non-ablative resurfacing induces significant reduction in the number of AK and improves the skin quality. Also all patients preferred fractional laser therapy above other AK treatment modalities.

  10. Targeting Neovascularization in Ischemic Retinopathy: Recent Advances

    PubMed Central

    Al-Shabrawey, Mohamed; Elsherbiny, Mohamed; Nussbaum, Julian; Othman, Amira; Megyerdi, Sylvia; Tawfik, Amany

    2014-01-01

    Pathological retinal neovascularization (RNV) is a common micro-vascular complication in several retinal diseases including retinopathy of prematurity, diabetic retinopathy, age-related macular degeneration and central vein occlusion. The current therapeutic modalities of RNV are invasive and although they may slow or halt the progression of the disease they are unlikely to restore normal acuity. Therefore, there is an urgent need to develop treatment modalities, which are less invasive and therefore associated with fewer procedural complications and systemic side effects. This review article summarizes our understanding of the pathophysiology and current treatment of RNV in ischemic retinopathies; lists potential therapeutic targets; and provides a framework for the development of future treatment modalities. PMID:25598837

  11. Treatment modality preferences and adherence to group treatment for panic disorder with agoraphobia.

    PubMed

    Perreault, Michel; Julien, Dominic; White, Noé Djawn; Bélanger, Claude; Marchand, André; Katerelos, Theodora; Milton, Diana

    2014-06-01

    To examine the relationship between preference for group psychotherapy and adherence to group cognitive-behavioral therapy (CBT) for clients with panic disorder with agoraphobia (PDA), 109 participants experiencing PDA completed a questionnaire measuring preference for group treatment (PGTQ) before beginning CBT groups. A t test was used to compare preference scores for group treatment to investigate whether participants who completed treatment differed from those who abandoned treatment. Participants who completed group therapy expressed higher preference for group treatment than participants who dropped out of treatment (t[107] = 1.99; p < 0.05). The PGTQ-4 presented adequate psychometric properties. Reliability analyses of the items retained after factorization demonstrated an acceptable level of internal consistency (Cronbach's alpha of 0.76). Preference for individual or group therapy appears to impact treatment retention for patients with PDA. Matching patients' preferences to the type of treatment modality used appears to be pertinent, especially for the treatment of anxiety disorders. In terms of practical implications, the rationale and benefits of group therapy should be explained to participants reluctant to engage in group therapy. Individual intervention or a combination of group and individual treatment could be considered for clients who are likely to drop out of group therapy.

  12. Treatment modalities and medication recommended by health care professionals for treating recurrent herpes labialis.

    PubMed

    Raborn, G Wayne; Chan, Karen S; Grace, Michael

    2004-01-01

    The authors conducted a survey to determine how health care professionals respond to patients' inquiries about cold sores, also known as recurrent herpes labialis, and their choices of treatment modalities and medications. The authors mailed a one-page, pretested survey to a random sample of dentists, pharmacists and family physicians in Alberta, Canada. After receiving ethics approval from the University of Alberta, Edmonton, the authors mailed 998 surveys. The response rate was 51 percent. Topical antiviral medication was the most common treatment recommended (63 percent). Over-the-counter medication was the first choice for pharmacists (83 percent) as compared with dentists (15 percent) and physicians (16 percent). Emotional stress (60 percent) was reported by patients to be the most common trigger, and pain or discomfort (81 percent) was their primary concern. Acyclovir ointment was the most common antiviral drug recommended or prescribed by health care professionals (60 percent), and cost was the major reason they gave for not recommending or prescribing antiviral drugs (73 percent). The authors found variation in treatment modalities and recommendations by each health profession, despite the fact that patients reported similar triggers and concerns. This may be due to individual patient need and the health care professional's lack of knowledge. Survey results may serve as a reference for health care professionals to use to determine how their choices of medications and treatment modalities compare with those of other practitioners. Professionals should know the benefits and limitations of all therapies, discuss them with the patients and select a treatment.

  13. Hyperbaric Oxygen Therapy—A Novel Treatment Modality in Oral Submucous Fibrosis: A Review

    PubMed Central

    Kumar, M. Ashwini; Radhika, Besta; Reddy, Satya Prakash; Yaga, Uday Shankar

    2015-01-01

    Oral submucous fibrosis (OSMF) is a chronic, debilitating disease characterized by juxta epithelial fibrosis of the oral cavity and regarded as a potentially malignant disorder. Numerous treatment modalities ranging from various drugs to behavioral therapy have been tried with inconsistent results with varying degrees of success reflecting low predictability, requiring further evaluation and standardization. Novel treatment modality such as Hyperbaric oxygen therapy (HBOT) involves inhalation of 100% oxygen at increased atmospheric pressure usually ranging between 2.0 and 2.5 atmospheres for periods between 60 and 120 min. HBOT which can increase oxygen tension and delivery to oxygen-deficient tissue, is a supplementary therapy to improve hypoxic environment of OSMF and also possesses potent anti-inflammatory properties. This article enlightens on possible beneficial effects of HBOT in the management of OSMF at cellular and molecular level. PMID:26155590

  14. A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

    DTIC Science & Technology

    2017-10-01

    Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of...PrCa are non-selective and provide only limited response rate Thus, novel treatment modalities are needed to treat advanced stage PrCa. In this...of ORM on MTA1 protein. Considering effective therapeutic index of ORM, we are also making more potent analogues of ORM. These findings suggest that

  15. Treatment modalities for burning mouth syndrome: a systematic review.

    PubMed

    de Souza, Isadora Follak; Mármora, Belkiss Câmara; Rados, Pantelis Varvaki; Visioli, Fernanda

    2018-06-01

    In the burning mouth syndrome (BMS), patients experience a burning sensation in the oral cavity with no associated injury or clinical manifestation. The etiology of this condition is still poorly understood, and therefore, treatment is challenging. The aim of this study is to perform a systematic review of treatment possibilities described in the literature for BMS. PubMed, Embase, and SciELO databases were searched for randomized clinical trials published between 1996 and 2016. Following application of inclusion and exclusion criteria, 29 papers were analyzed and divided into five subcategories according to the type of treatment described: antidepressants, alpha-lipoic acid, phytotherapeutic agents, analgesic and anti-inflammatory agents, and non-pharmacological therapies. In each category, the results found were compared with regard to the methodology employed, sample size, assessment method, presence or absence of adverse effects, and treatment outcomes. The analysis revealed that the use of antidepressants and alpha-lipoic acid has been showing promising results; however, more studies are necessary before we can have a first-line treatment strategy for patients with BMS. To review systematically the literature about Burning Mouth Syndrome treatment may aid the clinicians to choose the treatment modality to improve patients symptoms based on the best evidence.

  16. Different treatment modalities for refractory vaginismus in western Saudi Arabia.

    PubMed

    Fageeh, Wafa M K

    2011-06-01

    Although vaginismus is a common sexual dysfunction in Saudi Arabia, there are limited data concerning the treatment modalities associated with patients with symptoms of vaginismus. This study is aimed to evaluate the presentation and different modalities of management in patients with severe refractory vaginismus in western Saudi Arabia. Successful penetrative sexual intercourse suggesting that common elements of the therapies used were successful. A retrospective study of patients presenting with severe refractory vaginismus treated in Jeddah, Saudi Arabia. The subjects were 15 women with third to fourth degree vaginismus who presented to King Abdulazziz University Hospital between January 1, 2008 and January 1, 2009. The mean age of the participants was 23 years. The mean duration of marriage before seeking medical advice was 12 months. Six patients had undergone conventional therapy successfully. The other six cases, four of which had a previous history of treatment failure, and two who were unresponsive to 4 months of conventional therapy were offered botulinum toxin type A. Five patients who received the Botox therapy had satisfactory intercourse on the same day of the treatment. One patient required a repeat injection after 2 months for recurrent vaginismus. Three of the 15 patients refused the treatment as they were already divorced and had only come in to exclude organic causes for their condition. Vaginismus is an overlooked topic in conservative societies such as Saudi Arabia. For most patients, not knowing who to confide in or where to turn to plays a major role in the under diagnosis of vaginismus. Conventional therapy proved effective in mild and moderate cases, while botulinum toxin has a more rapid effect and was thus more effective in severe cases. © 2011 International Society for Sexual Medicine.

  17. Ocular sarcoidosis: new diagnostic modalities and treatment.

    PubMed

    Yang, Sung J; Salek, Sherveen; Rosenbaum, James T

    2017-09-01

    Ocular involvement in sarcoidosis is present in up to 80% of patients and is frequently manifested before diagnosis of the underlying systemic disease. Considering the therapeutic consequences, early diagnosis of the underlying disease is advantageous in patients presenting with ocular inflammation. There are several ocular findings suggestive of underlying sarcoidosis, such as granulomatous keratic precipitates, iris nodules, cells in the vitreous humor known as snowballs and snowbanks, and retinal periphlebitis. High suspicion is crucial for the diagnosis of sarcoidosis. This review on ocular sarcoidosis will mainly focus on new diagnostic and treatment modalities. Recent studies found possible new diagnostic indicators for the diagnosis of ocular sarcoidosis which include not only serum profiles but also vitreous sample analysis. Ophthalmologic imaging techniques have improved to investigate the ocular structure in detail. Results from recent uveitis clinical trials have included sarcoidosis as an underlying cause and have reported positive results. The diagnosis of ocular sarcoidosis can be challenging in some cases. High suspicion is important to diagnose ocular sarcoidosis with various laboratory and ophthalmic tools. There are many possible options for the treatment of ocular sarcoidosis including various biologic agents.

  18. Motivation and Readiness for Drug Treatment: Differences by Modality and Special Populations

    PubMed Central

    Melnick, Gerald; Hawke, Josephine; De Leon, George

    2014-01-01

    The purpose of this research is to expand our knowledge of motivational factors among admissions to various substance abuse treatment modalities and among those entering special programs. Differences in motivation are reported in a convenience sample of over 6000 admissions to 38 programs. Results from multilevel analyses show (1) an ordered increase in motivation by settings from referral to out patient, to methadone maintenance, to highest levels in residential programs; (2) significantly lower motivation among admissions to programs for special populations. Results are discussed in relation to the demand characteristics of treatment and non-recovery reasons for entering treatment. PMID:24735224

  19. Motivation and readiness for drug treatment: differences by modality and special populations.

    PubMed

    Melnick, Gerald; Hawke, Josephine; De Leon, George

    2014-01-01

    The purpose of this research is to expand our knowledge of motivational factors among admissions to various substance abuse treatment modalities and among those entering special programs. Differences in motivation are reported in a convenience sample of more than 6,000 admissions to 38 programs. Results from multilevel analyses show (a) an ordered increase in motivation by settings from referral to outpatient, to methadone maintenance, and to the highest levels in residential programs and (b) significantly lower motivation among admissions to programs for special populations. Results are discussed in relation to the demand characteristics of treatment and non-recovery reasons for entering treatment.

  20. The genetic basis of new treatment modalities in melanoma.

    PubMed

    Kunz, Manfred

    2015-01-01

    In recent years, intracellular signal transduction via RAS-RAF-MEK-ERK has been successfully targeted in new treatment approaches for melanoma using small molecule inhibitors against activated BRAF (V600E mutation) and activated MEK1/2. Also mutated c-KIT has been identified as a promising target. Meanwhile, evidence has been provided that combinations between BRAF inhibitors and MEK1/2 inhibitors are more promising than single-agent treatments. Moreover, new treatment algorithms favor sequential treatment using BRAF inhibitors and newly developed immunotherapies targeting common T lymphocyte antigen 4 (CTLA-4) or programmed cell death 1 (PD-1). In depth molecular analyses have uncovered new mechanisms of treatment resistance and recurrence, which may impact on future treatment decisions. Moreover, next-generation sequencing data have shown that recurrent lesions harbor specific genetic aberrations. At the same time, high throughput sequencing studies of melanoma unraveled a series of new treatment candidates for future treatment approaches such as ERBB4, GRIN2A, GRM3, and RAC1. More recent bioinformatic technologies provided genetic evidence for extensive tumor heterogeneity and tumor clonality of solid tumors, which might also be of relevance for melanoma. However, these technologies have not yet been applied to this tumor. In this review, an overview on the genetic basis of current treatment of melanoma, treatment resistance and recurrences including new treatment perspectives based on recent high-throughput sequencing data is provided. Moreover, future aspects of individualized treatment based on each patient's individual mutational landscape are discussed.

  1. Childhood Enuresis: Current Diagnostic Formulations, Salient Findings, and Effective Treatment Modalities.

    PubMed

    Thurber, Steven

    2017-06-01

    Enuresis constitutes a frequently encountered problem area for children that may adversely affect social and emotional adjustment. This type of incontinence has been of concern to the human family for centuries. A brief history of enuresis is presented followed by current conceptualizations, diagnostic criteria, prevalence rates and psychiatric comorbidities. Historic notions of causation together with ineffective, sometimes barbaric treatments are then discussed, ending with a presentation of evidence-based treatment modalities, with the urine alarm being an essential element of effective treatment. An intervention termed dry bed training combines the urine alarm with a series of procedures designed in part to reduce relapse potential and should be a primary consideration for implementation by treatment professionals. Finally, a brief case study is presented illustrating special etiological and treatment considerations with juvenile psychiatric patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Current and emerging therapeutic modalities for hyperhidrosis, part 1: conservative and noninvasive treatments.

    PubMed

    Ram, Ramin; Lowe, Nicholas J; Yamauchi, Paul S

    2007-03-01

    Approximately 1% to 3% of the US population has hyperhidrosis (HH). HH can be an incapacitating medical condition because it not only hinders patient quality of life but also causes the secondary effect of excess cutaneous sweat. There is a broad spectrum of treatment modalities including topical and systemic therapies, iontophoresis, localized neuroinhibitory injections, and surgical interventions. This article reviews HH and the conservative treatments for the condition.

  3. Kinesio taping compared to physical therapy modalities for the treatment of shoulder impingement syndrome.

    PubMed

    Kaya, Erkan; Zinnuroglu, Murat; Tugcu, Ilknur

    2011-02-01

    The purpose of this study was to determine and compare the efficacy of kinesio tape and physical therapy modalities in patients with shoulder impingement syndrome. Patients (n = 55) were treated with kinesio tape (n = 30) three times by intervals of 3 days or a daily program of local modalities (n = 25) for 2 weeks. Response to treatment was evaluated with the Disability of Arm, Shoulder, and Hand scale. Patients were questioned for the night pain, daily pain, and pain with motion. Outcome measures except for the Disability of Arm, Shoulder, and Hand scale were assessed at baseline, first, and second weeks of the treatment. Disability of Arm, Shoulder, and Hand scale was evaluated only before and after the treatment. Disability of Arm, Shoulder, and Hand scale and visual analog scale scores decreased significantly in both treatment groups as compared with the baseline levels. The rest, night, and movement median pain scores of the kinesio taping (20, 40, and 50, respectively) group were statistically significantly lower (p values were 0.001, 0.01, and 0.001, respectively) at the first week examination as compared with the physical therapy group (50, 70, and 70, respectively). However, there was no significant difference in the same parameters between two groups at the second week (0.109, 0.07, and 0.218 for rest, night, and movement median pain scores, respectively). Disability of Arm, Shoulder, and Hand scale scores of the kinesio taping group were significantly lower at the second week as compared with the physical therapy group. No side effects were observed. Kinesio tape has been found to be more effective than the local modalities at the first week and was similarly effective at the second week of the treatment. Kinesio taping may be an alternative treatment option in the treatment of shoulder impingement syndrome especially when an immediate effect is needed.

  4. Psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among American Indians in the Strong Heart Family Study

    PubMed Central

    Jacob, Michelle M.; Gonzales, Kelly L.; Calhoun, Darren; Beals, Janette; Muller, Clemma Jacobsen; Goldberg, Jack; Nelson, Lonnie; Welty, Thomas K.; Howard, Barbara V.

    2013-01-01

    Aims The aims of this paper are to examine the relationship between psychological trauma symptoms and Type 2 diabetes prevalence, glucose control, and treatment modality among 3,776 American Indians in Phase V of the Strong Heart Family Study. Methods This cross-sectional analysis measured psychological trauma symptoms using the National Anxiety Disorder Screening Day instrument, diabetes by American Diabetes Association criteria, and treatment modality by four categories: no medication, oral medication only, insulin only, or both oral medication and insulin. We used binary logistic regression to evaluate the association between psychological trauma symptoms and diabetes prevalence. We used ordinary least squares regression to evaluate the association between psychological trauma symptoms and glucose control. We used binary logistic regression to model the association of psychological trauma symptoms with treatment modality. Results Neither diabetes prevalence (22-31%; p = 0.19) nor control (8.0-8.6; p = 0.25) varied significantly by psychological trauma symptoms categories. However, diabetes treatment modality was associated with psychological trauma symptoms categories, as people with greater burden used either no medication, or both oral and insulin medications (odds ratio = 3.1, p < 0.001). Conclusions The positive relationship between treatment modality and psychological trauma symptoms suggests future research investigate patient and provider treatment decision making. PMID:24051029

  5. Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

    PubMed Central

    Arnold, L. Eugene; Hodgkins, Paul; Caci, Hervé; Kahle, Jennifer; Young, Susan

    2015-01-01

    Background Evaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood. Methods A systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment. Results The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length. Conclusions While the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age

  6. Platelet-rich plasma: combinational treatment modalities for musculoskeletal conditions.

    PubMed

    Andia, Isabel; Abate, Michele

    2018-04-01

    Current research on common musculoskeletal problems, including osteoarticular conditions, tendinopathies, and muscle injuries, focuses on regenerative translational medicine. Platelet-rich plasma therapies have emerged as a potential approach to enhance tissue repair and regeneration. Platelet-rich plasma application aims to provide supraphysiological concentrations of platelets and optionally leukocytes at injured/pathological tissues mimicking the initial stages of healing. However, the efficacy of platelet-rich plasma is controversial in chronic diseases because patients' outcomes show partial improvements. Platelet-rich plasma can be customized to specific conditions by selecting the most appropriate formulation and timing for application or by combining platelet-rich plasma with synergistic or complementary treatments. To achieve this goal, researchers should identify and enhance the main mechanisms of healing. In this review, the interactions between platelet-rich plasma and healing mechanisms were addressed and research opportunities for customized treatment modalities were outlined. The development of combinational platelet-rich plasma treatments that can be used safely and effectively to manipulate healing mechanisms would be valuable and would provide insights into the processes involved in physiological healing and pathological failure.

  7. [Pay attention to the application of the international intraocular retinoblastoma classification and sequential multiple modality treatment].

    PubMed

    Fan, X Q

    2017-08-11

    Retinoblastoma (RB) is the most common intraocular malignancy in childhood. It may seriously affect vision, and even threaten the life. The early diagnosis rate of RB in China remains low, and the majority of patients are at late phase with high rates of enucleation and mortality. The International Intraocular Retinoblastoma Classification and TNM staging system are guidances for therapeutic choices and bases for prognosis evaluation. Based on the sequential multi-method treatment modality, chemotherapy combined with local therapy is the mainstream in dealing with RB, which may maximize the results of eye saving and even vision retaining. New therapeutic techniques including supra-selective ophthalmic artery interventional chemotherapy and intravitreal chemotherapy can further improve the efficacy of treatment, especially the eye salvage rate. The overall level of RB treatment should be improved by promoting the international staging, new therapeutic techniques, and the sequential multiple modality treatment. (Chin J Ophthalmol, 2017, 53: 561 - 565) .

  8. Efficacy of ozone and other treatment modalities for retained placenta in dairy cows.

    PubMed

    Zobel, R; Tkalčić, S

    2013-02-01

    Retained placenta is a worldwide recognized clinical condition in puerperal cows, which can significantly affect their health and fertility. Available treatment modalities are often of questionable efficacy or associated with time constraints, practicality or monetary considerations for their wide application in a routine dairy practice. The objective of this study was to compare and assess the efficacy of different treatment options, including a novel ozone treatment, for the retained placenta. Two hundred cows diagnosed with retained placenta were divided into five treatment groups, each receiving a different treatment option. Group A (n = 40) was given a combination treatment of intrauterine ozone and parenteral cephalexin; group B (n = 40) was given intrauterine ozone; group C (n = 40) was given a combination of parenteral cephalexin and intrauterine antibiotic tablets; group D (n = 40) was given only parenteral cephalexin and group E (n = 40) was given parenteral prostaglandins in 11-day intervals. The control group (group Z, n = 200) included cows that gave birth without assistance and were not diagnosed with a retained placenta. The ozone treatment (groups A and B) was found to be the most effective modality resulting in the shortest period of days open, the smallest number of artificial inseminations until pregnancy, the smallest number of animals diagnosed with fever within 10 days post-calving, the highest percentage of animals pregnant within 200 days after calving and the smallest number of animals culled because of infertility, when compared to the other treatment groups. The intrauterine ozone flush therefore has a potential as an efficacious and cost-effective treatment option for retained placenta, with an overall positive effect on puerperal health and fertility in cows. © 2012 Blackwell Verlag GmbH.

  9. A refined surgical treatment modality for bromhidrosis: Subcutaneous scissor with micropore.

    PubMed

    Dai, Yeqin; Xu, Ai-E; He, Junhua

    2017-05-01

    Axillary bromhidrosis has a strong negative effect on one's social life. A high success rate and few complications are criteria for a surgical treatment. The objective of this study was to evaluate a new surgical treatment modality for bromhidrosis: subcutaneous scissor with micropore. Twenty patients with bromhidrosis were treated. Patients were placed in a supine position with their treated arms abducted to 110°. After injection of 60 mL of tumescent solution into each axilla, one small incision was made at the middle axillary of the hair-bearing area. The whole hair-bearing skin was undermined at the level of the superficial fat to obtain adequate skin eversion. The flaps were everted to offer full exposure of the apocrine glands, and meticulous excision of each gland was performed. Both sides were punctured with scalpel. The micropore was used for drainage, and whose width was just 3 mm. Finally, the incisions were re-approximated, and bulky compressive dressings were applied to the area for 72 hours. Of the 40 axillae (20 patients), 34 (85.0%) showed excellent results, and six (15.0%) had good results. Malodor was significantly decreased. There were no serious complications. This technique can produce excellent results with a lower complication rate than most other surgical modalities and can be performed without costly equipment. © 2017 Wiley Periodicals, Inc.

  10. In vivo tumor-targeted dual-modal fluorescence/CT imaging using a nanoprobe co-loaded with an aggregation-induced emission dye and gold nanoparticles.

    PubMed

    Zhang, Jimei; Li, Chan; Zhang, Xu; Huo, Shuaidong; Jin, Shubin; An, Fei-Fei; Wang, Xiaodan; Xue, Xiangdong; Okeke, C I; Duan, Guiyun; Guo, Fengguang; Zhang, Xiaohong; Hao, Jifu; Wang, Paul C; Zhang, Jinchao; Liang, Xing-Jie

    2015-02-01

    As an intensely studied computed tomography (CT) contrast agent, gold nanoparticle has been suggested to be combined with fluorescence imaging modality to offset the low sensitivity of CT. However, the strong quenching of gold nanoparticle on fluorescent dyes requires complicated design and shielding to overcome. Herein, we report a unique nanoprobe (M-NPAPF-Au) co-loading an aggregation-induced emission (AIE) red dye and gold nanoparticles into DSPE-PEG(2000) micelles for dual-modal fluorescence/CT imaging. The nanoprobe was prepared based on a facile method of "one-pot ultrasonic emulsification". Surprisingly, in the micelles system, fluorescence dye (NPAPF) efficiently overcame the strong fluorescence quenching of shielding-free gold nanoparticles and retained the crucial AIE feature. In vivo studies demonstrated the nanoprobe had superior tumor-targeting ability, excellent fluorescence and CT imaging effects. The totality of present studies clearly indicates the significant potential application of M-NPAPF-Au as a dual-modal non-invasive fluorescence/X-ray CT nanoprobe for in vivo tumor-targeted imaging and diagnosis. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Online control of reaching and pointing to visual, auditory, and multimodal targets: Effects of target modality and method of determining correction latency.

    PubMed

    Holmes, Nicholas P; Dakwar, Azar R

    2015-12-01

    Movements aimed towards objects occasionally have to be adjusted when the object moves. These online adjustments can be very rapid, occurring in as little as 100ms. More is known about the latency and neural basis of online control of movements to visual than to auditory target objects. We examined the latency of online corrections in reaching-to-point movements to visual and auditory targets that could change side and/or modality at movement onset. Visual or auditory targets were presented on the left or right sides, and participants were instructed to reach and point to them as quickly and as accurately as possible. On half of the trials, the targets changed side at movement onset, and participants had to correct their movements to point to the new target location as quickly as possible. Given different published approaches to measuring the latency for initiating movement corrections, we examined several different methods systematically. What we describe here as the optimal methods involved fitting a straight-line model to the velocity of the correction movement, rather than using a statistical criterion to determine correction onset. In the multimodal experiment, these model-fitting methods produced significantly lower latencies for correcting movements away from the auditory targets than away from the visual targets. Our results confirm that rapid online correction is possible for auditory targets, but further work is required to determine whether the underlying control system for reaching and pointing movements is the same for auditory and visual targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Glypican-1-antibody-conjugated Gd–Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer

    PubMed Central

    Zhu, Huanhuan; Le, Wenjun; Cui, Shaobin; Chen, Xin; Li, Wei; Zhang, Fulei; Huang, Yong; Sh, Donglu; Cui, Zheng; Shao, Chengwei; Chen, Bingdi

    2018-01-01

    Introduction Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. Materials and methods In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd–Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Results Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s−1 mM−1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s−1 mM−1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Conclusion Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC. PMID:29750031

  13. Glypican-1-antibody-conjugated Gd-Au nanoclusters for FI/MRI dual-modal targeted detection of pancreatic cancer.

    PubMed

    Huang, Xin; Fan, Chengqi; Zhu, Huanhuan; Le, Wenjun; Cui, Shaobin; Chen, Xin; Li, Wei; Zhang, Fulei; Huang, Yong; Sh, Donglu; Cui, Zheng; Shao, Chengwei; Chen, Bingdi

    2018-01-01

    Pancreatic cancer (PC) has a poor prognosis with high mortality, due to the lack of effective early diagnostic and prognostic tools. In order to target and diagnose PC, we developed a dual-modal imaging probe using Glypican-1 (GPC-1) antibody conjugated with Gd-Au nanoclusters (NCs; Gd-Au-NC-GPC-1). GPC-1 is a type of cell surface heparan sulfate proteoglycan, which is often highly expressed in PC. The probe was successfully prepared with a hydrodynamic diameter ranging from 13.5 to 24.4 nm. Spectral characteristics showed absorption at 280 nm and prominent emission at 650 nm. Confocal microscopic imaging showed effective detection of GPC-1 highly expressed PC cells by Gd-Au-NC-GPC-1, which was consistent with flow cytometry results. In vitro relaxivity characterization demonstrated that the r1 value of the probe was 17.722 s -1 mM -1 Gd, which was almost 4 times higher compared with that of Gd-diethylenetriaminepentacetate (DTPA; r1 value =4.6 s -1 mM -1 Gd). Gd-Au-NC-GPC-1 exhibited similar magnetic resonance (MR) signals when compared to Gd-DTPA even at lower Gd concentrations. Much higher MR signals were registered in PC cells (COLO-357) compared with normal cells (293T). Furthermore, Gd-Au-NC-GPC-1 could effectively detect PC cells in vivo by dual-modal fluorescence imaging/magnetic resonance imaging (FI/MRI) at 30 minutes postinjection. In addition, Gd-Au-NC-GPC-1 did not show significant biotoxicity to normal cells at tested concentrations both in vitro and in vivo. Gd-Au-NC-GPC-1 has demonstrated to be a promising dual-modal FI/MRI contrast agent for targeted diagnosis of PC.

  14. Pseudofolliculitis barbae: review and update on new treatment modalities.

    PubMed

    Garcia-Zuazaga, Jorge

    2003-07-01

    Pseudofolliculits barbae, PFB, is a common cutaneous disease encountered frequently in medical practice. PFB represents a chronic inflammatory condition of the hair follicle caused by ingrown hairs producing an inflammatory foreign body reaction. The pathogenesis of PFB is multifactorial. Factors such as hair type and direction of hair growth play a role in the initial inflammatory reaction. In the armed forces, PFB represents a real challenge for both the physician and the patient. The combat environment, with the recent threat of biological and chemical weapons, requires the servicemen to be clean-shaven for appropriate gas mask fitting around the face. This article will review the etiology, pathogenesis, classification, and newer treatment modalities in the management of PFB.

  15. Biomimetic one-pot synthesis of gold nanoclusters/nanoparticles for targeted tumor cellular dual-modality imaging

    NASA Astrophysics Data System (ADS)

    Lin, Jing; Zhou, Zhijun; Li, Zhiming; Zhang, Chunlei; Wang, Xiansong; Wang, Kan; Gao, Guo; Huang, Peng; Cui, Daxiang

    2013-04-01

    Biomimetic synthesis has become a promising green pathway to prepare nanomaterials. In this study, bovine serum albumin (BSA)-conjugated gold nanoclusters/nanoparticles were successfully synthesized in water at room temperature by a protein-directed, solution-phase, green synthetic method. The synthesized BSA-Au nanocomplexes have fluorescence emission (588 nm) of gold nanoclusters and surface plasmon resonance of gold nanoparticles. The BSA-Au nanocomplexes display non-cytotoxicity and excellent biocompatibility on MGC803 gastric cancer cells. After conjugation of folic acid molecules, the obtained BSA-Au nanocomplexes showed highly selective targeting for MGC803 cells and dual-modality dark-field and fluorescence imaging.

  16. ADMultiImg: a novel missing modality transfer learning based CAD system for diagnosis of MCI due to AD using incomplete multi-modality imaging data

    NASA Astrophysics Data System (ADS)

    Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

    2018-02-01

    Alzheimer's Disease (AD) is the most common cause of dementia and currently has no cure. Treatments targeting early stages of AD such as Mild Cognitive Impairment (MCI) may be most effective to deaccelerate AD, thus attracting increasing attention. However, MCI has substantial heterogeneity in that it can be caused by various underlying conditions, not only AD. To detect MCI due to AD, NIA-AA published updated consensus criteria in 2011, in which the use of multi-modality images was highlighted as one of the most promising methods. It is of great interest to develop a CAD system based on automatic, quantitative analysis of multi-modality images and machine learning algorithms to help physicians more adequately diagnose MCI due to AD. The challenge, however, is that multi-modality images are not universally available for many patients due to cost, access, safety, and lack of consent. We developed a novel Missing Modality Transfer Learning (MMTL) algorithm capable of utilizing whatever imaging modalities are available for an MCI patient to diagnose the patient's likelihood of MCI due to AD. Furthermore, we integrated MMTL with radiomics steps including image processing, feature extraction, and feature screening, and a post-processing for uncertainty quantification (UQ), and developed a CAD system called "ADMultiImg" to assist clinical diagnosis of MCI due to AD using multi-modality images together with patient demographic and genetic information. Tested on ADNI date, our system can generate a diagnosis with high accuracy even for patients with only partially available image modalities (AUC=0.94), and therefore may have broad clinical utility.

  17. Retrospective study of the physical therapy modalities applied in head and neck l ymphedema treatment.

    PubMed

    Tacani, Pascale Mutti; Franceschini, Juliana Pereira; Tacani, Rogério Eduardo; Machado, Aline Fernanda Perez; Montezello, Débora; Góes, João Carlos Guedes Sampaio; Marx, Angela

    2016-02-01

    Secondary lymphedema after head and neck cancer treatment is a serious complication and its management can be a challenge. The purpose of this study was to verify which physical therapy modalities were applied in the treatment of head and neck lymphedema through a retrospective analysis. A retrospective study was developed, based on the analysis of medical records of 32 patients treated in the physiotherapy outpatient department of the Brazilian Institute of Cancer Control (IBCC). The physiotherapy included manual lymphatic drainage, massage, exercises, patient education, and compression therapy with an average of 23.9 ± 14.8 sessions. Measurement results showed a significant reduction of face and neck lymphedema (p < .05) and pain (from 7.8 ± 2.2 to 3.6 ± 1.6; p < .001). The physical therapy modalities based on strategic manual lymphatic drainage, shoulder girdle massage, facial, tongue and neck exercises, compressive therapy at home, and patient education showed reduction of the lymphedema and pain, both of them secondary to head and neck cancer treatment. © 2014 Wiley Periodicals, Inc.

  18. Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea.

    PubMed

    Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

    2016-11-01

    Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP.This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA.Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively.The MAD treatment resulted in a significant reduction in apnea-hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA.These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP.

  19. Therapeutic outcomes of mandibular advancement devices as an initial treatment modality for obstructive sleep apnea

    PubMed Central

    Park, Pona; Jeon, Hyoung Won; Han, Doo Hee; Won, Tae-Bin; Kim, Dong-Young; Rhee, Chae-Seo; Kim, Hyun Jik

    2016-01-01

    Abstract Although continuous positive airway pressure (CPAP) is a highly efficacious treatment for obstructive sleep apnea (OSA), there is a need for alternative treatment options, such as sleep surgeries and mandibular advancement devices (MADs), to overcome the limitations of CPAP. This study aimed to analyze the therapeutic outcomes of OSA subjects who were treated with a MAD, and to estimate the clinical impact of MAD as a first-line treatment for OSA. Forty-seven patients diagnosed with OSA received an adjustable MAD as an initial treatment. Drug-induced sleep endoscopic findings and sleep parameters (both pre-MAD and post-MAD treatment), such as apnea index, oxygen saturation, and degree of daytime sleepiness, were assessed retrospectively. The MAD treatment resulted in a significant reduction in apnea–hypopnea index, and also a significant elevation in lowest oxygen saturation. Satisfactory results of MAD treatment as a first treatment modality were observed in 27 patients, and a successful outcome was reached in approximately 72% of patients. The OSA patients who had lower body mass index and upper airway narrowing at the level of palate and tongue base showed relatively higher rates of a satisfactory outcome even in cases of moderate or severe OSA. These results suggest that the use of a MAD may be an alternative treatment option in OSA patients with retropalatal and retroglossal area narrowing regardless of disease severity. Additionally, MADs can be recommended as an initial treatment modality, and the effectiveness of MADs in achieving success may not be inferior to CPAP. PMID:27861349

  20. High energy devices versus low energy devices in orthopedics treatment modalities

    NASA Astrophysics Data System (ADS)

    Schultheiss, Reiner

    2003-10-01

    The orthopedic consensus group defined in 1997 the 42 most likely relevant parameters of orthopedic shock wave devices. The idea of this approach was to correlate the different clinical outcomes with the physical properties of the different devices with respect to their acoustical waves. Several changes in the hypothesis of the dose effect relationship have been noticed since the first orthopedic treatments. The relation started with the maximum pressure p+, followed by the total energy, the energy density; and finally the single treatment approach using high, and then the multiple treatment method using low energy. Motivated by the reimbursement situation in Germany some manufacturers began to redefine high and low energy devices independent of the treatment modality. The OssaTron as a high energy, single treatment electro hydraulic device gained FDA approval as the first orthopedic ESWT device for plantar fasciitis and, more recently, for lateral epicondylitis. Two low energy devices have now also gained FDA approval based upon a single treatment. Comparing the acoustic data, differences between the OssaTron and the other devices are obvious and will be elaborated upon. Cluster analysis of the outcomes and the acoustical data are presented and new concepts will be suggested.

  1. Derivation of mean dose tolerances for new fractionation schemes and treatment modalities

    NASA Astrophysics Data System (ADS)

    Perkó, Zoltán; Bortfeld, Thomas; Hong, Theodore; Wolfgang, John; Unkelbach, Jan

    2018-02-01

    Avoiding toxicities in radiotherapy requires the knowledge of tolerable organ doses. For new, experimental fractionation schemes (e.g. hypofractionation) these are typically derived from traditional schedules using the biologically effective dose (BED) model. In this report we investigate the difficulties of establishing mean dose tolerances that arise since the mean BED depends on the entire spatial dose distribution, rather than on the dose level alone. A formula has been derived to establish mean physical dose constraints such that they are mean BED equivalent to a reference treatment scheme. This formula constitutes a modified BED equation where the influence of the spatial dose distribution is summarized in a single parameter, the dose shape factor. To quantify effects we analyzed 24 liver cancer patients for whom both proton and photon IMRT treatment plans were available. The results show that the standard BED equation—neglecting the spatial dose distribution—can overestimate mean dose tolerances for hypofractionated treatments by up to 20%. The shape difference between photon and proton dose distributions can cause 30-40% differences in mean physical dose for plans having identical mean BEDs. Converting hypofractionated, 5/15-fraction proton doses to mean BED equivalent photon doses in traditional 35-fraction regimens resulted in up to 10 Gy higher doses than applying the standard BED formula. The dose shape effect should be accounted for to avoid overestimation of mean dose tolerances, particularly when estimating constraints for hypofractionated regimens. Additionally, tolerances established for one treatment modality cannot necessarily be applied to other modalities with drastically different dose distributions, such as proton therapy. Last, protons may only allow marginal (5-10%) dose escalation if a fraction-size adjusted organ mean dose is constraining instead of a physical dose.

  2. [Modalities in the treatment of obstructive breathing in sleep].

    PubMed

    Vukčević, Miodrag

    2011-01-01

    The goals of OSAS therapy are to improve daytime symptoms especially excessive sleepiness, prevent neurocognitve, metabolic and cardiovascular consequences and quality of life in patients with sleep apnea. A variety of therapy exist starting from general measures that include weight reduction, change in life style, postional therapy, oral devices, upper airway surgery and pharmacotherapy. However, CPAP has been demonstrated to be the most important and highly effective therapy in these disorders. CPAP therapy dramatically improves symptoms and decreases cadriovascular and metabolic consequences stoping the occurence of the apneas. Hoewer, not all patients tolerate CPAP especially patients with milder forms of the disease. The individualised approach wich pay attention to different phenotypes and genotype could select patients for selecitively acting treatment modalities such us mandibular advancement devices and electical stimulation of the upper airway muscles.

  3. Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality.

    PubMed

    Iskandar, Shelly; de Jong, Cor Aj; Hidayat, Teddy; Siregar, Ike Mp; Achmad, Tri H; van Crevel, Reinout; van der Ven, Andre

    2012-01-01

    In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs. PWID were recruited by respondent-driven sampling in an urban setting in Java, Indonesia and interviewed with the Addiction Severity Index (ASI), Blood-Borne Virus Transmission Risk Assessment Questionnaires, and Knowledge Questionnaire on HIV/AIDS. The information regarding the use of substance abuse treatment and HIV program were based on questions in ASI. Seventy-seven percent of 210 PWID had accessed SAT at least once. PWID who had accessed a SAT modality reported more severe drug problems. The most widely used SAT were opioid substitution (57%) and traditional/faith-based treatment (56%). Accessing substitution treatment (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5-13.9) or residential drug-free treatment (adjusted OR = 3.7; 95% CI: 1.4-9.7) was significantly associated with HIV testing, whereas accessing substitution treatment (adjusted OR = 3.8; 95% CI: 1.9-7.5) or other medical services (adjusted OR = 3.1; 95% CI: 1.1-8.7) was significantly associated with HIV treatment. There was no significant association between accessing traditional/faith-based treatment and HIV testing and treatment. Efforts should be made to link HIV services with traditional/faith-based treatment to increase the coverage of HIV programs.

  4. Spatial Analysis of Case-Mix and Dialysis Modality Associations

    PubMed Central

    Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

    2016-01-01

    ♦ Background: Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ Methods: The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ Result: The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ Conclusions: The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be

  5. Spatial Analysis of Case-Mix and Dialysis Modality Associations.

    PubMed

    Phirtskhalaishvili, Tamar; Bayer, Florian; Edet, Stephane; Bongiovanni, Isabelle; Hogan, Julien; Couchoud, Cécile

    2016-01-01

    ♦ Health-care systems must attempt to provide appropriate, high-quality, and economically sustainable care that meets the needs and choices of patients with end-stage renal disease (ESRD). France offers 9 different modalities of dialysis, each characterized by dialysis technique, the extent of professional assistance, and the treatment site. The aim of this study was 1) to describe the various dialysis modalities in France and the patient characteristics associated with each of them, and 2) to analyze their regional patterns to identify possible unexpected associations between case-mixes and dialysis modalities. ♦ The clinical characteristics of the 37,421 adult patients treated by dialysis were described according to their treatment modality. Agglomerative hierarchical cluster analysis was used to aggregate the regions into clusters according to their use of these modalities and the characteristics of their patients. ♦ The gradient of patient characteristics was similar from home hemodialyis (HD) to in-center HD and from non-assisted automated peritoneal dialysis (APD) to assisted continuous ambulatory peritoneal dialysis (CAPD). Analyzing their spatial distribution, we found differences in the patient case-mix on dialysis across regions but also differences in the health-care provided for them. The classification of the regions into 6 different clusters allowed us to detect some unexpected associations between case-mixes and treatment modalities. ♦ The 9 modalities of treatment available make it theoretically possible to adapt treatment to patients' clinical characteristics and abilities. However, although we found an overall appropriate association of dialysis modalities to the case-mix, major inter-region heterogeneity and the low rate of peritoneal dialysis (PD) and home HD suggest that factors besides patients' clinical conditions impact the choice of dialysis modality. The French organization should now be evaluated in terms of patients' quality of

  6. Colorectal Cancer Screening: Stool DNA and Other Noninvasive Modalities.

    PubMed

    Bailey, James R; Aggarwal, Ashish; Imperiale, Thomas F

    2016-03-01

    Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.

  7. Multi-Modality Phantom Development

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

    Huber, Jennifer S.; Peng, Qiyu; Moses, William W.

    2009-03-20

    Multi-modality imaging has an increasing role in the diagnosis and treatment of a large number of diseases, particularly if both functional and anatomical information are acquired and accurately co-registered. Hence, there is a resulting need for multi modality phantoms in order to validate image co-registration and calibrate the imaging systems. We present our PET-ultrasound phantom development, including PET and ultrasound images of a simple prostate phantom. We use agar and gelatin mixed with a radioactive solution. We also present our development of custom multi-modality phantoms that are compatible with PET, transrectal ultrasound (TRUS), MRI and CT imaging. We describe bothmore » our selection of tissue mimicking materials and phantom construction procedures. These custom PET-TRUS-CT-MRI prostate phantoms use agargelatin radioactive mixtures with additional contrast agents and preservatives. We show multi-modality images of these custom prostate phantoms, as well as discuss phantom construction alternatives. Although we are currently focused on prostate imaging, this phantom development is applicable to many multi-modality imaging applications.« less

  8. Systematic review of treatment modalities for gingival depigmentation: a random-effects poisson regression analysis.

    PubMed

    Lin, Yi Hung; Tu, Yu Kang; Lu, Chun Tai; Chung, Wen Chen; Huang, Chiung Fang; Huang, Mao Suan; Lu, Hsein Kun

    2014-01-01

    Repigmentation variably occurs with different treatment methods in patients with gingival pigmentation. A systemic review was conducted of various treatment modalities for eliminating melanin pigmentation of the gingiva, comprising bur abrasion, scalpel surgery, cryosurgery, electrosurgery, gingival grafts, and laser techniques, to compare the recurrence rates (Rrs) of these treatment procedures. Electronic databases, including PubMed, Web of Science, Google, and Medline were comprehensively searched, and manual searches were conducted for studies published from January 1951 to June 2013. After applying inclusion and exclusion criteria, the final list of articles was reviewed in depth to achieve the objectives of this review. A Poisson regression was used to analyze the outcome of depigmentation using the various treatment methods. The systematic review was based on case reports mainly. In total, 61 eligible publications met the defined criteria. The various therapeutic procedures showed variable clinical results with a wide range of Rrs. A random-effects Poisson regression showed that cryosurgery (Rr = 0.32%), electrosurgery (Rr = 0.74%), and laser depigmentation (Rr = 1.16%) yielded superior result, whereas bur abrasion yielded the highest Rr (8.89%). Within the limit of the sampling level, the present evidence-based results show that cryosurgery exhibits the optimal predictability for depigmentation of the gingiva among all procedures examined, followed by electrosurgery and laser techniques. It is possible to treat melanin pigmentation of the gingiva with various methods and prevent repigmentation. Among those treatment modalities, cryosurgery, electrosurgery, and laser surgery appear to be the best choices for treating gingival pigmentation. © 2014 Wiley Periodicals, Inc.

  9. Cold atmospheric plasma, a novel promising anti-cancer treatment modality.

    PubMed

    Yan, Dayun; Sherman, Jonathan H; Keidar, Michael

    2017-02-28

    Over the past decade, cold atmospheric plasma (CAP), a near room temperature ionized gas has shown its promising application in cancer therapy. Two CAP devices, namely dielectric barrier discharge and plasma jet, show significantly anti-cancer capacity over dozens of cancer cell lines in vitro and several subcutaneous xenograft tumors in vivo. In contrast to conventional anti-cancer approaches and drugs, CAP is a selective anti-cancer treatment modality. Thus far establishing the chemical and molecular mechanism of the anti-cancer capacity of CAP is far from complete. In this review, we provide a comprehensive introduction of the basics of CAP, state of the art research in this field, the primary challenges, and future directions to cancer biologists.

  10. Characteristics and use of treatment modalities of patients with binge-eating disorder in the Department of Veterans Affairs.

    PubMed

    Bellows, Brandon K; DuVall, Scott L; Kamauu, Aaron W C; Supina, Dylan; Pawaskar, Manjiri; Babcock, Thomas; LaFleur, Joanne

    2016-04-01

    In 2013 binge-eating disorder (BED) was recognized as a formal diagnosis, but was historically included under the diagnosis code for eating disorder not otherwise specified (EDNOS). This study compared the characteristics and use of treatment modalities in BED patients to those with EDNOS without BED (EDNOS-only) and to matched-patients with no eating disorders (NED). Patients were identified for this study from electronic health records in the Department of Veterans Affairs from 2000 to 2011. Patients with BED were identified using natural language processing and patients with EDNOS-only were identified by ICD-9 code (307.50). First diagnosis defined index date for these groups. NED patients were frequency matched to BED patients up to 4:1, as available, on age, sex, BMI, depression, and index month encounter. Baseline characteristics and use of treatment modalities during the post-index year were compared using t-tests or chi-square tests. There were 593 BED, 1354 EDNOS-only, and 1895 matched-NED patients identified. Only 68 patients with BED had an EDNOS diagnosis. BED patients were younger (48.7 vs. 49.8years, p=0.04), more were male (72.2% vs. 62.8%, p<0.001) and obese (BMI 40.2 vs. 37.0, p<0.001) than EDNOS-only patients. In the follow-up period fewer BED (68.0%) than EDNOS-only patients (87.6%, p<0.001), but more BED than NED patients (51.9%, p<0.001) used at least one treatment modality. The characteristics of BED patients were different from those with EDNOS-only and NED as was their use of treatment modalities. These differences highlight the need for a separate identifier of BED. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Physical modalities in chronic pain management.

    PubMed

    Rakel, Barbara; Barr, John O

    2003-09-01

    The following conclusions can be made based on review of the evidence: There is limited but positive evidence that select physical modalities are effective in managing chronic pain associated with specific conditions experienced by adults and older individuals. Overall, studies have provided the most support for the modality of therapeutic exercise. Different physical modalities have similar magnitudes of effects on chronic pain. Therefore, selection of the most appropriate physical modality may depend on the desired functional outcome for the patient, the underlying impairment, and the patient's preference or prior experience with the modality. Certain patient characteristics may decrease the effectiveness of physical modalities, as has been seen with TENS. These characteristics include depression, high trait anxiety, a powerful others locus of control, obesity, narcotic use, and neuroticism. The effect on pain by various modalities is generally strongest in the short-term period immediately after the intervention series, but effects can last as long as 1 year after treatment (e.g., with massage). Most research has tested the effect of physical modalities on chronic low back pain and knee OA. The effectiveness of physical modalities for other chronic pain conditions needs to be evaluated more completely. Older and younger adults often experience similar effects on their perception of pain from treatment with physical modalities. Therefore, use of these modalities for chronic pain in older adults is appropriate, but special precautions need to be taken. Practitioners applying physical modalities need formal training that includes the risks and precautions for these modalities. If practitioners lack formal training in the use of physical modalities, or if modality use is not within their scope of practice, it is important to consult with and refer patients to members of the team who have this specialized training. Use of a multidisciplinary approach to chronic pain

  12. Aging and response interference across sensory modalities.

    PubMed

    Guerreiro, Maria J S; Adam, Jos J; Van Gerven, Pascal W M

    2014-06-01

    Advancing age is associated with decrements in selective attention. It was recently hypothesized that age-related differences in selective attention depend on sensory modality. The goal of the present study was to investigate the role of sensory modality in age-related vulnerability to distraction, using a response interference task. To this end, 16 younger (mean age = 23.1 years) and 24 older (mean age = 65.3 years) adults performed four response interference tasks, involving all combinations of visual and auditory targets and distractors. The results showed that response interference effects differ across sensory modalities, but not across age groups. These results indicate that sensory modality plays an important role in vulnerability to distraction, but not in age-related distractibility by irrelevant spatial information.

  13. IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

    DTIC Science & Technology

    2013-02-01

    therapies (surgery, radiation and chemotherapy) have reached a therapeutic ceiling in improving the five- year overall survival rate of non-small cell...poor understanding of the disease and its resistance to the therapy . Lung cancer is a heterogeneous disease, resulting from accumulated genetic... a new promising approach to treatment of lung cancer. The program project IMPACT has proposed to integrate targeted therapy in the lung cancer

  14. Selective targeting of bioengineered platelets to prostate cancer vasculature: new paradigm for therapeutic modalities

    PubMed Central

    Montecinos, Viviana P; Morales, Claudio H; Fischer, Thomas H; Burns, Sarah; San Francisco, Ignacio F; Godoy, Alejandro S; Smith, Gary J

    2015-01-01

    Androgen deprivation therapy (ADT) provides palliation for most patients with advanced prostate cancer (CaP); however, greater than 80% subsequently fail ADT. ADT has been indicated to induce an acute but transient destabilization of the prostate vasculature in animal models and humans. Human re-hydrated lyophilized platelets (hRL-P) were investigated as a prototype for therapeutic agents designed to target selectively the tumour-associated vasculature in CaP. The ability of hRL-P to bind the perturbed endothelial cells was tested using thrombin- and ADP-activated human umbilical vein endothelial cells (HUVEC), as well as primary xenografts of human prostate tissue undergoing acute vascular involution in response to ADT. hRL-P adhered to activated HUVEC in a dose-responsive manner. Systemically administered hRL-P, and hRL-P loaded with super-paramagnetic iron oxide (SPIO) nanoparticles, selectively targeted the ADT-damaged human microvasculature in primary xenografts of human prostate tissue. This study demonstrated that hRL-P pre-loaded with chemo-therapeutics or nanoparticles could provide a new paradigm for therapeutic modalities to prevent the rebound/increase in prostate vasculature after ADT, inhibiting the transition to castration-recurrent growth. PMID:25736582

  15. Ego mechanisms of defense are associated with patients' preference of treatment modality independent of psychological distress in end-stage renal disease.

    PubMed

    Hyphantis, Thomas; Katsoudas, Spiros; Voudiclari, Sonia

    2010-03-24

    Several parameters mediate the selection of treatment modality in end-stage renal disease (ESRD). The nephrology community suggests that patient preference should be the prime determinant of modality choice. We aimed to test whether ego mechanisms of defense are associated with patients' treatment modality preferences, independent of psychological distress. In 58 eligible ESRD patients who had themselves chosen their treatment modality, we administered the Symptom Distress Checklist-90-R and the Defense Style Questionnaire. Thirty-seven patients (53.4%) had chosen hemodialysis and 21 (46.6%) peritoneal dialysis. Patients who preferred peritoneal dialysis were younger (odds ratio [OR], 0.89; 95% confidence interval [CI]: 0.804-0.988), had received more education (OR, 8.84; 95% CI: 1.301-60.161), and were twice as likely to adopt an adaptive defense style as compared to patients who preferred hemodialysis (57.1% vs 27.0%, respectively; P < 0.033). On the contrary, the latter were more likely to adopt an image-distorting defense style (35.1% vs 14.3%; P = 0.038) and passive-aggressive defenses (OR, 0.73: 95% CI: 0.504-1.006). These results were independent of psychological distress. Our findings indicate that the patient's personality should be taken into account, if we are to better define which modalities are best suited to which patients. Also, physicians should bear in mind passive-aggressive behaviors that warrant attention and intervention in patients who preferred hemodialysis.

  16. Successful testing and treating of HIV/AIDS in Indonesia depends on the addiction treatment modality

    PubMed Central

    Iskandar, Shelly; de Jong, Cor AJ; Hidayat, Teddy; Siregar, Ike MP; Achmad, Tri H; van Crevel, Reinout; van der Ven, Andre

    2012-01-01

    Background In many settings, people who inject drugs (PWID) have limited access to human immunodeficiency virus (HIV) care which is provided in several hospitals and primary health centers in big cities. Substance abuse treatment (SAT) can be used as the entry-point to HIV programs. The aim of this study is to describe the characteristics of the PWID who had accessed SAT and determine which SAT modality associates significantly with HIV programs. Methods PWID were recruited by respondent-driven sampling in an urban setting in Java, Indonesia and interviewed with the Addiction Severity Index (ASI), Blood-Borne Virus Transmission Risk Assessment Questionnaires, and Knowledge Questionnaire on HIV/AIDS. The information regarding the use of substance abuse treatment and HIV program were based on questions in ASI. Results Seventy-seven percent of 210 PWID had accessed SAT at least once. PWID who had accessed a SAT modality reported more severe drug problems. The most widely used SAT were opioid substitution (57%) and traditional/faith-based treatment (56%). Accessing substitution treatment (adjusted odds ratio [OR] = 5.8; 95% confidence interval [CI]: 2.5–13.9) or residential drug-free treatment (adjusted OR = 3.7; 95% CI: 1.4–9.7) was significantly associated with HIV testing, whereas accessing substitution treatment (adjusted OR = 3.8; 95% CI: 1.9–7.5) or other medical services (adjusted OR = 3.1; 95% CI: 1.1–8.7) was significantly associated with HIV treatment. There was no significant association between accessing traditional/faith-based treatment and HIV testing and treatment. Conclusion Efforts should be made to link HIV services with traditional/faith-based treatment to increase the coverage of HIV programs. PMID:23293529

  17. Treat-to-target trials in diabetes.

    PubMed

    Wangnoo, Subhash K; Sethi, Bipin; Sahay, Rakesh K; John, Mathew; Ghosal, Samit; Sharma, Surendra K

    2014-03-01

    Treat-to-target is a therapeutic concept that considers well defined and specific physiologic targets as aims in controlling the pathophysiology of the disease. It has been widely used in diseases that pathophysiology includes, chronic metabolic and physiological disturbances, namely rheumatic conditions, vascular medicine and diabetes. In diabetes, the availability of "gold-standard" quantitative measures like fasting plasma glucose and glycated hemoglobin make the application of treat-to-target trials especially pertinent. Treatment modalities which have used single therapeutic agents or combinations or in combination with a variety of titration algorithms and implementation protocols have broadened our understanding of diabetes management with specific reference to insulin initiation and maintenance. Treat-to-target trials have been used to investigate a wide variety of questions including efficacy, safety, effect of treatment on comorbidities and patient satisfaction, ideal mechanisms to implement insulin initiation etc. A more generalized acceptance and implementation of treat-to-target trials may finally revolutionize diabetes management by combining aspects of individual care with standard treatment protocols.

  18. Solitary plasmacytoma: population-based analysis of survival trends and effect of various treatment modalities in the USA.

    PubMed

    Thumallapally, Nishitha; Meshref, Ahmed; Mousa, Mohammed; Terjanian, Terenig

    2017-01-05

    Solitary plasmacytoma (SP) is a localized neoplastic plasma cell disorder with an annual incidence of less than 450 cases. Given the rarity of this disorder, it is difficult to conduct large-scale population studies. Consequently, very limited information on the disorder is available, making it difficult to estimate the incidence and survival rates. Furthermore, limited information is available on the efficacy of various treatment modalities in relation to primary tumor sites. The data for this retrospective study were drawn from the Surveillance, Epidemiology and End Results (SEER) database, which comprises 18 registries; patient demographics, treatment modalities and survival rates were obtained for those diagnosed with SP from 1998 to 2007. Various prognostic factors were analyzed via Kaplan-Meier analysis and log-rank test, with 5-year relative survival rate defined as the primary outcome of interest. Cox regression analysis was employed in the multivariate analysis. The SEER search from 1998 to 2007 yielded records for 1691 SP patients. The median age at diagnosis was 63 years. The patient cohort was 62.4% male, 37.6% female, 80% Caucasian, 14.6% African American and 5.4% other races. Additionally, 57.8% had osseous plasmacytoma, and 31.9% had extraosseous involvement. Unspecified plasmacytoma was noted in 10.2% of patients. The most common treatment modalities were radiotherapy (RT) (48.8%), followed by combination surgery with RT (21.2%) and surgery alone (11.6%). Univariate analysis of prognostic factors revealed that the survival outcomes were better for younger male patients who received RT with surgery (p < 0.05). Additionally, patients who received neoadjuvant RT had increased survival rates compared to those receiving adjuvant RT (86% vs 73%, p < 0.05). Furthermore, the analyses revealed that 5-year survival rates for patients with axial plasmacytoma were superior when RT was combined with surgery (p < 0.05). In the multivariate analysis

  19. Novel minimally invasive multi-modality monitoring modalities in neurocritical care.

    PubMed

    Al-Mufti, Fawaz; Smith, Brendan; Lander, Megan; Damodara, Nitesh; Nuoman, Rolla; El-Ghanem, Mohammad; Kamal, Naveed; Al-Marsoummi, Sarmad; Alzubaidi, Basim; Nuoaman, Halla; Foreman, Brandon; Amuluru, Krishna; Gandhi, Chirag D

    2018-07-15

    Elevated intracranial pressure (ICP) following brain injury contributes to poor outcomes for patients, primarily by reducing the caliber of cerebral vasculature, and thereby reducing cerebral blood flow. Careful monitoring of ICP is critical in these patients in order to determine prognosis, implement treatment when ICP becomes elevated, and to judge responsiveness to treatment. Currently, the gold standard for monitoring is invasive pressure transducers, usually an intraventricular monitor, which presents significant risk of infection and hemorrhage. These risks made discovering non-invasive methods for monitoring ICP and cerebral perfusion a priority for researchers. Herein we sought to review recent publications on novel minimally invasive multi-modality monitoring techniques that provide surrogate data on ICP, cerebral oxygenation, metabolism and blood flow. While limitations in various forms preclude them from supplanting the use of invasive monitors, these modalities represent useful screening tools within our armamentarium that may be invaluable when the risks of invasive monitoring outweigh the associated benefits. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Pressure ulcers: Current understanding and newer modalities of treatment

    PubMed Central

    Bhattacharya, Surajit; Mishra, R. K.

    2015-01-01

    This article reviews the mechanism, symptoms, causes, severity, diagnosis, prevention and present recommendations for surgical as well as non-surgical management of pressure ulcers. Particular focus has been placed on the current understandings and the newer modalities for the treatment of pressure ulcers. The paper also covers the role of nutrition and pressure-release devices such as cushions and mattresses as a part of the treatment algorithm for preventing and quick healing process of these wounds. Pressure ulcers develop primarily from pressure and shear; are progressive in nature and most frequently found in bedridden, chair bound or immobile people. They often develop in people who have been hospitalised for a long time generally for a different problem and increase the overall time as well as cost of hospitalisation that have detrimental effects on patient's quality of life. Loss of sensation compounds the problem manifold, and failure of reactive hyperaemia cycle of the pressure prone area remains the most important aetiopathology. Pressure ulcers are largely preventable in nature, and their management depends on their severity. The available literature about severity of pressure ulcers, their classification and medical care protocols have been described in this paper. The present treatment options include various approaches of cleaning the wound, debridement, optimised dressings, role of antibiotics and reconstructive surgery. The newer treatment options such as negative pressure wound therapy, hyperbaric oxygen therapy, cell therapy have been discussed, and the advantages and disadvantages of current and newer methods have also been described. PMID:25991879

  1. Multisensory and Modality-Specific Influences on Adaptation to Optical Prisms

    PubMed Central

    Calzolari, Elena; Albini, Federica; Bolognini, Nadia; Vallar, Giuseppe

    2017-01-01

    Visuo-motor adaptation to optical prisms displacing the visual scene (prism adaptation, PA) is a method used for investigating visuo-motor plasticity in healthy individuals and, in clinical settings, for the rehabilitation of unilateral spatial neglect. In the standard paradigm, the adaptation phase involves repeated pointings to visual targets, while wearing optical prisms displacing the visual scene laterally. Here we explored differences in PA, and its aftereffects (AEs), as related to the sensory modality of the target. Visual, auditory, and multisensory – audio-visual – targets in the adaptation phase were used, while participants wore prisms displacing the visual field rightward by 10°. Proprioceptive, visual, visual-proprioceptive, auditory-proprioceptive straight-ahead shifts were measured. Pointing to auditory and to audio-visual targets in the adaptation phase produces proprioceptive, visual-proprioceptive, and auditory-proprioceptive AEs, as the typical visual targets did. This finding reveals that cross-modal plasticity effects involve both the auditory and the visual modality, and their interactions (Experiment 1). Even a shortened PA phase, requiring only 24 pointings to visual and audio-visual targets (Experiment 2), is sufficient to bring about AEs, as compared to the standard 92-pointings procedure. Finally, pointings to auditory targets cause AEs, although PA with a reduced number of pointings (24) to auditory targets brings about smaller AEs, as compared to the 92-pointings procedure (Experiment 3). Together, results from the three experiments extend to the auditory modality the sensorimotor plasticity underlying the typical AEs produced by PA to visual targets. Importantly, PA to auditory targets appears characterized by less accurate pointings and error correction, suggesting that the auditory component of the PA process may be less central to the building up of the AEs, than the sensorimotor pointing activity per se. These findings

  2. Colon Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Colon cancer treatment often involves open surgical resection as the primary treatment for localized disease. Other modalities include chemotherapy, targeted therapy, radiation therapy, and local ablation. Get detailed information about colon cancer treatment in this summary for clinicians.

  3. [Comparative evaluation of the effectiveness of various treatment modalities for accommodation disorders and acquired progressive myopia].

    PubMed

    Tarutta, E P; Tarasova, N A

    2015-01-01

    To evaluate the effectiveness of non-surgical treatment of accommodation disorders and progressive myopia in children. A total of 190 patients (380 eyes) with myopia aged from 6 to 18 years (10.79±0.18 years on average) were enrolled and divided into 9 groups depending on the treatment prescribed. Comparative evaluation of different hardware-based treatment modalities for progressive myopia allowed to work out their optimal combination: "Visotronic", "MACDEL 09", and magnetophoresis of Taufon 4%. Such courses, provided twice a year, were associated with optimization of accommodative response and 1.9-2.8 times reduction of the rate of myopia progression. On the contrary, pleoptic therapy showed a negative effect on accommodative tonus and the rate of progression of acquired myopia. Comparative evaluation of different hardware-based treatment modalities for progressive myopia and accommodation disorders allowed to work out their optimal combination: "Visotronic", "MACDEL 09" and magnetophoresis of Taufon 4%. This treatment, provided twice a year, allows to increase accommodative reserves and volume, improve objective accommodative response, and reduce accommodative hypertonus as well as the rate of myopia progression (1.9-2.8 times over a 1.5-year period). Under pleoptic therapy (specialized software, near field speckles, color pulse therapy, Ambliokor device), both accommodative tonus and the rate of myopia progression increased (1.3-1.5 and 1.6 times correspondingly).

  4. Selective Attention and Sensory Modality in Aging: Curses and Blessings.

    PubMed

    Van Gerven, Pascal W M; Guerreiro, Maria J S

    2016-01-01

    The notion that selective attention is compromised in older adults as a result of impaired inhibitory control is well established. Yet it is primarily based on empirical findings covering the visual modality. Auditory and especially, cross-modal selective attention are remarkably underexposed in the literature on aging. In the past 5 years, we have attempted to fill these voids by investigating performance of younger and older adults on equivalent tasks covering all four combinations of visual or auditory target, and visual or auditory distractor information. In doing so, we have demonstrated that older adults are especially impaired in auditory selective attention with visual distraction. This pattern of results was not mirrored by the results from our psychophysiological studies, however, in which both enhancement of target processing and suppression of distractor processing appeared to be age equivalent. We currently conclude that: (1) age-related differences of selective attention are modality dependent; (2) age-related differences of selective attention are limited; and (3) it remains an open question whether modality-specific age differences in selective attention are due to impaired distractor inhibition, impaired target enhancement, or both. These conclusions put the longstanding inhibitory deficit hypothesis of aging in a new perspective.

  5. Children's On-Line Processing of Epistemic Modals

    ERIC Educational Resources Information Center

    Moscati, Vincenzo; Zhan, Likan; Zhou, Peng

    2017-01-01

    In this paper we investigated the real-time processing of epistemic modals in five-year-olds. In a simple reasoning scenario, we monitored children's eye-movements while processing a sentence with modal expressions of different force ("might/must"). Children were also asked to judge the truth-value of the target sentences at the end of…

  6. Chained lightning: part III--Emerging technology, novel therapeutic strategies, and new energy modalities for radiosurgery.

    PubMed

    Hoh, Daniel J; Liu, Charles Y; Chen, Joseph C T; Pagnini, Paul G; Yu, Cheng; Wang, Michael Y; Apuzzo, Michael L J

    2007-12-01

    Radiosurgery is fundamentally the harnessing of energy and delivering it to a focal target for a therapeutic effect. The evolution of radiosurgical technology and practice has served toward refining methodologies for better conformal energy delivery. In the past, this has resulted in developing strategies for improved beam generation and delivery. Ultimately, however, our current instrumentation and treatment modalities may be approaching a practical limit with regard to further optimizing energy containment. In looking forward, several strategies are emerging to circumvent these limitations and improve conformal radiosurgery. Refinement of imaging techniques through functional imaging and nanoprobes for cancer detection may benefit lesion localization and targeting. Methods for enhancing the biological effect while reducing radiation-induced changes are being examined through dose fractionation schedules. Radiosensitizers and photosensitizers are being investigated as agents for modulating the biological response of tissues to radiation and alternative energy forms. Discovery of new energy modalities is being pursued through development of microplanar beams, free electron lasers, and high-intensity focused ultrasound. The exploration of these future possibilities will provide the tools for radiosurgical treatment of a broader spectrum of diseases for the next generation.

  7. Automatic selective attention as a function of sensory modality in aging.

    PubMed

    Guerreiro, Maria J S; Adam, Jos J; Van Gerven, Pascal W M

    2012-03-01

    It was recently hypothesized that age-related differences in selective attention depend on sensory modality (Guerreiro, M. J. S., Murphy, D. R., & Van Gerven, P. W. M. (2010). The role of sensory modality in age-related distraction: A critical review and a renewed view. Psychological Bulletin, 136, 975-1022. doi:10.1037/a0020731). So far, this hypothesis has not been tested in automatic selective attention. The current study addressed this issue by investigating age-related differences in automatic spatial cueing effects (i.e., facilitation and inhibition of return [IOR]) across sensory modalities. Thirty younger (mean age = 22.4 years) and 25 older adults (mean age = 68.8 years) performed 4 left-right target localization tasks, involving all combinations of visual and auditory cues and targets. We used stimulus onset asynchronies (SOAs) of 100, 500, 1,000, and 1,500 ms between cue and target. The results showed facilitation (shorter reaction times with valid relative to invalid cues at shorter SOAs) in the unimodal auditory and in both cross-modal tasks but not in the unimodal visual task. In contrast, there was IOR (longer reaction times with valid relative to invalid cues at longer SOAs) in both unimodal tasks but not in either of the cross-modal tasks. Most important, these spatial cueing effects were independent of age. The results suggest that the modality hypothesis of age-related differences in selective attention does not extend into the realm of automatic selective attention.

  8. Basic immunology of antibody targeted radiotherapy

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

    Wong, Jeffrey Y.C.

    2006-10-01

    Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy.

  9. Audiovisual synchrony enhances BOLD responses in a brain network including multisensory STS while also enhancing target-detection performance for both modalities

    PubMed Central

    Marchant, Jennifer L; Ruff, Christian C; Driver, Jon

    2012-01-01

    The brain seeks to combine related inputs from different senses (e.g., hearing and vision), via multisensory integration. Temporal information can indicate whether stimuli in different senses are related or not. A recent human fMRI study (Noesselt et al. [2007]: J Neurosci 27:11431–11441) used auditory and visual trains of beeps and flashes with erratic timing, manipulating whether auditory and visual trains were synchronous or unrelated in temporal pattern. A region of superior temporal sulcus (STS) showed higher BOLD signal for the synchronous condition. But this could not be related to performance, and it remained unclear if the erratic, unpredictable nature of the stimulus trains was important. Here we compared synchronous audiovisual trains to asynchronous trains, while using a behavioral task requiring detection of higher-intensity target events in either modality. We further varied whether the stimulus trains had predictable temporal pattern or not. Synchrony (versus lag) between auditory and visual trains enhanced behavioral sensitivity (d') to intensity targets in either modality, regardless of predictable versus unpredictable patterning. The analogous contrast in fMRI revealed BOLD increases in several brain areas, including the left STS region reported by Noesselt et al. [2007: J Neurosci 27:11431–11441]. The synchrony effect on BOLD here correlated with the subject-by-subject impact on performance. Predictability of temporal pattern did not affect target detection performance or STS activity, but did lead to an interaction with audiovisual synchrony for BOLD in inferior parietal cortex. PMID:21953980

  10. Radiobiological concepts for treatment planning of schemes that combines external beam radiotherapy and systemic targeted radiotherapy

    NASA Astrophysics Data System (ADS)

    Fabián Calderón Marín, Carlos; González González, Joaquín Jorge; Laguardia, Rodolfo Alfonso

    2017-09-01

    The combination of radiotherapy modalities with external bundles and systemic radiotherapy (CIERT) could be a reliable alternative for patients with multiple lesions or those where treatment planning maybe difficult because organ(s)-at-risk (OARs) constraints. Radiobiological models should have the capacity for predicting the biological irradiation response considering the differences in the temporal pattern of dose delivering in both modalities. Two CIERT scenarios were studied: sequential combination in which one modality is executed following the other one and concurrent combination when both modalities are running simultaneously. Expressions are provided for calculation of the dose-response magnitudes Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP). General results on radiobiological modeling using the linear-quadratic (LQ) model are also discussed. Inter-subject variation of radiosensitivity and volume irradiation effect in CIERT are studied. OARs should be under control during the planning in concurrent CIERT treatment as the administered activity is increased. The formulation presented here may be used for biological evaluation of prescriptions and biological treatment planning of CIERT schemes in clinical situation.

  11. Evaluation of the treatment modalities for neurosensory disturbances of the inferior alveolar nerve following retromolar bone harvesting for bone augmentation.

    PubMed

    Nogami, Shinnosuke; Yamauchi, Kensuke; Shiiba, Shunji; Kataoka, Yoshihiro; Hirayama, Bunichi; Takahashi, Tetsu

    2015-03-01

    The purpose of this study was to evaluate the treatment modalities for neurosensory disturbances (NSDs) of the inferior alveolar nerve occurring after retromolar bone harvesting for bone augmentation procedures before implant placement. One hundred four patients, of which 49 and 55 exhibited vertical or horizontal alveolar ridge defects in the mandible and maxilla, respectively, were enrolled. Nineteen patients underwent block bone grafting, 38 underwent guided bone generation or autogenous bone grafting combined with titanium mesh reconstruction, and 47 underwent sinus floor augmentation. Using a visual analog scale, we examined subjective symptoms and discomfort related to sensory alteration within the area of the NSDs in these patients. NSDs were clinically investigated using a two-point discrimination test with blunt-tipped calipers. In addition, neurometry was used for evaluation of trigeminal nerve injury. We tested three treatment modalities for NSDs: follow-up observation (no treatment), medication, and stellate ganglion block (SGB). A week after surgery, 26 patients (25.0%) experienced NSDs. Five patients received no treatment, 10 patients received medication, and 11 patients received SGB. Three months after surgery, patients in the medication and SGB group achieved complete recovery. Current perception threshold values recovered to near-baseline values at 3 months: recovery was much earlier in this group than in the other two groups. SGB can accelerate recovery from NSDs. Our results justify SGB as a reasonable treatment modality for NSDs occurring after the harvesting of retromolar bone grafts. Wiley Periodicals, Inc.

  12. Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics.

    PubMed

    Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

    2017-01-01

    Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe 3 O 4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic- co -glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T 2 -weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality

  13. Luminescent/magnetic PLGA-based hybrid nanocomposites: a smart nanocarrier system for targeted codelivery and dual-modality imaging in cancer theranostics

    PubMed Central

    Shen, Xue; Li, Tingting; Chen, Zhongyuan; Geng, Yue; Xie, Xiaoxue; Li, Shun; Yang, Hong; Wu, Chunhui; Liu, Yiyao

    2017-01-01

    Cancer diagnosis and treatment represent an urgent medical need given the rising cancer incidence over the past few decades. Cancer theranostics, namely, the combination of diagnostics and therapeutics within a single agent, are being developed using various anticancer drug-, siRNA-, or inorganic materials-loaded nanocarriers. Herein, we demonstrate a strategy of encapsulating quantum dots, superparamagnetic Fe3O4 nanocrystals, and doxorubicin (DOX) into biodegradable poly(d,l-lactic-co-glycolic acid) (PLGA) polymeric nanocomposites using the double emulsion solvent evaporation method, followed by coupling to the amine group of polyethyleneimine premodified with polyethylene glycol-folic acid (PEI-PEG-FA [PPF]) segments and adsorption of vascular endothelial growth factor (VEGF)-targeted small hairpin RNA (shRNA). VEGF is important for tumor growth, progression, and metastasis. These drug-loaded luminescent/magnetic PLGA-based hybrid nanocomposites (LDM-PLGA/PPF/VEGF shRNA) were fabricated for tumor-specific targeting, drug/gene delivery, and cancer imaging. The data showed that LDM-PLGA/PPF/VEGF shRNA nanocomposites can codeliver DOX and VEGF shRNA into tumor cells and effectively suppress VEGF expression, exhibiting remarkable synergistic antitumor effects both in vitro and in vivo. The cell viability waŝ14% when treated with LDM-PLGA/PPF/VEGF shRNA nanocomposites ([DOX] =25 μg/mL), and in vivo tumor growth data showed that the tumor volume decreased by 81% compared with the saline group at 21 days postinjection. Magnetic resonance and fluorescence imaging data revealed that the luminescent/magnetic hybrid nanocomposites may also be used as an efficient nanoprobe for enhanced T2-weighted magnetic resonance and fluorescence imaging in vitro and in vivo. The present work validates the great potential of the developed multifunctional LDM-PLGA/PPF/VEGF shRNA nanocomposites as effective theranostic agents through the codelivery of drugs/genes and dual-modality

  14. Chronic Lymphocytic Leukemia Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Chronic lymphocytic leukemia (CLL) treatment options can include observation, steroids, chemotherapy, targeted therapy, and/or stem cell transplant. Get detailed information about newly diagnosed and recurrent CLL and available treatment modalities in this summary for clinicians.

  15. Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

    PubMed

    Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

    2015-01-01

    Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

  16. Optimal Use of Combined Modality Therapy in the Treatment of Esophageal Cancer.

    PubMed

    Shaikh, Talha; Meyer, Joshua E; Horwitz, Eric M

    2017-07-01

    Esophageal cancer is associated with a poor prognosis with 5-year survival rates of approximately 15% to 20%. Although patients with early stage disease may adequately be treated with a single modality, combined therapy typically consisting of neoadjuvant chemoradiation followed by esophagectomy is being adopted increasingly in patients with locally advanced disease. In patients who are not surgical candidates, definitive chemoradiation is the preferred treatment approach. All patients with newly diagnosed esophageal cancer should be evaluated in the multidisciplinary setting by a surgeon, radiation oncologist, and medical oncologist owing to the importance of each specialty in the management of these patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Cervical Cancer Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Cervical cancer treatment modalities include surgery, radiation therapy, chemotherapy and targeted therapy. They may be used alone or in combination depending on tumor volume, spread pattern, and FIGO staging. Get detailed information about cervical cancer treatment in this summary for clinicians.

  18. Influence of auditory spatial attention on cross-modal semantic priming effect: evidence from N400 effect.

    PubMed

    Wang, Hongyan; Zhang, Gaoyan; Liu, Baolin

    2017-01-01

    Semantic priming is an important research topic in the field of cognitive neuroscience. Previous studies have shown that the uni-modal semantic priming effect can be modulated by attention. However, the influence of attention on cross-modal semantic priming is unclear. To investigate this issue, the present study combined a cross-modal semantic priming paradigm with an auditory spatial attention paradigm, presenting the visual pictures as the prime stimuli and the semantically related or unrelated sounds as the target stimuli. Event-related potentials results showed that when the target sound was attended to, the N400 effect was evoked. The N400 effect was also observed when the target sound was not attended to, demonstrating that the cross-modal semantic priming effect persists even though the target stimulus is not focused on. Further analyses revealed that the N400 effect evoked by the unattended sound was significantly lower than the effect evoked by the attended sound. This contrast provides new evidence that the cross-modal semantic priming effect can be modulated by attention.

  19. Neural practice effect during cross-modal selective attention: Supra-modal and modality-specific effects.

    PubMed

    Xia, Jing; Zhang, Wei; Jiang, Yizhou; Li, You; Chen, Qi

    2018-05-16

    Practice and experiences gradually shape the central nervous system, from the synaptic level to large-scale neural networks. In natural multisensory environment, even when inundated by streams of information from multiple sensory modalities, our brain does not give equal weight to different modalities. Rather, visual information more frequently receives preferential processing and eventually dominates consciousness and behavior, i.e., visual dominance. It remains unknown, however, the supra-modal and modality-specific practice effect during cross-modal selective attention, and moreover whether the practice effect shows similar modality preferences as the visual dominance effect in the multisensory environment. To answer the above two questions, we adopted a cross-modal selective attention paradigm in conjunction with the hybrid fMRI design. Behaviorally, visual performance significantly improved while auditory performance remained constant with practice, indicating that visual attention more flexibly adapted behavior with practice than auditory attention. At the neural level, the practice effect was associated with decreasing neural activity in the frontoparietal executive network and increasing activity in the default mode network, which occurred independently of the modality attended, i.e., the supra-modal mechanisms. On the other hand, functional decoupling between the auditory and the visual system was observed with the progress of practice, which varied as a function of the modality attended. The auditory system was functionally decoupled with both the dorsal and ventral visual stream during auditory attention while was decoupled only with the ventral visual stream during visual attention. To efficiently suppress the irrelevant visual information with practice, auditory attention needs to additionally decouple the auditory system from the dorsal visual stream. The modality-specific mechanisms, together with the behavioral effect, thus support the visual

  20. Adoption of endovenous laser treatment as the primary treatment modality for varicose veins: the Auckland City Hospital experience.

    PubMed

    Fernando, Ruchira S W; Muthu, Carl

    2014-08-01

    To assess the effectiveness of adopting endovenous laser treatment (EVLT) as the primary treatment modality for varicose veins at Auckland City Hospital (Auckland, New Zealand). The outcomes of 354 consecutive EVLT procedures performed between 2007 and 2013 were reviewed. Data was collected from a prospectively maintained procedural database and by retrospective chart review. Of the 319 patients who had an ultrasound, at 1 month post-procedure there was a saphenous vein occlusion rate of 96%. Side effects were minimal with no cases of DVT or skin burns and one case of self-limiting neuralgia. The procedure was well tolerated with a median pain score of 3. Since the adoption of EVLT there has been a large increase in the number of patients treated for varicose veins (28 in 2007 compared to 176 in 2013). EVLT is a safe and effective treatment for varicose veins and its adoption has allowed a large increase in the number of varicose vein patients treated at Auckland City Hospital.

  1. Unconscious Cross-Modal Priming of Auditory Sound Localization by Visual Words

    ERIC Educational Resources Information Center

    Ansorge, Ulrich; Khalid, Shah; Laback, Bernhard

    2016-01-01

    Little is known about the cross-modal integration of unconscious and conscious information. In the current study, we therefore tested whether the spatial meaning of an unconscious visual word, such as "up", influences the perceived location of a subsequently presented auditory target. Although cross-modal integration of unconscious…

  2. Treatment Needs of Driving While Intoxicated Offenders: The Need for a Multi-modal Approach to Treatment

    PubMed Central

    Mullen, Jillian; Ryan, Stacy R.; Mathias, Charles W.; Dougherty, Donald M.

    2015-01-01

    Objective This study aimed to characterize and compare the treatment needs of adults with driving while intoxicated (DWI) offenses recruited from a correctional residential treatment facility and the community to provide recommendations for treatment development. Method A total of 119 adults (59 Residential, 60 Community) with at least one DWI offense were administered clinical diagnostic interviews to assess substance use disorders and completed a battery of questionnaires assessing demographic characteristics, legal history, psychiatric diagnoses, medical diagnoses, and health care utilization. Results Almost all (96.6%) DWI offenders met clinical diagnostic criteria for an alcohol use disorder, approximately half of the sample also met diagnostic criteria for co-morbid substance use disorders and a substantial proportion also reported psychiatric and medical co-morbidities. However, a high percentage were not receiving treatment for these issues, most likely as a result of having limited access to care as the majority of participants had no current health insurance (64.45%) or primary care physician (74.0%). The residential sample had more extensive criminal histories compared to the community sample but was generally representative of the community in terms of their clinical characteristics. For instance, the groups did not differ in rates of substance use, psychiatric and medical health diagnoses or in the treatment of such issues, with the exception of alcohol abuse treatment. Conclusions DWI offenders represent a clinical population with high levels of complex and competing treatment needs which are not currently being met. Our findings demonstrate the need for standardized screening of DWI offenders and call for the development of a multi-modal treatment approach in efforts to reduce recidivism. PMID:25664371

  3. Modality comparison for small animal radiotherapy: A simulation study

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

    Bazalova, Magdalena, E-mail: bazalova@stanford.edu; Nelson, Geoff; Noll, John M.

    Purpose: Small animal radiation therapy has advanced significantly in recent years. Whereas in the past dose was delivered using a single beam and a lead shield for sparing of healthy tissue, conformal doses can be now delivered using more complex dedicated small animal radiotherapy systems with image guidance. The goal of this paper is to investigate dose distributions for three small animal radiation treatment modalities. Methods: This paper presents a comparison of dose distributions generated by the three approaches—a single-field irradiator with a 200 kV beam and no image guidance, a small animal image-guided conformal system based on a modified microCTmore » scanner with a 120 kV beam developed at Stanford University, and a dedicated conformal system, SARRP, using a 220 kV beam developed at Johns Hopkins University. The authors present a comparison of treatment plans for the three modalities using two cases: a mouse with a subcutaneous tumor and a mouse with a spontaneous lung tumor. A 5 Gy target dose was calculated using the EGSnrc Monte Carlo codes. Results: All treatment modalities generated similar dose distributions for the subcutaneous tumor case, with the highest mean dose to the ipsilateral lung and bones in the single-field plan (0.4 and 0.4 Gy) compared to the microCT (0.1 and 0.2 Gy) and SARRP (0.1 and 0.3 Gy) plans. The lung case demonstrated that due to the nine-beam arrangements in the conformal plans, the mean doses to the ipsilateral lung, spinal cord, and bones were significantly lower in the microCT plan (2.0, 0.4, and 1.9 Gy) and the SARRP plan (1.5, 0.5, and 1.8 Gy) than in single-field irradiator plan (4.5, 3.8, and 3.3 Gy). Similarly, the mean doses to the contralateral lung and the heart were lowest in the microCT plan (1.5 and 2.0 Gy), followed by the SARRP plan (1.7 and 2.2 Gy), and they were highest in the single-field plan (2.5 and 2.4 Gy). For both cases, dose uniformity was greatest in the single-field irradiator plan

  4. Multi-modal and targeted imaging improves automated mid-brain segmentation

    NASA Astrophysics Data System (ADS)

    Plassard, Andrew J.; D'Haese, Pierre F.; Pallavaram, Srivatsan; Newton, Allen T.; Claassen, Daniel O.; Dawant, Benoit M.; Landman, Bennett A.

    2017-02-01

    The basal ganglia and limbic system, particularly the thalamus, putamen, internal and external globus pallidus, substantia nigra, and sub-thalamic nucleus, comprise a clinically relevant signal network for Parkinson's disease. In order to manually trace these structures, a combination of high-resolution and specialized sequences at 7T are used, but it is not feasible to scan clinical patients in those scanners. Targeted imaging sequences at 3T such as F-GATIR, and other optimized inversion recovery sequences, have been presented which enhance contrast in a select group of these structures. In this work, we show that a series of atlases generated at 7T can be used to accurately segment these structures at 3T using a combination of standard and optimized imaging sequences, though no one approach provided the best result across all structures. In the thalamus and putamen, a median Dice coefficient over 0.88 and a mean surface distance less than 1.0mm was achieved using a combination of T1 and an optimized inversion recovery imaging sequences. In the internal and external globus pallidus a Dice over 0.75 and a mean surface distance less than 1.2mm was achieved using a combination of T1 and FGATIR imaging sequences. In the substantia nigra and sub-thalamic nucleus a Dice coefficient of over 0.6 and a mean surface distance of less than 1.0mm was achieved using the optimized inversion recovery imaging sequence. On average, using T1 and optimized inversion recovery together produced significantly improved segmentation results than any individual modality (p<0.05 wilcox sign-rank test).

  5. On modal cross-coupling in the asymptotic modal limit

    NASA Astrophysics Data System (ADS)

    Culver, Dean; Dowell, Earl

    2018-03-01

    The conditions under which significant modal cross-coupling occurs in dynamical systems responding to high-frequency, broadband forcing that excites many modes is studied. The modal overlap factor plays a key role in the analysis of these systems as the modal density (the ratio of number of modes to the frequency bandwidth) becomes large. The modal overlap factor is effectively the ratio of the width of a resonant peak (the damping ratio times the resonant frequency) to the average frequency interval between resonant peaks (or rather, the inverse of the modal density). It is shown that this parameter largely determines whether substantial modal cross-coupling occurs in a given system's response. Here, two prototypical systems are considered. The first is a simple rectangular plate whose significant modal cross-coupling is the exception rather than the norm. The second is a pair of rectangular plates attached at a point where significant modal cross-coupling is more likely to occur. We show that, for certain cases of modal density and damping, non-negligible cross coupling occurs in both systems. Under similar circumstances, the constraint force between the two plates in the latter system becomes broadband. The implications of this for using Asymptotic Modal Analysis (AMA) in multi-component systems are discussed.

  6. Mental Health Disorder Therapeutic Modalities Modified for the GMS.

    PubMed

    Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

    2017-12-01

    Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. The finding of this review confirms the

  7. Experiential Education, Outdoor Adventure As a Modality in Residential Treatment. A Survey of Programs, Principles, Research and Practice.

    ERIC Educational Resources Information Center

    Duindam, Ton

    Orthopedagogisch Centrum (OC) Michiel is a multifunctional regional institution in the Netherlands that serves troubled families and youth at risk. Outdoor programs are used as a treatment modality for adolescents with behavior disorders, drug addictions, or criminal records. Outward Bound was the first experiential outdoor program in the…

  8. A reformed surgical treatment modality for children with giant cystic craniopharyngioma.

    PubMed

    Zhu, Wanchun; Li, Xiang; He, Jintao; Sun, Tao; Li, Chunde; Gong, Jian

    2017-09-01

    , aspiration of cystic fluid in 2-day interval for continuously 7-10 days, and the delayed tumor resection. This combined treatment modality maybe an effective method to treat children with giant cystic craniopharyngiomas.

  9. Multi-Modality Imaging in the Evaluation and Treatment of Mitral Regurgitation.

    PubMed

    Bouchard, Marc-André; Côté-Laroche, Claudia; Beaudoin, Jonathan

    2017-10-13

    Mitral regurgitation (MR) is frequent and associated with increased mortality and morbidity when severe. It may be caused by intrinsic valvular disease (primary MR) or ventricular deformation (secondary MR). Imaging has a critical role to document the severity, mechanism, and impact of MR on heart function as selected patients with MR may benefit from surgery whereas other will not. In patients planned for a surgical intervention, imaging is also important to select candidates for mitral valve (MV) repair over replacement and to predict surgical success. Although standard transthoracic echocardiography is the first-line modality to evaluate MR, newer imaging modalities like three-dimensional (3D) transesophageal echocardiography, stress echocardiography, cardiac magnetic resonance (CMR), and computed tomography (CT) are emerging and complementary tools for MR assessment. While some of these modalities can provide insight into MR severity, others will help to determine its mechanism. Understanding the advantages and limitations of each imaging modality is important to appreciate their respective role for MR assessment and help to resolve eventual discrepancies between different diagnostic methods. With the increasing use of transcatheter mitral procedures (repair or replacement) for high-surgical-risk patients, multimodality imaging has now become even more important to determine eligibility, preinterventional planning, and periprocedural guidance.

  10. Quality of Life in 807 Patients with Vestibular Schwannoma: Comparing Treatment Modalities.

    PubMed

    Soulier, Géke; van Leeuwen, Bibian M; Putter, Hein; Jansen, Jeroen C; Malessy, Martijn J A; van Benthem, Peter Paul G; van der Mey, Andel G L; Stiggelbout, Anne M

    2017-07-01

    Objective In vestibular schwannoma treatment, the choice among treatment modalities is controversial. The first aim of this study was to examine the quality of life of patients with vestibular schwannoma having undergone observation, radiation therapy, or microsurgical resection. The second aim was to examine the relationship between perceived symptoms and quality of life. Last, the association between quality of life and time since treatment was studied. Study Design Cross-sectional study. Setting Tertiary referral center. Subjects and Methods A total of 1208 patients treated for sporadic vestibular schwannoma between 2004 and 2014 were mailed the disease-specific Penn Acoustic Neuroma Quality of Life (PANQOL) questionnaire and additional questions on symptoms associated with vestibular schwannoma. Total and domain scores were calculated and compared among treatment groups. Propensity scores were used, and results were stratified according to tumor size to control for potential confounders. Correlations were calculated to examine the relationship between self-reported symptoms and quality of life, as well as between quality of life and time since treatment. Results Patients with small tumors (≤10 mm) under observation showed a higher PANQOL score when compared with the radiation therapy and microsurgical resection groups. A strong negative correlation was found between self-reported symptoms and quality of life, with balance problems and vertigo having the largest impact. No correlation was found between PANQOL score and time since treatment. Conclusion This study suggests that patients with small vestibular schwannomas experience better quality of life when managed with observation than do patients who have undergone active treatment.

  11. Modal Logics with Counting

    NASA Astrophysics Data System (ADS)

    Areces, Carlos; Hoffmann, Guillaume; Denis, Alexandre

    We present a modal language that includes explicit operators to count the number of elements that a model might include in the extension of a formula, and we discuss how this logic has been previously investigated under different guises. We show that the language is related to graded modalities and to hybrid logics. We illustrate a possible application of the language to the treatment of plural objects and queries in natural language. We investigate the expressive power of this logic via bisimulations, discuss the complexity of its satisfiability problem, define a new reasoning task that retrieves the cardinality bound of the extension of a given input formula, and provide an algorithm to solve it.

  12. Choice of modality with the use of high-performance membrane and evaluation for clinical effects.

    PubMed

    Masakane, Ikuto

    2011-01-01

    The golden target for dialysis therapy should be to guarantee longer survival and to give a higher quality of life without dialysis-related complications. In order to achieve this target, the choice of dialysis modality and membrane is essential but we have not yet established what the best choice for a dialysis modality and membrane are. Generally, we choose a dialysis modality for better solute removal and better biocompatibility. In this issue we would like to propose that the patients' preference for dialysis therapy is a useful parameter in prescribing the dialysis modality. In our recent experience, chronic dialysis patients have had preferences on a dialysis modality and membrane, those being PMMA, EVAL, AN-69 and pre-dilution online HDF. These modalities could relieve them of uncomfortable dialysis-related symptoms such as insomnia, itchiness, irritability, and so on. Other characteristics of these modalities are of a nutritional advantage, a broad removal pattern of uremic toxins including low-molecular-weight protein and protein-bound uremic toxins, and good biocompatibility free from chemical components of dialysis membrane. In conclusion, patients' symptoms could be a useful parameter to choose a dialysis modality and membrane. Copyright © 2011 S. Karger AG, Basel.

  13. MO-DE-210-03: Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities

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

    Ding, K.

    Ultrasound imaging is an attractive method for image guided radiation treatment (IGRT), by itself or to complement other imaging modalities. It is inexpensive, portable and provides good soft tissue contrast. For challenging soft tissue targets such as pancreatic cancer, ultrasound imaging can be used in combination with pre-treatment MRI and/or CT to transfer important anatomical features for target localization at time of treatment. The non-invasive and non-ionizing nature of ultrasound imaging is particularly powerful for intra-fraction localization and monitoring. Recognizing these advantages, efforts are being made to incorporate novel robotic approaches to position and manipulate the ultrasound probe during irradiation.more » These recent enabling developments hold potential to bring ultrasound imaging to a new level of IGRT applications. However, many challenges, not limited to image registration, robotic deployment, probe interference and image acquisition rate, need to be addressed to realize the full potential of IGRT with ultrasound imaging. Learning Objectives: Understand the benefits and limitations in using ultrasound to augment MRI and/or CT for motion monitoring during radiation therapy delivery. Understanding passive and active robotic approaches to implement ultrasound imaging for intra-fraction monitoring. Understand issues of probe interference with radiotherapy treatment. Understand the critical clinical workflow for effective and reproducible IGRT using ultrasound guidance. The work of X.L. is supported in part by Elekta; J.W. and K.D. is supported in part by a NIH grant R01 CA161613 and by Elekta; D.H. is support in part by a NIH grant R41 CA174089.« less

  14. Online Multi-Modal Robust Non-Negative Dictionary Learning for Visual Tracking

    PubMed Central

    Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

    2015-01-01

    Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality. PMID:25961715

  15. Online multi-modal robust non-negative dictionary learning for visual tracking.

    PubMed

    Zhang, Xiang; Guan, Naiyang; Tao, Dacheng; Qiu, Xiaogang; Luo, Zhigang

    2015-01-01

    Dictionary learning is a method of acquiring a collection of atoms for subsequent signal representation. Due to its excellent representation ability, dictionary learning has been widely applied in multimedia and computer vision. However, conventional dictionary learning algorithms fail to deal with multi-modal datasets. In this paper, we propose an online multi-modal robust non-negative dictionary learning (OMRNDL) algorithm to overcome this deficiency. Notably, OMRNDL casts visual tracking as a dictionary learning problem under the particle filter framework and captures the intrinsic knowledge about the target from multiple visual modalities, e.g., pixel intensity and texture information. To this end, OMRNDL adaptively learns an individual dictionary, i.e., template, for each modality from available frames, and then represents new particles over all the learned dictionaries by minimizing the fitting loss of data based on M-estimation. The resultant representation coefficient can be viewed as the common semantic representation of particles across multiple modalities, and can be utilized to track the target. OMRNDL incrementally learns the dictionary and the coefficient of each particle by using multiplicative update rules to respectively guarantee their non-negativity constraints. Experimental results on a popular challenging video benchmark validate the effectiveness of OMRNDL for visual tracking in both quantity and quality.

  16. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  17. Cancer Nanotechnology: Recent Trends and Developments in Strategies for Targeting Cancer Cells to Improve Cancer Imaging and Treatment.

    PubMed

    Xu, Jingyao; Zhou, Xiaoling; Li, Yifei; Tian, Yudan

    2017-01-01

    Nanotechnology is a multidisciplinary field, which have the potential to cover applications in many subjects such as biology, chemistry and physics. The combined efforts of these subjects can lead to the successful engineering of nanodevices and nanovectors for targeted delivery and sensing/detection of cancer cells/tissues. The modulation of nanomaterials at surface and bulk level further adds value to this technology and develop strategies for early detection of precancerous and malignant cells from biological fluids. Furthermore, the novel nanotechnology-based imaging modalities have the prospects to offer non-invasive cancer imaging and treatment response study in real-time. This review covers the advantages of nanotechnology, which have been exploited for effective and targeted delivery of anti-cancer agents. Moreover, the initiatives taken by National Cancer Laboratory, USA to improve the clinical success of nanomedicines and nanovectors have also been comprehensively summarized. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Androgen Receptor-Targeted Treatments for Prostate Cancer: 35 Years' Progress with Antiandrogens.

    PubMed

    Crawford, E David; Schellhammer, Paul F; McLeod, David G; Moul, Judd W; Higano, Celestia S; Shore, Neal; Denis, Louis; Iversen, Peter; Eisenberger, Mario A; Labrie, Fernand

    2018-05-03

    Antiandrogens inhibit the androgen receptor (AR) and play an important role in the treatment of prostate cancer (PC). This review provides a historical perspective on the development and clinical benefit of antiandrogens in the treatment of PC. We searched PubMed ® for clinical trials with the search terms "antiandrogens" and "prostate cancer" combined with drug names for antiandrogens. This article represents a collaboration of clinical investigators who have made critical scientific contributions leading to the approval of antiandrogens for treating patients with PC. Antiandrogens differ in chemical structure and exert varying efficacy and safety profiles. The unfavorable therapeutic index of steroidal antiandrogens led to their replacement by safer nonsteroidal agents. Flutamide, nilutamide and bicalutamide, designed to target the AR, were developed primarily for use in combination with castration to provide "combined" androgen blockade. Modest clinical benefits were observed with the combination of first-generation antiandrogens and castration vs castration alone. With increased knowledge of the AR structure and its biological functions, a new generation of antiandrogens without agonist activity was designed to provide more potent inhibition of the AR. Randomized clinical trials in patients with metastatic castration-resistant PC exhibited significant survival benefits, which led to the approval, in August 2012, of enzalutamide. Apalutamide was recently approved, while darolutamide is not yet approved in the United States. These next-generation antiandrogens are being actively tested in earlier disease states such as nonmetastatic PC. Evolving knowledge of resistance mechanisms to AR-targeted treatments will stimulate research and drug discovery for additional compounds. Further testing in nonmetastatic castration-resistant PC as well as castration-sensitive disease states will hopefully augment our ability to treat a broader spectrum of PC patients

  19. Use of New Treatment Modalities for Non-small Cell Lung Cancer Care in the Medicare Population

    PubMed Central

    Vest, Michael T.; Herrin, Jeph; Soulos, Pamela R.; Decker, Roy H.; Tanoue, Lynn; Michaud, Gaetane; Kim, Anthony W.; Detterbeck, Frank; Morgensztern, Daniel

    2013-01-01

    Background: Many older patients with early stage non-small cell lung cancer (NSCLC) do not receive curative therapy. New surgical techniques and radiation therapy modalities, such as video-assisted thoracoscopic surgery (VATS), potentially allow more patients to receive treatment. The adoption of these techniques and their impact on access to cancer care among Medicare beneficiaries with stage I NSCLC are unknown. Methods: We used the Surveillance, Epidemiology and End Results-Medicare database to identify patients with stage I NSCLC diagnosed between 1998 and 2007. We assessed temporal trends and created hierarchical generalized linear models of the relationship between patient, clinical, and regional factors and type of treatment. Results: The sample comprised 13,458 patients with a mean age of 75.7 years. The proportion of patients not receiving any local treatment increased from 14.6% in 1998 to 18.3% in 2007. The overall use of surgical resection declined from 75.2% to 67.3% (P < .001), although the proportion of patients undergoing VATS increased from 11.3% to 32.0%. Similarly, although the use of new radiation modalities increased from 0% to 5.2%, the overall use of radiation remained stable. The oldest patients were less likely to receive surgical vs no treatment (OR, 0.12; 95% CI, 0.09-0.16) and more likely to receive radiation vs surgery (OR, 13.61; 95% CI, 9.75-19.0). Conclusion: From 1998 to 2007, the overall proportion of older patients with stage I NSCLC receiving curative local therapy decreased, despite the dissemination of newer, less-invasive forms of surgery and radiation. PMID:23187634

  20. Technological Advances in the Treatment of Cancer: Combining Modalities to Optimize Outcomes.

    PubMed

    Wong, Eric T; Toms, Steven A; Ahluwalia, Manmeet S

    2015-11-01

    The anticancer treatment modality tumor treating fields (TTFields; Optune, Novocure) use the lower frequency range of the electromagnetic spectrum to destroy tumor cells during mitosis. This treatment has been evaluated in several trials of patients with glioblastoma. In these patients, TTFields are delivered through 4 transducer arrays applied to the scalp. In a phase 3 clinical trial of patients with recurrent glioblastoma, TTFields were as effective as chemotherapy, and were associated with fewer and milder systemic toxicities. Data from a phase 3 trial in newly diagnosed glioblastoma suggested that the addition of TTFields to postoperative radiation therapy and chemotherapy represents an important advance in the management of newly diagnosed glioblastoma. Ongoing clinical trials are investigating the efficacy and safety of TTFields in other tumor types, including pancreatic cancer, mesothelioma, ovarian cancer, and non–small cell lung cancer. Other recent advances in the management of cancer have been seen with immunomodulatory therapy, including immune checkpoint inhibitors. Further study will be necessary to evaluate whether TTFields will enhance or impair other established and newly emerging therapies.

  1. A New Modality for Cancer Treatment--Nanoparticle Mediated Microwave Induced Photodynamic Therapy.

    PubMed

    Yao, Mengyu; Ma, Lun; Li, Lihua; Zhang, Junying; Lim, Rebecca; Chen, Wei; Zhang, Yu

    2016-10-01

    Photodynamic therapy (PDT) has attracted ever-growing attention as a promising modality for cancer treatment. However, due to poor tissue penetration by light, photodynamic therapy has rarely been used for deeply situated tumors. This problem can be solved if photosensitizers are activated by microwaves (MW) that are able to penetrate deeply into tissues. Here, for the first time, we report microwave-induced photodynamic therapy and exploit copper cysteamine nanoparticles as a new type of photosensitizer that can be activated by microwaves to produce singlet oxygen for cancer treatment. Both in vitro and in vivo studies on a rat osteosarcoma cell line (UMR 106-01) have shown significant cell destruction using copper cysteamine (Cu-Cy) under microwave activation. The heating effects and the release of copper ions from Cu-Cy upon MW stimulation are the main mechanisms for the generation of reactive oxygen species that are lethal bullets for cancer destruction. The copper cysteamine nanoparticle-based microwave-induced photodynamic therapy opens a new door for treating cancer and other diseases.

  2. Bacterial vaginosis: Etiology and modalities of treatment—A brief note

    PubMed Central

    Kumar, Nikhil; Behera, Beauty; Sagiri, Sai S.; Pal, Kunal; Ray, Sirsendu S.; Roy, Saroj

    2011-01-01

    A large women population of the world is suffering from a vaginal infection commonly known as bacterial vaginosis. The disease is associated with the decrease in the lactobacilli count in the vagina. Till date, there is a lack of full proof treatment modalities for the cure of the disease. The treatment includes the use of antimicrobials and/or acidifying agents and probiotics, either separately or in combination. This note discusses about the etiology and the various present-day modalities of treatment of bacterial vaginosis. PMID:22219582

  3. Mental Health Disorder Therapeutic Modalities Modified for the GMS

    PubMed Central

    Sumneangsanor, Tipsuda; Vuthiarpa, Sararud; Somprasert, Chomchueun

    2017-01-01

    Background: Mental health disorders can affect physical and psychological behaviors. The people of the Greater Mekong Subregion (GMS) have a high risk of mental health disorders, such as depression, stress, and substance abuse be-cause the people in this region are trafficked for forced sex work and various forms of forced labor. In these situations, vic-tims often endure violence and abuse from trafficking recruiters, employers, and other individuals. The purposes of this study were to identify the elements characterizing mental health disorders, especially in terms of depression, stress, and sub-stance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Methods: The researcher undertook a comparative analysis of the literature, reviews of epidemiological studies and mental disorder therapies, and overviews of previous research studies, were used to generate a synthesis of the existing knowledge of the mental disorder therapeutic modalities. Regarding the search methods, the data from the electronic databases PubMed, PsycINFO, Dynamed and ScienceDirect were supplemented with a manual reference search covering relevant studies from 2005 to 2016. Results: Thirty-one papers were included in the review of elements characterizing mental health disorders, especially in terms of depression, stress, and substance abuse, and to identify the treatment modalities for mental health disorders in the GMS. Nine papers defined characterizing mental health disorders, in terms of depression, stress, and substance abuse. Twenty-two papers showed the treatment modalities for mental health disorders that the treatment was effective, these in-cluded pharmacological treatments and psychological treatments, such as mindfulness-based cognitive therapy, biofeedback, and music therapy. Useful guidance can be provided for the prevention and treatment of mental health disorders, and for the care of people in the Greater Mekong Subregion. Conclusion: The

  4. New advances in targeted gastric cancer treatment.

    PubMed

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-08-14

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours.

  5. New advances in targeted gastric cancer treatment

    PubMed Central

    Lazăr, Daniela Cornelia; Tăban, Sorina; Cornianu, Marioara; Faur, Alexandra; Goldiş, Adrian

    2016-01-01

    Despite a decrease in incidence over past decades, gastric cancer remains a major global health problem. In the more recent period, survival has shown only minor improvement, despite significant advances in diagnostic techniques, surgical and chemotherapeutic approaches, the development of novel therapeutic agents and treatment by multidisciplinary teams. Because multiple genetic mutations, epigenetic alterations, and aberrant molecular signalling pathways are involved in the development of gastric cancers, recent research has attempted to determine the molecular heterogeneity responsible for the processes of carcinogenesis, spread and metastasis. Currently, some novel agents targeting a part of these dysfunctional molecular signalling pathways have already been integrated into the standard treatment of gastric cancer, whereas others remain in phases of investigation within clinical trials. It is essential to identify the unique molecular patterns of tumours and specific biomarkers to develop treatments targeted to the individual tumour behaviour. This review analyses the global impact of gastric cancer, as well as the role of Helicobacter pylori infection and the efficacy of bacterial eradication in preventing gastric cancer development. Furthermore, the paper discusses the currently available targeted treatments and future directions of research using promising novel classes of molecular agents for advanced tumours. PMID:27570417

  6. Surgery versus radiation therapy as single-modality treatment of tonsillar fossa carcinoma: the Roswell Park Cancer Institute experience (1971-1991).

    PubMed

    Hicks, W L; Kuriakose, M A; Loree, T R; Orner, J B; Schwartz, G; Mullins, A; Donaldson, C; Winston, J M; Bakamjian, V Y

    1998-07-01

    To compare the efficacy and treatment outcomes in patients with tonsillar fossa cancer using surgery or radiation as a single modality therapy. From 1971 to 1991 239 patients with oral pharyngeal cancer were treated at Roswell Park Cancer Institute. Of these patients 90 had tonsillar carcinoma. Seventy-six of these patients received either surgery (SA) (n = 56) or radiation therapy (RA) (n = 20) as single-modality therapy and are the subject of this review. All patients in the radiation arm of this review were surgical candidates who declined primary surgical therapy. Sixty-three percent of the SA and 80% of the RA treatment groups presented with either stage III or stage IV disease (P < or = .05). Forty-seven percent of the SA group and 52% of the RA patients had clinically positive regional disease at initial presentation. There was a predictable pattern of nodal presentation, with level II the most frequently involved region. The rate of occult metastasis was 27% and was evenly distributed between T1 and T4 disease. The overall local control rate in the SA group was 75%, compared with 60% in the RA group (P value was not significant). The disease-specific survival (all stages) was 61% in the SA group and 37% in the RA group (P < or = .05). The disease-free survival for stage III and stage IV disease in the SA group was 47% and in the RA group 27% (P < or = .05). Survival measured against clinical response to radiation therapy, in complete responders (all stages) was 83%; by contrast there were no survivors past 24 months in the partial response group (P < or = .001). The results from this study suggest that for early disease (stage I/II), surgery or radiation therapy as single-modality treatment is equally effective. For advanced disease radiation therapy is inferior to surgery as a single-modality treatment, as measured by ultimate survival and the local control of disease. There is, however, a subset of patients with advanced disease who respond to radiation

  7. Methotrexate in psoriasis: a systematic review of treatment modalities, incidence, risk factors and monitoring of liver toxicity.

    PubMed

    Montaudié, H; Sbidian, E; Paul, C; Maza, A; Gallini, A; Aractingi, S; Aubin, F; Bachelez, H; Cribier, B; Joly, P; Jullien, D; Le Maître, M; Misery, L; Richard, M-A; Ortonne, J-P

    2011-05-01

    To define practical use and to specify the ideal method for monitoring the liver toxicity of MTX in the management of psoriasis. To systematically review the literature regarding treatment modalities with methotrexate (MTX) in psoriasis, risk of MTX-mediated liver fibrosis and monitoring of hepatic toxicity. A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from 1980 to 2010 searching for randomized controlled trials and observational studies on methods of administering MTX in psoriasis and risk factors and assessment of liver toxicity. We limited the literature search to articles on human subjects over 19 years of age, articles in English or French on psoriasis and articles including psoriatic arthritis and original data. Among 949 references identified, 23 published studies were included. There were no studies focusing directly on the question of MTX treatment modalities. Treatment outcome appears to be dose dependent. A single study in rheumatoid arthritis showed the slightly superior efficacy of subcutaneous administration vs. oral dosing with a similar safety profile. Combination with folic acid may decrease the efficacy of MTX while improving tolerability. The extreme variability of the incidence of hepatic fibrosis in the literature does not allow the risk of hepatic fibrosis to be quantified. Type 2 diabetes and obesity, were associated with a significant increased risk of liver fibrosis. Hepatitis B and C and alcohol consumption were associated with a modest and non-significant increased risk of liver fibrosis. Procollagen III for detection of hepatic fibrosis dosing was the most extensively validated method to monitor liver fibrosis showing a sensitivity of 77.3% and a specificity of 91.5%. The Positive Predictive Value and Negative Predictive Value fluctuated depending on the prevalence of hepatic fibrosis. The sensitivities of the FibroTest and the fibroscan were of 83 and 50%, respectively, with specific

  8. Economic evaluation of bone stimulation modalities: A systematic review of the literature.

    PubMed

    Button, Melissa L; Sprague, Sheila; Gharsaa, Osama; Latouche, Sandra; Bhandari, Mohit

    2009-04-01

    Various bone stimulation modalities are commonly used in treatment of fresh fractures and nonunions; however, the effectiveness and efficiency of these modalities remain uncertain. A systematic review of trials evaluating the clinical and economical outcomes of ultrasounds, electrical stimulation, and extracorporeal sound waves on fracture healing was conducted. We searched four electronic databases for economic evaluations that assessed bone stimulation modalities using ultrasound therapy, electrical stimulation, or extracorporeal shock waves. In addition, we searched the references and related articles of eligible studies, and a content expert was contacted. Information on the clinical and economical outcomes of patients was independently extracted by reviewers. Fourteen studies met the inclusion criteria; therefore, very limited research was found on the cost associated with treatments and the corresponding outcomes. The data available focus primarily on the efficacy of newly introduced treatment methods for bone growth, but failed to incorporate the costs of implementing such treatments. One economic analysis was identified that assessed different treatment paths using ultrasound. A total cost savings of 24-40% per patient occurred when ultrasound was used for fresh fractures and nonunions (grade C recommendation). The results suggest that the ultrasound is a viable alternative for bone stimulation; however, the impacts of the other modalities are left unknown due to the lack of research available. Methodological limitations leave the overall economic and clinical impact of these modalities uncertain. Large, prospective, randomized controlled trials that include cost-effectiveness analyses are needed to further define the clinical effectiveness and financial burden associated with bone stimulation modalities.

  9. Behold the voice of wrath: cross-modal modulation of visual attention by anger prosody.

    PubMed

    Brosch, Tobias; Grandjean, Didier; Sander, David; Scherer, Klaus R

    2008-03-01

    Emotionally relevant stimuli are prioritized in human information processing. It has repeatedly been shown that selective spatial attention is modulated by the emotional content of a stimulus. Until now, studies investigating this phenomenon have only examined within-modality effects, most frequently using pictures of emotional stimuli to modulate visual attention. In this study, we used simultaneously presented utterances with emotional and neutral prosody as cues for a visually presented target in a cross-modal dot probe task. Response times towards targets were faster when they appeared at the location of the source of the emotional prosody. Our results show for the first time a cross-modal attentional modulation of visual attention by auditory affective prosody.

  10. A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma.

    PubMed

    Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

    2016-10-01

    Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on hypoxic tumor metabolism. Further studies are warranted to evaluate B-381 and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma.

  11. TARGETED TREATMENTS IN AUTISM AND FRAGILE X SYNDROME

    PubMed Central

    Gürkan, C. Kağan; Hagerman, Randi J.

    2012-01-01

    Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted as highly heritable, there is no genetic cure at this time. Autism is shown to be linked to several genes and is a feature of some complex genetic disorders, including fragile X syndrome (FXS), fragile X premutation involvement, tuberous sclerosis and Rett syndrome. The term autism spectrum disorders (ASDs) covers autism, Asperger syndrome and pervasive developmental disorders (PDD-NOS) and the etiologies are heterogeneous. In recent years, targeted treatments have been developed for several disorders that have a known specific genetic cause leading to autism. Since there are significant molecular and neurobiological overlaps among disorders, targeted treatments developed for a specific disorder may be helpful in ASD of unknown etiology. Examples of this are two drug classes developed to treat FXS, Arbaclofen, a GABAB agonist, and mGluR5 antagonists, and both may be helpful in autism without FXS. The mGluR5 antagonists are also likely to have a benefit in the aging problems of fragile X premutation carriers, the fragile X –associated tremor ataxia syndrome (FXTAS) and the Parkinsonism that can occur in aging patients with fragile X syndrome. Targeted treatments in FXS which has a well known genetic etiology may lead to new targeted treatments in autism. PMID:23162607

  12. Effectiveness of Treatment Modalities on Kidney Stone Recurrence.

    PubMed

    Zisman, Anna L

    2017-10-06

    Nephrolithiasis is highly prevalent across all demographic groups in the Western world and beyond, and its incidence rates are rising. In addition to the morbidity of the acute event, stone disease often becomes a lifelong problem that requires preventative therapy to diminish ongoing morbidity. Across the majority of stone types, increased fluid intake and targeted dietary modifications are mainstays of therapy. Specific dietary interventions associated with reduced calcium stone risk include adequate dietary calcium intake and restriction of sodium, protein, and oxalate intake, among others. Pharmaceutical therapy may be required if lifestyle changes are insufficient to minimize risk of stone recurrence, and must be targeted to the specific metabolic abnormalities portending risk for a given patient. Therapeutic options for idiopathic calcium stone disease include thiazides, citrate salts, and uric acid-lowering agents. Alkali salts are also the treatment of choice for uric acid stone disease. Management of struvite stone disease is largely surgical, but acetohydroxamic acid is a proven second line therapy. Cystinuria requires lifestyle modifications and may call for thiol-binding agents. Significant heterogeneity of the clinical population with stone disease has previously limited opportunities for large randomized controlled trials. However, as clinical phenotypes and genotypes are increasingly clarified, there are mounting opportunities for targeted randomized controlled trials in stone prevention. In the meantime, the currently available evidence for both lifestyle and pharmacologic interventions is reviewed herein. Copyright © 2017 by the American Society of Nephrology.

  13. Pheochromocytoma and Paraganglioma Treatment (PDQ®)—Health Professional Version

    Cancer.gov

    Pheochromocytoma and paraganglioma treatment is usually surgery, however, preoperative medical preparation is critical. Palliative care for metastatic disease may include chemotherapy, radiation therapy, targeted therapy, and other modalities. Get detailed information in this clinician summary.

  14. SU-E-J-109: Accurate Contour Transfer Between Different Image Modalities Using a Hybrid Deformable Image Registration and Fuzzy Connected Image Segmentation Method.

    PubMed

    Yang, C; Paulson, E; Li, X

    2012-06-01

    To develop and evaluate a tool that can improve the accuracy of contour transfer between different image modalities under challenging conditions of low image contrast and large image deformation, comparing to a few commonly used methods, for radiation treatment planning. The software tool includes the following steps and functionalities: (1) accepting input of images of different modalities, (2) converting existing contours on reference images (e.g., MRI) into delineated volumes and adjusting the intensity within the volumes to match target images (e.g., CT) intensity distribution for enhanced similarity metric, (3) registering reference and target images using appropriate deformable registration algorithms (e.g., B-spline, demons) and generate deformed contours, (4) mapping the deformed volumes on target images, calculating mean, variance, and center of mass as the initialization parameters for consecutive fuzzy connectedness (FC) image segmentation on target images, (5) generate affinity map from FC segmentation, (6) achieving final contours by modifying the deformed contours using the affinity map with a gradient distance weighting algorithm. The tool was tested with the CT and MR images of four pancreatic cancer patients acquired at the same respiration phase to minimize motion distortion. Dice's Coefficient was calculated against direct delineation on target image. Contours generated by various methods, including rigid transfer, auto-segmentation, deformable only transfer and proposed method, were compared. Fuzzy connected image segmentation needs careful parameter initialization and user involvement. Automatic contour transfer by multi-modality deformable registration leads up to 10% of accuracy improvement over the rigid transfer. Two extra proposed steps of adjusting intensity distribution and modifying the deformed contour with affinity map improve the transfer accuracy further to 14% averagely. Deformable image registration aided by contrast adjustment

  15. Imaging Ultrasound Guidance and on-line Estimation of Thermal Behavior in HIFU Exposed Targets

    NASA Astrophysics Data System (ADS)

    Chauhan, Sunita; Haryanto, Amir

    2006-05-01

    Elevated temperatures have been used for many years to combat several diseases including treatment of certain types of cancers/tumors. High Intensity Focused Ultrasound (HIFU) has emerged as a potential non-invasive modality for trackless targeting of deep-seated cancers of human body. For the procedures which require thermal elevation such as hyperthermia and tissue ablation, temperature becomes a parameter of vital importance in order to monitor the treatment on-line. Also, embedding invasive temperature probes for this purpose beats the supremacy of the non-invasive ablating modality. In this paper, we describe the use of a non-invasive and inexpensive conventional imaging ultrasound modality for lesion positioning and estimation of thermal behavior of the tissue on exposure to HIFU. Representative results of our online lesion tracking algorithm for discerning lesioning behavior using image capture, processing and phase-shift measurements are presented.

  16. Fragile X Syndrome and Targeted Treatment Trials

    PubMed Central

    Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

    2014-01-01

    Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism. PMID:22009360

  17. Fragile X syndrome and targeted treatment trials.

    PubMed

    Hagerman, Randi; Lauterborn, Julie; Au, Jacky; Berry-Kravis, Elizabeth

    2012-01-01

    Work in recent years has revealed an abundance of possible new treatment targets for fragile X syndrome (FXS). The use of animal models, including the fragile X knockout mouse which manifests a phenotype very similar to FXS in humans, has resulted in great strides in this direction of research. The lack of Fragile X Mental Retardation Protein (FMRP) in FXS causes dysregulation and usually overexpression of a number of its target genes, which can cause imbalances of neurotransmission and deficits in synaptic plasticity. The use of metabotropic glutamate receptor (mGluR) blockers and gamma amino-butyric acid (GABA) agonists have been shown to be efficacious in reversing cellular and behavioral phenotypes, and restoring proper brain connectivity in the mouse and fly models. Proposed new pharmacological treatments and educational interventions are discussed in this chapter. In combination, these various targeted treatments show promising preliminary results in mitigating or even reversing the neurobiological abnormalities caused by loss of FMRP, with possible translational applications to other neurodevelopmental disorders including autism.

  18. Radiomics based targeted radiotherapy planning (Rad-TRaP): a computational framework for prostate cancer treatment planning with MRI.

    PubMed

    Shiradkar, Rakesh; Podder, Tarun K; Algohary, Ahmad; Viswanath, Satish; Ellis, Rodney J; Madabhushi, Anant

    2016-11-10

    Radiomics or computer - extracted texture features have been shown to achieve superior performance than multiparametric MRI (mpMRI) signal intensities alone in targeting prostate cancer (PCa) lesions. Radiomics along with deformable co-registration tools can be used to develop a framework to generate targeted focal radiotherapy treatment plans. The Rad-TRaP framework comprises three distinct modules. Firstly, a module for radiomics based detection of PCa lesions on mpMRI via a feature enabled machine learning classifier. The second module comprises a multi-modal deformable co-registration scheme to map tissue, organ, and delineated target volumes from MRI onto CT. Finally, the third module involves generation of a radiomics based dose plan on MRI for brachytherapy and on CT for EBRT using the target delineations transferred from the MRI to the CT. Rad-TRaP framework was evaluated using a retrospective cohort of 23 patient studies from two different institutions. 11 patients from the first institution were used to train a radiomics classifier, which was used to detect tumor regions in 12 patients from the second institution. The ground truth cancer delineations for training the machine learning classifier were made by an experienced radiation oncologist using mpMRI, knowledge of biopsy location and radiology reports. The detected tumor regions were used to generate treatment plans for brachytherapy using mpMRI, and tumor regions mapped from MRI to CT to generate corresponding treatment plans for EBRT. For each of EBRT and brachytherapy, 3 dose plans were generated - whole gland homogeneous ([Formula: see text]) which is the current clinical standard, radiomics based focal ([Formula: see text]), and whole gland with a radiomics based focal boost ([Formula: see text]). Comparison of [Formula: see text] against conventional [Formula: see text] revealed that targeted focal brachytherapy would result in a marked reduction in dosage to the OARs while ensuring that the

  19. Treatment modalities in children with teeth affected by molar-incisor enamel hypomineralisation (MIH): A systematic review.

    PubMed

    Lygidakis, N A

    2010-04-01

    This was to review the literature concerning the treatment of permanent teeth with molar-incisor hypomineralised enamel (MIH), comment about possible shortcomings and propose areas of future research. A search of MedLine, Scopus, ResearchGate, Isis and Google Scholar databases was conducted using all terms relevant to the subject. Relevant papers published in English were identified after a review of their titles, abstracts or full reading of the papers. Of 189 references initially found, 66 papers were included; 34 directly relevant to the subject. From the latter, only 14 concerned laboratory or clinical studies dealing with treatment for MIH. Since 2000 11 reviews evaluated, to a certain extent, treatment options for affected teeth. Analysis of the proposed treatment modalities indicated options for prevention, restorations, and adhesion to hypomineralised enamel, full coronal coverage and extraction followed by orthodontics. Based on these findings, a treatment decision plan is proposed. Although treatment approaches for MIH have started to be clearer, long-term clinical trials, supported by laboratory studies, should be conducted to further facilitate the clinical management of this dental defect.

  20. Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor-Associated Angiogenesis

    DTIC Science & Technology

    2016-09-01

    AWARD NUMBER: W81XWH-15-1-0296 TITLE: Targeting MEK5 Enhances Radiosensitivity of Human Prostate Cancer and Impairs Tumor- Associated...3. DATES COVERED 31 Aug 2015 - 30 Aug 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting MEK5 Enhances Radiosensitivity of Human Prostate...therapeutic modality for the treatment of human prostate cancer. However, tumors often demonstrate resistance to ionizing radiation and continue to

  1. Pathways and therapeutic targets in melanoma

    PubMed Central

    Shtivelman, Emma; Davies, Michael A.; Hwu, Patrick; Yang, James; Lotem, Michal; Oren, Moshe; Flaherty, Keith T.; Fisher, David E.

    2014-01-01

    This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma. Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments. Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis. This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors. The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research. The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy. PMID:24743024

  2. Novel Therapeutic Target for the Treatment of Lupus

    DTIC Science & Technology

    2014-09-01

    AWARD NUMBER: W81XWH-12-1-0205 TITLE: Novel Therapeutic Target for the Treatment of Lupus PRINCIPAL INVESTIGATOR: Lisa Laury-Kleintop...SUBTITLE 5a. CONTRACT NUMBER Novel Therapeutic Target for the Treatment of Lupus 5b. GRANT NUMBER W81XWH-12-1-0205 5c. PROGRAM ELEMENT NUMBER 6...Systemic lupus erythematosus, autoantibodies. 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 7 19a. NAME OF

  3. Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

    PubMed Central

    Ostrowski, Robert P.; Stępień, Katarzyna; Pucko, Emanuela; Matyja, Ewa

    2016-01-01

    The effectiveness and efficacy of hyperbaric oxygen (HBO) preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering. PMID:27826422

  4. Thermoresponsive core-shell magnetic nanoparticles for combined modalities of cancer therapy.

    PubMed

    Purushotham, S; Chang, P E J; Rumpel, H; Kee, I H C; Ng, R T H; Chow, P K H; Tan, C K; Ramanujan, R V

    2009-07-29

    Thermoresponsive polymer-coated magnetic nanoparticles loaded with anti-cancer drugs are of considerable interest for novel multi-modal cancer therapies. Such nanoparticles can be used for magnetic drug targeting followed by simultaneous hyperthermia and drug release. Gamma-Fe(2)O(3) iron oxide magnetic nanoparticles (MNP) with average sizes of 14, 19 and 43 nm were synthesized by high temperature decomposition. Composite magnetic nanoparticles (CNP) of 43 nm MNP coated with the thermoresponsive polymer poly-n-isopropylacrylamide (PNIPAM) were prepared by dispersion polymerization of n-isopropylacrylamide monomer in the presence of the MNP. In vitro drug release of doxorubicin-(dox) loaded dehydrated CNP at temperatures below and above the lower critical solution temperature of PNIPAM (34 degrees C) revealed a weak dependence of drug release on swelling behavior. The particles displayed Fickian diffusion release kinetics; the maximum dox release at 42 degrees C after 101 h was 41%. In vitro simultaneous hyperthermia and drug release of therapeutically relevant quantities of dox was achieved, 14.7% of loaded dox was released in 47 min at hyperthermia temperatures. In vivo magnetic targeting of dox-loaded CNP to hepatocellular carcinoma (HCC) in a buffalo rat model was studied by magnetic resonance imaging (MRI) and histology. In summary, the good in vitro and in vivo performance of the doxorubicin-loaded thermoresponsive polymer-coated magnetic nanoparticles suggests considerable promise for applications in multi-modal treatment of cancer.

  5. Dutch modality exclusivity norms: Simulating perceptual modality in space.

    PubMed

    Speed, Laura J; Majid, Asifa

    2017-12-01

    Perceptual information is important for the meaning of nouns. We present modality exclusivity norms for 485 Dutch nouns rated on visual, auditory, haptic, gustatory, and olfactory associations. We found these nouns are highly multimodal. They were rated most dominant in vision, and least in olfaction. A factor analysis identified two main dimensions: one loaded strongly on olfaction and gustation (reflecting joint involvement in flavor), and a second loaded strongly on vision and touch (reflecting joint involvement in manipulable objects). In a second study, we validated the ratings with similarity judgments. As expected, words from the same dominant modality were rated more similar than words from different dominant modalities; but - more importantly - this effect was enhanced when word pairs had high modality strength ratings. We further demonstrated the utility of our ratings by investigating whether perceptual modalities are differentially experienced in space, in a third study. Nouns were categorized into their dominant modality and used in a lexical decision experiment where the spatial position of words was either in proximal or distal space. We found words dominant in olfaction were processed faster in proximal than distal space compared to the other modalities, suggesting olfactory information is mentally simulated as "close" to the body. Finally, we collected ratings of emotion (valence, dominance, and arousal) to assess its role in perceptual space simulation, but the valence did not explain the data. So, words are processed differently depending on their perceptual associations, and strength of association is captured by modality exclusivity ratings.

  6. Inhalable Magnetic Nanoparticles for Targeted Hyperthermia in Lung Cancer Therapy

    PubMed Central

    Sadhukha, Tanmoy; Wiedmann, Timothy Scott; Panyam, Jayanth

    2015-01-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. PMID:23591395

  7. An Event-Related Potential Study of Cross-modal Morphological and Phonological Priming

    PubMed Central

    Justus, Timothy; Yang, Jennifer; Larsen, Jary; de Mornay Davies, Paul; Swick, Diane

    2009-01-01

    The current work investigated whether differences in phonological overlap between the past- and present-tense forms of regular and irregular verbs can account for the graded neurophysiological effects of verb regularity observed in past-tense priming designs. Event-related potentials were recorded from sixteen healthy participants who performed a lexical-decision task in which past-tense primes immediately preceded present-tense targets. To minimize intra-modal phonological priming effects, cross-modal presentation between auditory primes and visual targets was employed, and results were compared to a companion intra-modal auditory study (Justus, Larsen, de Mornay Davies, & Swick, 2008). For both regular and irregular verbs, faster response times and reduced N400 components were observed for present-tense forms when primed by the corresponding past-tense forms. Although behavioral facilitation was observed with a pseudopast phonological control condition, neither this condition nor an orthographic-phonological control produced significant N400 priming effects. Instead, these two types of priming were associated with a post-lexical anterior negativity (PLAN). Results are discussed with regard to dual- and single-system theories of inflectional morphology, as well as intra- and cross-modal prelexical priming. PMID:20160930

  8. Experience with free fibula transfer with screw fixation as a primary modality of treatment for congenital pseudarthosis of tibia in children - Series of 26 cases

    PubMed Central

    Kalra, Guru Dayal Singh; Agarwal, Amit

    2012-01-01

    Background: Congenital pseudarthrosis is one of the greatest challenges of paediatric orthopaedic practice. Treatment options and literature addressing this condition are numerous, reflecting the difficulty in management. We aimed to study the effectiveness of free fibula transfer as a primary modality of treatment in children with this condition in terms of achieving length, union, and normal axis of the involved leg. Materials and Methods: During the period of 2001 to 2010, 26 children with congenital pseudarthrosis of tibia between age group of 2-8 years were evaluated and were reconstructed using contra-lateral free fibula graft, and then patients were followed up for 5 years subsequently. Patients were examined and time of bony union, weight bearing ability and walking without support were noted. Any complication directly or indirectly related to surgery with any complication seen in the due course of follow up of 5 years was also taken care of. Results: In our experience with treatment of congenital pseudarthrosis over a span of 10 years with free fibula transfer, the results have been gratifying with no flap loss. All our patients had UNEVENTFUL post-op recovery. Only 2 patients out of 26 had non-union, for which cancellous bone grafting was done (7.6%). Most of the patients were ambulatory with support by 3-6 months and continued to walk without support after a span of 18-24 months. The incidence of stress fracture in our study over the follow-up period was 4 out of 26 pts (15.3%). None of them had any deformity in the donor leg. Conclusion: When compared to other surgical modalities of treatment of the problem in question, vascularised free fibula transfer has emerged as a real saviour with good patient compliance and less complication rate in our study. It achieves the desired target with no residual deformities and near normal to normal gait with no stigma of bone removal from other leg. PMID:23450675

  9. Combating atherosclerosis with targeted nanomedicines: recent advances and future prospective

    PubMed Central

    Nakhlband, Ailar; Eskandani, Morteza; Saeedi, Nazli; Ghaffari, Samad; Garjani, Alireza

    2018-01-01

    Introduction: Cardiovascular diseases (CVDs) is recognized as the leading cause of mortality worldwide. The increasing prevalence of such disease demands novel therapeutic and diagnostic approaches to overcome associated clinical/social issues. Recent advances in nanotechnology and biological sciences have provided intriguing insights to employ targeted Nanomachines to the desired location as imaging, diagnosis, and therapeutic modalities. Nanomedicines as novel tools for enhanced drug delivery, imaging, and diagnosis strategies have shown great promise to combat cardiovascular diseases. Methods: In the current study, we intend to review the most recent studies on the nano-based strategies for improved management of CVDs. Results: A cascade of events results in the formation of atheromatous plaque and arterial stenosis. Furthermore, recent studies have shown that nanomedicines have displayed unique functionalities and provided de novo applications in the diagnosis and treatment of atherosclerosis. Conclusion: Despite some limitations, nanomedicines hold considerable potential in the prevention, diagnosis, and treatment of various ailments including atherosclerosis. Fewer side effects, amenable physicochemical properties and multi-potential application of such nano-systems are recognized through various investigations. Therefore, it is strongly believed that with targeted drug delivery to atherosclerotic lesions and plaque, management of onset and progression of disease would be more efficient than classical treatment modalities. PMID:29713603

  10. Modality and Task Switching Interactions using Bi-Modal and Bivalent Stimuli

    ERIC Educational Resources Information Center

    Sandhu, Rajwant; Dyson, Benjamin J.

    2013-01-01

    Investigations of concurrent task and modality switching effects have to date been studied under conditions of uni-modal stimulus presentation. As such, it is difficult to directly compare resultant task and modality switching effects, as the stimuli afford both tasks on each trial, but only one modality. The current study investigated task and…

  11. Breast Cancer: Conventional Diagnosis and Treatment Modalities and Recent Patents and Technologies

    PubMed Central

    Nounou, Mohamed I.; ElAmrawy, Fatema; Ahmed, Nada; Abdelraouf, Kamilia; Goda, Satyanarayana; Syed-Sha-Qhattal, Hussaini

    2015-01-01

    Breast cancer is the most prevalent cancer among women worldwide. However, increased survival is due to the dramatic advances in the screening methods, early diagnosis, and breakthroughs in treatments. Over the course of the last decade, many acquisitions have taken place in this critical field of research in the pharmaceutical industry. Advances in molecular biology and pharmacology aided in better understanding of breast cancer, enabling the design of smarter therapeutics able to target cancer and respond to its microenvironment efficiently. Patents and research papers investigating diagnosis and treatment strategies for breast cancer using novel technologies have been surveyed for the past 15 years. Various nanocarriers have been introduced to improve the therapeutic efficacy of anticancer drugs, including liposomes, polymeric micelles, quantum dots, nanoparticles, and dendrimers. This review provides an overview of breast cancer, conventional therapy, novel technologies in the management of breast cancer, and rational approaches for targeting breast cancer. HIGHLIGHTS Breast cancer is the most common cancer in women worldwide. However, survival rates vary widely, optimistically heading toward a positive trend. Increased survival is due to the drastic shift in the screening methods, early diagnosis, and breakthroughs in treatments. Different strategies of breast cancer classification and staging have evolved over the years. Intrinsic (molecular) subtyping is essential in clinical trials and well understanding of the disease. Many novel technologies are being developed to detect distant metastases and recurrent disease as well as to assess response to breast cancer management. Intensive research efforts are actively ongoing to take novel breast cancer therapeutics to potential clinical application. Most of the recent research papers and patents discuss one of the following strategies: the development of new drug entities that specifically target the breast tumor

  12. Targeting of tumor endothelial cells combining 2 Gy/day of X-ray with Everolimus is the effective modality for overcoming clinically relevant radioresistant tumors

    PubMed Central

    Kuwahara, Yoshikazu; Mori, Miyuki; Kitahara, Shuji; Fukumoto, Motoi; Ezaki, Taichi; Mori, Shiro; Echigo, Seishi; Ohkubo, Yasuhito; Fukumoto, Manabu

    2014-01-01

    Radiotherapy is widely used to treat cancer because it has the advantage of physically and functionally conserving the affected organ. To improve radiotherapy and investigate the molecular mechanisms of cellular radioresistance, we established a clinically relevant radioresistant (CRR) cell line, SAS-R, from SAS cells. SAS-R cells continue to proliferate when exposed to fractionated radiation (FR) of 2 Gy/day for more than 30 days in vitro. A xenograft tumor model of SAS-R was also resistant to 2 Gy/day of X-rays for 30 days. The density of blood vessels in SAS-R tumors was higher than in SAS tumors. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, sensitized microvascular endothelial cells to radiation, but failed to radiosensitize SAS and SAS-R cells in vitro. Everolimus with FR markedly reduced SAS and SAS-R tumor volumes. Additionally, the apoptosis of endothelial cells (ECs) increased in SAS-R tumor tissues when both Everolimus and radiation were administered. Both CD34-positive and tomato lectin-positive blood vessel densities in SAS-R tumor tissues decreased remarkably after the Everolimus and radiation treatment. Everolimus-induced apoptosis of vascular ECs in response to radiation was also followed by thrombus formation that leads to tumor necrosis. We conclude that FR combined with Everolimus may be an effective modality to overcome radioresistant tumors via targeting tumor ECs. PMID:24464839

  13. Folate receptor targeted, rare-earth oxide nanocrystals for bi-modal fluorescence and magnetic imaging of cancer cells.

    PubMed

    Setua, Sonali; Menon, Deepthy; Asok, Adersh; Nair, Shantikumar; Koyakutty, Manzoor

    2010-02-01

    Targeted cancer imaging using rare-earth oxide nanocrystals, free from heavy metals (Cd, Se, Te, Hg and Pb), showing bright red-fluorescence and magnetic resonance imaging (MRI) is presented. Y(2)O(3) nanocrystals (YO NC) doped in situ with fluorescent (Eu(3+)) and paramagnetic (Gd(3+)) impurities and conjugated with a potential cancer targeting ligand, folic acid (FA), were prepared using an all-aqueous wet-chemical process. Structural, optical and magnetic properties of these multifunctional nanocrystals were investigated by X-ray diffraction, electron microscopy, photoluminescence and magnetization studies. Highly monodisperse nanocrystals of size approximately 20 nm with cubic bixbyite crystal structure showed bright red-fluorescence when doped with Eu(3+). Co-doping with Gd(3+) and mild air drying resulted significantly enhanced fluorescence quantum efficiency of approximately 60% together with paramagnetic functionality, enabling T(1)-weighted MR contrast with approximately 5 times higher spin-lattice relaxivity compared to the clinically used Gd(3+) contrast agent. Cytotoxicity and reactive oxygen stress studies show no toxicity by YO NC in both normal and cancer cells up to higher doses of 500 microm and longer incubation time, 48h. Cancer targeting capability of FA conjugated NCs was demonstrated on folate receptor positive (FR+) human nasopharyngeal carcinoma cells (KB) with FR depressed KB (FRd) and FR negative (FR-) lung cancer cells A549 as controls. Fluorescence microscopy and flow-cytometry data show highly specific binding and cellular uptake of large concentration of FA conjugated NCs on FR+ve cells compared to the controls. Thus, the present study reveals, unique bi-modal contrast imaging capability, non-toxicity and cancer targeting capability of multiple impurities doped rare-earth oxide nanocrystals that can find promising application in molecular imaging.

  14. Targeted therapies for the treatment of leukemia.

    PubMed

    Stull, Dawn Marie

    2003-05-01

    To review novel targeted therapies for the treatment of leukemia. Professional journals, books, and government publications. Nonspecific cytotoxic chemotherapeutic agents provide marginal therapeutic benefit and significant toxicity when used in the treatment of leukemia. There is a tremendous need for new therapies with increased efficacy and decreased adverse effects. Advances in molecular science, genetics, and immunology, along with improved laboratory technology, have led to the discovery of unique targets integral to the growth and proliferation of malignant cells which are providing the foundation for the development of a new generation of antitumor agents. Nurses must be prepared to educate patients, administer novel therapies, and manage side effects.

  15. Tumor treating fields - an emerging cancer treatment modality.

    PubMed

    Davis, Mary Elizabeth

    2013-08-01

    Tumor treating fields (TTFs) are an evolving new anticancer modality. The U.S. Food and Drug Administration has approved the first device, the NovoTTF-100A™, that uses this technology and is indicated for use in progressive glioblastoma multiforme after standard therapies have failed. Promising clinical trial results will likely lead to expanded uses in primary brain tumors and other cancer types. This article will review the concept of TTFs and their mechanism of action, and overview the TTF device and its approved usage.

  16. Modal analysis using a Fourier analyzer, curve-fitting, and modal tuning

    NASA Technical Reports Server (NTRS)

    Craig, R. R., Jr.; Chung, Y. T.

    1981-01-01

    The proposed modal test program differs from single-input methods in that preliminary data may be acquired using multiple inputs, and modal tuning procedures may be employed to define closely spaced frquency modes more accurately or to make use of frequency response functions (FRF's) which are based on several input locations. In some respects the proposed modal test proram resembles earlier sine-sweep and sine-dwell testing in that broadband FRF's are acquired using several input locations, and tuning is employed to refine the modal parameter estimates. The major tasks performed in the proposed modal test program are outlined. Data acquisition and FFT processing, curve fitting, and modal tuning phases are described and examples are given to illustrate and evaluate them.

  17. MicroRNA-targeted therapeutics for lung cancer treatment.

    PubMed

    Xue, Jing; Yang, Jiali; Luo, Meihui; Cho, William C; Liu, Xiaoming

    2017-02-01

    Lung cancer is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRNAs) are endogenous non-coding small RNAs that repress the expression of a broad array of target genes. Many efforts have been made to therapeutically target miRNAs in cancer treatments using miRNA mimics and miRNA antagonists. Areas covered: This article summarizes the recent findings with the role of miRNAs in lung cancer, and discusses the potential and challenges of developing miRNA-targeted therapeutics in this dreadful disease. Expert opinion: The development of miRNA-targeted therapeutics has become an important anti-cancer strategy. Results from both preclinical and clinical trials of microRNA replacement therapy have shown some promise in cancer treatment. However, some obstacles, including drug delivery, specificity, off-target effect, toxicity mediation, immunological activation and dosage determination should be addressed. Several delivery strategies have been employed, including naked oligonucleotides, liposomes, aptamer-conjugates, nanoparticles and viral vectors. However, delivery remains a main challenge in miRNA-targeting therapeutics. Furthermore, immune-related serious adverse events are also a concern, which indicates the complexity of miRNA-based therapy in clinical settings.

  18. Cross-Modal Retrieval With CNN Visual Features: A New Baseline.

    PubMed

    Wei, Yunchao; Zhao, Yao; Lu, Canyi; Wei, Shikui; Liu, Luoqi; Zhu, Zhenfeng; Yan, Shuicheng

    2017-02-01

    Recently, convolutional neural network (CNN) visual features have demonstrated their powerful ability as a universal representation for various recognition tasks. In this paper, cross-modal retrieval with CNN visual features is implemented with several classic methods. Specifically, off-the-shelf CNN visual features are extracted from the CNN model, which is pretrained on ImageNet with more than one million images from 1000 object categories, as a generic image representation to tackle cross-modal retrieval. To further enhance the representational ability of CNN visual features, based on the pretrained CNN model on ImageNet, a fine-tuning step is performed by using the open source Caffe CNN library for each target data set. Besides, we propose a deep semantic matching method to address the cross-modal retrieval problem with respect to samples which are annotated with one or multiple labels. Extensive experiments on five popular publicly available data sets well demonstrate the superiority of CNN visual features for cross-modal retrieval.

  19. Does sensitivity in binary choice tasks depend on response modality?

    PubMed

    Szumska, Izabela; van der Lubbe, Rob H J; Grzeczkowski, Lukasz; Herzog, Michael H

    2016-07-01

    In most models of vision, a stimulus is processed in a series of dedicated visual areas, leading to categorization of this stimulus, and possible decision, which subsequently may be mapped onto a motor-response. In these models, stimulus processing is thought to be independent of the response modality. However, in theories of event coding, common coding, and sensorimotor contingency, stimuli may be very specifically mapped onto certain motor-responses. Here, we compared performance in a shape localization task and used three different response modalities: manual, saccadic, and verbal. Meta-contrast masking was employed at various inter-stimulus intervals (ISI) to manipulate target visibility. Although we found major differences in reaction times for the three response modalities, accuracy remained at the same level for each response modality (and all ISIs). Our results support the view that stimulus-response (S-R) associations exist only for specific instances, such as reflexes or skills, but not for arbitrary S-R pairings. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. A Hypoxia-Targeted Boron Neutron Capture Therapy Agent for the Treatment of Glioma

    PubMed Central

    Luderer, Micah John; Muz, Barbara; de la Puente, Pilar; Chavalmane, Sanmathi; Kapoor, Vaishali; Marcelo, Raymundo; Biswas, Pratim; Thotala, Dinesh; Rogers, Buck; Azab, Abdel Kareem

    2016-01-01

    Purpose Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation has been limited by the poor tumor selectivity of agents. To address this unmet need, a boronated 2-nitroimidazole derivative (B-381) was synthesized and evaluated for its capability of targeting hypoxic glioma cells. Methods B-381 has been synthesized from a 1-step reaction. Using D54 and U87 glioma cell lines, the in vitro cytotoxicity and cellular accumulation of B-381 has been evaluated under normoxic and hypoxic conditions compared to L-boronophenylalanine (BPA). Furthermore, tumor retention of B-381 was evaluated in vivo. Results B-381 had low cytotoxicity in normal and cancer cells. Unlike BPA, B-381 illustrated preferential retention in hypoxic glioma cells compared to normoxic glioma cells and normal tissues in vitro. In vivo, B-381 illustrated significantly higher long-term tumor retention compared to BPA, with 9.5-fold and 6.5-fold higher boron levels at 24 and 48 h, respectively. Conclusions B-381 represents a new class of BNCT agents in which their selectivity to tumors is based on tumor hypoxic metabolism, and further studies are warranted to evaluate this compound and similar compounds as preclinical candidates for future BNCT clinical trials for the treatment of glioma. PMID:27401411

  1. Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

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

    Halasz, Lia M.; Jacene, Heather A.; Catalano, Paul J.

    2012-08-01

    Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT.more » Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.« less

  2. Nano-displacement sensor based on photonic crystal fiber modal interferometer.

    PubMed

    Dash, Jitendra Narayan; Jha, Rajan; Villatoro, Joel; Dass, Sumit

    2015-02-15

    A stable nano-displacement sensor based on large mode area photonic crystal fiber (PCF) modal interferometer is presented. The compact setup requires simple splicing of a small piece of PCF with a single mode fiber (SMF). The excitation and recombination of modes is carried out in a single splice. The use of a reflecting target creates an extra cavity that discretizes the interference pattern of the mode interferometer, boosting the displacement resolution to nanometer level. The proposed modal interferometric based displacement sensor is highly stable and shows sensitivity of 32  pm/nm.

  3. Tumor responsive targeted multifunctional nanosystems for cancer imaging, chemo- and siRNA therapy

    NASA Astrophysics Data System (ADS)

    Savla, Ronak

    Cancer is one of the most insidious diseases. Compromising of over 100 different types and sharing the unifying factors of uncontrolled growth and metastasis, unmet clinical needs in terms of cancer diagnosis and treatment continue to exist. It is widely accepted that most forms of cancer are treatable or even curable if detected before widespread metastasis occurs. Nearly a quarter of deaths in the United States is the result of cancer and it only trails heart disease in terms of annual mortality. Surgery, chemotherapy, and radiation therapy are the primary treatment modalities for cancer. Research in these procedures has resulted in substantial benefits for cancer patients, but there is still room for an improvement. However, a time has been reached at which it appears that the benefits from these modalities have been reached the maximum. Therefore, it is vital to develop new strategies for the diagnosis and treatment of cancer. The field of nanotechnology is concerned with structures in the nanometer size range and holds the potential to drastically impact and improve the lives of patients suffering from cancer. Not only can nanotechnology improve current methods of diagnosis and treatment, it has a possibility of introducing newer and better modalities. The overall purpose of this work is to develop novel nanotechnology-based methodologies for the diagnosis and treatment of various forms of cancers. The first aim of the project is the development of a multifunctional targeted nanosystem for the delivery of siRNA to overcome drug resistance. The second aspect is the synthesis of a quantum dot-based delivery system that releases drug in response to pH changes. The third aim is the development of a targeted, tumor environment responsive magnetic resonance nanoparticle contrast agent coupled with a nanoparticle-based treatment.

  4. Folic acid-conjugated GdPO4:Tb3+@SiO2 Nanoprobe for folate receptor-targeted optical and magnetic resonance bi-modal imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xianzhu; Zhang, Xiaoying; Wu, Yanli

    2016-11-01

    Both fluorescent and magnetic nanoprobes have great potential applications for diagnostics and therapy. In the present work, a folic acid-conjugated and silica-modified GdPO4:Tb3+ (GdPO4:Tb3+@SiO2-FA) dual nanoprobe was strategically designed and synthesized for the targeted dual-modality optical and magnetic resonance (MR) imaging via a facile aqueous method. Their structural, optical, and magnetic properties were determined using transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared (FTIR), ultraviolet-visible spectra (UV-Vis), photoluminescence (PL), and superconducting quantum interference device (SQUID). These results indicated that GdPO4:Tb3+@SiO2-FA were uniform monodisperse core-shell structured nanorods (NRs) with an average length of 200 nm and an average width of 25 nm. The paramagnetic property of the synthesized GdPO4:Tb3+@SiO2-FA NRs was confirmed with its linear hysteresis plot (M-H). In addition, the NRs displayed an obvious T1-weighted effect and thus it could potentially serve as a T1-positive contrast agent. The NRs emitted green lights due to the 5D4 → 7F5 transition of the Tb3+. The in vitro assays with NCI-H460 lung cancer cells and human embryonic kidney cell line 293T cells indicated that the GdPO4:Tb3+@SiO2-FA nanoprobe could specifically bind the cells bearing folate receptors (FR). The MTT assay of the NRs revealed that its cytotoxicity was very low. Further in vivo MRI experiments distinctively depict enhanced anatomical features in a xenograft tumor. These results suggest that the GdPO4:Tb3+@SiO2-FA NPs have excellent imaging and cell-targeting abilities for the folate receptor-targeted dual-modality optical and MR imaging and can be potentially used as the nanoprobe for bioimaging.

  5. Perception about the importance and use of therapeutic massage as a treatment modality among physical therapists working in Saudi Arabia

    PubMed Central

    Zafar, Hamayun; Oluseye, Kamaldeen; Alghadir, Ahmad; Iqbal, Zaheen A.

    2015-01-01

    [Purpose] To report perceptions about the importance and use of therapeutic massage as a treatment modality among physical therapists working in Saudi Arabia. [Subjects and Methods] A 21-item structured questionnaire was used to assess various domains including the demographic and professional characteristics of physical therapists and their perceptions about the importance and use of therapeutic massage in their daily practice. The questionnaire was uploaded online and the web link was sent to 140 members of the Saudi Physical Therapy Association (SPTA). [Results] The overall response rate was 86%. Among the respondents, 31% reported occasional use of therapeutic massage in their clinical practice, and 55% reported to have received formal training for therapeutic massage. Use of therapeutic massage was more common among female physical therapists. [Conclusion] Many physical therapists working in Saudi Arabia consider therapeutic massage to be an important treatment modality, but its use is relatively limited, either due to the time and effort required to dispense it, or the lack of scientific evidence for its efficacy. PMID:26180330

  6. Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

    PubMed

    Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

    2018-03-15

    Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

  7. Choice of radiotherapy planning modality influences toxicity in the treatment of locally advanced esophageal cancer.

    PubMed

    Mackley, Heath B; Adelstein, Jonathan S; Reddy, Chandana A; Adelstein, David J; Rice, Thomas W; Saxton, Jerrold P; Videtic, Gregory M M

    2008-01-01

    Three-dimensional computed tomography-based radiotherapy planning (3DCTP) is increasingly employed in the treatment of esophageal cancer. It is unknown whether a 3DCTP approach influences outcomes compared to two-dimensional planning (2DP). This study compares clinical outcomes for homogeneously treated patient cohorts stratified by planning modality. A retrospective chart review was conducted on patients with T3/4 and/or node-positive esophageal carcinoma treated at the Cleveland Clinic between July 1, 2003 and May 31, 2006 who were managed with an institutional regimen consisting of preoperative radiotherapy, whether 3DCTP or 2DP [30 Gy/20 fractions/1.5 Gy twice daily over 2 weeks], with concurrent cisplatin and 5-fluorouracil the first week. Following definitive resection, an identical postoperative course of concurrent chemoradiotherapy (CRT) was delivered. One hundred and forty-one patients completed preoperative CRT and were available for review. The median follow-up of living patients is 21.7 months. Fifty-five percent underwent 3DCTP and 45% had 2DP. The treatment groups were similar, with the exception of clinical stage group, with 2DP having more stage II and fewer stage III patients than 3DCTP (p = 0.02). 3DCTP plans had significantly smaller field sizes by area (p < 0.0001). Pathologic response, locoregional control, distant control, and overall survival were equivalent between the two planning modalities. Esophagitis was significantly less common with a 3D approach compared to 2D planning (49% vs. 71%, p = 0.0096), with other toxicities equivalent between the groups. 3DCTP reduces acute esophagitis in patients receiving multimodality therapy for esophageal cancer without compromising clinical outcomes.

  8. Inhalable magnetic nanoparticles for targeted hyperthermia in lung cancer therapy.

    PubMed

    Sadhukha, Tanmoy; Wiedmann, Timothy S; Panyam, Jayanth

    2013-07-01

    Lung cancer (specifically, non-small cell lung cancer; NSCLC) is the leading cause of cancer-related deaths in the United States. Poor response rates and survival with current treatments clearly indicate the urgent need for developing an effective means to treat NSCLC. Magnetic hyperthermia is a non-invasive approach for tumor ablation, and is based on heat generation by magnetic materials, such as superparamagnetic iron oxide (SPIO) nanoparticles, when subjected to an alternating magnetic field. However, inadequate delivery of magnetic nanoparticles to tumor cells can result in sub-lethal temperature change and induce resistance while non-targeted delivery of these particles to the healthy tissues can result in toxicity. In our studies, we evaluated the effectiveness of tumor-targeted SPIO nanoparticles for magnetic hyperthermia of lung cancer. EGFR-targeted, inhalable SPIO nanoparticles were synthesized and characterized for targeting lung tumor cells as well as for magnetic hyperthermia-mediated antitumor efficacy in a mouse orthotopic model of NSCLC. Our results show that EGFR targeting enhances tumor retention of SPIO nanoparticles. Further, magnetic hyperthermia treatment using targeted SPIO nanoparticles resulted in significant inhibition of in vivo lung tumor growth. Overall, this work demonstrates the potential for developing an effective anticancer treatment modality for the treatment of NSCLC based on targeted magnetic hyperthermia. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Central and Peripheral Molecular Targets for Anti-Obesity Pharmacotherapy

    PubMed Central

    Valentino, Michael A.; Lin, Jieru E.; Waldman, Scott A.

    2011-01-01

    Obesity has emerged as one of the principle worldwide health concerns of the modern era, and there exists a tremendous unmet clinical need for safe and effective therapies to combat this global pandemic. The prevalence of obesity and its associated co-morbidities, including cardiovascular and metabolic diseases, has focused drug discovery and development on generating effective modalities for the treatment and prevention of obesity. Early efforts in the field of obesity pharmacotherapy centered on agents with indeterminate mechanisms of action producing treatment paradigms characterized by significant off-target effects. During the past two decades, new insights have been made into the physiologic regulation of energy balance and the subordinate central and peripheral circuits coordinating appetite, metabolism, and lipogenesis. These studies have revealed previously unrecognized molecular targets for controlling appetite and managing weight from which has emerged a new wave of targeted pharmacotherapies to prevent and control obesity. PMID:20445536

  10. A complications-based clinical staging of obesity to guide treatment modality and intensity

    PubMed Central

    Daniel, Sunil; Soleymani, Taraneh; Garvey, William T.

    2014-01-01

    Purpose of review The current medical model for obesity management is BMI-centric because BMI is the predominant measure used to gauge disease severity, as well as indications for various treatment modalities. Recent advancements in therapy and understanding of the relationship between BMI and obesity-related complications call for a re-examination of this approach. Recent findings Advancements in treatment, including the recent approval of two new weight loss medications in the USA, have enabled development of new medical models for management of obesity. On the basis of accumulating data demonstrating the benefits of weight loss regarding multiple obesity-related complications (e.g., diabetes prevention, type 2 diabetes mellitus, cardiovascular disease risk, nonalcoholic steatohepatitis, sleep apnea), a complications-centric model is proposed that employs weight loss as a tool to treat and prevent obesity comorbidities. This model assures that the aggressiveness of therapy is commensurate with disease severity, and that therapy is directed at those obese patients who will benefit most from weight loss therapy. The treatment algorithm is comprehensive in addressing complications and quantitative when possible in the staging of risk or disease severity. Summary A complications-centric approach to obesity management identifies patients who will benefit most from weight loss, and optimizes patient outcomes, benefit/risk ratio, and the cost–effectiveness of interventions. PMID:23974764

  11. Understanding the tissue interaction of new treatment modalities in laparoscopic surgery in view of safe and effective application (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Grimbergen, Matthijs C. M.; Klaessens, John H.; van der Veen, Albert J.; Verdaasdonk, Rudolf M.

    2016-03-01

    During laparoscopic surgery, devices are require to either cut, ablate or coagulate tissue and veins with high precision and controlled lateral damage preferably in an one-for-all modality. The tissue interactions of 3 new treatment modalities were studied using special imaging techniques to obtain a better understanding the working mechanism in view of effective and safe application. The Plasmajet produces a high temperature ionized gas 'flame' directed to the tissue surface at the tip of a 4 mm diameter rigid hand piece. The Lumenis DUO CO2 laser enables endoscopic laser energy delivery through a 1 mm outer diameter flexible hollow waveguide. The 2 µm 'Thulium' laser is delivered by (standard) 400 µm diameter optical fiber. Thermal imaging and Schlieren techniques were used to assess the superficial ablative and coagulation effects these surgical instruments scanning at preset velocities and distances from the surface of biological tissues and phantoms . The CO2 was very effective in tissue ablation even at a distance up to 10 mm due to a very small diverging beam from the hollow waveguide. In contrast, the Thulium laser showed less ablation and increasing coagulation at larger distance to the tissue. The gas 'flame' of the Plasmajet spread the thermal energy over the surface for effective superficial ablation and coagulation. However, the pressure of the gas flow is substantial on the tissue surface creating turbulence and even indirect cooling. The specific ablation and coagulation effects of the three treatment modalities have to be appreciate and the effective and safe application will depend on the preference and skills of the surgeon

  12. Are there differential symptom profiles that improve in response to different pharmacological treatments of premenstrual syndrome/premenstrual dysphoric disorder?

    PubMed

    Halbreich, Uriel; O'Brien, P M Shaughn; Eriksson, Elias; Bäckström, Torbjörn; Yonkers, Kimberly A; Freeman, Ellen W

    2006-01-01

    Current evidence suggests that the accepted treatments for premenstrual syndrome (PMS)/premenstrual dysphoric disorder (PMDD) have similar overall efficacy. While these treatments are more effective than placebo, response rates associated with them are far from satisfactory (<60%), such that, irrespective of treatment modality, there remain a significant number of women who are unresponsive to current conventional pharmacological therapy. The available data on response rates of specific types of premenstrual symptoms to, or symptom profiles that are most amenable to, each treatment modality are limited and not well defined because most studies were not designed to assess specific symptom profiles. Those studies that have attempted to evaluate which symptom profiles respond to specific therapies have revealed variations within the individual modalities, as well as between the different modalities. It appears that suppression of ovulation ameliorates a broad range of behavioural as well as physical premenstrual symptoms. SSRIs are most effective for irritability and anxiety symptoms, with lesser efficacy for 'atypical' premenstrual symptoms. GABAergic compounds are most efficacious for anxiety and anxious/depressive symptoms, while dopamine agonists, particularly bromocriptine, are perhaps most efficacious for mastalgia. Overall treatment response rates may improve if treatments are targeted at well-defined subgroups of patients. Re-analysis of available datasets from randomised clinical trials may shed more light on the notion that targeting women with specific premenstrual symptom profiles for specific treatment modalities would improve response rates beyond the current ceiling of approximately 60%. Such information would also improve understanding of the putative pathophysiological mechanisms underlying PMS and PMDD, and may point to a more specific diagnosis of these conditions.

  13. Dual-modality imaging with a ultrasound-gamma device for oncology

    NASA Astrophysics Data System (ADS)

    Polito, C.; Pellegrini, R.; Cinti, M. N.; De Vincentis, G.; Lo Meo, S.; Fabbri, A.; Bennati, P.; Cencelli, V. Orsolini; Pani, R.

    2018-06-01

    Recently, dual-modality systems have been developed, aimed to correlate anatomical and functional information, improving disease localization and helping oncological or surgical treatments. Moreover, due to the growing interest in handheld detectors for preclinical trials or small animal imaging, in this work a new dual modality integrated device, based on a Ultrasounds probe and a small Field of View Single Photon Emission gamma camera, is proposed.

  14. Mitochondria-Targeting Magnetic Composite Nanoparticles for Enhanced Phototherapy of Cancer.

    PubMed

    Guo, Ranran; Peng, Haibao; Tian, Ye; Shen, Shun; Yang, Wuli

    2016-09-01

    Photothermal therapy (PTT) and photodynamic therapy (PDT) are promising cancer treatment modalities in current days while the high laser power density demand and low tumor accumulation are key obstacles that have greatly restricted their development. Here, magnetic composite nanoparticles for dual-modal PTT and PDT which have realized enhanced cancer therapeutic effect by mitochondria-targeting are reported. Integrating PTT agent and photosensitizer together, the composite nanoparticles are able to generate heat and reactive oxygen species (ROS) simultaneously upon near infrared (NIR) laser irradiation. After surface modification of targeting ligands, the composite nanoparticles can be selectively delivered to the mitochondria, which amplify the cancer cell apoptosis induced by hyperthermia and the cytotoxic ROS. In this way, better photo therapeutic effects and much higher cytotoxicity are achieved by utilizing the composite nanoparticles than that treated with the same nanoparticles missing mitochondrial targeting unit at a low laser power density. Guided by NIR fluorescence imaging and magnetic resonance imaging, then these results are confirmed in a humanized orthotropic lung cancer model. The composite nanoparticles demonstrate high tumor accumulation and excellent tumor regression with minimal side effect upon NIR laser exposure. Therefore, the mitochondria-targeting composite nanoparticles are expected to be an effective phototherapeutic platform in oncotherapy. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Development of a multi-modal Monte-Carlo radiation treatment planning system combined with PHITS

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

    Kumada, Hiroaki; Nakamura, Takemi; Komeda, Masao

    A new multi-modal Monte-Carlo radiation treatment planning system is under development at Japan Atomic Energy Agency. This system (developing code: JCDS-FX) builds on fundamental technologies of JCDS. JCDS was developed by JAEA to perform treatment planning of boron neutron capture therapy (BNCT) which is being conducted at JRR-4 in JAEA. JCDS has many advantages based on practical accomplishments for actual clinical trials of BNCT at JRR-4, the advantages have been taken over to JCDS-FX. One of the features of JCDS-FX is that PHITS has been applied to particle transport calculation. PHITS is a multipurpose particle Monte-Carlo transport code, thus applicationmore » of PHITS enables to evaluate doses for not only BNCT but also several radiotherapies like proton therapy. To verify calculation accuracy of JCDS-FX with PHITS for BNCT, treatment planning of an actual BNCT conducted at JRR-4 was performed retrospectively. The verification results demonstrated the new system was applicable to BNCT clinical trials in practical use. In framework of R and D for laser-driven proton therapy, we begin study for application of JCDS-FX combined with PHITS to proton therapy in addition to BNCT. Several features and performances of the new multimodal Monte-Carlo radiotherapy planning system are presented.« less

  16. Modal sound transmission loss of a single leaf panel: Effects of inter-modal coupling.

    PubMed

    Wang, Chong

    2015-06-01

    Sound transmission through a single leaf panel has mostly been discussed and explained by using the approaching wave concept, from which the well-known mass law can be derived. In this paper, the modal behavior in sound transmission coefficients is explored, and it is shown that the mutual modal radiation impedances in modal sound transmission coefficients may not be ignored even for a panel immersed in a light fluid. By introducing the equivalent modal impedance which incorporates the inter-modal coupling effect, an analytical expression for the modal sound transmission coefficient is derived, and the overall sound transmission coefficient is simply a modal superposition of modal sound transmission coefficients. A good correlation is obtained between analytical calculation and boundary element method. In addition, it is found that inter-modal coupling has noticeable effects in modal sound transmission coefficients in the subsonic region but may be ignored as modes become supersonic. It is also shown that the well-known mass law performance is attributed to all the supersonic modes.

  17. Methodologies in the modeling of combined chemo-radiation treatments

    NASA Astrophysics Data System (ADS)

    Grassberger, C.; Paganetti, H.

    2016-11-01

    The variety of treatment options for cancer patients has increased significantly in recent years. Not only do we combine radiation with surgery and chemotherapy, new therapeutic approaches such as immunotherapy and targeted therapies are starting to play a bigger role. Physics has made significant contributions to radiation therapy treatment planning and delivery. In particular, treatment plan optimization using inverse planning techniques has improved dose conformity considerably. Furthermore, medical physics is often the driving force behind tumor control and normal tissue complication modeling. While treatment optimization and outcome modeling does focus mainly on the effects of radiation, treatment modalities such as chemotherapy are treated independently or are even neglected entirely. This review summarizes the published efforts to model combined modality treatments combining radiation and chemotherapy. These models will play an increasing role in optimizing cancer therapy not only from a radiation and drug dosage standpoint, but also in terms of spatial and temporal optimization of treatment schedules.

  18. An innovative pre-targeting strategy for tumor cell specific imaging and therapy

    NASA Astrophysics Data System (ADS)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-08-01

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

  19. Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults.

    PubMed

    Lee, Ahreum; Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

    2018-04-11

    Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standar Desviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition.

  20. Multisensory Integration Strategy for Modality-Specific Loss of Inhibition Control in Older Adults

    PubMed Central

    Ryu, Hokyoung; Kim, Jae-Kwan; Jeong, Eunju

    2018-01-01

    Older adults are known to have lesser cognitive control capability and greater susceptibility to distraction than young adults. Previous studies have reported age-related problems in selective attention and inhibitory control, yielding mixed results depending on modality and context in which stimuli and tasks were presented. The purpose of the study was to empirically demonstrate a modality-specific loss of inhibitory control in processing audio-visual information with ageing. A group of 30 young adults (mean age = 25.23, Standard Deviation (SD) = 1.86) and 22 older adults (mean age = 55.91, SD = 4.92) performed the audio-visual contour identification task (AV-CIT). We compared performance of visual/auditory identification (Uni-V, Uni-A) with that of visual/auditory identification in the presence of distraction in counterpart modality (Multi-V, Multi-A). The findings showed a modality-specific effect on inhibitory control. Uni-V performance was significantly better than Multi-V, indicating that auditory distraction significantly hampered visual target identification. However, Multi-A performance was significantly enhanced compared to Uni-A, indicating that auditory target performance was significantly enhanced by visual distraction. Additional analysis showed an age-specific effect on enhancement between Uni-A and Multi-A depending on the level of visual inhibition. Together, our findings indicated that the loss of visual inhibitory control was beneficial for the auditory target identification presented in a multimodal context in older adults. A likely multisensory information processing strategy in the older adults was further discussed in relation to aged cognition. PMID:29641462

  1. Targeted treatments for fragile X syndrome.

    PubMed

    Berry-Kravis, Elizabeth; Knox, Andrew; Hervey, Crystal

    2011-09-01

    Fragile X syndrome (FXS) is the most common identifiable genetic cause of intellectual disability and autistic spectrum disorders (ASD), with up to 50% of males and some females with FXS meeting criteria for ASD. Autistic features are present in a very high percent of individuals with FXS, even those who do not meet full criteria for ASD. Recent major advances have been made in the understanding of the neurobiology and functions of FMRP, the FMR1 (fragile X mental retardation 1) gene product, which is absent or reduced in FXS, largely based on work in the fmr1 knockout mouse model. FXS has emerged as a disorder of synaptic plasticity associated with abnormalities of long-term depression and long-term potentiation and immature dendritic spine architecture, related to the dysregulation of dendritic translation typically activated by group I mGluR and other receptors. This work has led to efforts to develop treatments for FXS with neuroactive molecules targeted to the dysregulated translational pathway. These agents have been shown to rescue molecular, spine, and behavioral phenotypes in the FXS mouse model at multiple stages of development. Clinical trials are underway to translate findings in animal models of FXS to humans, raising complex issues about trial design and outcome measures to assess cognitive change that might be associated with treatment. Genes known to be causes of ASD interact with the translational pathway defective in FXS, and it has been hypothesized that there will be substantial overlap in molecular pathways and mechanisms of synaptic dysfunction between FXS and ASD. Therefore, targeted treatments developed for FXS may also target subgroups of ASD, and clinical trials in FXS may serve as a model for the development of clinical trial strategies for ASD and other cognitive disorders.

  2. Comparison of the effects of intensive insulin treatment modalities on cardiovascular biomarkers in type 1 diabetes mellitus.

    PubMed

    Cetinkalp, Sevki; Felekoglu, Canan; Karadeniz, Muammer; Boyacıoglu, Hayal; Delen, Yasemin; Yildirim, Eser; Yilmaz, Candeger

    2015-01-01

    To evaluate effects of intensive insulin treatment modalities on cardiovascular biomarkers in patients with type 1 diabetes mellitus (T1DM). A total of 25 patients with T1DM receiving intensive insulin therapy either in the form of continuous insulin pump (IP group; n=13) or as multiple daily injections (MDI group; n=12) and 13 controls (control group, n=13) were included. Data on demographics, anthropometrics, diabetes history, and laboratory findings including glycemic and lipid parameters, and cardiovascular biomarkers [C-reactive protein (mg/dL), homocysteine (μmol/L), fibrinogen (mg/dL), oxidized LDL (ng/dL), PAI-1 (ng/mL), MCP-1 (pg/mL) and VEGF (pg/mL)] were recorded in each group. Correlation of cardiovascular biomarkers to other parameters was also evaluated in T1DM patients. Apart from significantly higher mean (SD) values for HbA1c [6.1 (0.3) vs. 5.6 (0.5)% (43 (3) vs. 38 (5) mmol/mol), p<0.05)] and HDL-cholesterol [71.5 (13.6) vs. 58.2 (10.8), p<0.01) in the IP than in the MDI group, no significance difference was noted between insulin treatment modalities as well as between patient and control groups in terms of demographic, anthropometric and laboratory parameters. Negative correlation of MCP-1 to treatment duration (r=-0.615, p=0.025), and HDL-c to CRP (r=-0.685, p=0.010) and VEGF (r=-0.678, p=0.011) was noted in IP group, whereas positive correlation of PAI-1 to diabetes age (r=0.805, p=0.002) and treatment duration was noted in MDI group. Our findings in a cohort of T1DM patients with optimal glycemic control revealed that intensive insulin therapy was not associated with an increase in atherosclerotic markers in T1DM, regardless of whether continuous IP infusion or MDIs was administered. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

  3. Shivering Treatments for Targeted Temperature Management: A Review

    PubMed Central

    Jain, Akash; Gray, Maria; Slisz, Stephanie; Haymore, Joseph; Badjatia, Neeraj; Kulstad, Erik

    2018-01-01

    ABSTRACT Background: Shivering is common during targeted temperature management, and control of shivering can be challenging if clinicians are not familiar with the available options and recommended approaches. Purpose: The purpose of this review was to summarize the most relevant literature regarding various treatments available for control of shivering and suggest a recommended approach based on latest data. Methods: The electronic databases PubMed/MEDLINE and Google Scholar were used to identify studies for the literature review using the following keywords alone or in combination: “shivering treatment,” “therapeutic hypothermia,” “core temperature modulation devices,” and “targeted temperature management.” Results: Nonpharmacologic methods were found to have a very low adverse effect profile and ease of use but some limitations in complete control of shivering. Pharmacologic methods can effectively control shivering, but some have adverse effects, such that risks and benefits to the patient have to be balanced. Conclusion: An approach is provided which suggests that treatment for shivering control in targeted temperature management should be initiated before the onset of therapeutic hypothermia or prior to any attempt at lowering patient core temperature, with medications including acetaminophen, buspirone, and magnesium sulfate, ideally with the addition of skin counterwarming. After that, shivering intervention should be determined with the help of a shivering scale, and stepwise escalation can be implemented that balances shivering treatment with sedation, aiming to provide the most shivering reduction with the least sedating medications and reserving paralytics for the last line of treatment. PMID:29278601

  4. Multiple sclerosis - New treatment modalities

    PubMed Central

    Totaro, Rocco; Di Carmine, Caterina; Marini, Carmine; Carolei, Antonio

    2015-01-01

    Ever since the introduction of the first disease modifying therapies, the concept of multiple sclerosis treatment algorithms developed ceaselessly. The increasing number of available drugs is paralleled by impelling issue of ensuring the most appropriate treatment to the right patient at the right time. The purpose of this review is to describe novel agents recently approved for multiple sclerosis treatment, namely teriflunomide, alemtuzumab and dimethylfumarate, focusing on mechanism of action, efficacy data in experimental setting, safety and tolerability. The place in therapy of newer treatment implies careful balancing of risk-benefit profile as well as accurate patient selection. Hence the widening of therapeutic arsenal provides greater opportunity for personalized therapy but also entails a complex trade-off between efficacy, tolerability, safety and eventually patient preference. PMID:26831413

  5. Impact of salvage treatment modalities in patients with positive FDG-PET/CT after R-CHOP chemotherapy for aggressive B-cell non-Hodgkin lymphoma.

    PubMed

    Chin, Vicky; Fulham, Michael; Hertzberg, Mark; Jackson, Michael; Lindeman, Robert; Brighton, Timothy; Kidson-Gerber, Giselle; Wegner, Eva A; Cheung, Carol; MacCallum, Susan; Williams, Janet; Thompson, Stephen R

    2018-06-01

    To compare outcomes of different salvage treatment modalities in patients with aggressive B-cell non-Hodgkin lymphoma (NHL) who remain FDG-PET positive after R-CHOP chemotherapy. Existing data on these patients with FDG-PET primary refractory disease are limited. Patients with diffuse large B-cell lymphoma or grade 3 follicular lymphoma were retrospectively reviewed from the Prince of Wales Hospital databases. Eligibility criteria were: age≥18 years, treated with R-CHOP, with positive post-chemotherapy FDG-PET. Salvage treatment modalities were: radical radiotherapy (RT, dose≥30 Gy), high dose chemotherapy and autologous stem cell transplant (ASCT), or non-radical management. Survival was calculated from date of post-chemotherapy FDG-PET to last follow-up. Twenty-six patients from 2003-2015 met the inclusion criteria. Median age was 60 (range 19-84). Most had adverse baseline features: 21 (81%) stage III-IV, 24 (92%) bulky disease and nine (35%) skeletal involvement. Characteristics of PET-positivity post-chemotherapy were single site in 16 (62%), sites of prior bulk in 24 of 24, skeletal sites in five of nine, and able to be encompassed by RT in 21 (81%). Salvage treatment was: radical RT in 17 (65%), ASCT in four (15%) and non-radical in five (20%). Median follow-up of surviving patients was 31 months. Kaplan-Meier estimates of 3-year PFS and OS were 41% and 52%, respectively. By salvage modality, 3-year PFS was 51% for RT, 25% for ASCT and 20% for non-radical treatment, (P = 0.453); 3-year OS was respectively 65%, 25% and 40% (P = 0.173). Patients with FDG-PET positive disease after R-CHOP for aggressive B-cell NHL are salvageable with radiotherapy. © 2018 The Royal Australian and New Zealand College of Radiologists.

  6. Treatment Targets in Inflammatory Bowel Disease: Current Status in Daily Practice.

    PubMed

    Römkens, Tessa E H; Gijsbers, Kim; Kievit, Wietske; Hoentjen, Frank; Drenth, Joost P H

    2016-12-01

    Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists. Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets. Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn's disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and 'macroscopic normal mucosa' in CD (66%). More stringent and mucosa-driven treatment targets as 'deep remission' and 'mucosal healing' have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score

  7. Visual tracking for multi-modality computer-assisted image guidance

    NASA Astrophysics Data System (ADS)

    Basafa, Ehsan; Foroughi, Pezhman; Hossbach, Martin; Bhanushali, Jasmine; Stolka, Philipp

    2017-03-01

    With optical cameras, many interventional navigation tasks previously relying on EM, optical, or mechanical guidance can be performed robustly, quickly, and conveniently. We developed a family of novel guidance systems based on wide-spectrum cameras and vision algorithms for real-time tracking of interventional instruments and multi-modality markers. These navigation systems support the localization of anatomical targets, support placement of imaging probe and instruments, and provide fusion imaging. The unique architecture - low-cost, miniature, in-hand stereo vision cameras fitted directly to imaging probes - allows for an intuitive workflow that fits a wide variety of specialties such as anesthesiology, interventional radiology, interventional oncology, emergency medicine, urology, and others, many of which see increasing pressure to utilize medical imaging and especially ultrasound, but have yet to develop the requisite skills for reliable success. We developed a modular system, consisting of hardware (the Optical Head containing the mini cameras) and software (components for visual instrument tracking with or without specialized visual features, fully automated marker segmentation from a variety of 3D imaging modalities, visual observation of meshes of widely separated markers, instant automatic registration, and target tracking and guidance on real-time multi-modality fusion views). From these components, we implemented a family of distinct clinical and pre-clinical systems (for combinations of ultrasound, CT, CBCT, and MRI), most of which have international regulatory clearance for clinical use. We present technical and clinical results on phantoms, ex- and in-vivo animals, and patients.

  8. Individualised treatment targets in patients with type-2 diabetes and hypertension.

    PubMed

    Schmieder, Roland E; Tschöpe, Diethelm; Koch, Cornelia; Ouarrak, Taoufik; Gitt, Anselm K

    2018-01-22

    Patients with type-2 diabetes mellitus (T2DM) are at high risk of cardiovascular events, accentuated in the presence of hypertension. At present, it is unclear to what extent the guidelines for the management of T2DM, advocating reduction in HbA1c levels to below target levels, are being adhered to in clinical practice. DIALOGUE was a prospective, observational, non-interventional registry performed across multiple centres in Germany. Patients aged 18 years or older who had T2DM and hypertension for whom the treating physician considered blood glucose lowering medication as inadequate and/or not safe/tolerable and chose to add a further oral drug or switch drug treatment were included. Patients were assigned a treatment target HbA1c value (≤ 6.5% [strict]; > 6.5 to ≤ 7.0% [intermediate]; > 7.0 to ≤ 7.5% [lenient]). 8568 patients with T2DM and hypertension were enrolled. 6691 (78.1%) had 12-month follow-up. Patients who were assigned a strict HbA1c treatment target (n = 2644) were younger, had shorter diabetes duration, and less comorbidity in comparison to those with intermediate (n = 2912) or lenient targets (n = 1135). Only 53.1% of patients achieved their HbA1c treatment target (46.2% [strict], 56.8% [intermediate], 59.4% [lenient]). There was little sign of treatment intensification for patients that had not achieved their HbA1c target. Achievement of treatment targets was poor, leaving many patients with sub-optimal blood glucose levels. The apparent reluctance of physicians to intensify antidiabetic drug therapy is alarming, especially considering the evidence pointing to an association of hyperglycaemia and microvascular complications in patients with T2DM.

  9. Determining the effectiveness of various treatment modalities in carpal tunnel syndrome by ultrasonography and comparing ultrasonographic findings with other outcomes.

    PubMed

    Soyupek, Feray; Yesildag, Ahmet; Kutluhan, Suleyman; Askin, Ayhan; Ozden, Ahmet; Uslusoy, Gokcen Ay; Demirci, Seden

    2012-10-01

    Firstly, we aimed to determine the effectiveness of various treatment modalities using ultrasonography (US), and secondly, we aimed to assess the correlations between the ultrasonographic findings and electrophysiological tests, symptom severity, functional status and physical findings. 74 hands of 47 patients with carpal tunnel syndrome (CTS) were randomly treated by applying wrist splinting alone in the neutral position (23 hands), phonophoresis with corticosteroid (PCS) (28 hands) and phonophoresis with non-steroid anti-inflamatory drug (PNSAI) (23 hands). The cross-sectional area (CSA) of the median nerve (MN) was determined by ultrasound on the initial and at the 3 months after treatment. MN conduction studies were performed on the initial visit and 3 months after treatment. The patients completed the Boston symptom severity questionnaire. For clinical evaluation, we used Phalen's and Tinel's signs. We could find reduction in CSA of MN in PCS group (P < 0.001). The CSA of MN was inversely correlated with motor sensory and median nerve conduction velocity (NCV) (r = 0.421, r = 0.213, respectively). Statistically significant correlations were not detected between ultrasonographic parameters and clinical evaluation parameters (P > 0.05) and also between ultrasonographic parameters and BQ scores (P > 0.05). Although there was some improvement in clinical parameters, ultrasonographic parameters did not change in P-NSAI group. The most effective treatment modality was P-CS according to ultrasonographic and other findings. Although there were inverse correlations between the CSA of MN and sensory and motor MN conduction velocity, no relationship was found between symptom severity, functional status and US findings or electrophysiological studies.

  10. Multishaker modal testing

    NASA Technical Reports Server (NTRS)

    Craig, R. R., Jr.

    1983-01-01

    Procedures for improving the modal modeling of structures using test data and to determine appropriate analytical models based on substructure experimental data were explored. Two related research topics were considered in modal modeling: using several independently acquired columns of frequency response data, and modal modeling using simultaneous multi-point excitation. In component mode synthesis modeling, the emphasis is on determining the best way to employ complex modes and residuals.

  11. Cerebral arteriovenous malformations and seizures: differential impact on the time to seizure-free state according to the treatment modalities.

    PubMed

    Hyun, Seung-Jae; Kong, Doo-Sik; Lee, Jung-Il; Kim, Jong-Soo; Hong, Seung-Chyul

    2012-06-01

    To determine the prognostic factors for the incidence and the outcome of seizure in patients with cerebral arteriovenous malformation (AVM) and to identify the time to seizure-free state according to the treatment modalities. Between 1995 and 2008, the multidisciplinary team at our institution treated 399 patients with cerebral AVMs. Treatment consisted of surgical resection, radiosurgery, and embolization, either alone or in combination. The median follow-up period was 6.0 years (range, 3.0-16.2 years). Eighty-six patients (21.5 %) experienced seizures before treatment. We investigated the variables associated with seizure incidence and seizure outcome and analyzed the outcomes of seizure among each treatment modality. After treatment, 60 (70 %) patients were seizure-free. Compared with 313 patients who did not experience seizures, we found that younger age (≤ 35 years), size ≥ 3 cm, and location of temporal lobe were associated with seizures (p < 0.05). Short seizure history, accompanying intracerebral hemorrhage, generalized tonic-clonic type seizure, deep-seated or infratentorial AVM, complete obliteration of AVM, and a favorable neurological outcome at 12 months were closely associated with Engel Class I outcomes (p < 0.05). Seizure-free outcomes after microsurgery, radiosurgery, or embolization were 78 %, 66 %, and 50 %, respectively. The overall annual bleeding rate was 1.0 % and 2.2 % in microsurgery-treated and radiosurgery-treated AVMs, respectively. In the surgery group, the median time to seizure-free status was 1.1 months (95 % CI, 0.7-1.2 months), whereas the radiosurgery group and embolization-alone group showed 20.5 months (95 % CI, 18.3-23.8 months), and 8.1 months (95 % CI, 6.0-13.5 months), respectively. A multidisciplinary team approach for cerebral AVMs achieved satisfactory seizure control results. Microsurgery led to the highest percentage of seizure-free outcomes and had the lowest annual bleeding rate, whereas radiosurgery had a higher

  12. MIND: modality independent neighbourhood descriptor for multi-modal deformable registration.

    PubMed

    Heinrich, Mattias P; Jenkinson, Mark; Bhushan, Manav; Matin, Tahreema; Gleeson, Fergus V; Brady, Sir Michael; Schnabel, Julia A

    2012-10-01

    Deformable registration of images obtained from different modalities remains a challenging task in medical image analysis. This paper addresses this important problem and proposes a modality independent neighbourhood descriptor (MIND) for both linear and deformable multi-modal registration. Based on the similarity of small image patches within one image, it aims to extract the distinctive structure in a local neighbourhood, which is preserved across modalities. The descriptor is based on the concept of image self-similarity, which has been introduced for non-local means filtering for image denoising. It is able to distinguish between different types of features such as corners, edges and homogeneously textured regions. MIND is robust to the most considerable differences between modalities: non-functional intensity relations, image noise and non-uniform bias fields. The multi-dimensional descriptor can be efficiently computed in a dense fashion across the whole image and provides point-wise local similarity across modalities based on the absolute or squared difference between descriptors, making it applicable for a wide range of transformation models and optimisation algorithms. We use the sum of squared differences of the MIND representations of the images as a similarity metric within a symmetric non-parametric Gauss-Newton registration framework. In principle, MIND would be applicable to the registration of arbitrary modalities. In this work, we apply and validate it for the registration of clinical 3D thoracic CT scans between inhale and exhale as well as the alignment of 3D CT and MRI scans. Experimental results show the advantages of MIND over state-of-the-art techniques such as conditional mutual information and entropy images, with respect to clinically annotated landmark locations. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. ErbB-targeted CAR T-cell immunotherapy of cancer.

    PubMed

    Whilding, Lynsey M; Maher, John

    2015-01-01

    Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

  14. Identifying Molecular Targets for PTSD Treatment Using Single Prolonged Stress

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0377 TITLE: Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress PRINCIPAL...TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-13-1-0377 Identifying Molecular Targets For PTSD Treatment Using Single Prolonged Stress 5b. GRANT...brain GR and β-AR expression alters glutamatergic and GABAergic function in neural circuits that mediate SPS-induced deficits in extinction retention

  15. A novel treatment modality in patients with premature ejaculation resistant to conventional methods: the neuromodulation of dorsal penile nerves by pulsed radiofrequency.

    PubMed

    Basal, Seref; Goktas, Serdar; Ergin, Atilla; Yildirim, Ibrahim; Atim, Abdulkadir; Tahmaz, Lutfi; Dayanc, Murat

    2010-01-01

    Premature ejaculation (PE) is the most common sexual problem experienced by men, and it affects 20%-30% of them. Pulsed radiofrequency (PRF) neuromodulation has been shown to be an effective treatment for a wide range of pain conditions. We used PRF to treat PE by desensitizing dorsal penile nerves in patients resistant to conventional treatments. Fifteen patients with a lifelong history of PE, defined as an intravaginal ejaculatory latency time (IELT) of <1 minute that occurred in more than 90% of acts of intercourse and was resistant to conventional treatments, were enrolled in this study. Patients with erectile dysfunction were excluded. The mean age of the patients was 39 +/- 9 years. Before and 3 weeks after the treatment, IELT and sexual satisfaction score (SSS; for patients and their partners) were obtained. The mean IELTs before and 3 weeks after procedure were 18.5 +/- 17.9 and 139.9 +/- 55.1 seconds, respectively. Side effects did not occur. Mean SSSs of patients before and after treatment were 1.3 +/- 0.3 and 4.6 +/- 0.5, and mean SSSs of partners before and after treatment were 1.3 +/- 0.4 and 4.4 +/- 0.5, respectively. In all cases, IELT and SSS were significantly increased (P < .05). None of the patients or their wives reported any treatment failure during the follow-up period. The mean follow-up time was 8.3 +/- 1.9 months. It is early to conclude that this new treatment modality might be used widely for the treatment of PE; however, because it is an innovative modality, placebo-controlled studies (eg, sham procedure), with larger numbers of patients and including assessment of penile sensitivity (eg, biothesiometry), are needed.

  16. Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

    PubMed

    Lin, Qiaoya; Jin, Cheng S; Huang, Huang; Ding, Lili; Zhang, Zhihong; Chen, Juan; Zheng, Gang

    2014-08-13

    The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Targeted flock/herd and individual ruminant treatment approaches.

    PubMed

    Kenyon, F; Jackson, F

    2012-05-04

    In Europe, most nematodoses are subclinical involving morbid rather than mortal effects and control is largely achieved using anthelmintics. In cattle, the genera most associated with sub-optimal performance are Ostertagia and Cooperia whereas in sheep and goats, subclinical losses are most often caused by Teladorsagia and Trichostrongylus. In some regions, at certain times, other species such as Nematodirus and Haemonchus also cause disease in sheep and goats. Unfortunately, anthelmintic resistance has now become an issue for European small ruminant producers. One of the key aims of the EU-funded PARASOL project was to identify low input and sustainable approaches to control nematode parasites in ruminants using refugia-based strategies. Two approaches to optimise anthelmintic treatments in sheep and cattle were studied; targeted treatments (TT) - whole-group treatments optimised on the basis of a marker of infection e.g. faecal egg count (FEC), and targeted selected treatment (TST) - treatments given to identified individuals to provide epidemiological and/or production benefits. A number of indicators for TT and TST were assessed to define parasitological and production-system specific indicators for treatment that best suited the regions where the PARASOL studies were conducted. These included liveweight gain, production efficiency, FEC, body condition score and diarrhoea score in small ruminants, and pepsinogen levels and Ostertagia bulk milk tank ELISA in cattle. The PARASOL studies confirmed the value of monitoring FEC as a means of targeting whole-flock treatments in small ruminants. In cattle, bulk milk tank ELISA and serum pepsinogen assays could be used retrospectively to determine the levels of exposure and hence, in the next season to optimise anthelmintic usage. TST approaches in sheep and goats examined production efficiency and liveweight gain as indicators for treatment and confirmed the value of this approach in maintaining performance and

  18. SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

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

    Bichay, T; Mayville, A

    2016-06-15

    Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

  19. Computing the modal mass from the state space model in combined experimental-operational modal analysis

    NASA Astrophysics Data System (ADS)

    Cara, Javier

    2016-05-01

    Modal parameters comprise natural frequencies, damping ratios, modal vectors and modal masses. In a theoretic framework, these parameters are the basis for the solution of vibration problems using the theory of modal superposition. In practice, they can be computed from input-output vibration data: the usual procedure is to estimate a mathematical model from the data and then to compute the modal parameters from the estimated model. The most popular models for input-output data are based on the frequency response function, but in recent years the state space model in the time domain has become popular among researchers and practitioners of modal analysis with experimental data. In this work, the equations to compute the modal parameters from the state space model when input and output data are available (like in combined experimental-operational modal analysis) are derived in detail using invariants of the state space model: the equations needed to compute natural frequencies, damping ratios and modal vectors are well known in the operational modal analysis framework, but the equation needed to compute the modal masses has not generated much interest in technical literature. These equations are applied to both a numerical simulation and an experimental study in the last part of the work.

  20. Releasing the Constraints on Aphasia Therapy: The Positive Impact of Gesture and Multimodality Treatments

    ERIC Educational Resources Information Center

    Rose, Miranda L.

    2013-01-01

    Purpose: There is a 40-year history of interest in the use of arm and hand gestures in treatments that target the reduction of aphasic linguistic impairment and compensatory methods of communication (Rose, 2006). Arguments for constraining aphasia treatment to the verbal modality have arisen from proponents of constraint-induced aphasia therapy…

  1. Risk of major depression in patients with chronic renal failure on different treatment modalities: A matched-cohort and population-based study in Taiwan.

    PubMed

    Chen, Shih-Feng; Wang, I-Jen; Lang, Hui-Chu

    2016-01-01

    The influence of different treatment modalities on the risk of developing major depression in patients with chronic renal failure (CRF) is not well understood. We aimed to explore the incidence of major depression among patients with CRF who were on different dialysis modalities, who had received renal transplantation (RT), and those who had not yet received any of the aforementioned renal replacement therapies. We conducted a population-based retrospective cohort study using a national health insurance research database. This study investigated 89,336 study controls, 17,889 patients with chronic kidney disease on conservative treatment, 3823 patients on hemodialysis (HD), 351 patients on peritoneal dialysis (PD), and 322 patients who had RT. We followed all individuals until the occurrence of major depression or the date of loss to follow-up. The PD group had the highest risk (hazard ratio [HR] 2.43; 95% confidence interval [CI] 1.26-4.69), whereas the RT group had the lowest risk (HR 0.18; 95% CI 0.03-1.29) of developing major depression compared with the control group. Patients initiated on PD had a higher risk of developing major depression than patients initiated on HD (pairwise comparison: HR 2.20; 95% CI 1.09-4.46). Different treatment modalities are associated with different risks of developing major depression in patients with CRF. Among renal replacement therapies, patients who have had RT have the lowest risk of developing major depression. Patients who initiate renal therapy on PD may have a higher risk of major depression compared with patients who initiate renal therapy on HD. © 2015 International Society for Hemodialysis.

  2. Modal identification experiment

    NASA Technical Reports Server (NTRS)

    Kvaternik, Raymond G.

    1992-01-01

    , selection of target vibration modes, and the appropriate type of data analysis scheme. The purpose of this talk is to provide an executive-summary-type overview of the modal identification experiment which has emerged from the conceptual design studies conducted to-date. Emphasis throughout is on those aspects of the experiment which should be of interest to those attending the subject utilization conference. The presentation begins with some preparatory remarks to provide background and motivation for the experiment, describe the experiment in general terms, and cite the specific technical objectives. This is followed by a summary of the major results of the conceptual design studies conducted to define the baseline experiment. The baseline experiment which has resulted from the studies is then described.

  3. Priming within and across modalities: exploring the nature of rCBF increases and decreases.

    PubMed

    Badgaiyan, R D; Schacter, D L; Alpert, N M

    2001-02-01

    Neuroimaging studies suggest that within-modality priming is associated with reduced regional cerebral blood flow (rCBF) in the extrastriate area, whereas cross-modality priming is associated with increased rCBF in prefrontal cortex. To characterize the nature of rCBF changes in within- and cross-modality priming, we conducted two neuroimaging experiments using positron emission tomography (PET). In experiment 1, rCBF changes in within-modality auditory priming on a word stem completion task were observed under same- and different-voice conditions. Both conditions were associated with decreased rCBF in extrastriate cortex. In the different-voice condition there were additional rCBF changes in the middle temporal gyrus and prefrontal cortex. Results suggest that the extrastriate involvement in within-modality priming is sensitive to a change in sensory modality of target stimuli between study and test, but not to a change in the feature of a stimulus within the same modality. In experiment 2, we studied cross-modality priming on a visual stem completion test after encoding under full- and divided-attention conditions. Increased rCBF in the anterior prefrontal cortex was observed in the full- but not in the divided-attention condition. Because explicit retrieval is compromised after encoding under the divided-attention condition, prefrontal involvement in cross-modality priming indicates recruitment of an aspect of explicit retrieval mechanism. The aspect of explicit retrieval that is most likely to be involved in cross-modality priming is the familiarity effect. Copyright 2001 Academic Press.

  4. Targeted therapies in the treatment of urothelial cancers.

    PubMed

    Aragon-Ching, Jeanny B; Trump, Donald L

    2017-07-01

    Progress has been slow in systemic management of locally advanced and metastatic bladder cancer over the past 20 years. However, the recent approval of immunotherapy with atezolizumab and nivolumab for second-line salvage therapy may usher in an era of more rapid improvement. Systemic treatment is suboptimal and is an area of substantial unmet medical need. The recent findings from The Cancer Genome Atlas project revealed promising pathways that may be amenable to targeted therapies. Promising results with treatment using vascular endothelial growth factor inhibitors such as ramucirumab, sunitinib or bevacizumab, and human epidermal growth factor receptor 2 targeted therapies, epidermal growth factor receptor inhibitors, and fibroblast growth factor receptor inhibitors, are undergoing clinical trials and are discussed later. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Implementation and applications of dual-modality imaging

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce H.; Barber, William C.; Funk, Tobias; Hwang, Andrew B.; Taylor, Carmen; Sun, Mingshan; Seo, Youngho

    2004-06-01

    In medical diagnosis, functional or physiological data can be acquired using radionuclide imaging with positron emission tomography or with single-photon emission computed tomography. However, anatomical or structural data can be acquired using X-ray computed tomography. In dual-modality imaging, both radionuclide and X-ray detectors are incorporated in an imaging system to allow both functional and structural data to be acquired in a single procedure without removing the patient from the imaging system. In a clinical setting, dual-modality imaging systems commonly are used to localize radiopharmaceutical uptake with respect to the patient's anatomy. This helps the clinician to differentiate disease from regions of normal radiopharmaceutical accumulation, to improve diagnosis or cancer staging, or to facilitate planning for radiation therapy or surgery. While initial applications of dual-modality imaging were developed for clinical imaging on humans, it now is recognized that these systems have potentially important applications for imaging small animals involved in experimental studies including basic investigations of mammalian biology and development of new pharmaceuticals for diagnosis or treatment of disease.

  6. What the patient wants: Addressing patients' treatment targets in an integrative group psychotherapy programme.

    PubMed

    Kealy, David; Joyce, Anthony S; Weber, Rainer; Ehrenthal, Johannes C; Ogrodniczuk, John S

    2018-02-13

    Limited empirical attention has been devoted to individualized treatment objectives in intensive group therapy for personality dysfunction. This study investigated patients' ratings of distress associated with individual therapy goals - referred to as target object severity - in an intensive Evening Treatment Programme for patients with personality dysfunction. Change in target objective severity was examined in a sample of 81 patients who completed treatment in an intensive, integrative group therapy programme. Correlation and regression analyses were used to examine associations between change in target object severity and patients' pre-treatment diagnosis, symptom distress, and treatment outcome expectancy, and between change in target objective severity and patients' ratings of group therapy process (group climate, therapeutic alliance, group cohesion). The relationship between change in target objective severity and longer-range life satisfaction was also examined in a subsample of patients who rated life satisfaction at follow-up. While change in target objective severity was not significantly related to pre-treatment variables, significant associations were found with several aspects of group therapy process. Patients' experience of a highly engaged group climate was uniquely associated with improvement in target object severity. Such improvement was significantly related to longer-term life satisfaction after controlling for general symptom change. The working atmosphere in group therapy contributes to patients' progress regarding individual treatment targets, and such progress is an important factor in later satisfaction. Attention to individualized treatment targets deserves further clinical and research attention in the context of integrative group therapy for personality dysfunction. This study found that patients attending an integrative group treatment programme for personality dysfunction experienced significant improvement in severity of distress

  7. Targeted radiotherapy with gold nanoparticles: current status and future perspectives

    PubMed Central

    Ngwa, Wilfred; Kumar, Rajiv; Sridhar, Srinivas; Korideck, Houari; Zygmanski, Piotr; Cormack, Robert A; Berbeco, Ross; Makrigiorgos, G Mike

    2014-01-01

    Radiation therapy (RT) is the treatment of cancer and other diseases with ionizing radiation. The ultimate goal of RT is to destroy all the disease cells while sparing healthy tissue. Towards this goal, RT has advanced significantly over the past few decades in part due to new technologies including: multileaf collimator-assisted modulation of radiation beams, improved computer-assisted inverse treatment planning, image guidance, robotics with more precision, better motion management strategies, stereotactic treatments and hypofractionation. With recent advances in nanotechnology, targeted RT with gold nanoparticles (GNPs) is actively being investigated as a means to further increase the RT therapeutic ratio. In this review, we summarize the current status of research and development towards the use of GNPs to enhance RT. We highlight the promising emerging modalities for targeted RT with GNPs and the corresponding preclinical evidence supporting such promise towards potential clinical translation. Future prospects and perspectives are discussed. PMID:24978464

  8. Cross-Modal Attention Effects in the Vestibular Cortex during Attentive Tracking of Moving Objects.

    PubMed

    Frank, Sebastian M; Sun, Liwei; Forster, Lisa; Tse, Peter U; Greenlee, Mark W

    2016-12-14

    The midposterior fundus of the Sylvian fissure in the human brain is central to the cortical processing of vestibular cues. At least two vestibular areas are located at this site: the parietoinsular vestibular cortex (PIVC) and the posterior insular cortex (PIC). It is now well established that activity in sensory systems is subject to cross-modal attention effects. Attending to a stimulus in one sensory modality enhances activity in the corresponding cortical sensory system, but simultaneously suppresses activity in other sensory systems. Here, we wanted to probe whether such cross-modal attention effects also target the vestibular system. To this end, we used a visual multiple-object tracking task. By parametrically varying the number of tracked targets, we could measure the effect of attentional load on the PIVC and the PIC while holding the perceptual load constant. Participants performed the tracking task during functional magnetic resonance imaging. Results show that, compared with passive viewing of object motion, activity during object tracking was suppressed in the PIVC and enhanced in the PIC. Greater attentional load, induced by increasing the number of tracked targets, was associated with a corresponding increase in the suppression of activity in the PIVC. Activity in the anterior part of the PIC decreased with increasing load, whereas load effects were absent in the posterior PIC. Results of a control experiment show that attention-induced suppression in the PIVC is stronger than any suppression evoked by the visual stimulus per se. Overall, our results suggest that attention has a cross-modal modulatory effect on the vestibular cortex during visual object tracking. In this study we investigate cross-modal attention effects in the human vestibular cortex. We applied the visual multiple-object tracking task because it is known to evoke attentional load effects on neural activity in visual motion-processing and attention-processing areas. Here we

  9. Cortical GABAergic Interneurons in Cross-Modal Plasticity following Early Blindness

    PubMed Central

    Desgent, Sébastien; Ptito, Maurice

    2012-01-01

    Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field. PMID:22720175

  10. A wide-angle high Mach number modal expansion for infrasound propagation.

    PubMed

    Assink, Jelle; Waxler, Roger; Velea, Doru

    2017-03-01

    The use of modal expansions to solve the problem of atmospheric infrasound propagation is revisited. A different form of the associated modal equation is introduced, valid for wide-angle propagation in atmospheres with high Mach number flow. The modal equation can be formulated as a quadratic eigenvalue problem for which there are simple and efficient numerical implementations. A perturbation expansion for the treatment of attenuation, valid for stratified media with background flow, is derived as well. Comparisons are carried out between the proposed algorithm and a modal algorithm assuming an effective sound speed, including a real data case study. The comparisons show that the effective sound speed approximation overestimates the effect of horizontal wind on sound propagation, leading to errors in traveltime, propagation path, trace velocity, and absorption. The error is found to be dependent on propagation angle and Mach number.

  11. Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

    PubMed Central

    Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

    2017-01-01

    Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

  12. MO-AB-BRA-02: A Novel Scatter Imaging Modality for Real-Time Image Guidance During Lung SBRT

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

    Redler, G; Bernard, D; Templeton, A

    2015-06-15

    Purpose: A novel scatter imaging modality is developed and its feasibility for image-guided radiation therapy (IGRT) during stereotactic body radiation therapy (SBRT) for lung cancer patients is assessed using analytic and Monte Carlo models as well as experimental testing. Methods: During treatment, incident radiation interacts and scatters from within the patient. The presented methodology forms an image of patient anatomy from the scattered radiation for real-time localization of the treatment target. A radiographic flat panel-based pinhole camera provides spatial information regarding the origin of detected scattered radiation. An analytical model is developed, which provides a mathematical formalism for describing themore » scatter imaging system. Experimental scatter images are acquired by irradiating an object using a Varian TrueBeam accelerator. The differentiation between tissue types is investigated by imaging simple objects of known compositions (water, lung, and cortical bone equivalent). A lung tumor phantom, simulating materials and geometry encountered during lung SBRT treatments, is fabricated and imaged to investigate image quality for various quantities of delivered radiation. Monte Carlo N-Particle (MCNP) code is used for validation and testing by simulating scatter image formation using the experimental pinhole camera setup. Results: Analytical calculations, MCNP simulations, and experimental results when imaging the water, lung, and cortical bone equivalent objects show close agreement, thus validating the proposed models and demonstrating that scatter imaging differentiates these materials well. Lung tumor phantom images have sufficient contrast-to-noise ratio (CNR) to clearly distinguish tumor from surrounding lung tissue. CNR=4.1 and CNR=29.1 for 10MU and 5000MU images (equivalent to 0.5 and 250 second images), respectively. Conclusion: Lung SBRT provides favorable treatment outcomes, but depends on accurate target localization. A

  13. Evaluation of the Spies™ modalities image quality

    PubMed Central

    Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed; Barreiro, Aarón; Orosa, Andrea; Serviàn, Pol; Gavrilov, Pavel; Proietti, Silvia; Traxer, Olivier

    2017-01-01

    Introduction The Spies™ system (Karl-Storz®) was introduced into digital ureteroscopy to improve endoscopic vision. To date, there is no data to either indicate which of the Spies modalities is better for improving diagnosis and treatment procedures, nor to compare the modalities in terms of image quality. The aim of this study was to evaluate and compare the image quality of five Spies™ modalities (SM) to the standard white light in an in-vitro model. Materials and Methods Two standardized grids and 3 stones of different composition were recorded in white light and the 5SM (Clara, Chroma, Clara+Chroma), Spectra A and B) using 4 standardized aqueous scenarios. Twelve templates were done in order to simultaneously compare the same objective in the different modalities. Six urologists, five medical students, five urology residents, and five persons not involved with urology evaluated each video on a scale of 1 (very bad) to 5 (very good). Results Comparing white light to SM, subjects scored better the quality of Clara and Clara+Chroma than white light (p=0.0139 and p<0.05) and scored worse Spectra A and B (p=0.0005 and p=0.0023)). When comparing Clara to the other SM, it was ranked equivalent to Clara+Chroma (p=0.67) and obtained a higher rank than Chroma, Spectra A and B (p<0.05, p=0.0001 and p=0.0001). In the multivariate analysis mean scores were higher among urologists. Conclusion In all analyzed scenarios, the subjects ranked Clara and Clara+Chroma as the modalities with better image quality compared to white light. PMID:28338307

  14. Cross-modal prediction changes the timing of conscious access during the motion-induced blindness.

    PubMed

    Chang, Acer Y C; Kanai, Ryota; Seth, Anil K

    2015-01-01

    Despite accumulating evidence that perceptual predictions influence perceptual content, the relations between these predictions and conscious contents remain unclear, especially for cross-modal predictions. We examined whether predictions of visual events by auditory cues can facilitate conscious access to the visual stimuli. We trained participants to learn associations between auditory cues and colour changes. We then asked whether congruency between auditory cues and target colours would speed access to consciousness. We did this by rendering a visual target subjectively invisible using motion-induced blindness and then gradually changing its colour while presenting congruent or incongruent auditory cues. Results showed that the visual target gained access to consciousness faster in congruent than in incongruent trials; control experiments excluded potentially confounding effects of attention and motor response. The expectation effect was gradually established over blocks suggesting a role for extensive training. Overall, our findings show that predictions learned through cross-modal training can facilitate conscious access to visual stimuli. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury

    DTIC Science & Technology

    2014-11-01

    Award Number: W81XWH-11-2-0011 TITLE: Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury PRINCIPAL INVESTIGATOR...Oct 2014 4. TITLE AND SUBTITLE Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...fluid percussion, traumatic brain injury, blood brain barrier, neuroinflammation, neurological dysfunction, endocannabinoids , microglia and 16

  16. Medication burden in CKD-5D: impact of dialysis modality and setting.

    PubMed

    Parker, Kathrine; Nikam, Milind; Jayanti, Anuradha; Mitra, Sandip

    2014-12-01

    Medication adherence is thought to be around 50% in the general and dialysis population. Reducing the pill burden (PB) reduces regime complexity and can improve adherence. Increased adherence should lead to improvement in treatment outcomes and patient quality of life. There is currently little published data on PB in CKD-5D across dialysis modalities. This is a retrospective, single renal network study. All in-centre HD (MHD), peritoneal dialysis (PD) and home HD (HHD) patients were identified in the Greater Manchester East sector renal network. Information collected included age, sex, comorbidities, daily PB, dialysis vintage and adequacy. Data were retrieved from a customized renal database, clinic and discharge letters with cross validation from the general practitioner when needed. Two hundred and thirty-six prevalent dialysis patients were studied. HHD patients had a significantly lower PB (11 ± 7 pills/day) compared with PD and MHD (16 ± 7 pills/day). The HHD patients required fewer BP medications to meet the recommended target. HD setting was the only significant factor for reducing PB. For home therapies (HHD versus PD), weekly Kt/v and serum phosphate were significant factors influencing PB. When comparing all modalities, OR of PB ≥ 15/day for MHD versus HHD was 3.9 and PD versus HHD was 4.9. The influence of HHD is dominant above factors such as comorbidities or clinical variables in reducing PB for MHD. Higher clearances achieved by HHD could explain differences in PB with PD. This is the first comparative study of PB across all dialysis modalities and factors that influence it. The PB advantage in HHD may result in greater adherence and might contribute to the outcome benefit often seen with this modality. Higher clearances achieved by HHD could explain differences in PB with PD but the precise reasons for lower PB remain speculative and deserve further research in larger settings.

  17. Emerging strategies of targeting lipoprotein lipase for metabolic and cardiovascular diseases

    PubMed Central

    Geldenhuys, Werner J.; Lin, Li; Darvesh, Altaf S.; Sadana, Prabodh

    2017-01-01

    Although statins and other pharmacological approaches have improved the management of lipid abnormalities, there exists a need for newer treatment modalities especially for the management of hypertriglyceridemia. Lipoprotein lipase (LPL), by promoting hydrolytic cleavage of the triglyceride core of lipoproteins, is a crucial node in the management of plasma lipid levels. Although LPL expression and activity modulation is observed as a pleiotropic action of some the commonly used lipid lowering drugs, the deliberate development of drugs targeting LPL has not occurred yet. In this review, we present the biology of LPL, highlight the LPL modulation property of currently used drugs and review the novel emerging approaches to target LPL. PMID:27771332

  18. Pain and disability determine treatment modality for older patients with adult scoliosis, while deformity guides treatment for younger patients.

    PubMed

    Bess, Shay; Boachie-Adjei, Oheneba; Burton, Doug; Cunningham, Matthew; Shaffrey, Chris; Shelokov, Alexis; Hostin, Richard; Schwab, Frank; Wood, Kirkham; Akbarnia, Behrooz

    2009-09-15

    Multi-center, retrospective review. Identify age associated clinical and radiographic features correlating with AS treatment. Little information exists about factors determining treatment for adult scoliosis (AS). Existing studies have not evaluated age stratified differences. Multicenter, retrospective review of 290 patients treated for AS. Patients divided into operative (OP) or nonoperative (NON), and age stratified into 3 groups (G1 = <50 years, G2 = 50-65 years, G3 = >65 years). Demographic and spinopelvic radiographic parameters evaluated. Health-related quality of life (HRQL) measures included SRS-22, Oswestry Disability Index (ODI), visual analog pain scale. Treatment groups (OP, n = 137; NON, n = 153) demonstrated similar age (OP = 52.7 years; NON = 55.5 years; P > 0.05) and comorbidities. OP had larger thoracic curves than NON (OP = 51 degrees, NON = 45 degrees; P < 0.05). OP had worse HRQL scores than NON (SRS = 2.95 vs. 3.12, P < 0.05; ODI = 33.4 vs. 28.7, P < 0.05; visual analog pain scale = 6.9 vs. 5.6, P < 0.05, respectively). Age stratification of OP demonstrated larger curves in G1 and G2 versus G3, progressively worsening sagittal imbalance in older age groups, and worse HRQL scores in G3 versus G1 and G2. Age stratification of NON demonstrated worsening sagittal imbalance with age, however, other radiographic values and HRQL scores were similar between all NON age groups. Treatment stratification of age groups demonstrated G1-OP had greater deformity than G1-NON (mean thoracic curve: G1-OP = 53 degrees, G1-NON = 43 degrees; P < 0.05) but similar HRQL values. Whereas G2 and G3-OP had similar radiographic coronal and sagittal values as G2 and G3-NON, but worse HRQL scores. Counter to previous reports, age, comorbidities, and sagittal balance did not influence treatment modality for AS. Operative treatment for younger patients was driven by increased coronal plane deformity. Conversely, pain and disability mandated treatment for older patients

  19. Cross-modal perceptual load: the impact of modality and individual differences.

    PubMed

    Sandhu, Rajwant; Dyson, Benjamin James

    2016-05-01

    Visual distractor processing tends to be more pronounced when the perceptual load (PL) of a task is low compared to when it is high [perpetual load theory (PLT); Lavie in J Exp Psychol Hum Percept Perform 21(3):451-468, 1995]. While PLT is well established in the visual domain, application to cross-modal processing has produced mixed results, and the current study was designed in an attempt to improve previous methodologies. First, we assessed PLT using response competition, a typical metric from the uni-modal domain. Second, we looked at the impact of auditory load on visual distractors, and of visual load on auditory distractors, within the same individual. Third, we compared individual uni- and cross-modal selective attention abilities, by correlating performance with the visual Attentional Network Test (ANT). Fourth, we obtained a measure of the relative processing efficiency between vision and audition, to investigate whether processing ease influences the extent of distractor processing. Although distractor processing was evident during both attend auditory and attend visual conditions, we found that PL did not modulate processing of either visual or auditory distractors. We also found support for a correlation between the uni-modal (visual) ANT and our cross-modal task but only when the distractors were visual. Finally, although auditory processing was more impacted by visual distractors, our measure of processing efficiency only accounted for this asymmetry in the auditory high-load condition. The results are discussed with respect to the continued debate regarding the shared or separate nature of processing resources across modalities.

  20. Electrotherapy modalities for adhesive capsulitis (frozen shoulder).

    PubMed

    Page, Matthew J; Green, Sally; Kramer, Sharon; Johnston, Renea V; McBain, Brodwen; Buchbinder, Rachelle

    2014-10-01

    Adhesive capsulitis (also termed frozen shoulder) is a common condition characterised by spontaneous onset of pain, progressive restriction of movement of the shoulder and disability that restricts activities of daily living, work and leisure. Electrotherapy modalities, which aim to reduce pain and improve function via an increase in energy (electrical, sound, light, thermal) into the body, are often delivered as components of a physical therapy intervention. This review is one in a series of reviews which form an update of the Cochrane review 'Physiotherapy interventions for shoulder pain'. To synthesise the available evidence regarding the benefits and harms of electrotherapy modalities, delivered alone or in combination with other interventions, for the treatment of adhesive capsulitis. We searched CENTRAL, MEDLINE, EMBASE, CINAHL Plus and the ClinicalTrials.gov and World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) clinical trials registries up to May 2014, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials to identify any other potentially relevant trials. We included randomised controlled trials (RCTs) and controlled clinical trials using a quasi-randomised method of allocation that included adults with adhesive capsulitis and compared any electrotherapy modality to placebo, no treatment, a different electrotherapy modality, or any other intervention. The two main questions of the review focused on whether electrotherapy modalities are effective compared to placebo or no treatment, or if they are an effective adjunct to manual therapy or exercise (or both). The main outcomes of interest were participant-reported pain relief of 30% or greater, overall pain, function, global assessment of treatment success, active shoulder abduction, quality of life, and the number of participants experiencing any adverse event. Two review authors independently selected trials for inclusion

  1. Etiology, distribution, treatment modalities and complications of maxillofacial fractures

    PubMed Central

    Pham-Dang, Nathalie; Barthélémy, Isabelle; Orliaguet, Thierry; Artola, Alain; Mondié, Jean M.

    2014-01-01

    Purpose: This study evaluated the trends and factors associated with maxillofacial fractures treated from 1997 to 2007 in the Oral and Maxillofacial Surgery Department of the Clermont-Ferrand University Hospital. Material and Methods: This study included 364 patients of which 82% were men and 45%, 20-29-years old. The etiology, anatomical distribution, treatment modality and complications of maxillofacial fractures were examined. Results: Overall, interpersonal violence, traffic accidents and falls were the most common mechanisms of injury. There was a decreasing trend in traffic accidents and increasing one in falls as a cause of fracture over the 11-years period of this study. Young male patients were preferentially victim of interpersonal violence and traffic accidents, while middle-aged ones were of falls and work-related accidents. Middle-aged female patients were preferentially victim of traffic accidents and interpersonal violence, while older ones were of falls. And the number of fractures per patient varied according to the mechanism of injury: low after work-related accidents and high after traffic accidents. About two-third of fractures involved the mandible. Most of these mandibular fractures were treated by osteosynthesis with or without intermaxillary fixation, with the proportion of the latter increasing over time. There were very few postoperative infections and only in mandible. Conclusions: Maxillofacial fractures predominantly occur in young men, due to interpersonal violence. There is nevertheless an increasing trend in falls as a cause of fracture, especially in female patients, consistent with the increasing trend in presentation of older people. Most maxillofacial fractures involve the mandible and there is an increasing trend in treating these fractures by osteosynthesis without intermaxillary fixation. Antibiotic prophylaxis associated with dental hygiene care can be indicated to prevent postoperative infections. Key words

  2. Modality-specificity of Selective Attention Networks.

    PubMed

    Stewart, Hannah J; Amitay, Sygal

    2015-01-01

    To establish the modality specificity and generality of selective attention networks. Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled "general attention." The third component was labeled "auditory attention," as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as "spatial orienting" and "spatial conflict," respectively-they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task-all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location). These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific.

  3. Thermoradiation therapy in combined modality treatment for locally advanced laryngeal and hypopharyngeal cancer

    NASA Astrophysics Data System (ADS)

    Choynzonov, E. L.; Startseva, Zh. A.; Gribova, O. V.; Mukhamedov, M. R.; Spivakova, I. O.

    2017-09-01

    The article presents the results of combined modality treatment for stage III-IV (T3N0-2M0) laryngeal and hypopharyngeal cancers. All patients (55) were divided into 2 groups. Group I patients (n = 25) received pre-operative thermoradiation therapy and Group II patients (n = 30) received pre-operative radiation therapy alone. The follow-up period was 6-24 months. In Group I patients, partial tumor regression was achieved in 21 (84%) patients and stable disease was observed in 4 (16%) patients. In group II patients, partial tumor regression and stable disease were diagnosed in 18 (60%) and 12 (49%) patients, respectively. Local and regional recurrences occurred in 1 patient (4%) of Group I within the first year of follow-up and in 11 patients of Group II (7 within the first year and 4 within two years of follow-up). The 2-year overall survival rate was 100% in Group I patients and 76.7% ± 10.1% in Group II patients. Disease-free survival rates were 96.6 ± 3.5% and 63.3 ± 13.9%, respectively.

  4. Modality-specific effects on crosstalk in task switching: evidence from modality compatibility using bimodal stimulation.

    PubMed

    Stephan, Denise Nadine; Koch, Iring

    2016-11-01

    The present study was aimed at examining modality-specific influences in task switching. To this end, participants switched either between modality compatible tasks (auditory-vocal and visual-manual) or incompatible spatial discrimination tasks (auditory-manual and visual-vocal). In addition, auditory and visual stimuli were presented simultaneously (i.e., bimodally) in each trial, so that selective attention was required to process the task-relevant stimulus. The inclusion of bimodal stimuli enabled us to assess congruence effects as a converging measure of increased between-task interference. The tasks followed a pre-instructed sequence of double alternations (AABB), so that no explicit task cues were required. The results show that switching between two modality incompatible tasks increases both switch costs and congruence effects compared to switching between two modality compatible tasks. The finding of increased congruence effects in modality incompatible tasks supports our explanation in terms of ideomotor "backward" linkages between anticipated response effects and the stimuli that called for this response in the first place. According to this generalized ideomotor idea, the modality match between response effects and stimuli would prime selection of a response in the compatible modality. This priming would cause increased difficulties to ignore the competing stimulus and hence increases the congruence effect. Moreover, performance would be hindered when switching between modality incompatible tasks and facilitated when switching between modality compatible tasks.

  5. Non-target screening to trace ozonation transformation products in a wastewater treatment train including different post-treatments.

    PubMed

    Schollée, Jennifer E; Bourgin, Marc; von Gunten, Urs; McArdell, Christa S; Hollender, Juliane

    2018-05-25

    Ozonation and subsequent post-treatments are increasingly implemented in wastewater treatment plants (WWTPs) for enhanced micropollutant abatement. While this technology is effective, micropollutant oxidation leads to the formation of ozonation transformation products (OTPs). Target and suspect screening provide information about known parent compounds and known OTPs, but for a more comprehensive picture, non-target screening is needed. Here, sampling was conducted at a full-scale WWTP to investigate OTP formation at four ozone doses (2, 3, 4, and 5 mg/L, ranging from 0.3 to 1.0 gO 3 /gDOC) and subsequent changes during five post-treatment steps (i.e., sand filter, fixed bed bioreactor, moving bed bioreactor, and two granular activated carbon (GAC) filters, relatively fresh and pre-loaded). Samples were measured with online solid-phase extraction coupled to liquid chromatography high-resolution tandem mass spectrometry (LC-HRMS/MS) using electrospray ionization (ESI) in positive and negative modes. Existing non-target screening workflows were adapted to (1) examine the formation of potential OTPs at four ozone doses and (2) compare the removal of OTPs among five post-treatments. In (1), data processing included principal component analysis (PCA) and chemical knowledge on possible oxidation reactions to prioritize non-target features likely to be OTPs. Between 394 and 1328 unique potential OTPs were detected in positive ESI for the four ozone doses tested; between 12 and 324 unique potential OTPs were detected in negative ESI. At a specific ozone dose of 0.5 gO 3 /gDOC, 27 parent compounds were identified and were related to 69 non-target features selected as potential OTPs. Two OTPs were confirmed with reference standards (venlafaxine N-oxide and chlorothiazide); 34 other potential OTPs were in agreement with literature data and/or reaction mechanisms. In (2), hierarchical cluster analysis (HCA) was applied on profiles detected in positive ESI mode across the

  6. PIRATE: pediatric imaging response assessment and targeting environment

    NASA Astrophysics Data System (ADS)

    Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

    2010-02-01

    By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

  7. Why we should not routinely apply irreversible electroporation as an alternative curative treatment modality for localized prostate cancer at this stage.

    PubMed

    Wendler, J J; Ganzer, R; Hadaschik, B; Blana, A; Henkel, T; Köhrmann, K U; Machtens, S; Roosen, A; Salomon, G; Sentker, L; Witzsch, U; Schlemmer, H P; Baumunk, D; Köllermann, J; Schostak, M; Liehr, U B

    2017-01-01

    Irreversible electroporation (IRE), a new tissue ablation procedure available since 2007, could meet the requirements for ideal focal therapy of prostate cancer with its postulated features, especially the absence of a thermal ablation effect. Thus far, there is not enough evidence of its effectiveness or adverse effects to justify its use as a definitive treatment option for localized prostate cancer. Moreover, neither optimal nor individual treatment parameters nor uniform endpoints have been defined thus far. No advantages over established treatment procedures have as yet been demonstrated. Nevertheless, IRE is now being increasingly applied for primary prostate cancer therapy outside clinical trials, not least through active advertising in the lay press. This review reflects the previous relevant literature on IRE of the prostate or prostate cancer and shows why we should not adopt IRE as a routine treatment modality at this stage.

  8. Physiological Modalities for Relaxation Skill Transfer in Biofeedback Games.

    PubMed

    Parnandi, Avinash; Gutierrez-Osuna, Ricardo

    2017-03-01

    We present an adaptive biofeedback game for teaching self-regulation of stress. Our approach consists of monitoring the user's physiology during gameplay and adapting the game using a positive feedback loop that rewards relaxing behaviors and penalizes states of high arousal. We evaluate the approach using a casual game under three biofeedback modalities: electrodermal activity, heart rate variability, and breathing rate. The three biosignals can be measured noninvasively with wearable sensors, and represent different degrees of voluntary control and selectivity toward arousal. We conducted an experiment trial with 25 participants to compare the three modalities against a standard treatment (deep breathing) and a control condition (the game without biofeedback). Our results indicate that breathing-based game biofeedback is more effective in inducing relaxation during treatment than the other four groups. Participants in this group also showed greater retention of the relaxation skills (without biofeedback) during a subsequent stressor.

  9. Bi-modal radiofrequency treatment for coexisting neuralgia and neuropathy in adjacent divisions of the trigeminal nerve.

    PubMed

    Bhatjiwale, M; Bhatjiwale, M; Naik, L D; Chopade, P

    2018-05-29

    Trigeminal neuralgia and deafferentation neuropathic pain, or trigeminal neuropathy, are different symptomatologies, rarely reported to present together. The case of a 65-year-old gentleman suffering from trigeminal neuralgia of the maxillary and mandibular division is reported. He first underwent an infraorbital neurectomy that was complicated by deafferentation neuropathic pain, whilst his mandibular neuralgia continued. He was treated successfully for both the neuropathic and neuralgic symptoms in the same session using ultra-extended euthermic pulsed radiofrequency treatment for the maxillary division (V2) and radiofrequency thermocoagulation for the mandibular division (V3). This report is novel in describing the use of dual modalities in the same session for two distinct coexisting clinical entities in two different divisions of the same cranial nerve. The use of ultra-extended pulsed radiofrequency treatment for neuropathic pain in this case is also unique. Nearly 2years after the procedure, the patient continues to have complete pain relief. Copyright © 2018 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. Targeted Treatment Options in Mastocytosis

    PubMed Central

    Vaes, Mélanie; Benghiat, Fleur Samantha; Hermine, Olivier

    2017-01-01

    Mastocytosis refers to a heterogeneous group of disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin (cutaneous mastocytosis when only in the skin, CM) or in various organs (systemic mastocytosis, SM). This leads to a wide variety of clinical manifestations resulting from excessive mediator release in CM and benign forms of SM (indolent SM, ISM) and from tissue mast cell infiltration causing multiorgan dysfunction and failure in more aggressive subtypes (aggressive SM, ASM, or mast cell leukemia). In addition, SM may be associated with hematological neoplasms (AHN). While treatment of ISM primarily aims at symptom management with anti-mediator therapies, cytoreductive and targeted therapies are needed to control the expansion of neoplastic mast cells in advanced forms of SM, in order to improve overall survival. Mast cell accumulation results from a gain-of-function mutation (mostly the D816V mutation) within the KIT tyrosine kinase domain expressed by mast cells and additional genetic and epigenetic mutations may further determine the features of the disease (ASM and AHN). Consequently, tyrosine kinase inhibitors and targeted therapies directed against the oncogenic signaling machinery downstream of KIT are attractive therapeutic approaches. A better understanding of the relative contribution of these genetic and epigenetic events to the molecular pathogenesis of mastocytosis is of particular interest for the development of targeted therapies and therefore to better choose patient subgroups that would best benefit from a given therapeutic strategy. PMID:28775983

  11. Electrotherapy modalities for rotator cuff disease.

    PubMed

    Page, Matthew J; Green, Sally; Mrocki, Marshall A; Surace, Stephen J; Deitch, Jessica; McBain, Brodwen; Lyttle, Nicolette; Buchbinder, Rachelle

    2016-06-10

    Management of rotator cuff disease may include use of electrotherapy modalities (also known as electrophysical agents), which aim to reduce pain and improve function via an increase in energy (electrical, sound, light, or thermal) into the body. Examples include therapeutic ultrasound, low-level laser therapy (LLLT), transcutaneous electrical nerve stimulation (TENS), and pulsed electromagnetic field therapy (PEMF). These modalities are usually delivered as components of a physical therapy intervention. This review is one of a series of reviews that form an update of the Cochrane review, 'Physiotherapy interventions for shoulder pain'. To synthesise available evidence regarding the benefits and harms of electrotherapy modalities for the treatment of people with rotator cuff disease. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (January 1966 to March 2015), Ovid EMBASE (January 1980 to March 2015), CINAHL Plus (EBSCOhost, January 1937 to March 2015), ClinicalTrials.gov and the WHO ICTRP clinical trials registries up to March 2015, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials, to identify potentially relevant trials. We included randomised controlled trials (RCTs) and quasi-randomised trials, including adults with rotator cuff disease (e.g. subacromial impingement syndrome, rotator cuff tendinitis, calcific tendinitis), and comparing any electrotherapy modality with placebo, no intervention, a different electrotherapy modality or any other intervention (e.g. glucocorticoid injection). Trials investigating whether electrotherapy modalities were more effective than placebo or no treatment, or were an effective addition to another physical therapy intervention (e.g. manual therapy or exercise) were the main comparisons of interest. Main outcomes of interest were overall pain, function, pain on motion, patient-reported global assessment of treatment success

  12. An innovative pre-targeting strategy for tumor cell specific imaging and therapy.

    PubMed

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-09-21

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the "biotin-avidin" interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.

  13. Targeting protein-trafficking pathways alters melanoma treatment sensitivity

    PubMed Central

    Huang, Zhi-ming; Chinen, Milka; Chang, Philip J.; Xie, Tong; Zhong, Lily; Demetriou, Stephanie; Patel, Mira P.; Scherzer, Rebecca; Sviderskaya, Elena V.; Bennett, Dorothy C.; Millhauser, Glenn L.; Oh, Dennis H.; Cleaver, James E.; Wei, Maria L.

    2012-01-01

    Protein-trafficking pathways are targeted here in human melanoma cells using methods independent of oncogene mutational status, and the ability to up-regulate and down-regulate tumor treatment sensitivity is demonstrated. Sensitivity of melanoma cells to cis-diaminedichloroplatinum II (cDDP, cis-platin), carboplatin, dacarbazine, or temozolomide together with velaparib, an inhibitor of poly (ADP ribose) polymerase 1, is increased by up to 10-fold by targeting genes that regulate both protein trafficking and the formation of melanosomes, intracellular organelles unique to melanocytes and melanoma cells. Melanoma cells depleted of either of the protein-trafficking regulators vacuolar protein sorting 33A protein (VPS33A) or cappuccino protein (CNO) have increased nuclear localization of cDDP, increased nuclear DNA damage by platination, and increased apoptosis, resulting in increased treatment sensitivity. Depleted cells also exhibit a decreased proportion of intracellular, mature melanosomes compared with undepleted cells. Modulation of protein trafficking via cell-surface signaling by binding the melanocortin 1 receptor with the antagonist agouti-signaling protein decreased the proportion of mature melanosomes formed and increased cDDP sensitivity, whereas receptor binding with the agonist melanocyte-stimulating hormone resulted in an increased proportion of mature melanosomes formed and in decreased sensitivity (i.e., increased resistance) to cDDP. Mutation of the protein-trafficking gene Hps6, known to impair the formation of mature melanosomes, also increased cDDP sensitivity. Together, these results indicate that targeting protein-trafficking molecules markedly increases melanoma treatment sensitivity and influences the degree of melanosomes available for sequestration of therapeutic agents. PMID:22203954

  14. Odors Bias Time Perception in Visual and Auditory Modalities

    PubMed Central

    Yue, Zhenzhu; Gao, Tianyu; Chen, Lihan; Wu, Jiashuang

    2016-01-01

    Previous studies have shown that emotional states alter our perception of time. However, attention, which is modulated by a number of factors, such as emotional events, also influences time perception. To exclude potential attentional effects associated with emotional events, various types of odors (inducing different levels of emotional arousal) were used to explore whether olfactory events modulated time perception differently in visual and auditory modalities. Participants were shown either a visual dot or heard a continuous tone for 1000 or 4000 ms while they were exposed to odors of jasmine, lavender, or garlic. Participants then reproduced the temporal durations of the preceding visual or auditory stimuli by pressing the spacebar twice. Their reproduced durations were compared to those in the control condition (without odor). The results showed that participants produced significantly longer time intervals in the lavender condition than in the jasmine or garlic conditions. The overall influence of odor on time perception was equivalent for both visual and auditory modalities. The analysis of the interaction effect showed that participants produced longer durations than the actual duration in the short interval condition, but they produced shorter durations in the long interval condition. The effect sizes were larger for the auditory modality than those for the visual modality. Moreover, by comparing performance across the initial and the final blocks of the experiment, we found odor adaptation effects were mainly manifested as longer reproductions for the short time interval later in the adaptation phase, and there was a larger effect size in the auditory modality. In summary, the present results indicate that odors imposed differential impacts on reproduced time durations, and they were constrained by different sensory modalities, valence of the emotional events, and target durations. Biases in time perception could be accounted for by a framework of

  15. A Noninvasive Imaging Modality for Cardiac Arrhythmias

    PubMed Central

    Burnes, John E.; Taccardi, Bruno; Rudy, Yoram

    2007-01-01

    Background The last decade witnessed an explosion of information regarding the genetic, molecular, and mechanistic basis of heart disease. Translating this information into clinical practice requires the development of novel functional imaging modalities for diagnosis, localization, and guided intervention. A noninvasive modality for imaging cardiac arrhythmias is not yet available. Present electrocardiographic methods cannot precisely localize a ventricular tachycardia (VT) or its key reentrant circuit components. Recently, we developed a noninvasive electrocardiographic imaging modality (ECGI) that can reconstruct epicardial electrophysiological information from body surface potentials. Here, we extend its application to image reentrant arrhythmias. Methods and Results Epicardial potentials were recorded during VT with a 490 electrode sock during an open chest procedure in 2 dogs with 4-day-old myocardial infarctions. Body surface potentials were generated from these epicardial potentials in a human torso model. Realistic geometry errors and measurement noise were added to the torso data, which were then used to noninvasively reconstruct epicardial isochrones, electrograms, and potentials with excellent accuracy. ECGI reconstructed the reentry pathway and its key components, including (1) the central common pathway, (2) the VT exit site, (3) lines of block, and (4) regions of slow and fast conduction. This allowed for detailed characterization of the reentrant circuit morphology. Conclusions ECGI can noninvasively image arrhythmic activation on the epicardium during VT to identify and localize key components of the arrhythmogenic pathway that can be effective targets for antiarrhythmic intervention. PMID:11044435

  16. Memory Characteristics and Modality in Multimedia Learning: An Aptitude-Treatment-Interaction Study

    ERIC Educational Resources Information Center

    Seufert, Tina; Schutze, Maren; Brunken, Roland

    2009-01-01

    According to the modality effect in multimedia, a text accompanying a picture should be auditorily presented instead of visually in order to avoid split of attention. In two experimental studies (34 and 78 participants, respectively), the impact and possible compensatory effects of two aptitude variables, that is, memory strategy skills and…

  17. Treatment modalities in sinonasal undifferentiated carcinoma: an analysis from the national cancer database.

    PubMed

    Khan, Mohemmed N; Konuthula, Neeraja; Parasher, Arjun; Genden, Eric M; Miles, Brett A; Govindaraj, Satish; Iloreta, Alfred M

    2017-02-01

    Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of unknown etiology with a poor overall prognosis. Its relative rarity has made it difficult to determine the impact of different treatment modalities on survival. Retrospective study of cases in the National Cancer Data Base (NCDB). NCDB cases that were diagnosed as having SNUC between January 1, 2004, and December 31, 2013 were included in the analysis. Outcomes of patients treated with surgery followed adjuvant chemoradiotherapy were compared with definitive chemoradiotherapy. A 5-year survival rate of 42.2% was observed in the 460 patients in the analysis. American Joint Committee on Cancer (AJCC) clinical staging data were available for 304 patients. Of these patients, 60.2% had advanced tumors (AJCC stage 3 or 4). Surgery followed by adjuvant chemoradiotherapy was associated with better survival than definitive chemoradiotherapy (55.8% vs 42.6%, p = 0.007) in the study population. However, in late-stage tumors, there was no difference in survival between the 2 treatment groups (p = 0.22). For late-stage tumors, the time to initiation of adjuvant therapy was 49.2 ± 5.1 days for the surgery plus adjuvant therapy group as compared with 25.9 ± 2.6 days in the definitive chemoradiotherapy group (p < 0.0001), yet this did not appear to affect outcomes. No differences in age, gender, race, Charlson-Deyo score, facility type (academic vs nonacademic), or radiation dose were found between the 2 treatment groups (p > 0.05). Margin status played a critical role in the success of surgical resection, as no patients with positive margin status receiving adjuvant therapy survived to 5 years. Surgery may play a role in a multimodality approach to treatment of late-stage SNUC if the tumor is amenable to surgical resection and negative margins can be reliably obtained. However, in cases where there may be difficulty obtaining negative margins, or this is considered unlikely preoperatively, surgical

  18. Treatments for pregnancy-related lumbopelvic pain: a systematic review of physiotherapy modalities.

    PubMed

    Gutke, Annelie; Betten, Carola; Degerskär, Kristina; Pousette, Sara; Olsén, Monika Fagevik

    2015-11-01

    To explore the effect of physiotherapeutic interventions on pregnancy-related lumbopelvic pain. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials, PEDro, CINAHL, AMED, and SCOPUS databases were searched up to December 2014 for studies written in English, French, German or Scandinavian languages that evaluated physiotherapeutic modalities for preventing and treating pregnancy-related lumbopelvic pain. For lumbopelvic pain during pregnancy, the evidence was strong for positive effects of acupuncture and pelvic belts. The evidence was low for exercise in general and for specific stabilizing exercises. The evidence was very limited for efficacy of water gymnastics, progressive muscle relaxation, a specific pelvic tilt exercise, osteopathic manual therapy, craniosacral therapy, electrotherapy and yoga. For postpartum lumbopelvic pain, the evidence was very limited for clinic-based treatment concepts, including specific stabilizing exercises, and for self-management interventions for women with severe disabilities. No specific adverse events were reported for any intervention. No meta-analysis could be performed because of study heterogeneity. The levels of evidence were strong for a positive effect of acupuncture and pelvic belts, but weak for an effect of specific exercises. Caution should prevail in choosing other interventions for pregnancy-related lumbopelvic pain. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

  19. Delivery of therapeutics using nanocarriers for targeting cancer cells and cancer stem cells.

    PubMed

    Krishnamurthy, Sangeetha; Ke, Xiyu; Yang, Yi Yan

    2015-01-01

    Development of cancer resistance, cancer relapse and metastasis are attributed to the presence of cancer stem cells (CSCs). Eradication of this subpopulation has been shown to increase life expectancy of patients. Since the discovery of CSCs a decade ago, several strategies have been devised to specifically target them but with limited success. Nanocarriers have recently been employed to deliver anti-CSC therapeutics for reducing the population of CSCs at the tumor site with great success. This review discusses the different therapeutic strategies that have been employed using nanocarriers, their advantages, success in targeting CSCs and the challenges that are to be overcome. Exploiting this new modality of cancer treatment in the coming decade may improve outcomes profoundly with promise of effective treatment response and reducing relapse and metastasis.

  20. Photochemical activation of MH3-B1/rGel: a HER2-targeted treatment approach for ovarian cancer

    PubMed Central

    Bull-Hansen, Bente; Berstad, Maria B.; Berg, Kristian; Cao, Yu; Skarpen, Ellen; Fremstedal, Ane Sofie; Rosenblum, Michael G.; Peng, Qian; Weyergang, Anette

    2015-01-01

    HER2-targeted therapy has been shown to have limited efficacy in ovarian cancer despite frequent overexpression of this receptor. Photochemical internalization (PCI) is a modality for cytosolic drug delivery, currently undergoing clinical evaluation. In the present project we studied the application of PCI in combination with the HER2-targeted recombinant fusion toxin, MH3-B1/rGel, for the treatment of ovarian cancer. The SKOV-3 cell line, resistant to trastuzumab- and MH3-B1/rGel- monotherapy, was shown to respond strongly to PCI of MH3-B1/rGel to a similar extent as observed for the treatment-sensitive SK-BR-3 breast cancer cells. Extensive hydrolytic degradation of MH3-B1/rGel in acidic endocytic vesicles was indicated as the mechanism of MH3-B1/rGel resistance in SKOV-3 cells. This was shown by the positive Pearson's correlation coefficient between Alexa488-labeled MH3-B1/rGel and Lysotracker in SKOV-3 cells in contrast to the negative Pearson's correlation coefficient in SK-BR-3 cells. The application of PCI to induce the release of MH3-B1/rGel was also demonstrated to be effective on SKOV-3 xenografts. Application of PCI with MH3-B1/rGel was further found highly effective in the HER2 expressing HOC-7 and NuTu-19 ovarian cancer cell lines. The presented results warrant future development of PCI in combination with MH3-B1/rGel as a novel therapeutic approach in preclinical models of ovarian cancer. PMID:26002552

  1. The impact of targeted Rheumatoid Arthritis pharmacological treatment on mental health: A systematic review and network meta-analysis.

    PubMed

    Matcham, Faith; Galloway, James; Hotopf, Matthew; Roberts, Emmert; Scott, Ian C; Steer, Sophia; Norton, Sam

    2018-06-06

    Rheumatoid Arthritis (RA) pharmacotherapy may impact mental health (MH) outcomes by improving pain and stiffness; and potentially via targeting inflammatory processes common to RA and depression. The objectives of this review were to i) ascertain the frequency of MH assessment in RA pharmacotherapy trials; ii) quantify the efficacy of RA pharmacotherapy efficacy on MH outcomes; iii) explore the clinical and demographic factors related to MH outcomes. CENTRAL, PsychINFO, Web of Science, Medline, Embase and CINAHL were systematically searched from inception to March 2017 for randomised trials of disease-modifying anti-rheumatic drugs (DMARDs) in adult RA patients. The primary outcome was MH; self-reported physical health was extracted as a secondary outcome. Pairwise meta-analysis (PMA) created pooled effect sizes and 95%CIs for comparisons of all treatments versus comparators (active or placebo). Network meta-analysis (NMA) provided effect size estimates of targeted biologic DMARDs (bDMARDs) versus conventional synthetic DMARDs (csDMARDs) using indirect comparisons of different treatment modalities. 71 eligible studies were identified. 57 studies were included in the PMA, representing 23,535 patients. bDMARDs showed small effects on MH (standardised mean difference (SMD) versus csDMARDs = 0.19 to 0.30), and moderate effects on self-reported physical health (SMD versus csDMARDs = 0.46 to 0.50), with NMA determining no significant differences in effectiveness between bDMARD mode of action on either outcome. Effective pharmacotherapy alone is unlikely to substantially improve MH outcomes for most RA patients. Integrated MH care provided within routine clinical practice is essential to optimise mental and physical health outcomes. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. Treatment of pneumothorax following acupuncture: is a closed thoracostomy necessary for a first choice of treatment modality?

    PubMed

    Kim, Eung-Soo; Kang, Jong-Yael; Pyo, Chang-Hae; Rhee, Gwang-Woo

    2009-02-01

    Acupuncture is currently the most popular of all forms of complementary and alternative medicine, and acupuncture is not dangerous in the hands of a trained practitioner. However, complications of acupuncture including pneumothorax have been reported. Despite the use of fine needles in acupuncture, the lung-collapsed degree of acupuncture pneumothorax is relatively high. In general, the treatment modality of acupuncture pneumothorax is closed thoracostomy with a chest tube of larger diameter. However, the treatment of acupuncture pneumothorax frequently faces controversy concerning the necessity of a standard chest drain insertion. This was a retrospective study from March 1994 to February 2004. Nine (9) patients were admitted due to pneumothorax following acupuncture from March 1994 to February 2004 in Hanil General Hospital, KEPCO Medical Foundation (Seoul, Republic of Korea). Five (5) patients had a moderate degree of pneumothoraces, while 4 patients had a severe degree of pneumothoraces. Four (4) patients were treated by closed thoracostomy with a standard chest drain and the other four patients were treated by the percutaneous chest drainage with a narrow-bore central venous catheter. One (1) patient with a mild degree of pneumothorax was treated only by nasal oxygen inhalation. One (1) patient was treated by video-assisted thoracic surgery after the closed thoracostomy due to continuous air leak. We treated the acupuncture pneumothorax by making a choice between the closed thoracostomy and the percutaneous chest drainage based on a smoking history and chest radiographic findings. In the absence of smoking history and pulmonary emphysema or bullae, we got favorable results, not by the closed thoracostomy but only by the percutaneous chest drainage with a narrow-bore central venous catheter.

  3. Targeted mass treatment for syphilis with oral azithromycin.

    PubMed

    Rekart, Michael L; Patrick, David M; Chakraborty, Bubli; Maginley, Juanita J L; Jones, H D; Bajdik, Chris D; Pourbohloul, Babak; Brunham, Robert C

    2003-01-25

    From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001targeted mass treatment for syphilis, even though feasible, should not be done routinely.

  4. Modality-specificity of Selective Attention Networks

    PubMed Central

    Stewart, Hannah J.; Amitay, Sygal

    2015-01-01

    Objective: To establish the modality specificity and generality of selective attention networks. Method: Forty-eight young adults completed a battery of four auditory and visual selective attention tests based upon the Attention Network framework: the visual and auditory Attention Network Tests (vANT, aANT), the Test of Everyday Attention (TEA), and the Test of Attention in Listening (TAiL). These provided independent measures for auditory and visual alerting, orienting, and conflict resolution networks. The measures were subjected to an exploratory factor analysis to assess underlying attention constructs. Results: The analysis yielded a four-component solution. The first component comprised of a range of measures from the TEA and was labeled “general attention.” The third component was labeled “auditory attention,” as it only contained measures from the TAiL using pitch as the attended stimulus feature. The second and fourth components were labeled as “spatial orienting” and “spatial conflict,” respectively—they were comprised of orienting and conflict resolution measures from the vANT, aANT, and TAiL attend-location task—all tasks based upon spatial judgments (e.g., the direction of a target arrow or sound location). Conclusions: These results do not support our a-priori hypothesis that attention networks are either modality specific or supramodal. Auditory attention separated into selectively attending to spatial and non-spatial features, with the auditory spatial attention loading onto the same factor as visual spatial attention, suggesting spatial attention is supramodal. However, since our study did not include a non-spatial measure of visual attention, further research will be required to ascertain whether non-spatial attention is modality-specific. PMID:26635709

  5. Targeting Insulin Signaling for the Treatment of Alzheimer's Disease.

    PubMed

    Chen, Yanxing; Zhang, Jianfang; Zhang, Baorong; Gong, Cheng-Xin

    2016-01-01

    Sporadic Alzheimer's disease (AD) is caused by multiple etiological factors, among which impaired brain insulin signaling and decreased brain glucose metabolism are important metabolic factors. Contrary to previous belief that insulin would not act in the brain, studies in the last three decades have proven important roles of insulin and insulin signaling in various biological functions in the brain. Impaired brain insulin signaling or brain insulin resistance and its role in the molecular pathogenesis of sporadic AD have been demonstrated. Thus, targeting brain insulin signaling for the treatment of cognitive impairment and AD has now attracted much attention in the field of AD drug discovery. This article reviews recent studies that target brain insulin signaling, especially those investigations on intranasal insulin administration and drugs that improve insulin sensitivity, including incretins, dipeptidyl peptidase IV inhibitors, thiazolidinediones, and metformin. These drugs have been previously approved for the treatment of diabetes mellitus, which could expedite their development for the treatment of AD. Although larger clinical trials are needed for validating their efficacy for the treatment of cognitive impairment and AD, results of animal studies and clinical trials available to date are encouraging.

  6. Multi-Modal Treatment of Nocturnal Enuresis.

    ERIC Educational Resources Information Center

    Mohr, Caroline; Sharpley, Christopher F.

    1988-01-01

    The article reports a multimodal treatment of nocturnal enuresis and anxious behavior in a mildly mentally retarded woman. Behavioral treatment and removal of caffeine from the subject's diet eliminated both nocturnal enuresis and anxious behavior. (Author/DB)

  7. Silent music reading: auditory imagery and visuotonal modality transfer in singers and non-singers.

    PubMed

    Hoppe, Christian; Splittstößer, Christoph; Fliessbach, Klaus; Trautner, Peter; Elger, Christian E; Weber, Bernd

    2014-11-01

    In daily life, responses are often facilitated by anticipatory imagery of expected targets which are announced by associated stimuli from different sensory modalities. Silent music reading represents an intriguing case of visuotonal modality transfer in working memory as it induces highly defined auditory imagery on the basis of presented visuospatial information (i.e. musical notes). Using functional MRI and a delayed sequence matching-to-sample paradigm, we compared brain activations during retention intervals (10s) of visual (VV) or tonal (TT) unimodal maintenance versus visuospatial-to-tonal modality transfer (VT) tasks. Visual or tonal sequences were comprised of six elements, white squares or tones, which were low, middle, or high regarding vertical screen position or pitch, respectively (presentation duration: 1.5s). For the cross-modal condition (VT, session 3), the visuospatial elements from condition VV (session 1) were re-defined as low, middle or high "notes" indicating low, middle or high tones from condition TT (session 2), respectively, and subjects had to match tonal sequences (probe) to previously presented note sequences. Tasks alternately had low or high cognitive load. To evaluate possible effects of music reading expertise, 15 singers and 15 non-musicians were included. Scanner task performance was excellent in both groups. Despite identity of applied visuospatial stimuli, visuotonal modality transfer versus visual maintenance (VT>VV) induced "inhibition" of visual brain areas and activation of primary and higher auditory brain areas which exceeded auditory activation elicited by tonal stimulation (VT>TT). This transfer-related visual-to-auditory activation shift occurred in both groups but was more pronounced in experts. Frontoparietal areas were activated by higher cognitive load but not by modality transfer. The auditory brain showed a potential to anticipate expected auditory target stimuli on the basis of non-auditory information and

  8. Targeted enzyme prodrug therapies.

    PubMed

    Schellmann, N; Deckert, P M; Bachran, D; Fuchs, H; Bachran, C

    2010-09-01

    The cure of cancer is still a formidable challenge in medical science. Long-known modalities including surgery, chemotherapy and radiotherapy are successful in a number of cases; however, invasive, metastasized and inaccessible tumors still pose an unresolved and ongoing problem. Targeted therapies designed to locate, detect and specifically kill tumor cells have been developed in the past three decades as an alternative to treat troublesome cancers. Most of these therapies are either based on antibody-dependent cellular cytotoxicity, targeted delivery of cytotoxic drugs or tumor site-specific activation of prodrugs. The latter is a two-step procedure. In the first step, a selected enzyme is accumulated in the tumor by guiding the enzyme or its gene to the neoplastic cells. In the second step, a harmless prodrug is applied and specifically converted by this enzyme into a cytotoxic drug only at the tumor site. A number of targeting systems, enzymes and prodrugs were investigated and improved since the concept was first envisioned in 1974. This review presents a concise overview on the history and latest developments in targeted therapies for cancer treatment. We cover the relevant technologies such as antibody-directed enzyme prodrug therapy (ADEPT), gene-directed enzyme prodrug therapy (GDEPT) as well as related therapies such as clostridial- (CDEPT) and polymer-directed enzyme prodrug therapy (PDEPT) with emphasis on prodrug-converting enzymes, prodrugs and drugs.

  9. Modal cost analysis for simple continua

    NASA Technical Reports Server (NTRS)

    Hu, A.; Skelton, R. E.; Yang, T. Y.

    1988-01-01

    The most popular finite element codes are based upon appealing theories of convergence of modal frequencies. For example, the popularity of cubic elements for beam-like structures is due to the rapid convergence of modal frequencies and stiffness properties. However, for those problems in which the primary consideration is the accuracy of response of the structure at specified locations, it is more important to obtain accuracy in the modal costs than in the modal frequencies. The modal cost represents the contribution of a mode in the norm of the response vector. This paper provides a complete modal cost analysis for simple continua such as beam-like structures. Upper bounds are developed for mode truncation errors in the model reduction process and modal cost analysis dictates which modes to retain in order to reduce the model for control design purposes.

  10. Evaluation of the Spies TM modalities image quality.

    PubMed

    Emiliani, Esteban; Talso, Michele; Baghdadi, Mohammed; Barreiro, Aaron; Orosa, Andrea; Serviàn, Pol; Gavrilov, Pavel; Proietti, Silvia; Traxer, Olivier

    2017-01-01

    The Spies™ system (Karl-Storz®) was introduced into digital ureteroscopy to improve endoscopic vision. To date, there is no data to either indicate which of the Spies modalities is better for improving diagnosis and treatment procedures, nor to compare the modalities in terms of image quality. The aim of this study was to evaluate and compare the image quality of five Spies™ modalities (SM) to the standard white light in an in-vitro model. Two standardized grids and 3 stones of different composition were recorded in white light and the 5SM (Clara, Chroma, Clara+Chroma), Spectra A and B) using 4 standardized aqueous scenarios. Twelve templates were done in order to simultaneously compare the same objective in the different modalities. Six urologists, five medical students, five urology residents, and five persons not involved with urology evaluated each video on a scale of 1 (very bad) to 5 (very good). Comparing white light to SM, subjects scored better the quality of Clara and Clara+Chroma than white light (p=0.0139 and p<0.05) and scored worse Spectra A and B (p=0.0005 and p=0.0023). When comparing Clara to the other SM, it was ranked equivalent to Clara+Chroma (p=0.67) and obtained a higher rank than Chroma, Spectra A and B (p<0.05, p=0.0001 and p=0.0001). In the multivariate analysis mean scores were higher among urologists. In all analyzed scenarios, the subjects ranked Clara and Clara+Chroma as the modalities with better image quality compared to white light. Copyright® by the International Brazilian Journal of Urology.

  11. HEAVY-DUTY DIESEL VEHICLE MODAL EMISSION MODEL (HDDV-MEM): VOLUME I: MODAL EMISSION MODELING FRAMEWORK; VOLUME II: MODAL COMPONENTS AND OUTPUTS

    EPA Science Inventory

    This research outlines a proposed Heavy-Duty Diesel Vehicle Modal Emission Modeling Framework (HDDV-MEMF) for heavy-duty diesel-powered trucks and buses. The heavy-duty vehicle modal modules being developed under this research effort, although different, should be compatible wi...

  12. Construction of specific magnetic resonance imaging/optical dual-modality molecular probe used for imaging angiogenesis of gastric cancer.

    PubMed

    Yan, Xuejie; Song, Xiaoyan; Wang, Zhenbo

    2017-05-01

    The purpose of the study was to construct specific magnetic resonance imaging (MRI)/optical dual-modality molecular probe. Tumor-bearing animal models were established. MRI/optical dual-modality molecular probe was construed by coupling polyethylene glycol (PEG)-modified nano-Fe 3 O 4 with specific targeted cyclopeptide GX1 and near-infrared fluorescent dyes Cy5.5. MRI/optical imaging effects of the probe were observed and the feasibility of in vivo double-modality imaging was discussed. It was found that, the double-modality probe was of high stability; tumor signal of the experimental group tended to be weak after injection of the probe, but rose to a level which was close to the previous level after 18 h (p > 0.05). We successively completed the construction of an ideal MRI/optical dual-modality molecular probe. MRI/optical dual-modality molecular probe which can selectively gather in gastric cancer is expected to be a novel probe used for diagnosing gastric cancer in the early stage.

  13. Therapeutic Potential of Thymoquinone in Glioblastoma Treatment: Targeting Major Gliomagenesis Signaling Pathways

    PubMed Central

    Chowdhury, Fabliha Ahmed; Hossain, Md Kamal; Mostofa, A. G. M.; Akbor, Maruf Mohammad

    2018-01-01

    Glioblastoma multiforme (GBM) is one of the most devastating brain tumors with median survival of one year and presents unique challenges to therapy because of its aggressive behavior. Current treatment strategy involves surgery, radiotherapy, immunotherapy, and adjuvant chemotherapy even though optimal management requires a multidisciplinary approach and knowledge of potential complications from both the disease and its treatment. Thymoquinone (TQ), the main bioactive component of Nigella sativa L., has exhibited anticancer effects in numerous preclinical studies. Due to its multitargeting nature, TQ interferes in a wide range of tumorigenic processes and counteract carcinogenesis, malignant growth, invasion, migration, and angiogenesis. TQ can specifically sensitize tumor cells towards conventional cancer treatments and minimize therapy-associated toxic effects in normal cells. Its potential to enter brain via nasal pathway due to volatile nature of TQ adds another advantage in overcoming blood-brain barrier. In this review, we summarized the potential role of TQ in different signaling pathways in GBM that have undergone treatment with standard therapeutic modalities or with TQ. Altogether, we suggest further comprehensive evaluation of TQ in preclinical and clinical level to delineate its implied utility as novel therapeutics to combat the challenges for the treatment of GBM. PMID:29651429

  14. DARPin-targeting of Measles Virus: Unique Bispecificity, Effective Oncolysis, and Enhanced Safety

    PubMed Central

    Friedrich, Katrin; Hanauer, Jan RH; Prüfer, Steffen; Münch, Robert C; Völker, Iris; Filippis, Christodoulos; Jost, Christian; Hanschmann, Kay-Martin; Cattaneo, Roberto; Peng, Kah-Whye; Plückthun, Andreas; Buchholz, Christian J; Cichutek, Klaus; Mühlebach, Michael D

    2013-01-01

    Oncolytic virotherapy is an emerging treatment modality that uses replication-competent viruses to destroy cancers. Many naturally occurring viruses have a preferential, although nonexclusive, tropism for tumors and tumor cells. In addition, specific targeting of cancer cells can be achieved at the virus entry level. We optimized retargeting of cell entry by elongating the measles virus attachment protein with designed ankyrin repeat proteins (DARPins), while simultaneously ablating entry through the natural receptors. DARPin-targeted viruses were strongly attenuated in off-target tissue, thereby enhancing safety, but completely eliminated tumor xenografts. Taking advantage of the unique properties of DARPins of being fused without generating folding problems, we generated a virus simultaneous targeting two different tumor markers. The bispecific virus retained the original oncolytic efficacy, while providing proof of concept for a strategy to counteract issues of resistance development. Thus, DARPin-targeting opens new prospects for the development of personalized, targeted therapeutics. PMID:23380817

  15. Prostate Stem Cell Antigen: A Prospective Therapeutic and Diagnostic Target

    PubMed Central

    Raff, Adam B.; Gray, Andrew; Kast, W. Martin

    2009-01-01

    The development of novel clinical tools to combat cancer is an intense field of research and recent efforts have been directed at the identification of proteins that may provide diagnostic, prognostic and/or therapeutic applications due to their restricted expression. To date, a number of protein candidates have emerged as potential clinical tools in the treatment of prostate cancer. Discovered over ten year ago, prostate stem cell antigen (PSCA) is a cell surface antigen that belongs to the Ly-6/Thy-1 family of glycosylphosphatidylinositol-anchored proteins. PSCA is highly overexpressed in human prostate cancer, with limited expression in normal tissues, making it an ideal target for both diagnosis and therapy. Several studies have now clearly correlated the expression of PSCA with relevant clinical benchmarks, such as Gleason score and metastasis, while others have demonstrated the efficacy of PSCA targeting in treatment through various modalities. The purpose of this review is to present the current body of knowledge about PSCA and its potential role in the treatment of human prostate cancer. PMID:18838214

  16. Cross-modal detection using various temporal and spatial configurations.

    PubMed

    Schirillo, James A

    2011-01-01

    To better understand temporal and spatial cross-modal interactions, two signal detection experiments were conducted in which an auditory target was sometimes accompanied by an irrelevant flash of light. In the first, a psychometric function for detecting a unisensory auditory target in varying signal-to-noise ratios (SNRs) was derived. Then auditory target detection was measured while an irrelevant light was presented with light/sound stimulus onset asynchronies (SOAs) between 0 and ±700 ms. When the light preceded the sound by 100 ms or was coincident, target detection (d') improved for low SNR conditions. In contrast, for larger SOAs (350 and 700 ms), the behavioral gain resulted from a change in both d' and response criterion (β). However, when the light followed the sound, performance changed little. In the second experiment, observers detected multimodal target sounds at eccentricities of ±8°, and ±24°. Sensitivity benefits occurred at both locations, with a larger change at the more peripheral location. Thus, both temporal and spatial factors affect signal detection measures, effectively parsing sensory and decision-making processes.

  17. Timing and Targeting of Treatment in Left Ventricular Hypertrophy.

    PubMed

    Nam, Deokhwa; Reineke, Erin L

    2017-01-01

    In most clinical cases, left ventricular hypertrophy (LVH) occurs over time from persistent cardiac stress. At the molecular level, this results in both transient and long-term changes to metabolic, sarcomeric, ion handling, and stress signaling pathways. Although this is initially an adaptive change, the mechanisms underlying LVH eventually lead to maladaptive changes including fibrosis, decreased cardiac function, and failure. Understanding the regulators of long-term changes, which are largely driven by transcriptional remodeling, is a crucial step in identifying novel therapeutic targets for preventing the downstream negative effects of LVH and treatments that could reverse or prevent it. The development of effective therapeutics, however, will require a critical understanding of what to target, how to modify important pathways, and how to identify the stage of pathology in which a specific treatment should be used.

  18. Targeting circuits

    PubMed Central

    Rajasethupathy, Priyamvada; Ferenczi, Emily; Deisseroth, Karl

    2017-01-01

    Current optogenetic methodology enables precise inhibition or excitation of neural circuits, spanning timescales as needed from the acute (milliseconds) to the chronic (many days or more), for experimental modulation of network activity and animal behavior. Such broad temporal versatility, unique to optogenetic control, is particularly powerful when combined with brain activity measurements that span both acute and chronic timescales as well. This enables, for instance, the study of adaptive circuit dynamics across the intact brain, and tuning interventions to match activity patterns naturally observed during behavior in the same individual. Although the impact of this approach has been greater on basic research than on clinical translation, it is natural to ask if specific neural circuit activity patterns discovered to be involved in controlling adaptive or maladaptive behaviors could become targets for treatment of neuropsychiatric diseases. Here we consider the landscape of such ideas related to therapeutic targeting of circuit dynamics, taking note of developments not only in optical but also in ultrasonic, magnetic, and thermal methods. We note the recent emergence of first-in-kind optogenetically-guided clinical outcomes, as well as opportunities related to the integration of interventions and readouts spanning diverse circuit-physiology, molecular, and behavioral modalities. PMID:27104976

  19. Modality independence of order coding in working memory: Evidence from cross-modal order interference at recall.

    PubMed

    Vandierendonck, André

    2016-01-01

    Working memory researchers do not agree on whether order in serial recall is encoded by dedicated modality-specific systems or by a more general modality-independent system. Although previous research supports the existence of autonomous modality-specific systems, it has been shown that serial recognition memory is prone to cross-modal order interference by concurrent tasks. The present study used a serial recall task, which was performed in a single-task condition and in a dual-task condition with an embedded memory task in the retention interval. The modality of the serial task was either verbal or visuospatial, and the embedded tasks were in the other modality and required either serial or item recall. Care was taken to avoid modality overlaps during presentation and recall. In Experiment 1, visuospatial but not verbal serial recall was more impaired when the embedded task was an order than when it was an item task. Using a more difficult verbal serial recall task, verbal serial recall was also more impaired by another order recall task in Experiment 2. These findings are consistent with the hypothesis of modality-independent order coding. The implications for views on short-term recall and the multicomponent view of working memory are discussed.

  20. Modal-space reference-model-tracking fuzzy control of earthquake excited structures

    NASA Astrophysics Data System (ADS)

    Park, Kwan-Soon; Ok, Seung-Yong

    2015-01-01

    This paper describes an adaptive modal-space reference-model-tracking fuzzy control technique for the vibration control of earthquake-excited structures. In the proposed approach, the fuzzy logic is introduced to update optimal control force so that the controlled structural response can track the desired response of a reference model. For easy and practical implementation, the reference model is constructed by assigning the target damping ratios to the first few dominant modes in modal space. The numerical simulation results demonstrate that the proposed approach successfully achieves not only the adaptive fault-tolerant control system against partial actuator failures but also the robust performance against the variations of the uncertain system properties by redistributing the feedback control forces to the available actuators.

  1. Targeted Treatments in Autism and Fragile X Syndrome

    ERIC Educational Resources Information Center

    Gurkan, C. Kagan; Hagerman, Randi J.

    2012-01-01

    Autism is a neurodevelopmental disorder consisting of a constellation of symptoms that sometimes occur as part of a complex disorder characterized by impairments in social interaction, communication and behavioral domains. It is a highly disabling disorder and there is a need for treatment targeting the core symptoms. Although autism is accepted…

  2. MicroRNA as therapeutic targets for treatment of depression

    PubMed Central

    Hansen, Katelin F; Obrietan, Karl

    2013-01-01

    Depression is a potentially life-threatening mental disorder affecting approximately 300 million people worldwide. Despite much effort, the molecular underpinnings of clinical depression remain poorly defined, and current treatments carry limited therapeutic efficacy and potentially burdensome side effects. Recently, small noncoding RNA molecules known as microRNA (miRNA) have gained prominence as a target for therapeutic intervention, given their capacity to regulate neuronal physiology. Further, mounting evidence suggests a prominent role for miRNA in depressive molecular signaling. Recent studies have demonstrated that dysregulation of miRNA expression occurs in animal models of depression, and in the post-mortem tissue of clinically depressed patients. Investigations into depression-associated miRNA disruption reveals dramatic effects on downstream targets, many of which are thought to contribute to depressive symptoms. Furthermore, selective serotonin reuptake inhibitors, as well as other antidepressant drugs, have the capacity to reverse aberrant depressive miRNA expression and their downstream targets. Given the powerful effects that miRNA have on the central nervous system transcriptome, and the aforementioned studies, there is a compelling rationale to begin to assess the potential contribution of miRNA to depressive etiology. Here, we review the molecular biology of miRNA, our current understanding of miRNA in relation to clinical depression, and the utility of targeting miRNA for antidepressant treatment. PMID:23935365

  3. EGFR, HER2 and VEGF pathways: validated targets for cancer treatment.

    PubMed

    Press, Michael F; Lenz, Heinz-Josef

    2007-01-01

    Targeted therapies are rationally designed to interfere with specific molecular events that are important in tumour growth, progression or survival. Several targeted therapies with anti-tumour activity in human cancer cell lines and xenograft models have now been shown to produce objective responses, delay disease progression and, in some cases, improve survival of patients with advanced malignancies. These targeted therapies include cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody; gefitinib and erlotinib, EGFR-specific tyrosine kinase inhibitors; trastuzumab, an anti-human EGFR type 2 (HER2)-related monoclonal antibody; lapatinib, a dual inhibitor of both EGFR- and HER2-associated tyrosine kinases; and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody. On the basis of preclinical and clinical evidence, EGFR, HER2 and VEGF represent validated targets for cancer therapy and remain the subject of intensive investigation. Both EGFR and HER2 are targets found on cancer cells, whereas VEGF is a target that acts in the tumour microenvironment. Clinical studies are focusing on how to best incorporate targeted therapy into current treatment regimens and other studies are exploring whether different strategies for inhibiting these targets will offer greater benefit. It is clear that optimal use of targeted therapy will depend on understanding how these drugs work mechanistically, and recognising that their activities may differ across patient populations, tumour types and disease stages, as well as when and how they are used in cancer treatment. The results achieved with targeted therapies to date are promising, although they illustrate the need for additional preclinical and clinical study.

  4. Analysis of the costs of dialysis and the effects of an incentive mechanism for low-cost dialysis modalities.

    PubMed

    Cleemput, Irina; De Laet, Chris

    2013-05-01

    Treatment costs of end-stage renal disease with dialysis are high and vary between dialysis modalities. Public healthcare payers aim at stimulating the use of less expensive dialysis modalities, with maintenance of healthcare quality. This study examines the effects of Belgian financial incentive mechanisms for the use of low-cost dialysis treatments. First, the costs of different dialysis modalities were calculated from the hospital's perspective. Data were obtained through a hospital survey. The balance between costs and revenues was simulated for an average Belgian dialysis programme. Incremental profits were calculated in function of the proportion of patients on alternative dialysis modalities. Hospital haemodialysis is the most expensive modality per patient year, followed by peritoneal dialysis and finally satellite haemodialysis. Under current reimbursement rules mean profits of a dialysis programme are maximal if about 28% of patients are treated with a low-cost dialysis modality. This is only slightly lower than the observed percentage in Belgian dialysis centres in the same period. In Belgium, the financial incentives for the use of low-cost dialysis modalities only had a modest impact due to the continuing profits that could be generated by high-cost dialysis. Profit neutrality is crucial for the success of any financial incentive mechanism for low-cost dialysis modalities. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  5. Radiotherapy as valid modality for hepatocellular carcinoma with portal vein tumor thrombosis

    PubMed Central

    Yu, Jeong Il; Park, Hee Chul

    2016-01-01

    Although the current standard treatment for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is sorafenib, many previous studies have established the need for a reliable local modality for PVTT control, which is a major cause of liver function deterioration and metastasis. Additionally, there is growing evidence for the prognostic significance of PVTT classification according to the location of tumor thrombosis. Favorable outcomes can be obtained by applying local modalities, including surgery or transarterial chemoembolization, especially in second-order or distal branch PVTT. Rapid control of PVTT could maintain or improve liver function and reduce intrahepatic as well as distant metastasis. Radiotherapy (RT) is one of the main locoregional treatment modalities in oncologic fields, but has rarely been used in HCC because of concerns regarding hepatic toxicity. However, with the development of advanced techniques, RT has been increasingly applied in HCC management. Randomized studies have yet to definitively prove the benefit of RT, but several comparative studies have justified the application of RT in HCC. The value of RT is especially noticeable in HCC with PVTT; several prospective and retrospective studies have reported favorable outcomes, including a 40% to 60% objective response rate and median overall survival of 15 mo to 20 mo in responders. In this review, we evaluate the role of RT as an alternative local modality in HCC with PVTT. PMID:27570422

  6. Multi-modal myocontrol: Testing combined force- and electromyography.

    PubMed

    Nowak, Markus; Eiband, Thomas; Castellini, Claudio

    2017-07-01

    Myocontrol, that is control of prostheses using bodily signals, has proved in the decades to be a surprisingly hard problem for the scientific community of assistive and rehabilitation robotics. In particular, traditional surface electromyography (sEMG) seems to be no longer enough to guarantee dexterity (i.e., control over several degrees of freedom) and, most importantly, reliability. Multi-modal myocontrol is concerned with the idea of using novel signal gathering techniques as a replacement of, or alongside, sEMG, to provide high-density and diverse signals to improve dexterity and make the control more reliable. In this paper we present an offline and online assessment of multi-modal sEMG and force myography (FMG) targeted at hand and wrist myocontrol. A total number of twenty sEMG and FMG sensors were used simultaneously, in several combined configurations, to predict opening/closing of the hand and activation of two degrees of freedom of the wrist of ten intact subjects. The analysis was targeted at determining the optimal sensor combination and control parameters; the experimental results indicate that sEMG sensors alone perform worst, yielding a nRMSE of 9.1%, while mixing FMG and sEMG or using FMG only reduces the nRMSE to 5.2-6.6%. To validate these results, we engaged the subject with median performance in an online goal-reaching task. Analysis of this further experiment reveals that the online behaviour is similar to the offline one.

  7. The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors

    PubMed Central

    Mi, Zhibao; Novitzky, Dimitri; Collins, Joseph F; Cooper, David KC

    2015-01-01

    The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu’s multiple comparisons with the best (MCB) – adapted from the Dunnett’s multiple comparisons with control (MCC) – has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation. PMID:25565890

  8. Hyperglycemia Associated With Targeted Oncologic Treatment: Mechanisms and Management.

    PubMed

    Goldman, Jonathan W; Mendenhall, Melody A; Rettinger, Sarah R

    2016-07-29

    : Molecularly targeted cancer therapy has rapidly changed the landscape of oncologic care, often improving patients' prognosis without causing as substantial a quality-of-life decrement as cytotoxic chemotherapy does. Nevertheless, targeted agents can cause side effects that may be less familiar to medical oncologists and that require the attention and expertise of subspecialists. In this review, we focus on hyperglycemia, which can occur with use of new anticancer agents that interact with cell proliferation pathways. Key mediators of these pathways include the tyrosine kinase receptors insulin growth factor receptor 1 (IGF-1R) and epidermal growth factor receptor (EGFR), as well as intracellular signaling molecules phosphatidylinositol 3-kinase (PI3K), AKT, and mammalian target of rapamycin (mTOR). We summarize available information on hyperglycemia associated with agents that inhibit these molecules within the larger context of adverse event profiles. The highest incidence of hyperglycemia is observed with inhibition of IGF-1R or mTOR, and although the incidence is lower with PI3K, AKT, and EGFR inhibitors, hyperglycemia is still a common adverse event. Given the interrelationships between the IGF-1R and cell proliferation pathways, it is important for oncologists to understand the etiology of hyperglycemia caused by anticancer agents that target those pathways. We also discuss monitoring and management approaches for treatment-related hyperglycemia for some of these agents, with a focus on our experience during the clinical development of the EGFR inhibitor rociletinib. Treatment-related hyperglycemia is associated with several anticancer agents. Many cancer patients may also have preexisting or undiagnosed diabetes or glucose intolerance. Screening can identify patients at risk for hyperglycemia before treatment with these agents. Proper monitoring and management of symptoms, including lifestyle changes and pharmacologic intervention, may allow patients to

  9. Application of Nanotechnology in the Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment

    DTIC Science & Technology

    2007-12-01

    used in detection, diagnosis, and treatment of cancer . When loaded with chemotherapeutic agents, nanoparticle delivery to cancerous tissues...Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment PRINCIPAL INVESTIGATOR: Colleen Feltmate, M.D. CONTRACTING ORGANIZATION...5a. CONTRACT NUMBER Application of Nanotechnology in the Targeted Release of Anticancer Drugs in Ovarian Cancer Treatment 5b. GRANT NUMBER

  10. Somatostatin Analogues for Receptor Targeted Photodynamic Therapy

    PubMed Central

    Kaščáková, Slávka; Hofland, Leo J.; De Bruijn, Henriette S.; Ye, Yunpeng; Achilefu, Samuel; van der Wansem, Katy; van der Ploeg-van den Heuvel, Angelique; van Koetsveld, Peter M.; Brugts, Michael P.; van der Lelij, Aart-Jan; Sterenborg, Henricus J. C. M.; ten Hagen, Timo L. M.; Robinson, Dominic J.; van Hagen, Martin P.

    2014-01-01

    Photodynamic therapy (PDT) is an established treatment modality, used mainly for anticancer therapy that relies on the interaction of photosensitizer, light and oxygen. For the treatment of pathologies in certain anatomical sites, improved targeting of the photosensitizer is necessary to prevent damage to healthy tissue. We report on a novel dual approach of targeted PDT (vascular and cellular targeting) utilizing the expression of neuropeptide somatostatin receptor (sst2) on tumor and neovascular-endothelial cells. We synthesized two conjugates containing the somatostatin analogue [Tyr3]-octreotate and Chlorin e6 (Ce6): Ce6-K3-[Tyr3]-octreotate (1) and Ce6-[Tyr3]-octreotate-K3-[Tyr3]-octreotate (2). Investigation of the uptake and photodynamic activity of conjugates in-vitro in human erythroleukemic K562 cells showed that conjugation of [Tyr3]-octreotate with Ce6 in conjugate 1 enhances uptake (by a factor 2) in cells over-expressing sst2 compared to wild-type cells. Co-treatment with excess free Octreotide abrogated the phototoxicity of conjugate 1 indicative of a specific sst2-mediated effect. In contrast conjugate 2 showed no receptor-mediated effect due to its high hydrophobicity. When compared with un-conjugated Ce6, the PDT activity of conjugate 1 was lower. However, it showed higher photostability which may compensate for its lower phototoxicity. Intra-vital fluorescence pharmacokinetic studies of conjugate 1 in rat skin-fold observation chambers transplanted with sst2 + AR42J acinar pancreas tumors showed significantly different uptake profiles compared to free Ce6. Co-treatment with free Octreotide significantly reduced conjugate uptake in tumor tissue (by a factor 4) as well as in the chamber neo-vasculature. These results show that conjugate 1 might have potential as an in-vivo sst2 targeting photosensitizer conjugate. PMID:25111655

  11. Dielectric studies on struvite urinary crystals, a gateway to the new treatment modality for urolithiasis

    NASA Astrophysics Data System (ADS)

    Rajan, Reshma; Raj, N. Arunai Nambi; Madeswaran, S.; Babu, D. Rajan

    2015-09-01

    Struvite or magnesium ammonium phosphate hexahydrate (MAPH) are biological crystals, found in the kidney, which are formed due to the infection caused by urea splitting bacteria in the urinary tract. The struvite crystals observe different morphologies and were developed using single diffusion gel growth technique. The crystalline nature and its composition were studied from different characterization techniques like X-ray Diffraction (XRD) and FTIR. The dielectric behavior of the developed crystal was studied by varying temperature and at different frequencies. The parameters like dielectric constant, dielectric loss, ac conductivity, ac resistivity, impedance and admittance of the struvite crystals were calculated. The studies proved that the dielectric loss or dissipation heat is high in lower frequencies at normal body temperature, which develops a plasma state in the stones and in turn leads to the disintegration of urinary stones. The dielectric nature of the stones leads to the dielectric therapy, which will be a gateway for future treatment modality for urolithiasis.

  12. Comparison of small molecules and oligonucleotides that target a toxic, non-coding RNA.

    PubMed

    Costales, Matthew G; Rzuczek, Suzanne G; Disney, Matthew D

    2016-06-01

    Potential RNA targets for chemical probes and therapeutic modalities are pervasive in the transcriptome. Oligonucleotide-based therapeutics are commonly used to target RNA sequence. Small molecules are emerging as a modality to target RNA structures selectively, but their development is still in its infancy. In this work, we compare the activity of oligonucleotides and several classes of small molecules that target the non-coding r(CCUG) repeat expansion (r(CCUG)(exp)) that causes myotonic dystrophy type 2 (DM2), an incurable disease that is the second-most common cause of adult onset muscular dystrophy. Small molecule types investigated include monomers, dimers, and multivalent compounds synthesized on-site by using RNA-templated click chemistry. Oligonucleotides investigated include phosphorothioates that cleave their target and vivo-morpholinos that modulate target RNA activity via binding. We show that compounds assembled on-site that recognize structure have the highest potencies amongst small molecules and are similar in potency to a vivo-morpholino modified oligonucleotide that targets sequence. These studies are likely to impact the design of therapeutic modalities targeting other repeats expansions that cause fragile X syndrome and amyotrophic lateral sclerosis, for example. Copyright © 2016. Published by Elsevier Ltd.

  13. Rational chemical design of the next generation of molecular imaging probes based on physics and biology: mixing modalities, colors and signals

    PubMed Central

    Longmire, Michelle R.; Ogawa, Mikako; Choyke, Peter L.

    2012-01-01

    In recent years, numerous in vivo molecular imaging probes have been developed. As a consequence, much has been published on the design and synthesis of molecular imaging probes focusing on each modality, each type of material, or each target disease. More recently, second generation molecular imaging probes with unique, multi-functional, or multiplexed characteristics have been designed. This critical review focuses on (i) molecular imaging using combinations of modalities and signals that employ the full range of the electromagnetic spectra, (ii) optimized chemical design of molecular imaging probes for in vivo kinetics based on biology and physiology across a range of physical sizes, (iii) practical examples of second generation molecular imaging probes designed to extract complementary data from targets using multiple modalities, color, and comprehensive signals (277 references). PMID:21607237

  14. Stem cell transplant in inflammatory bowel disease: a promising modality of treatment for a complicated disease course.

    PubMed

    Salem, George A; Selby, George B

    2017-01-01

    Inflammatory bowel disease (IBD) is a complex, relapsing and remitting, disease characterized by an exaggerated immune response in a susceptible host. The symptoms and complications of the disease can be debilitating. Advances in medical treatment in the last decade changed the course of the disease in many patients. Despite the use of novel agents for controlling disease, a proportion of patients' disease courses continue to be either refractory, or become resistant, to available therapeutic options. Stem-cell therapy, with hematopoietic stem cells (HSCs) or mesenchymal stem cells (MSCs), is a promising modality of treatment for severe refractory cases, mainly Crohn's disease (CD) patients. HSCs have the ability to migrate to damaged tissue, which provides them with further properties to differentiate to epithelial or immune-modulatory cells to restore normal mucosal tissue and integrity. MSCs therapy is a promising model for patients with perianal CD due to their immunosuppressive properties, ability to migrate to areas of injury, and demonstration of colonic healing, including fistulizing tracts. The results from ongoing clinical trials will provide a valuable understanding of the future of stem-cell therapy as a treatment option in refractory cases of IBD, a disease whose pathogenesis remains unknown, and is notoriously difficult to treat.

  15. SU-E-T-560: Inter- and Intra-Fraction Variations in Esophageal Dose for Lung Cancer Patients, and the Impact of Setup Technique and Treatment Modality.

    PubMed

    Carroll, M; Cheung, J; Zhang, L; Court, L

    2012-06-01

    To understand the dose-response of the esophagus in photon and proton therapy, it is important to appreciate the variations in delivered dose caused by inter- and intra-fraction motion. Four lung cancer patients were identified who had experienced grade 3 esophagitis during their treatment, and for whom their esophagus was close, but not encompassed by, the treatment volume. Each patient had been treated with proton therapy using 35-37 2Gy fractions, and had received weekly 4DCT imaging. IMRT plans were also created using the same treatment planning constraints. In-house image registration software was used to deform the esophagus contour from the treatment plan to each phase of the 4DCT for each weekly image set. Daily setup using both bony and soft tissue (GTV) registration was simulated, and the treatment dose calculated for each CT image. Changes to the esophagus DVH relative to the treatment plan were quantified in terms of the relative volume of the esophagus receiving 45, 55, and 65Gy (V45, V55 and V65). For all combinations of treatment modality (photon, proton) and setup method (bony, GTV), intra-fraction motion resulted in a range of V45, V55 and V65 from 3.6 to 5.5%. Inter-fraction motion comparing daily exhale or inhale phases showed the range of V45, V55 and V65 from 8.5 to 18.6% (exhale) and 9.8 to 16.3% (inhale). Inter-fractional motion resulted in larger variations in dose delivered to the esophagus than intra-fractional motion. The inter-fraction range for V45, V55 and V65 varied by around 10% between patients. The treatment modality (photon, proton) and setup technique (bony, GTV) had minimal impact on the results. © 2012 American Association of Physicists in Medicine.

  16. Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections

    DTIC Science & Technology

    1987-10-01

    observed with free MTP-PE. In addition to our observations on peritoneal and alveolar macrophages, we also examined the effect of MTP-PE treatment on liver...Ir OIC FILE COPY C2 ILn 00 NM AD _____ N SELECTIVE TARGETING OF ANTIVIRAL AND IMMUNOMODULATING AGENTS IN THE TREATMENT OF ARENAVIRUS INFECTIONS "Kc...Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Injections 12. PERSONAL AUTHOR(S) J. David Gangemi 13a. TYPE OF

  17. Small Intracranial Aneurysm Treatment Using Target (®) Ultrasoft (™) Coils.

    PubMed

    Jindal, Gaurav; Miller, Timothy; Iyohe, Moronke; Shivashankar, Ravi; Prasad, Vikram; Gandhi, Dheeraj

    2016-06-01

    The introduction of small, soft, complex-shaped microcoils has helped facilitate the endovascular treatment of small intracranial aneurysms (IAs) over the last several years. Here, we evaluate the initial safety and efficacy of treating small IAs using only Target(®) Ultrasoft(™) coils. A retrospective review of a prospectively maintained clinical database at a single, high volume, teaching hospital was performed from September 2011 to May 2015. IAs smaller than or equal to 5.0 mm in maximal dimension treated with only Target(®) Ultrasoft(™) coils were included. A total of 50 patients with 50 intracranial aneurysms were included. Subarachnoid hemorrhage from index aneurysm rupture was the indication for treatment in 23 of 50 (46%) cases, and prior subarachnoid hemorrhage (SAH) from another aneurysm was the indication for treatment in eight of 50 (16%) cases. The complete aneurysm occlusion rate was 70% (35/50), the minimal residual aneurysm rate was 14% (7/50), and residual aneurysm rate was 16% (8/50). One intraoperative aneurysm rupture occurred. Three patients died during hospitalization from clinical sequelae of subarachnoid hemorrhage. Follow-up at a mean of 13.6 months demonstrated complete aneurysm occlusion in 75% (30/40) of cases, near complete occlusion in 15% (6/40) of cases, and residual aneurysm in 10% (4/40) of cases, all four of which were retreated. Our initial results using only Target(®) Ultrasoft(™) coils for the endovascular treatment of small intracranial aneurysms demonstrate initial excellent safety and efficacy profiles.

  18. Perception of Scenes in Different Sensory Modalities: A Result of Modal Completion.

    PubMed

    Gruber, Ronald R; Block, Richard A

    2017-01-01

    Dynamic perception includes amodal and modal completion, along with apparent movement. It fills temporal gaps for single objects. In 2 experiments, using 6 stimulus presentation conditions involving 3 sensory modalities, participants experienced 8-10 sequential stimuli (200 ms each) with interstimulus intervals (ISIs) of 0.25-7.0 s. Experiments focused on spatiotemporal completion (walking), featural completion (object changing), auditory, completion (falling bomb), and haptic changes (insect crawling). After each trial, participants judged whether they experienced the process of "happening " or whether they simply knew that the process must have occurred. The phenomenon was frequency independent, being reported at short ISIs but not at long ISIs. The phenomenon involves dynamic modal completion and possibly also conceptual processes.

  19. Gene Therapy and Targeted Toxins for Glioma

    PubMed Central

    Castro, Maria G.; Candolfi, Marianela; Kroeger, Kurt; King, Gwendalyn D.; Curtin, James F.; Yagiz, Kader; Mineharu, Yohei; Assi, Hikmat; Wibowo, Mia; Muhammad, AKM Ghulam; Foulad, David; Puntel, Mariana; Lowenstein, Pedro R.

    2011-01-01

    The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of nine to twelve months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, only the most efficacious are further transitioned into clinical trial paradigms. Clinical trials reported to date are summarized including results from conditionally cytotoxic, targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors. PMID:21453286

  20. Multifunctional Nanocarriers for diagnostics, drug delivery and targeted treatment across blood-brain barrier: perspectives on tracking and neuroimaging.

    PubMed

    Bhaskar, Sonu; Tian, Furong; Stoeger, Tobias; Kreyling, Wolfgang; de la Fuente, Jesús M; Grazú, Valeria; Borm, Paul; Estrada, Giovani; Ntziachristos, Vasilis; Razansky, Daniel

    2010-03-03

    Nanotechnology has brought a variety of new possibilities into biological discovery and clinical practice. In particular, nano-scaled carriers have revolutionalized drug delivery, allowing for therapeutic agents to be selectively targeted on an organ, tissue and cell specific level, also minimizing exposure of healthy tissue to drugs. In this review we discuss and analyze three issues, which are considered to be at the core of nano-scaled drug delivery systems, namely functionalization of nanocarriers, delivery to target organs and in vivo imaging. The latest developments on highly specific conjugation strategies that are used to attach biomolecules to the surface of nanoparticles (NP) are first reviewed. Besides drug carrying capabilities, the functionalization of nanocarriers also facilitate their transport to primary target organs. We highlight the leading advantage of nanocarriers, i.e. their ability to cross the blood-brain barrier (BBB), a tightly packed layer of endothelial cells surrounding the brain that prevents high-molecular weight molecules from entering the brain. The BBB has several transport molecules such as growth factors, insulin and transferrin that can potentially increase the efficiency and kinetics of brain-targeting nanocarriers. Potential treatments for common neurological disorders, such as stroke, tumours and Alzheimer's, are therefore a much sought-after application of nanomedicine. Likewise any other drug delivery system, a number of parameters need to be registered once functionalized NPs are administered, for instance their efficiency in organ-selective targeting, bioaccumulation and excretion. Finally, direct in vivo imaging of nanomaterials is an exciting recent field that can provide real-time tracking of those nanocarriers. We review a range of systems suitable for in vivo imaging and monitoring of drug delivery, with an emphasis on most recently introduced molecular imaging modalities based on optical and hybrid contrast, such as

  1. Hand Movement Deviations in a Visual Search Task with Cross Modal Cuing

    ERIC Educational Resources Information Center

    Aslan, Asli; Aslan, Hurol

    2007-01-01

    The purpose of this study is to demonstrate the cross-modal effects of an auditory organization on a visual search task and to investigate the influence of the level of detail in instructions describing or hinting at the associations between auditory stimuli and the possible locations of a visual target. In addition to measuring the participants'…

  2. Cross-modal and modality-specific expectancy effects between pain and disgust

    PubMed Central

    Sharvit, Gil; Vuilleumier, Patrik; Delplanque, Sylvain; Corradi-Dell’ Acqua, Corrado

    2015-01-01

    Pain sensitivity increases when a noxious stimulus is preceded by cues predicting higher intensity. However, it is unclear whether the modulation of nociception by expectancy is sensory-specific (“modality based”) or reflects the aversive-affective consequence of the upcoming event (“unpleasantness”), potentially common with other negative events. Here we compared expectancy effects for pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Indeed both pain and disgust are aversive, associated with threat to the organism, and processed in partly overlapping brain networks. Participants saw cues predicting the unpleasantness (high/low) and the modality (pain/disgust) of upcoming thermal or olfactory stimulations, and rated the associated unpleasantness after stimuli delivery. Results showed that identical thermal stimuli were perceived as more unpleasant when preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was found for olfactory disgust. Critically, cross-modal expectancy effects were observed on inconsistent trials when thermal stimuli were preceded by high-disgust cues or olfactory stimuli preceded by high-pain cues. However, these effects were stronger in consistent than inconsistent conditions. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences. PMID:26631975

  3. Assisted reproduction and risk of preterm birth in singletons by infertility diagnoses and treatment modalities: a population-based study.

    PubMed

    Dunietz, Galit Levi; Holzman, Claudia; Zhang, Yujia; Li, Chenxi; Todem, David; Boulet, Sheree L; McKane, Patricia; Kissin, Dmitry M; Copeland, Glenn; Bernson, Dana; Diamond, Michael P

    2017-11-01

    The purpose of this study is to examine the spectrum of infertility diagnoses and assisted reproductive technology (ART) treatments in relation to risk of preterm birth (PTB) in singletons. Population-based assisted reproductive technology surveillance data for 2000-2010 were linked with birth certificates from three states: Florida, Massachusetts, and Michigan, resulting in a sample of 4,370,361 non-ART and 28,430 ART-related singletons. Logistic regression models with robust variance estimators were used to compare PTB risk among singletons conceived with and without ART, the former grouped by parental infertility diagnoses and treatment modalities. Demographic and pregnancy factors were included in adjusted analyses. ART was associated with increased PTB risk across all infertility diagnosis groups and treatment types: for conventional ART, adjusted relative risks ranged from 1.4 (95% CI 1.0, 1.9) for male infertility to 2.4 (95% CI 1.8, 3.3) for tubal ligation. Adding intra-cytoplasmic sperm injection and/or assisted hatching to conventional ART treatment did not alter associated PTB risks. Singletons conceived by mothers without infertility diagnosis and with donor semen had an increased PTB risk relative to non-ART singletons. PTB risk among ART singletons is increased within each treatment type and all underlying infertility diagnosis, including male infertility. Preterm birth in ART singletons may be attributed to parental infertility, ART treatments, or their combination.

  4. Dual-modality imaging

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce; Tang, H. Roger; Da Silva, Angela J.; Wong, Kenneth H.; Iwata, Koji; Wu, Max C.

    2001-09-01

    In comparison to conventional medical imaging techniques, dual-modality imaging offers the advantage of correlating anatomical information from X-ray computed tomography (CT) with functional measurements from single-photon emission computed tomography (SPECT) or with positron emission tomography (PET). The combined X-ray/radionuclide images from dual-modality imaging can help the clinician to differentiate disease from normal uptake of radiopharmaceuticals, and to improve diagnosis and staging of disease. In addition, phantom and animal studies have demonstrated that a priori structural information from CT can be used to improve quantification of tissue uptake and organ function by correcting the radionuclide data for errors due to photon attenuation, partial volume effects, scatter radiation, and other physical effects. Dual-modality imaging therefore is emerging as a method of improving the visual quality and the quantitative accuracy of radionuclide imaging for diagnosis of patients with cancer and heart disease.

  5. Verruca plana as a complication of CO2 laser treatment: a case report.

    PubMed

    Winn, Aubrey E; Kentosh, Joshua; Bingham, Jonathan L

    2015-04-01

    Carbon dioxide (CO2) laser treatment is a common therapeutic modality for many dermatologic conditions. It uses a high energy, infrared beam of light, which selectively targets water-containing tissue resulting in controlled ablative resurfacing. This modality, however, can manifest significant cosmetic side effects. Here we report a case of verruca plana manifesting as a response to CO2 laser treatment. A 74-year-old female with recent Mohs surgery for a basal cell carcinoma, presented for full-face-fractionated CO2 treatment to address her surgical scars in addition to treating her mild diffuse actinic damage. Six weeks post treatment, the patient developed erythematous thin plaques over the areas that had been treated. Histology was consistent with verruca plana. Lesions showed mild improvement with topical tretinoin. Verruca plana are benign and typically self-limited; however, they can present a significant cosmetic burden to patients and are an important complication to consider when performing elective cosmetic procedures.

  6. Overview and recent advances in the treatment of neuroblastoma.

    PubMed

    Whittle, Sarah B; Smith, Valeria; Doherty, Erin; Zhao, Sibo; McCarty, Scott; Zage, Peter E

    2017-04-01

    Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.

  7. In Search of New Therapeutic Targets in Obesity Treatment: Sirtuins

    PubMed Central

    Kurylowicz, Alina

    2016-01-01

    Most of the available non-invasive medical therapies for obesity are non-efficient in a long-term evaluation; therefore there is a constant need for new methods of treatment. Research on calorie restriction has led to the discovery of sirtuins (silent information regulators, SIRTs), enzymes regulating different cellular pathways that may constitute potential targets in the treatment of obesity. This review paper presents the role of SIRTs in the regulation of glucose and lipid metabolism as well as in the differentiation of adipocytes. How disturbances of SIRTs’ expression and activity may lead to the development of obesity and related complications is discussed. A special emphasis is placed on polymorphisms in genes encoding SIRTs and their possible association with susceptibility to obesity and metabolic complications, as well as on data regarding altered expression of SIRTs in human obesity. Finally, the therapeutic potential of SIRTs-targeted strategies in the treatment of obesity and related disorders is discussed. PMID:27104517

  8. SU-F-J-160: Clinical Evaluation of Targeting Accuracy in Radiosurgery Using Tractography

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

    Juh, R; Han, J; Kim, C

    Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 males, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve. Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated. Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement. Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and

  9. Noise elimination algorithm for modal analysis

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

    Bao, X. X., E-mail: baoxingxian@upc.edu.cn; Li, C. L.; Xiong, C. B.

    2015-07-27

    Modal analysis is an ongoing interdisciplinary physical issue. Modal parameters estimation is applied to determine the dynamic characteristics of structures under vibration excitation. Modal analysis is more challenging for the measured vibration response signals are contaminated with noise. This study develops a mathematical algorithm of structured low rank approximation combined with the complex exponential method to estimate the modal parameters. Physical experiments using a steel cantilever beam with ten accelerometers mounted, excited by an impulse load, demonstrate that this method can significantly eliminate noise from measured signals and accurately identify the modal frequencies and damping ratios. This study provides amore » fundamental mechanism of noise elimination using structured low rank approximation in physical fields.« less

  10. Cross-modal decoupling in temporal attention.

    PubMed

    Mühlberg, Stefanie; Oriolo, Giovanni; Soto-Faraco, Salvador

    2014-06-01

    Prior studies have repeatedly reported behavioural benefits to events occurring at attended, compared to unattended, points in time. It has been suggested that, as for spatial orienting, temporal orienting of attention spreads across sensory modalities in a synergistic fashion. However, the consequences of cross-modal temporal orienting of attention remain poorly understood. One challenge is that the passage of time leads to an increase in event predictability throughout a trial, thus making it difficult to interpret possible effects (or lack thereof). Here we used a design that avoids complete temporal predictability to investigate whether attending to a sensory modality (vision or touch) at a point in time confers beneficial access to events in the other, non-attended, sensory modality (touch or vision, respectively). In contrast to previous studies and to what happens with spatial attention, we found that events in one (unattended) modality do not automatically benefit from happening at the time point when another modality is expected. Instead, it seems that attention can be deployed in time with relative independence for different sensory modalities. Based on these findings, we argue that temporal orienting of attention can be cross-modally decoupled in order to flexibly react according to the environmental demands, and that the efficiency of this selective decoupling unfolds in time. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

    PubMed

    Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

    2018-01-01

    The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

  12. Ares I-X In-Flight Modal Identification

    NASA Technical Reports Server (NTRS)

    Bartkowicz, Theodore J.; James, George H., III

    2011-01-01

    Operational modal analysis is a procedure that allows the extraction of modal parameters of a structure in its operating environment. It is based on the idealized premise that input to the structure is white noise. In some cases, when free decay responses are corrupted by unmeasured random disturbances, the response data can be processed into cross-correlation functions that approximate free decay responses. Modal parameters can be computed from these functions by time domain identification methods such as the Eigenvalue Realization Algorithm (ERA). The extracted modal parameters have the same characteristics as impulse response functions of the original system. Operational modal analysis is performed on Ares I-X in-flight data. Since the dynamic system is not stationary due to propellant mass loss, modal identification is only possible by analyzing the system as a series of linearized models over short periods of time via a sliding time-window of short time intervals. A time-domain zooming technique was also employed to enhance the modal parameter extraction. Results of this study demonstrate that free-decay time domain modal identification methods can be successfully employed for in-flight launch vehicle modal extraction.

  13. Treatment of Pediculosis Capitis

    PubMed Central

    Verma, Prashant; Namdeo, Chaitanya

    2015-01-01

    An endeavour to delineate the salient details of the treatment of head lice infestation has been made in the present article. Treatment modalities including over the counter permethrin and pyrethrin, and prescription medicines, including malathion, lindane, benzyl alcohol, spinosad are discussed. Salient features of alternative medicine and physical treatment modalities are outlined. The problem of resistance to treatment has also been taken cognizance of. PMID:26120148

  14. IDENTIFYING AND TARGETING TUMOR-INITIATING CELLS IN THE TREATMENT OF BREAST CANCER

    PubMed Central

    Wei, Wei; Lewis, Michael T.

    2015-01-01

    Breast cancer is the most common cancer in women (exclusive of skin cancer), and is the second leading cause of cancer-related deaths. Although conventional and targeted therapies have improved survival rates, there are still considerable challenges in treating breast cancer, including treatment resistance, disease recurrence, and metastasis. Treatment resistance can be either de novo - due to traits that tumor cells possess prior to treatment, or acquired, - due to traits that tumor cells gain in response to treatment. A recently proposed mechanism of de novo resistance invokes existence of a specialized subset of cancer cells defined as tumor-initiating cells (TICs), or cancer stem cells (CSC). TICs have the capacity to self-renew and regenerate new tumors that consist of all clonally-derived cell types present in the parental tumor. There are data to suggest that TICs are resistant to many conventional cancer therapies, and survive treatment in spite of dramatic shrinkage of the tumor. Residual TICs can then eventually regrow resulting in disease relapse. It is also hypothesized that TIC may be responsible for metastatic disease. If these hypotheses are correct, targeting TICs may be imperative to achieve cure. In this review, we discuss evidence for breast TICs and their apparent resistance to conventional chemotherapy and radiotherapy, as well as to various targeted therapies. We also address the potential impact of breast TIC plasticity and metastatic potential on therapeutic strategies. Finally, we describe several genes and signaling pathways that appear important for TIC function that may represent promising therapeutic targets. PMID:25876646

  15. Visual and cross-modal cues increase the identification of overlapping visual stimuli in Balint's syndrome.

    PubMed

    D'Imperio, Daniela; Scandola, Michele; Gobbetto, Valeria; Bulgarelli, Cristina; Salgarello, Matteo; Avesani, Renato; Moro, Valentina

    2017-10-01

    Cross-modal interactions improve the processing of external stimuli, particularly when an isolated sensory modality is impaired. When information from different modalities is integrated, object recognition is facilitated probably as a result of bottom-up and top-down processes. The aim of this study was to investigate the potential effects of cross-modal stimulation in a case of simultanagnosia. We report a detailed analysis of clinical symptoms and an 18 F-fluorodeoxyglucose (FDG) brain positron emission tomography/computed tomography (PET/CT) study of a patient affected by Balint's syndrome, a rare and invasive visual-spatial disorder following bilateral parieto-occipital lesions. An experiment was conducted to investigate the effects of visual and nonvisual cues on performance in tasks involving the recognition of overlapping pictures. Four modalities of sensory cues were used: visual, tactile, olfactory, and auditory. Data from neuropsychological tests showed the presence of ocular apraxia, optic ataxia, and simultanagnosia. The results of the experiment indicate a positive effect of the cues on the recognition of overlapping pictures, not only in the identification of the congruent valid-cued stimulus (target) but also in the identification of the other, noncued stimuli. All the sensory modalities analyzed (except the auditory stimulus) were efficacious in terms of increasing visual recognition. Cross-modal integration improved the patient's ability to recognize overlapping figures. However, while in the visual unimodal modality both bottom-up (priming, familiarity effect, disengagement of attention) and top-down processes (mental representation and short-term memory, the endogenous orientation of attention) are involved, in the cross-modal integration it is semantic representations that mainly activate visual recognition processes. These results are potentially useful for the design of rehabilitation training for attentional and visual-perceptual deficits.

  16. Does the modality effect exist? And if so, which modality effect?

    PubMed

    Reinwein, Joachim

    2012-02-01

    The modality effect is a central issue in multimedia learning [see Mayer (Cambridge University Press, 2005a), for a review]. Sweller's Cognitive Load Theory (CLT), for example, presumes that an illustrated text is better understood when presented visually rather than orally. The predictive power of CLT lies in how it links in to Baddeley's (1986) model of working memory and Penney's (Mem Cognit 17:398-442, 1989) Separate-Streams Hypothesis. Ginns's (Learn Instr 4:313-331, 2005) recent meta-analysis also supports the modality effect (d = 0.72, based on 43 independent effects). This article replicates the meta-analysis of the modality effect based on 86 independent effects (with within-study subgroups as the unit of analysis and with mean of the outcomes as the dependent measure), with results showing a reduction of the overall effect size by almost half (d = 0.38), and even more when Duval and Tweedie's Trim and Fill method is used to correct publication bias (d = 0.20). This article also widens the scope of the analysis of moderator variables (e.g. Pace of presentation, Type of visualization, Research group) as well as their potentially confounded effects. Finally, it is argued that, for theoretical reasons, the so-called modality effect cannot be based on Penney's or Baddeley's theories and must be explained in a different way.

  17. Dominant modal decomposition method

    NASA Astrophysics Data System (ADS)

    Dombovari, Zoltan

    2017-03-01

    The paper deals with the automatic decomposition of experimental frequency response functions (FRF's) of mechanical structures. The decomposition of FRF's is based on the Green function representation of free vibratory systems. After the determination of the impulse dynamic subspace, the system matrix is formulated and the poles are calculated directly. By means of the corresponding eigenvectors, the contribution of each element of the impulse dynamic subspace is determined and the sufficient decomposition of the corresponding FRF is carried out. With the presented dominant modal decomposition (DMD) method, the mode shapes, the modal participation vectors and the modal scaling factors are identified using the decomposed FRF's. Analytical example is presented along with experimental case studies taken from machine tool industry.

  18. Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury

    DTIC Science & Technology

    2012-11-01

    DATES COVERED 4 October 2011- 3 October 2012 4. TITLE AND SUBTITLE Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury 5a...interventions aimed at modulation of the endocannabinoid (EC) system targeting degradation of 20arachidonoyl glycerlol (2- AG) and N-arachidonoyl...percussion, traumatic brain injury, blood brain barrier, neuroinflammination, neurological dysfunction, endocannabinoids . 16. SECURITY CLASSIFICATION

  19. Targeting HER2 in the treatment of non-small cell lung cancer.

    PubMed

    Mar, Nataliya; Vredenburgh, James J; Wasser, Jeffrey S

    2015-03-01

    Oncogenic driver mutations have emerged as major treatment targets for molecular therapies in a variety of cancers. HER2 positivity has been well-studied in breast cancer, but its importance is still being explored in non-small cell lung cancer (NSCLC). Laboratory methods for assessment of HER2 positivity in NSCLC include immunohistochemistry (IHC) for protein overexpression, fluorescent in situ hybridization (FISH) for gene amplification, and next generation sequencing (NGS) for gene mutations. The prognostic and predictive significance of these tests remain to be validated, with an emerging association between HER2 gene mutations and response to HER2 targeted therapies. Despite the assay used to determine the HER2 status of lung tumors, all patients with advanced HER2 positive lung adenocarcinoma should be evaluated for treatment with targeted agents. Several clinical approaches for inclusion of these drugs into patient treatment plans exist, but there is no defined algorithm specific to NSCLC. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Treatment of lateral epicondilitis using three different local injection modalities: a randomized prospective clinical trial.

    PubMed

    Dogramaci, Yunus; Kalaci, Aydiner; Savaş, Nazan; Duman, I Gokhan; Yanat, A Nedim

    2009-10-01

    To determine the effectiveness of three different local injection modalities in the treatment of lateral epicondilitis. In a prospective randomized study on lateral epicondilitis, 75 patients were divided into three equal groups A, B and C (n = 25) and were treated using three different method of local injection. The patients in group A were treated with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine), those in group B were treated with injection of local anaesthetic (1 mL lidocaine) combined with peppering technique and those in group C with local injection of a steroid (1 mL triamcinolone) combined with local anaesthetic (1 mL lidocaine) and peppering technique. The outcome was defined by measuring the elbow pain during the activity using a 10-cm visual analogue scale (VAS) and satisfaction with the treatment using a scoring system based on the criteria of the Verhaar et al. at 3 weeks and 6 months after the injection and compared with the pre-treatment condition. There were significant (P = 0.006) differences in the successful outcomes between the three groups at 6 months. In group C in which local steroid + peppering injection technique were used; excellent results were obtained in 84% of patients comparing to 36% and 48% for patients in groups A and B, respectively. The successful outcomes were statistically higher in group C comparing to group A (P = 0.002) and group B (P = 0.011). In all groups, there was a significantly lower pain (VAS) at the 3-week and 6-month follow-ups comparing to the pre-treatment condition. VAS measured at 6-month follow-up were significantly lower in group C comparing to other groups (P = 0.002). In the treatment of lateral epicondilitis, combination of corticosteroid injections with peppering is more effective than corticosteroid injections or peppering injections alone and produces better clinical results.

  1. Diabetic foot disease: From the evaluation of the “foot at risk” to the novel diabetic ulcer treatment modalities

    PubMed Central

    Amin, Noha; Doupis, John

    2016-01-01

    The burden of diabetic foot disease (DFD) is expected to increase in the future. The incidence of DFD is still rising due to the high prevalence of DFD predisposing factors. DFD is multifactorial in nature; however most of the diabetic foot amputations are preceded by foot ulceration. Diabetic peripheral neuropathy (DPN) is a major risk factor for foot ulceration. DPN leads to loss of protective sensation resulting in continuous unconscious traumas. Patient education and detection of high risk foot are essential for the prevention of foot ulceration and amputation. Proper assessment of the diabetic foot ulceration and appropriate management ensure better prognosis. Management is based on revascularization procedures, wound debridement, treatment of infection and ulcer offloading. Management and type of dressing applied are tailored according to the type of wound and the foot condition. The scope of this review paper is to describe the diabetic foot syndrome starting from the evaluation of the foot at risk for ulceration, up to the new treatment modalities. PMID:27076876

  2. Adaptation of Physiological and Cognitive Workload via Interactive Multi-modal Displays

    DTIC Science & Technology

    2014-05-28

    peer-reviewed journals (N/A for none) 09/07/2013 Received Paper 8.00 James Merlo, Joseph E. Mercado , Jan B.F. Van Erp, Peter A. Hancock. Improving...08, . : , Mr. Joseph Mercado , Mr. Timothy White, Dr. Peter Hancock. Effects of Cross-Modal Sensory Cueing Automation Failurein a Target Detection Task...fields:...... ...... ...... ...... ...... PERCENT_SUPPORTEDNAME FTE Equivalent: Total Number: Discipline Joseph Mercado 0.50 Timothy White 0.50 1.00 2

  3. Results of a systematic literature review of treatment modalities for jugulotympanic paraganglioma, stratified per Fisch class.

    PubMed

    Jansen, T T G; Timmers, H J L M; Marres, H A M; Kaanders, J H A M; Kunst, H P M

    2018-04-01

    Key for successful jugulotympanic paraganglioma management is a personalised approach aiming for the best practice for each individual patient. To this end, a systematic review is performed, evaluating the local control and complication rates for the different treatment modalities stratified by the broadly accepted Fisch classification. A systematic literature review according to the PRISMA statement was performed. A detailed overview of individual treatment outcomes per Fisch class is provided. Local control, cranial nerve damage, complications, function recovery. Eighteen studies were selected, resembling 83 patients treated with radiotherapy and 299 with surgery. Excellent local control was found post-surgery for class A and B tumours, and risk of cranial nerve damage was <1%. For class C1-4 tumours, local control was 80%-95% post-surgery (84% post-radiotherapy), and cranial nerve damage was found in 71%-76% (none post-radiotherapy; P < .05). There was no difference in treatment outcomes between tumours of different C class. For class C1-4De/Di tumours, local control was 38%-86% (98% post-radiotherapy; P < .05) and cranial nerve damage/complication rates were 67%-100% (3% post-radiotherapy; P < .05). C1-4DeDi tumours showed lesser local control and cranial nerve damage rates when compared to C1-4De tumours. An individual risk is constituted for surgery and radiotherapy, stratified per Fisch class. For class A and B tumours, surgery is a suitable treatment option. For class C and D tumours, radiotherapy results in lower complication rates and similar or better local control rates when compared to the surgical group. © 2017 John Wiley & Sons Ltd.

  4. Modality-specific selective attention attenuates multisensory integration.

    PubMed

    Mozolic, Jennifer L; Hugenschmidt, Christina E; Peiffer, Ann M; Laurienti, Paul J

    2008-01-01

    Stimuli occurring in multiple sensory modalities that are temporally synchronous or spatially coincident can be integrated together to enhance perception. Additionally, the semantic content or meaning of a stimulus can influence cross-modal interactions, improving task performance when these stimuli convey semantically congruent or matching information, but impairing performance when they contain non-matching or distracting information. Attention is one mechanism that is known to alter processing of sensory stimuli by enhancing perception of task-relevant information and suppressing perception of task-irrelevant stimuli. It is not known, however, to what extent attention to a single sensory modality can minimize the impact of stimuli in the unattended sensory modality and reduce the integration of stimuli across multiple sensory modalities. Our hypothesis was that modality-specific selective attention would limit processing of stimuli in the unattended sensory modality, resulting in a reduction of performance enhancements produced by semantically matching multisensory stimuli, and a reduction in performance decrements produced by semantically non-matching multisensory stimuli. The results from two experiments utilizing a cued discrimination task demonstrate that selective attention to a single sensory modality prevents the integration of matching multisensory stimuli that is normally observed when attention is divided between sensory modalities. Attention did not reliably alter the amount of distraction caused by non-matching multisensory stimuli on this task; however, these findings highlight a critical role for modality-specific selective attention in modulating multisensory integration.

  5. Cross-modal integration of lexical-semantic features during word processing: evidence from oscillatory dynamics during EEG.

    PubMed

    van Ackeren, Markus J; Rueschemeyer, Shirley-Ann

    2014-01-01

    In recent years, numerous studies have provided converging evidence that word meaning is partially stored in modality-specific cortical networks. However, little is known about the mechanisms supporting the integration of this distributed semantic content into coherent conceptual representations. In the current study we aimed to address this issue by using EEG to look at the spatial and temporal dynamics of feature integration during word comprehension. Specifically, participants were presented with two modality-specific features (i.e., visual or auditory features such as silver and loud) and asked to verify whether these two features were compatible with a subsequently presented target word (e.g., WHISTLE). Each pair of features described properties from either the same modality (e.g., silver, tiny  =  visual features) or different modalities (e.g., silver, loud  =  visual, auditory). Behavioral and EEG data were collected. The results show that verifying features that are putatively represented in the same modality-specific network is faster than verifying features across modalities. At the neural level, integrating features across modalities induces sustained oscillatory activity around the theta range (4-6 Hz) in left anterior temporal lobe (ATL), a putative hub for integrating distributed semantic content. In addition, enhanced long-range network interactions in the theta range were seen between left ATL and a widespread cortical network. These results suggest that oscillatory dynamics in the theta range could be involved in integrating multimodal semantic content by creating transient functional networks linking distributed modality-specific networks and multimodal semantic hubs such as left ATL.

  6. Modal strain energies in COSMIC NASTRAN

    NASA Technical Reports Server (NTRS)

    Snyder, B. D.; Venkayya, V. B.

    1989-01-01

    A computer program was developed to take a NASTRAN output file from a normal modes analysis and calculate the modal strain energies of selected elements. The FORTRAN program can determine the modal strain energies for CROD, CBAR, CELAS, CTRMEM, CQDMEM2, and CSHEAR elements. Modal strain energies are useful in estimating damping in structures.

  7. SU-E-J-34: Clinical Evaluation of Targeting Accuracy and Tractogrphy Delineation of Radiosurgery

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

    Juh, R; Suh, T; Kim, Y

    2014-06-01

    Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. The efficiency of radiosurgery is related to its highly precise targeting. We assessed clinically the targeting accuracy of radiosurgery with Gamma knife. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Methods: Sixteen TN patients (2 females, 4 male, average age 65.3 years) treated with Gamma Knife radiosurgery, 40 Gy/50% isodosemore » line underwent 1.5Tesla MR trigeminal nerve . Target accuracy was assessed from deviation of the coordinates of the target compared with the center of enhancement on post MRI. Radiation dose delivered at the borders of contrast enhancement was evaluated Results: The median deviation of the coordinates between the intended target and the center of contrast enhancement was within 1mm. The radiation doses fitting within the borders of the contrast enhancement the target ranged from 37.5 to 40 Gy. Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive, since FA changes were detected regardless of trigeminal nerve enhancement Conclusion: The median deviation found in clinical assessment of gamma knife treatment for TN Is low and compatible with its high rate of efficiency. DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment

  8. The modality effect of ego depletion: Auditory task modality reduces ego depletion.

    PubMed

    Li, Qiong; Wang, Zhenhong

    2016-08-01

    An initial act of self-control that impairs subsequent acts of self-control is called ego depletion. The ego depletion phenomenon has been observed consistently. The modality effect refers to the effect of the presentation modality on the processing of stimuli. The modality effect was also robustly found in a large body of research. However, no study to date has examined the modality effects of ego depletion. This issue was addressed in the current study. In Experiment 1, after all participants completed a handgrip task, one group's participants completed a visual attention regulation task and the other group's participants completed an auditory attention regulation task, and then all participants again completed a handgrip task. The ego depletion phenomenon was observed in both the visual and the auditory attention regulation task. Moreover, participants who completed the visual task performed worse on the handgrip task than participants who completed the auditory task, which indicated that there was high ego depletion in the visual task condition. In Experiment 2, participants completed an initial task that either did or did not deplete self-control resources, and then they completed a second visual or auditory attention control task. The results indicated that depleted participants performed better on the auditory attention control task than the visual attention control task. These findings suggest that altering task modality may reduce ego depletion. © 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.

  9. Structure-based receptor MIMICS targeted against bacterial superantigen toxins

    DOEpatents

    Gupta, Goutam [Santa Fe, NM; Hong-Geller, Elizabeth [Los Alamos, NM; Shiflett, Patrick R [Los Alamos, NM; Lehnert, Nancy M [Albuquerque, NM

    2009-08-18

    The invention provides therapeutic compositions useful in the treatment of bacterial superantigen mediated conditions, such as Toxic Shock Syndrome. The compositions comprise genetically engineered bifunctional polypeptides containing a specific T-cell receptor binding domain and a specific MHC class II receptor binding domain, each targeting non-overlapping epitopes on a superantigen molecule against which they are designed. The anti-superantigen "receptor mimetics" or "chimeras" are rationally designed to recreate the modality of superantigen binding directly to both the TCR and the MHC-II receptor, and are capable of acting as decoys for superantigen binding, effectively out-competing the host T-cell and MHC-II receptors, the natural host receptors.

  10. A refined Frequency Domain Decomposition tool for structural modal monitoring in earthquake engineering

    NASA Astrophysics Data System (ADS)

    Pioldi, Fabio; Rizzi, Egidio

    2017-07-01

    Output-only structural identification is developed by a refined Frequency Domain Decomposition ( rFDD) approach, towards assessing current modal properties of heavy-damped buildings (in terms of identification challenge), under strong ground motions. Structural responses from earthquake excitations are taken as input signals for the identification algorithm. A new dedicated computational procedure, based on coupled Chebyshev Type II bandpass filters, is outlined for the effective estimation of natural frequencies, mode shapes and modal damping ratios. The identification technique is also coupled with a Gabor Wavelet Transform, resulting in an effective and self-contained time-frequency analysis framework. Simulated response signals generated by shear-type frames (with variable structural features) are used as a necessary validation condition. In this context use is made of a complete set of seismic records taken from the FEMA P695 database, i.e. all 44 "Far-Field" (22 NS, 22 WE) earthquake signals. The modal estimates are statistically compared to their target values, proving the accuracy of the developed algorithm in providing prompt and accurate estimates of all current strong ground motion modal parameters. At this stage, such analysis tool may be employed for convenient application in the realm of Earthquake Engineering, towards potential Structural Health Monitoring and damage detection purposes.

  11. An investigation into NVC characteristics of vehicle behaviour using modal analysis

    NASA Astrophysics Data System (ADS)

    Hanouf, Zahir; Faris, Waleed F.; Ahmad, Kartini

    2017-03-01

    NVC characterizations of vehicle behavior is one essential part of the development targets in automotive industries. Therefore understanding dynamic behavior of each structural part of the vehicle is a major requirement in improving the NVC characteristics of a vehicle. The main focus of this research is to investigate structural dynamic behavior of a passenger car using modal analysis part by part technique and apply this method to derive the interior noise sources. In the first part of this work computational modal analysis part by part tests were carried out to identify the dynamic parameters of the passenger car. Finite elements models of the different parts of the car are constructed using VPG 3.2 software. Ls-Dyna pre and post processing was used to identify and analyze the dynamic behavior of each car components panels. These tests had successfully produced natural frequencies and their associated mode shapes of such panels like trunk, hood, roof and door panels. In the second part of this research, experimental modal analysis part by part is performed on the selected car panels to extract modal parameters namely frequencies and mode shapes. The study establishes the step-by-step procedures to carry out experimental modal analysis on the car structures, using single input excitation and multi-output responses (SIMO) technique. To ensure the validity of the results obtained by the previous method an inverse method was done by fixing the response and moving the excitation and the results found were absolutely the same. Finally, comparison between results obtained from both analyses showed good similarity in both frequencies and mode shapes. Conclusion drawn from this part of study was that modal analysis part-by-part can be strongly used to establish the dynamic characteristics of the whole car. Furthermore, the developed method is also can be used to show the relationship between structural vibration of the car panels and the passengers’ noise comfort

  12. Interleukin-17 inhibitors. A new era in treatment of psoriasis and other skin diseases.

    PubMed

    Wasilewska, Agnieszka; Winiarska, Marta; Olszewska, Małgorzata; Rudnicka, Lidia

    2016-08-01

    Psoriasis is a chronic skin disease caused by the excessive secretion of inflammatory cytokines. Available therapeutic options include biologic drugs such as tumor necrosis factor alpha inhibitors and interleukin 12/23 (IL-12/23) inhibitors. The recent discovery of IL-17, which contributes to development of psoriasis, opened new possibilities for further treatment modalities. Currently, one anti-IL17 biological agent is approved for the treatment - a fully human monoclonal antibody that targets IL-17A (secukinumab). Further clinical trials, including a humanized IgG4 specific for IL-17 (ixekizumab) and a fully human antibody that targets the IL-17 receptor A (brodalumab).

  13. Natural Killer Cell Immunotherapy Targeting Cancer Stem Cells

    PubMed Central

    Luna, Jesus I; Grossenbacher, Steven K.; Murphy, William J; Canter, Robert J

    2017-01-01

    Introduction Standard cytoreductive cancer therapy, such as chemotherapy and radiotherapy, are frequently resisted by a small portion of cancer cells with “stem-cell” like properties including quiescence and repopulation. Immunotherapy represents a breakthrough modality for improving oncologic outcomes in cancer patients. Since the success of immunotherapy is not contingent on target cell proliferation, it may also be uniquely suited to address the problem of resistance and repopulation exerted by cancer stem cells (CSCs). Areas covered Natural killer (NK) cells have long been known for their ability to reject allogeneic hematopoietic stem cells, and there are increasing data demonstrating that NK cells can selectively identify and lyse CSCs. In this report, we review the current knowledge of CSCs and NK cells and highlight recent studies that support the concept that NK cells are capable of targeting CSC in solid tumors, especially in the context of combination therapy simultaneously targeting non-CSCs and CSCs. Expert Opinion Unlike cytotoxic cancer treatments, NK cells are able to target and eliminate quiescent/non-proliferating cells such as CSCs, and these enigmatic cells are an important source of relapse and metastasis. NK targeting of CSCs represents a novel and potentially high impact method to capitalize on the intrinsic therapeutic potential of NK cells. PMID:27960589

  14. An Investigation of Feasibility and Safety of Bi-Modal Stimulation for the Treatment of Tinnitus: An Open-Label Pilot Study.

    PubMed

    Hamilton, Caroline; D'Arcy, Shona; Pearlmutter, Barak A; Crispino, Gloria; Lalor, Edmund C; Conlon, Brendan J

    2016-12-01

    Tinnitus is the perception of sound in the absence of an external auditory stimulus. It is widely believed that tinnitus, in patients with associated hearing loss, is a neurological phenomenon primarily affecting the central auditory structures. However, there is growing evidence for the involvement of the somatosensory system in this form of tinnitus. For this reason it has been suggested that the condition may be amenable to bi-modal stimulation of the auditory and somatosensory systems. We conducted a pilot study to investigate the feasibility and safety of a device that delivers simultaneous auditory and somatosensory stimulation to treat the symptoms of chronic tinnitus. A cohort of 54 patients used the stimulation device for 10 weeks. Auditory stimulation was delivered via headphones and somatosensory stimulation was delivered via electrical stimulation of the tongue. Patient usage, logged by the device, was used to classify patients as compliant or noncompliant. Safety was assessed by reported adverse events and changes in tinnitus outcome measures. Response to treatment was assessed using tinnitus outcome measures: Minimum Masking Level (MML), Tinnitus Loudness Matching (TLM), and Tinnitus Handicap Inventory (THI). The device was well tolerated by patients and no adverse events or serious difficulties using the device were reported. Overall, 68% of patients met the defined compliance threshold. Compliant patients (N = 30) demonstrated statistically significant improvements in mean outcome measures after 10 weeks of treatment: THI (-11.7 pts, p < 0.001), TLM (-7.5dB, p < 0.001), and MML (-9.7dB, p < 0.001). The noncompliant group (N = 14) demonstrated no statistical improvements. This study demonstrates the feasibility and safety of a new bi-modal stimulation device and supports the potential efficacy of this new treatment for tinnitus. © 2016 Neuromod Devices Ltd. Neuromodulation: Technology at the Neural Interface published by Wiley

  15. Targeting Heat Shock Protein 90 for the Treatment of Malignant Pheochromocytoma

    PubMed Central

    Giubellino, Alessio; Sourbier, Carole; Lee, Min-Jung; Scroggins, Brad; Bullova, Petra; Landau, Michael; Ying, Weiwen; Neckers, Len

    2013-01-01

    Metastatic pheochromocytoma represents one of the major clinical challenges in the field of neuroendocrine oncology. Recent molecular characterization of pheochromocytoma suggests new treatment options with targeted therapies. In this study we investigated the 90 kDa heat shock protein (Hsp90) as a potential therapeutic target for advanced pheochromocytoma. Both the first generation, natural product Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin), and the second-generation synthetic Hsp90 inhibitor STA-9090 (ganetespib) demonstrated potent inhibition of proliferation and migration of pheochromocytoma cell lines and induced degradation of key Hsp90 clients. Furthermore, ganetespib induced dose-dependent cytotoxicity in primary pheochromocytoma cells. Using metastatic models of pheochromocytoma, we demonstrate the efficacy of 17-AAG and ganetespib in reducing metastatic burden and increasing survival. Levels of Hsp70 in plasma from the xenograft studies served as a proximal biomarker of drug treatment. Our study suggests that targeting Hsp90 may benefit patients with advanced pheochromocytoma. PMID:23457505

  16. Print media representations of UK Accident and Emergency treatment targets: Winter 2014-2015.

    PubMed

    Grant, Aimee; Hoyle, Louise

    2017-12-01

    To undertake an analysis of UK national daily newspaper coverage of accident and emergency treatment targets, in order to understand whether the media could be seen to be creating a scandal. Emergency department treatment targets have become common in developed countries. In the UK, hospitals are required to treat and discharge patients within four hours, and statistics are published daily. Breaches of targets are regularly reported by the UK print media. Exploratory research of tabloid newspaper articles that reported on four-hour treatment targets in the UK during a seven-month period over the winter of 2014-2015 (n = 1,317). An interpretivist thematic approach was used during analysis. The main "problem" identified by newspapers was the failure to meet the target, rather than negative effects on patient care (where they existed). Proposed solutions were diverse. Many articles did not describe who was to blame for the failure. We conclude that the media created a feeling of scandal, and hypothesise that this is related to political reasons and the availability of data on a daily basis. It is important for nursing staff to understand the influence of the media on patients and how stories are reported. © 2017 John Wiley & Sons Ltd.

  17. Polyarteritis nodosa: MDCT as a 'One-Stop Shop' Modality for Whole-Body Arterial Evaluation

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

    Tsai, W.-L.; Tsai, I-C.; Lee Tain, E-mail: s841082@ym.edu.t

    Polyarteritis nodosa is a rare disease, which is characterized by aneurysm formation and occlusion in the arteries of multiple systems. Due to its extensive involvement, whole-body evaluation is necessary for diagnosis and treatment monitoring. We report a case of polyarteritis nodosa using multidetector-row computed tomography (MDCT) as a 'one-stop shop' modality for whole-body arterial evaluation. With precise protocol design, MDCT can be used as a reliable noninvasive modality providing comprehensive whole-body arterial evaluation.

  18. Multi-modality molecular imaging: pre-clinical laboratory configuration

    NASA Astrophysics Data System (ADS)

    Wu, Yanjun; Wellen, Jeremy W.; Sarkar, Susanta K.

    2006-02-01

    In recent years, the prevalence of in vivo molecular imaging applications has rapidly increased. Here we report on the construction of a multi-modality imaging facility in a pharmaceutical setting that is expected to further advance existing capabilities for in vivo imaging of drug distribution and the interaction with their target. The imaging instrumentation in our facility includes a microPET scanner, a four wavelength time-domain optical imaging scanner, a 9.4T/30cm MRI scanner and a SPECT/X-ray CT scanner. An electronics shop and a computer room dedicated to image analysis are additional features of the facility. The layout of the facility was designed with a central animal preparation room surrounded by separate laboratory rooms for each of the major imaging modalities to accommodate the work-flow of simultaneous in vivo imaging experiments. This report will focus on the design of and anticipated applications for our microPET and optical imaging laboratory spaces. Additionally, we will discuss efforts to maximize the daily throughput of animal scans through development of efficient experimental work-flows and the use of multiple animals in a single scanning session.

  19. Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury

    DTIC Science & Technology

    2013-11-01

    COVERED 4 October 201 - 3 October 201 4. TITLE AND SUBTITLE Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury 5a. CONTRACT...injury, blood brain barrier, neuroinflammation, neurological dysfunction, endocannabinoids Table of Contents Introduction...promote neuroinflammation and potentially lead to neurodegeneration. We have previously demonstrated that treatments to the endocannabinoid system 2

  20. Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

    PubMed Central

    Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

    2015-01-01

    Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

  1. Communication modality sampling for a toddler with Angelman syndrome.

    PubMed

    Hyppa Martin, Jolene; Reichle, Joe; Dimian, Adele; Chen, Mo

    2013-10-01

    Vocal, gestural, and graphic communication modes were implemented concurrently with a toddler with Angelman syndrome to identify the most efficiently learned communication mode to emphasize in an initial augmentative communication system. Symbols representing preferred objects were introduced in vocal, gestural, and graphic communication modes using an alternating treatment single-subject experimental design. Conventionally accepted prompting strategies were used to teach symbols in each communication mode. Because the learner did not vocally imitate, vocal mode intervention focused on increasing vocal frequency as an initial step. When graphic and gestural mode performances were compared, the learner most accurately produced requests in graphic mode (percentage of nonoverlapping data = 96). Given the lack of success in prompting vocal productions, a comparison between vocal and the other two communication modes was not made. A growing body of evidence suggests that concurrent modality sampling is a promising low-inference, data-driven procedure that can be used to inform selection of a communication mode(s) for initial emphasis with young children. Concurrent modality sampling can guide clinical decisions regarding the allocation of treatment resources to promote success in building an initial communicative repertoire.

  2. Conceptual Structure within and between Modalities

    PubMed Central

    Dilkina, Katia; Lambon Ralph, Matthew A.

    2012-01-01

    Current views of semantic memory share the assumption that conceptual representations are based on multimodal experience, which activates distinct modality-specific brain regions. This proposition is widely accepted, yet little is known about how each modality contributes to conceptual knowledge and how the structure of this contribution varies across these multiple information sources. We used verbal feature lists, features from drawings, and verbal co-occurrence statistics from latent semantic analysis to examine the informational structure in four domains of knowledge: perceptual, functional, encyclopedic, and verbal. The goals of the analysis were three-fold: (1) to assess the structure within individual modalities; (2) to compare structures between modalities; and (3) to assess the degree to which concepts organize categorically or randomly. Our results indicated significant and unique structure in all four modalities: perceptually, concepts organize based on prominent features such as shape, size, color, and parts; functionally, they group based on use and interaction; encyclopedically, they arrange based on commonality in location or behavior; and verbally, they group associatively or relationally. Visual/perceptual knowledge gives rise to the strongest hierarchical organization and is closest to classic taxonomic structure. Information is organized somewhat similarly in the perceptual and encyclopedic domains, which differs significantly from the structure in the functional and verbal domains. Notably, the verbal modality has the most unique organization, which is not at all categorical but also not random. The idiosyncrasy and complexity of conceptual structure across modalities raise the question of how all of these modality-specific experiences are fused together into coherent, multifaceted yet unified concepts. Accordingly, both methodological and theoretical implications of the present findings are discussed. PMID:23293593

  3. A single institution experience of combined modality management of extra skeletal Ewings sarcoma.

    PubMed

    Venkitaraman, Ramachandran; George, Mathew K; Ramanan, S Ganapathy; Sagar, T G

    2007-01-11

    Extraskeletal Ewings sarcoma are rare tumors for which there is no consensus on optimal management. A retrospective review of the clinical features, treatment and outcome of patients with extraskeletal Ewings sarcoma who reported to a single institution between January 1992-December 2003 is reported. A total of 19 patients with extraskeletal Ewings sarcoma were identified. Of these, 4 patients had metastatic disease at presentation and 15 patients with non-metastatic disease received combined modality treatment with primary combination chemotherapy followed by local treatment with radiotherapy or surgery. Disease free survival and overall survival for patients with non metastatic disease after combined modality treatment were 60% and 30% respectively. The significant predictors for prolonged disease free survival and overall survival were high haemoglobin (p = 0.002), low lactate dehydrogenase (p = 0.028), chemotherapy with Vincristine, Adriamycin, Cyclophosphamide, Ifosfamide and Etoposide regime (p = 0.008) and complete response to chemotherapy (p = 0.001). Aggressive combination chemotherapy followed by complete surgery or radiotherapy to a dose of more than 50 Gy is essential to confer optimal outcome for patients with extraskeletal Ewings sarcoma.

  4. Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatment, and Therapeutic Modalities

    DTIC Science & Technology

    2011-02-01

    Thrombocytopenia, Grade 3 in 1 patient • Hypomagnesemia, Grade 3 in 1 patient • Hypokalemia, Grade 3 in 2 patient • Pneumonia , Grade 3 in 7 patients...urgently needed. While the molecular events involved in lung cancer pathogenesis are being unraveled by ongoing large scale genomics, proteomics, and...tumor initiation, progression and metastasis are an important first step leading to the development of new prognostic markers and targets for therapy

  5. Experimental modal analysis of the fuselage panels of an Aero Commander aircraft

    NASA Technical Reports Server (NTRS)

    Geisler, D.

    1981-01-01

    The reduction of interior noise in light aircraft was investigated with emphasis the thin fuselage sidewall. The approach used is theoretical and involves modeling of the sidewall panels and stiffeners. Experimental data obtained from tests investigating the effects of mass and stiffness treatments to the sidewalls are presented. The dynamic characteristics of treated panels are contrasted with the untreated sidewall panels using experimental modal analysis techniques. The results include the natural frequencies, modal dampling, and mode shapes of selected panels. Frequency response functions, data relating to the global fuselage response, and acoustic response are also presented.

  6. Palateless custom bar supported overdenture: a treatment modality to treat patient with severe gag reflex.

    PubMed

    Singh, Kunwarjeet; Gupta, Nidhi

    2012-01-01

    To suggest a custom bar supported overdenture treatment modality for prosthodontic management of patients with severe gag reflex. Some patients have a severe gag reflex and cannot tolerate conventional maxillary complete dentures with maximum palatal coverage and extensions of all borders. The condition further gets complicated in patients suffering from respiratory problems along with severe gag reflex. Severe gagging acts as a barrier to treat such patients with accepted clinical procedures and prevent patients from wearing the prosthesis. By saving some of the remaining natural teeth and fabricating, a horse shoe shape palateless simple tooth or bar supported overdenture can be successfully used for treating such patients. The remaining maxillary right and left canines were prepared with the tapered round end diamond bur to receive copings of custom bar after intentional root canal treatment of same teeth. Impression was made with light body and putty of the polyvinyl siloxane elastomer with double step putty wash technique. Impression was poured with die stone. Wax pattern of copings with bar was fabricated with inlay wax which was invested and casted. After retrieving the bar, it was finished and its fit was evaluated. The coping-bar assembly was finally cemented with the glass ionomer cement. Palateless overdenture was fabricated by conventional technique used for the fabrication of complete denture. Palateless custom bar supported overdenture procedure can be successfully used for the management of patients with severe gag reflex with improved denture retention, stability, chewing efficiency and comfort of the patient.

  7. Recent advances in aptamer-armed multimodal theranostic nanosystems for imaging and targeted therapy of cancer.

    PubMed

    Vandghanooni, Somayeh; Eskandani, Morteza; Barar, Jaleh; Omidi, Yadollah

    2018-05-30

    The side effects of chemotherapeutics during the course of cancer treatment limit their clinical outcomes. The most important mission of the modern cancer therapy modalities is the delivery of anticancer drugs specifically to the target cells/tissue in order to avoid/reduce any inadvertent non-specific impacts on the healthy normal cells. Nanocarriers decorated with a designated targeting ligand such as aptamers (Aps) and antibodies (Abs) are able to deliver cargo molecules to the target cells/tissue without affecting other neighboring cells, resulting in an improved treatment of cancer. For targeted therapy of cancer, different ligands (e.g., protein, peptide, Abs, Aps and small molecules) have widely been used in the development of different targeting drug delivery systems (DDSs). Of these homing agents, nucleic acid Aps show unique targeting potential with high binding affinity to a variety of biological targets (e.g., genes, peptides, proteins, and even cells and organs). Aps have widely been used as the targeting agent, in large part due to their unique 3D structure, simplicity in synthesis and functionalization, high chemical flexibility, low immunogenicity and toxicity, and cell/tissue penetration capability in some cases. Here, in this review, we provide important insights on Ap-decorated multimodal nanosystems (NSs) and discuss their applications in targeted therapy and imaging of cancer. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Modal noise in multimode optical fibers

    NASA Astrophysics Data System (ADS)

    Rawson, E. G.; Goodman, J. W.

    1983-03-01

    A changing speckle pattern exists at the output of a multimode optical fiber if the optical source is sufficiently coherent. When spatial filtration (for example, at a misaligned connector) or polarization filtration (for example, in certain access couplers) occurs in the presence of such speckle, the optical signal power fluctuates; such fluctuations are called 'modal noise'. This paper reviews modal noise theory and experiment, including the prediction and measurement of the modal noise signal-to-noise ratio in the presence of spatial filtration and constrained total guided power. It also presents new results relating to modal noise effects in fiber branching devices such as star couplers, access couplers, and power dividers.

  9. Cognitive Function as a Trans-Diagnostic Treatment Target in Stimulant Use Disorders

    PubMed Central

    Sofuoglu, Mehmet; DeVito, Elise E.; Waters, Andrew J.; Carroll, Kathleen M.

    2016-01-01

    Stimulant use disorder is an important public health problem, with an estimated 2.1 million current users in the United States alone. No pharmacological treatments are approved by the U.S. Food and Drug Administration (FDA) for stimulant use disorder and behavioral treatments have variable efficacy and limited availability. Most individuals with stimulant use disorder have other comorbidities, most with overlapping symptoms and cognitive impairments. The goal of this article is to present a rationale for cognition as a treatment target in stimulant use disorder, and to outline potential treatment approaches. Rates of lifetime comorbid psychiatric disorders among people with stimulant use disorders are estimated at 65% - 73%, with the most common being mood disorders (13% - 64%) and anxiety disorders (21% - 50%), as well as non-substance induced psychotic disorders (under 10%). There are several models of addictive behavior, but the dual process model particularly highlights the relevance of cognitive impairments and biases to the development and maintenance of addiction. This model explains addictive behavior as a balance between automatic processes and executive control, which in turn are related to individual (genetics, comorbid disorders, psychosocial factors) and other (craving, triggers, drug use) factors. Certain cognitive impairments, such as attentional bias and approach bias, are most relevant to automatic processes, while sustained attention, response inhibition, and working memory are primarily related to executive control. These cognitive impairments and biases are also common in disorders frequently comorbid with stimulant use disorder, and predict poor treatment retention and clinical outcomes. As such, they may serve as feasible trans-diagnostic treatment targets. There are promising pharmacological, cognitive, and behavioral approaches that aim to enhance cognitive function. Pharmacotherapies target cognitive impairments associated with executive

  10. Attentional reorienting triggers spatial asymmetries in a search task with cross-modal spatial cueing

    PubMed Central

    Paladini, Rebecca E.; Diana, Lorenzo; Zito, Giuseppe A.; Nyffeler, Thomas; Wyss, Patric; Mosimann, Urs P.; Müri, René M.; Nef, Tobias

    2018-01-01

    Cross-modal spatial cueing can affect performance in a visual search task. For example, search performance improves if a visual target and an auditory cue originate from the same spatial location, and it deteriorates if they originate from different locations. Moreover, it has recently been postulated that multisensory settings, i.e., experimental settings, in which critical stimuli are concurrently presented in different sensory modalities (e.g., visual and auditory), may trigger asymmetries in visuospatial attention. Thereby, a facilitation has been observed for visual stimuli presented in the right compared to the left visual space. However, it remains unclear whether auditory cueing of attention differentially affects search performance in the left and the right hemifields in audio-visual search tasks. The present study investigated whether spatial asymmetries would occur in a search task with cross-modal spatial cueing. Participants completed a visual search task that contained no auditory cues (i.e., unimodal visual condition), spatially congruent, spatially incongruent, and spatially non-informative auditory cues. To further assess participants’ accuracy in localising the auditory cues, a unimodal auditory spatial localisation task was also administered. The results demonstrated no left/right asymmetries in the unimodal visual search condition. Both an additional incongruent, as well as a spatially non-informative, auditory cue resulted in lateral asymmetries. Thereby, search times were increased for targets presented in the left compared to the right hemifield. No such spatial asymmetry was observed in the congruent condition. However, participants’ performance in the congruent condition was modulated by their tone localisation accuracy. The findings of the present study demonstrate that spatial asymmetries in multisensory processing depend on the validity of the cross-modal cues, and occur under specific attentional conditions, i.e., when visual

  11. Restricted Acoustic Modal Analysis Applied to Internal Combustor Spectra and Cross-Spectra Measurements

    NASA Technical Reports Server (NTRS)

    Miles, Jeffrey Hilton

    2006-01-01

    A treatment of the modal decomposition of the pressure field in a combustor as determined by two Kulite pressure measurements is developed herein. It is applied to a Pratt & Whitney PW4098 engine combustor over a range of operating conditions. For modes other than the plane wave the new part of the treatment is the assumption that there are distinct frequency bands in which the individual modes, including the plane wave mode, overlap such that if circumferential mode m and circumferential mode m-1 are present than circumferential mode m 2 is not. Consequently, in the analysis used herein at frequencies above the first cut-off mode frequency, only pairs of circumferential modes are individually present at each frequency. Consequently, this is a restricted modal analysis. A new result is that the successful use of the same modal span frequencies over a range of operating conditions for this particular engine suggests that the temperature, T, and the velocity, v, of the flow at each operating condition are related by c(sup 2)-v(sup 2) = a constant where c is the speed of sound.

  12. Is Angiosome-Targeted Angioplasty Effective for Limb Salvage and Wound Healing in Diabetic Foot? : A Meta-Analysis.

    PubMed

    Chae, Kum Ju; Shin, Jin Yong

    2016-01-01

    Given that the efficacy of employing angiosome-targeted angioplasty in the treatment of diabetic foot remains controversial, this study was conducted to examine its efficacy. We performed a systematic literature review and meta-analysis using core databases, extracting the treatment modality of angiosome-targeted angioplasty as the predictor variable, and limb salvage, wound healing, and revision rate as the outcome variables. We used the Newcastle-Ottawa Scale to assess the study quality, along with the Cochrane Risk of Bias Tool. We evaluated publication bias using a funnel plot. The search strategy identified 518 publications. After screening these, we selected four articles for review. The meta-analysis revealed that overall limb salvage and wound healing rates were significantly higher (Odds ratio = 2.209, 3.290, p = 0.001, p<0.001) in patients who received angiosome-targeted angioplasty than in those who received nonangiosome-targeted angioplasty. The revision rate between the angiosome and nonangiosome groups was not significantly different (Odds ratio = 0.747, p = 0.314). Although a further randomized controlled trial is required for confirmation, angiosome-targeted angioplasty in diabetic foot was more effective than nonangiosome-targeted angioplasty with respect to wound healing and limb salvage.

  13. Picosecond 532-nm neodymium-doped yttrium aluminium garnet laser-a novel and promising modality for the treatment of café-au-lait macules.

    PubMed

    Artzi, Ofir; Mehrabi, Joseph N; Koren, Amir; Niv, Roni; Lapidoth, Moshe; Levi, Assi

    2018-05-01

    Café-au-lait macules (CALMs) present as benign hyperpigmented, well-circumscribed spots on the skin for which many patients seek treatment for aesthetic reasons. The objective of this study is to report our experience in treating CALMs using a picosecond 532-nm neodymium-doped yttrium aluminium garnet (PS 532 nm) laser. This is a retrospective case series of 16 patients with CALMs who were treated by a PS 532-nm laser (1-4 treatments, 4-8 weeks apart). Response as seen on clinical photographs was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 5 (95-100% improvement). Patient satisfaction and tolerance were documented at final visit. The results of 15 patients demonstrated significant improvement (average 3.43), and their satisfaction and tolerance levels were high. One patient had no response whatsoever to treatment. The PS 532-nm laser is a promising novel modality for the treatment of CALMs.

  14. DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS.

    PubMed

    Ahmari, Susanne E; Dougherty, Darin D

    2015-08-01

    Obsessive-compulsive disorder (OCD) is a chronic, severe mental illness with up to 2-3% prevalence worldwide. In fact, OCD has been classified as one of the world's 10 leading causes of illness-related disability according to the World Health Organization, largely because of the chronic nature of disabling symptoms.([1]) Despite the severity and high prevalence of this chronic and disabling disorder, there is still relatively limited understanding of its pathophysiology. However, this is now rapidly changing due to development of powerful technologies that can be used to dissect the neural circuits underlying pathologic behaviors. In this article, we describe recent technical advances that have allowed neuroscientists to start identifying the circuits underlying complex repetitive behaviors using animal model systems. In addition, we review current surgical and stimulation-based treatments for OCD that target circuit dysfunction. Finally, we discuss how findings from animal models may be applied in the clinical arena to help inform and refine targeted brain stimulation-based treatment approaches. © 2015 Wiley Periodicals, Inc.

  15. Beyond Monoamines-Novel Targets for Treatment-Resistant Depression: A Comprehensive Review

    PubMed Central

    Rosenblat, Christian; McIntyre, Roger S.; Alves, Gilberto S.; Fountoulakis, Konstantinos N.; Carvalho, André F.

    2015-01-01

    Major depressive disorder (MDD) is a leading cause of disability worldwide. Current first line therapies target modulation of the monoamine system. A large variety of agents are currently available that effectively alter monoamine levels; however, approximately one third of MDD patients remain treatment refractory after adequate trials of multiple monoamine based therapies. Therefore, patients with treatment-resistant depression (TRD) may require modulation of pathways outside of the classic monoamine system. The purpose of this review was thus to discuss novel targets for TRD, to describe their potential mechanisms of action, the available clinical evidence for these targets, the limitations of available evidence as well as future research directions. Several alternate pathways involved in the patho-etiology of TRD have been uncovered including the following: inflammatory pathways, the oxidative stress pathway, the hypothalamic-pituitary-adrenal (HPA) axis, the metabolic and bioenergetics system, neurotrophic pathways, the glutamate system, the opioid system and the cholinergic system. For each of these systems, several targets have been assessed in preclinical and clinical models. Preclinical models strongly implicate these pathways in the patho-etiology of MDD. Clinical trials for TRD have been conducted for several novel targets; however, most of the trials discussed are small and several are uncontrolled. Therefore, further clinical trials are required to assess the true efficacy of these targets for TRD. As well, several promising novel agents have been clinically tested in MDD populations, but have yet to be assessed specifically for TRD. Thus, their applicability to TRD remains unknown. PMID:26467412

  16. Dosimetric evaluation of 4 different treatment modalities for curative-intent stereotactic body radiation therapy for isolated thoracic spinal metastases

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

    Yang, Jun; Department of Oncology, First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road, Weihui, Henan, 453100; Ma, Lin

    2016-07-01

    To investigate the dosimetric characteristics of 4 SBRT-capable dose delivery systems, CyberKnife (CK), Helical TomoTherapy (HT), Volumetric Modulated Arc Therapy (VMAT) by Varian RapidArc (RA), and segmental step-and-shoot intensity-modulated radiation therapy (IMRT) by Elekta, on isolated thoracic spinal lesions. CK, HT, RA, and IMRT planning were performed simultaneously for 10 randomly selected patients with 6 body types and 6 body + pedicle types with isolated thoracic lesions. The prescription was set with curative intent and dose of either 33 Gy in 3 fractions (3F) or 40 Gy in 5F to cover at least 90% of the planning target volume (PTV),more » correspondingly. Different dosimetric indices, beam-on time, and monitor units (MUs) were evaluated to compare the advantages/disadvantages of each delivery modality. In ensuring the dose-volume constraints for cord and esophagus of the premise, CK, HT, and RA all achieved a sharp conformity index (CI) and a small penumbra volume compared to IMRT. RA achieved a CI comparable to those from CK, HT, and IMRT. CK had a heterogeneous dose distribution in the target as its radiosurgical nature with less dose uniformity inside the target. CK had the longest beam-on time and the largest MUs, followed by HT and RA. IMRT presented the shortest beam-on time and the least MUs delivery. For the body-type lesions, CK, HT, and RA satisfied the target coverage criterion in 6 cases, but the criterion was satisfied in only 3 (50%) cases with the IMRT technique. For the body + pedicle-type lesions, HT satisfied the criterion of the target coverage of ≥90% in 4 of the 6 cases, and reached a target coverage of 89.0% in another case. However, the criterion of the target coverage of ≥90% was reached in 2 cases by CK and RA, and only in 1 case by IMRT. For curative-intent SBRT of isolated thoracic spinal lesions, RA is the first choice for the body-type lesions owing to its delivery efficiency (time); the second choice is CK or HT; HT

  17. Short-Term Memory in Mathematics-Proficient and Mathematics-Disabled Students as a Function of Input-Modality/Output-Modality Pairings.

    ERIC Educational Resources Information Center

    Webster, Raymond E.

    1980-01-01

    A significant two-way input modality by output modality interaction suggested that short term memory capacity among the groups differed as a function of the modality used to present the items in combination with the output response required. (Author/CL)

  18. Personalized Antidepressant Selection and Pathway to Novel Treatments: Clinical Utility of Targeting Inflammation

    PubMed Central

    Jha, Manish K.; Trivedi, Madhukar H.

    2018-01-01

    Major depressive disorder (MDD) is a chronic condition that affects one in six adults in the US during their lifetime. The current practice of antidepressant medication prescription is a trial-and-error process. Additionally, over a third of patients with MDD fail to respond to two or more antidepressant treatments. There are no valid clinical markers to personalize currently available antidepressant medications, all of which have similar mechanisms targeting monoamine neurotransmission. The goal of this review is to summarize the recent findings of immune dysfunction in patients with MDD, the utility of inflammatory markers to personalize treatment selection, and the potential of targeting inflammation to develop novel antidepressant treatments. To personalize antidepressant prescription, a c-reactive protein (CRP)-matched treatment assignment can be rapidly implemented in clinical practice with point-of-care fingerstick tests. With this approach, 4.5 patients need to be treated for 1 additional remission as compared to a CRP-mismatched treatment assignment. Anti-cytokine treatments may be effective as novel antidepressants. Monoclonal antibodies against proinflammatory cytokines, such as interleukin 6, interleukin 17, and tumor necrosis factor α, have demonstrated antidepressant effects in patients with chronic inflammatory conditions who report significant depressive symptoms. Additional novel antidepressant strategies targeting inflammation include pharmaceutical agents that block the effect of systemic inflammation on the central nervous system. In conclusion, inflammatory markers offer the potential not only to personalize antidepressant prescription but also to guide the development of novel mechanistically-guided antidepressant treatments. PMID:29329256

  19. Fluids and Combustion Facility: Fluids Integrated Rack Modal Model Correlation

    NASA Technical Reports Server (NTRS)

    McNelis, Mark E.; Suarez, Vicente J.; Sullivan, Timothy L.; Otten, Kim D.; Akers, James C.

    2005-01-01

    The Fluids Integrated Rack (FIR) is one of two racks in the Fluids and Combustion Facility on the International Space Station. The FIR is dedicated to the scientific investigation of space system fluids management supporting NASA s Exploration of Space Initiative. The FIR hardware was modal tested and FIR finite element model updated to satisfy the International Space Station model correlation criteria. The final cross-orthogonality results between the correlated model and test mode shapes was greater than 90 percent for all primary target modes.

  20. Targeting the interleukin pathway in the treatment of asthma.

    PubMed

    Chung, Kian Fan

    2015-09-12

    Asthma is a common heterogeneous disease with a complex pathophysiology. Current therapies based on inhaled corticosteroids and longacting β2 agonists are effective in controlling asthma in most, but not all patients, with a few patients falling into the severe asthma category. Severe asthma is characterised by poor asthma control, recurrent exacerbations, and chronic airflow obstruction despite adequate and, in many cases, high-dose treatments. There is strong evidence supporting the role for interleukins derived from T-helper-2 (Th2) cells and innate lymphoid cells, such as interleukins 4, 5, and 13, as underlying the eosinophilic and allergic inflammatory processes in nearly half of these patients. An anti-IgE antibody, omalizumab, which binds to circulating IgE, a product of B cells from the actions of interleukin 4 and interleukin 13, is used as treatment for severe allergic asthma. Studies examining cytokine blockers such as anti-interleukin-5, anti-interleukin-4Rα, and anti-interleukin-13 monoclonal antibodies in patients with severe asthma with recurrent exacerbations and high blood eosinophil counts despite use of inhaled corticosteroids have reported improved outcomes in terms of exacerbations, asthma control, and forced expiratory volume in 1 s. The US Food and Drug Administration's recommendation to use an anti-interleukin-5 antibody for the treatment of severe eosinophilic asthma suggests that there will be a therapeutic place for these anti-Th2 agents. Biomarkers should be used to identify the right patients for such targeted approaches. More guidance will be needed as to which patients should receive each of these classes of selective antibody-based treatments. Currently, there is no treatment that targets the cytokines driving asthma associated with non-eosinophilic inflammation and low Th2 expression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. New Therapeutic Modalities of Retinal Laser Injury.

    DTIC Science & Technology

    1992-03-31

    Clawticarroni New Therapeutic Modalities for Retinal Laser Injury 1 2 . PERSONAL AUTHOR(S) Tim T.Lar. Ph.D., .and Mark Q.M. Tso. M.D. 13a. TYPE OF...Experimental treatment of retinal laser Injury 4 1.3: Clinical therapy 4 1.4: Our hypothesis and approaches 4 Chapter 2 : Accidental laser Injury to the...human retina 7 2.1: Introduction 7 2.2: Case 1 7 2.3: Case 2 8 2.4: General comments 9 2.5: Clinical course 10 2.6: Implications 10 Chapter 3: Sub

  2. Paclitaxel targets VEGF-mediated angiogenesis in ovarian cancer treatment

    PubMed Central

    Ai, Bin; Bie, Zhixin; Zhang, Shuai; Li, Ailing

    2016-01-01

    Ovarian cancer is one of the gynecologic cancers with the highest mortality, wherein vascular endothelial growth factor (VEGF) is involved in regulating tumor vascularization, growth, migration, and invasion. VEGF-mediated angiogenesis in tumors has been targeted in various cancer treatments, and anti-VEGF therapy has been used clinically for treatment of several types of cancer. Paclitaxel is a natural antitumor agent in the standard front-line treatment that has significant efficiency to treat advanced cancers, including ovarian cancer. Although platinum/paclitaxel-based chemotherapy has good response rates, most patients eventually relapse because the disease develops drug resistance. We aim to review the recent advances in paclitaxel treatment of ovarian cancer via antiangiogenesis. Single-agent therapy may be used in selected cases of ovarian cancer. However, to prevent drug resistance, drug combinations should be identified for optimal effectiveness and existing therapies should be improved. PMID:27648354

  3. The role of PET in target localization for radiotherapy treatment planning.

    PubMed

    Rembielak, Agata; Price, Pat

    2008-02-01

    Positron emission tomography (PET) is currently accepted as an important tool in oncology, mostly for diagnosis, staging and restaging purposes. It provides a new type of information in radiotherapy, functional rather than anatomical. PET imaging can also be used for target volume definition in radiotherapy treatment planning. The need for very precise target volume delineation has arisen with the increasing use of sophisticated three-dimensional conformal radiotherapy techniques and intensity modulated radiation therapy. It is expected that better delineation of the target volume may lead to a significant reduction in the irradiated volume, thus lowering the risk of treatment complications (smaller safety margins). Better tumour visualisation also allows a higher dose of radiation to be applied to the tumour, which may lead to better tumour control. The aim of this article is to review the possible use of PET imaging in the radiotherapy of various cancers. We focus mainly on non-small cell lung cancer, lymphoma and oesophageal cancer, but also include current opinion on the use of PET-based planning in other tumours including brain, uterine cervix, rectum and prostate.

  4. Advances in the treatment of portal hypertension in cirrhosis.

    PubMed

    Kimer, N; Wiese, S; Mo, S; Møller, S; Bendtsen, F

    2016-08-01

    Non-selective beta-blockers and handling of esophageal varices has been key elements in the treatment of portal hypertension in recent decades. Liver vein catheterization has been essential in diagnosis and monitoring of portal hypertension, but ongoing needs for noninvasive tools has led to research in areas of both biomarkers, and transient elastography, which displays promising results in discerning clinically significant portal hypertension. Novel research into the areas of hepatic stellate cell function and the dynamic components of portal hypertension has revealed promising areas of treatment modalities, targeting intestinal decontamination, angiogenesis, inflammation and oxidative stress. Future studies may reveal if these initiatives lead to developments of new drugs for treatment of portal hypertension.

  5. [Current Status of Targeted Treatment in Breast Cancer].

    PubMed

    Seiffert, Katharina; Schmalfeldt, Barbara; Müller, Volkmar

    2017-11-01

    Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Reimbursement and economic factors influencing dialysis modality choice around the world

    PubMed Central

    Just, Paul M.; de Charro, Frank Th.; Tschosik, Elizabeth A.; Noe, Les L.; Bhattacharyya, Samir K.; Riella, Miguel C.

    2008-01-01

    The worldwide incidence of kidney failure is on the rise and treatment is costly; thus, the global burden of illness is growing. Kidney failure patients require either a kidney transplant or dialysis to maintain life. This review focuses on the economics of dialysis. Alternative dialysis modalities are haemodialysis (HD) and peritoneal dialysis (PD). Important economic factors influencing dialysis modality selection include financing, reimbursement and resource availability. In general, where there is little or no facility or physician reimbursement or payment for PD, the share of PD is very low. Regarding resource availability, when centre HD capacity is high, there is an incentive to use that capacity rather than place patients on home dialysis. In certain countries, there is interest in revising the reimbursement structure to favour home-based therapies, including PD and home HD. Modality selection is influenced by employment status, with an association between being employed and PD as the modality choice. Cost drivers differ for PD and HD. PD is driven mainly by variable costs such as solutions and tubing, while HD is driven mainly by fixed costs of facility space and staff. Many cost comparisons of dialysis modalities have been conducted. A key factor to consider in reviewing cost comparisons is the perspective of the analysis because different costs are relevant for different perspectives. In developed countries, HD is generally more expensive than PD to the payer. Additional research is needed in the developing world before conclusive statements may be made regarding the relative costs of HD and PD. PMID:18234844

  7. The evolving role of targeted drugs in the treatment of Hodgkin lymphoma.

    PubMed

    Eichenauer, Dennis A; Engert, Andreas

    2017-09-01

    Hodgkin lymphoma (HL) is a B-cell-derived malignancy mostly affecting young adults. More than 80% of patients are cured after stage-adapted first-line treatment with chemotherapy and/or radiotherapy. About 50% of patients with disease recurrence achieve long-term remission with second-line treatment consisting of high-dose chemotherapy and autologous stem cell transplantation. However, HL treatment is often associated with acute toxicity and in part life-threatening late effects. Implementing targeted drugs may reduce toxicity and potentially further optimize efficacy. In recent years, the CD30-directed antibody-drug conjugate brentuximab vedotin (BV) and anti-PD-1 antibodies, nivolumab and pembrolizumab, underwent extensive evaluation in HL. They have exhibited encouraging single agent activity and a favorable toxicity profile in patients with multiple relapses. Therefore, they are currently under investigation in different additional indications. Areas covered: This article gives an overview over clinical trials evaluating targeted drugs either as single agent or as part of combination therapies in HL patients. Expert commentary: A multitude of targeted drugs are investigated in HL. Promising data have particularly emerged from studies with BV and anti-PD-1 antibodies. However, mature data needed for final conclusions are still pending.

  8. Targeted treatment in primary care for low back pain: the treatment system and clinical training programmes used in the IMPaCT Back study (ISRCTN 55174281)

    PubMed Central

    Sowden, Gail; Hill, Jonathan C; Konstantinou, Kika; Khanna, Meenee; Main, Chris J; Salmon, Paula; Somerville, Simon; Wathall, Simon; Foster, Nadine E

    2012-01-01

    Background. The IMPaCT Back study (IMplementation to improve Patient Care through Targeted treatment for Back pain) is a quality improvement study which aims to investigate the effects of introducing and supporting a subgrouping for targeted treatment system for patients with low back pain (LBP) in primary care. This paper details the subgrouping for targeted treatment system and the clinical training and mentoring programmes aimed at equipping clinicians to deliver it. The subgrouping and targeted treatment system. This system differs from ‘one-size fits all’ usual practice as it suggests that first contact health care practitioners should systematically allocate LBP patients to one of the three subgroups according to key modifiable prognostic indicators for chronicity. Patients in each subgroup (those at low, medium or high risk of chronicity) are then managed according to a targeted treatment system of increasing complexity. The subgrouping tools. Subgrouping tools help guide clinical decision-making about treatment and onward referral. Two subgrouping tools have been used in the IMPaCT Back study, a 9-item version used by participating physiotherapists and a 6-item version used by GPs. The targeted treatments. The targeted treatments include a minimal intervention delivered by GPs (for those patients at low risk of poor outcome) or referral to primary care physiotherapists who can apply physiotherapy approaches to addressing pain and disability (for those at medium risk) and additional cognitive-behavioural approaches to help address psychological and social obstacles to recovery (for those at high risk). The training packages. Building on previous interventions for other pilot studies and randomized trials, we have developed and delivered clinical training and support programmes for GPs and physiotherapists. Discussion. This paper describes in detail the IMPaCT Back study’s subgrouping for targeted treatment system and the training and mentoring packages

  9. Multi-Modal Use of a Socially Directed Call in Bonobos

    PubMed Central

    Genty, Emilie; Clay, Zanna; Hobaiter, Catherine; Zuberbühler, Klaus

    2014-01-01

    ‘Contest hoots’ are acoustically complex vocalisations produced by adult and subadult male bonobos (Pan paniscus). These calls are often directed at specific individuals and regularly combined with gestures and other body signals. The aim of our study was to describe the multi-modal use of this call type and to clarify its communicative and social function. To this end, we observed two large groups of bonobos, which generated a sample of 585 communicative interactions initiated by 10 different males. We found that contest hooting, with or without other associated signals, was produced to challenge and provoke a social reaction in the targeted individual, usually agonistic chase. Interestingly, ‘contest hoots’ were sometimes also used during friendly play. In both contexts, males were highly selective in whom they targeted by preferentially choosing individuals of equal or higher social rank, suggesting that the calls functioned to assert social status. Multi-modal sequences were not more successful in eliciting reactions than contest hoots given alone, but we found a significant difference in the choice of associated gestures between playful and agonistic contexts. During friendly play, contest hoots were significantly more often combined with soft than rough gestures compared to agonistic challenges, while the calls' acoustic structure remained the same. We conclude that contest hoots indicate the signaller's intention to interact socially with important group members, while the gestures provide additional cues concerning the nature of the desired interaction. PMID:24454745

  10. Integrating Conceptual Knowledge Within and Across Representational Modalities

    PubMed Central

    McNorgan, Chris; Reid, Jackie; McRae, Ken

    2011-01-01

    Research suggests that concepts are distributed across brain regions specialized for processing information from different sensorimotor modalities. Multimodal semantic models fall into one of two broad classes differentiated by the assumed hierarchy of convergence zones over which information is integrated. In shallow models, communication within- and between-modality is accomplished using either direct connectivity, or a central semantic hub. In deep models, modalities are connected via cascading integration sites with successively wider receptive fields. Four experiments provide the first direct behavioral tests of these models using speeded tasks involving feature inference and concept activation. Shallow models predict no within-modal versus cross-modal difference in either task, whereas deep models predict a within-modal advantage for feature inference, but a cross-modal advantage for concept activation. Experiments 1 and 2 used relatedness judgments to tap participants’ knowledge of relations for within- and cross-modal feature pairs. Experiments 3 and 4 used a dual feature verification task. The pattern of decision latencies across Experiments 1 to 4 is consistent with a deep integration hierarchy. PMID:21093853

  11. Integrating conceptual knowledge within and across representational modalities.

    PubMed

    McNorgan, Chris; Reid, Jackie; McRae, Ken

    2011-02-01

    Research suggests that concepts are distributed across brain regions specialized for processing information from different sensorimotor modalities. Multimodal semantic models fall into one of two broad classes differentiated by the assumed hierarchy of convergence zones over which information is integrated. In shallow models, communication within- and between-modality is accomplished using either direct connectivity, or a central semantic hub. In deep models, modalities are connected via cascading integration sites with successively wider receptive fields. Four experiments provide the first direct behavioral tests of these models using speeded tasks involving feature inference and concept activation. Shallow models predict no within-modal versus cross-modal difference in either task, whereas deep models predict a within-modal advantage for feature inference, but a cross-modal advantage for concept activation. Experiments 1 and 2 used relatedness judgments to tap participants' knowledge of relations for within- and cross-modal feature pairs. Experiments 3 and 4 used a dual-feature verification task. The pattern of decision latencies across Experiments 1-4 is consistent with a deep integration hierarchy. Copyright © 2010 Elsevier B.V. All rights reserved.

  12. An augmented Lagrangian trust region method for inclusion boundary reconstruction using ultrasound/electrical dual-modality tomography

    NASA Astrophysics Data System (ADS)

    Liang, Guanghui; Ren, Shangjie; Dong, Feng

    2018-07-01

    The ultrasound/electrical dual-modality tomography utilizes the complementarity of ultrasound reflection tomography (URT) and electrical impedance tomography (EIT) to improve the speed and accuracy of image reconstruction. Due to its advantages of no-invasive, no-radiation and low-cost, ultrasound/electrical dual-modality tomography has attracted much attention in the field of dual-modality imaging and has many potential applications in industrial and biomedical imaging. However, the data fusion of URT and EIT is difficult due to their different theoretical foundations and measurement principles. The most commonly used data fusion strategy in ultrasound/electrical dual-modality tomography is incorporating the structured information extracted from the URT into the EIT image reconstruction process through a pixel-based constraint. Due to the inherent non-linearity and ill-posedness of EIT, the reconstructed images from the strategy suffer from the low resolution, especially at the boundary of the observed inclusions. To improve this condition, an augmented Lagrangian trust region method is proposed to directly reconstruct the shapes of the inclusions from the ultrasound/electrical dual-modality measurements. In the proposed method, the shape of the target inclusion is parameterized by a radial shape model whose coefficients are used as the shape parameters. Then, the dual-modality shape inversion problem is formulated by an energy minimization problem in which the energy function derived from EIT is constrained by an ultrasound measurements model through an equality constraint equation. Finally, the optimal shape parameters associated with the optimal inclusion shape guesses are determined by minimizing the constrained cost function using the augmented Lagrangian trust region method. To evaluate the proposed method, numerical tests are carried out. Compared with single modality EIT, the proposed dual-modality inclusion boundary reconstruction method has a higher

  13. Targeted Doxorubicin-Loaded Bacterially Derived Nano-Cells for the Treatment of Neuroblastoma.

    PubMed

    Sagnella, Sharon M; Trieu, Jennifer; Brahmbhatt, Himanshu; MacDiarmid, Jennifer A; MacMillan, Alex; Whan, Renee M; Fife, Christopher M; McCarroll, Joshua A; Gifford, Andrew J; Ziegler, David S; Kavallaris, Maria

    2018-05-01

    Advanced stage neuroblastoma is an aggressive disease with limited treatment options for patients with drug-resistant tumors. Targeted delivery of chemotherapy for pediatric cancers offers promise to improve treatment efficacy and reduce toxicity associated with systemic chemotherapy. The EnGeneIC Dream Vector (EDV TM ) is a nanocell, which can package chemotherapeutic drugs and target tumors via attachment of bispecific proteins to the surface of the nanocell. Phase I trials in adults with refractory tumors have shown an acceptable safety profile. Herein we investigated the activity of EGFR-targeted and doxorubicin-loaded EDV TM ( EGFR EDV TM Dox ) for the treatment of neuroblastoma. Two independent neuroblastoma cell lines with variable expression of EGFR protein [SK-N-BE(2), high; SH-SY-5Y, low] were used. EGFR EDV TM Dox induced apoptosis in these cells compared to control, doxorubicin, or non-doxorubicin loaded EGFR EDV TM In three-dimensional tumor spheroids, imaging and fluorescence life-time microscopy revealed that EGFR EDV TM Dox had a marked enhancement of doxorubicin penetration compared to doxorubicin alone, and improved penetration compared to non-EGFR-targeted EDV TM Dox , with enhanced spheroid penetration leading to increased apoptosis. In two independent orthotopic human neuroblastoma xenograft models, short-term studies (28 days) of tumor-bearing mice led to a significant decrease in tumor size in EGFR EDV TM Dox -treated animals compared to control, doxorubicin, or non-EGFR EDV TM Dox There was increased TUNEL staining of tumors at day 28 compared to control, doxorubicin, or non-EGFR EDV TM Dox Moreover, overall survival was increased in neuroblastoma mice treated with EGFR EDV TM Dox ( P < 0007) compared to control. Drug-loaded bispecific-antibody targeted EDVs TM offer a highly promising approach for the treatment of aggressive pediatric malignancies such as neuroblastoma. Mol Cancer Ther; 17(5); 1012-23. ©2018 AACR . ©2018 American

  14. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia.

    PubMed

    Morin, Mélanie; Carroll, Marie-Soleil; Bergeron, Sophie

    2017-07-01

    Pelvic floor muscle physical therapy is recommended in clinical guidelines for women with provoked vestibulodynia (PVD). Including isolated or combined treatment modalities, physical therapy is viewed as an effective first-line intervention, yet no systematic review concerning the effectiveness of physical therapy has been conducted. To systematically appraise the current literature on the effectiveness of physical therapy modalities for decreasing pain during intercourse and improving sexual function in women with PVD. A systematic literature search using PubMed, Scopus, CINHAL, and PEDro was conducted until October 2016. Moreover, a manual search from reference lists of included articles was performed. Ongoing trials also were reviewed using clinicaltrial.gov and ISRCTNregistry. Randomized controlled trials, prospective and retrospective cohorts, and case reports evaluating the effect of isolated or combined physical therapy modalities in women with PVD were included in the review. Main outcome measures were pain during intercourse, sexual function, and patient's perceived improvement. The literature search resulted in 43 eligible studies including 7 randomized controlled trials, 20 prospective studies, 5 retrospective studies, 6 case reports, and 6 study protocols. Most studies had a high risk of bias mainly associated with the lack of a comparison group. Another common bias was related to insufficient sample size, non-validated outcomes, non-standardized intervention, and use of other ongoing treatment. The vast majority of studies showed that physical therapy modalities such as biofeedback, dilators, electrical stimulation, education, multimodal physical therapy, and multidisciplinary approaches were effective for decreasing pain during intercourse and improving sexual function. The positive findings for the effectiveness of physical therapy modalities in women with PVD should be investigated further in robust and well-designed randomized controlled trials

  15. Arithmetic Memory Is Modality Specific.

    PubMed

    Myers, Timothy; Szücs, Dénes

    2015-01-01

    In regards to numerical cognition and working memory, it is an open question as to whether numbers are stored into and retrieved from a central abstract representation or from separate notation-specific representations. This study seeks to help answer this by utilizing the numeral modality effect (NME) in three experiments to explore how numbers are processed by the human brain. The participants were presented with numbers (1-9) as either Arabic digits or written number words (Arabic digits and dot matrices in Experiment 2) at the first (S1) and second (S2) stimuli. The participant's task was to add the first two stimuli together and verify whether the answer (S3), presented simultaneously with S2, was correct. We hypothesized that if reaction time (RT) at S2/S3 depends on the modality of S1 then numbers are retrieved from modality specific memory stores. Indeed, RT depended on the modality of S1 whenever S2 was an Arabic digit which argues against the concept of numbers being stored and retrieved from a central, abstract representation.

  16. Arithmetic Memory Is Modality Specific

    PubMed Central

    Myers, Timothy; Szücs, Dénes

    2015-01-01

    In regards to numerical cognition and working memory, it is an open question as to whether numbers are stored into and retrieved from a central abstract representation or from separate notation-specific representations. This study seeks to help answer this by utilizing the numeral modality effect (NME) in three experiments to explore how numbers are processed by the human brain. The participants were presented with numbers (1–9) as either Arabic digits or written number words (Arabic digits and dot matrices in Experiment 2) at the first (S1) and second (S2) stimuli. The participant’s task was to add the first two stimuli together and verify whether the answer (S3), presented simultaneously with S2, was correct. We hypothesized that if reaction time (RT) at S2/S3 depends on the modality of S1 then numbers are retrieved from modality specific memory stores. Indeed, RT depended on the modality of S1 whenever S2 was an Arabic digit which argues against the concept of numbers being stored and retrieved from a central, abstract representation. PMID:26716692

  17. NTCP reduction for advanced head and neck cancer patients using proton therapy for complete or sequential boost treatment versus photon therapy.

    PubMed

    Jakobi, Annika; Stützer, Kristin; Bandurska-Luque, Anna; Löck, Steffen; Haase, Robert; Wack, Linda-Jacqueline; Mönnich, David; Thorwarth, Daniel; Perez, Damien; Lühr, Armin; Zips, Daniel; Krause, Mechthild; Baumann, Michael; Perrin, Rosalind; Richter, Christian

    2015-01-01

    To determine by treatment plan comparison differences in toxicity risk reduction for patients with head and neck squamous cell carcinoma (HNSCC) from proton therapy either used for complete treatment or sequential boost treatment only. For 45 HNSCC patients, intensity-modulated photon (IMXT) and proton (IMPT) treatment plans were created including a dose escalation via simultaneous integrated boost with a one-step adaptation strategy after 25 fractions for sequential boost treatment. Dose accumulation was performed for pure IMXT treatment, pure IMPT treatment and for a mixed modality treatment with IMXT for the elective target followed by a sequential boost with IMPT. Treatment plan evaluation was based on modern normal tissue complication probability (NTCP) models for mucositis, xerostomia, aspiration, dysphagia, larynx edema and trismus. Individual NTCP differences between IMXT and IMPT (∆NTCPIMXT-IMPT) as well as between IMXT and the mixed modality treatment (∆NTCPIMXT-Mix) were calculated. Target coverage was similar in all three scenarios. NTCP values could be reduced in all patients using IMPT treatment. However, ∆NTCPIMXT-Mix values were a factor 2-10 smaller than ∆NTCPIMXT-IMPT. Assuming a threshold of ≥ 10% NTCP reduction in xerostomia or dysphagia risk as criterion for patient assignment to IMPT, less than 15% of the patients would be selected for a proton boost, while about 50% would be assigned to pure IMPT treatment. For mucositis and trismus, ∆NTCP ≥ 10% occurred in six and four patients, respectively, with pure IMPT treatment, while no such difference was identified with the proton boost. The use of IMPT generally reduces the expected toxicity risk while maintaining good tumor coverage in the examined HNSCC patients. A mixed modality treatment using IMPT solely for a sequential boost reduces the risk by 10% only in rare cases. In contrast, pure IMPT treatment may be reasonable for about half of the examined patient cohort considering

  18. Causal Inference for Cross-Modal Action Selection: A Computational Study in a Decision Making Framework.

    PubMed

    Daemi, Mehdi; Harris, Laurence R; Crawford, J Douglas

    2016-01-01

    Animals try to make sense of sensory information from multiple modalities by categorizing them into perceptions of individual or multiple external objects or internal concepts. For example, the brain constructs sensory, spatial representations of the locations of visual and auditory stimuli in the visual and auditory cortices based on retinal and cochlear stimulations. Currently, it is not known how the brain compares the temporal and spatial features of these sensory representations to decide whether they originate from the same or separate sources in space. Here, we propose a computational model of how the brain might solve such a task. We reduce the visual and auditory information to time-varying, finite-dimensional signals. We introduce controlled, leaky integrators as working memory that retains the sensory information for the limited time-course of task implementation. We propose our model within an evidence-based, decision-making framework, where the alternative plan units are saliency maps of space. A spatiotemporal similarity measure, computed directly from the unimodal signals, is suggested as the criterion to infer common or separate causes. We provide simulations that (1) validate our model against behavioral, experimental results in tasks where the participants were asked to report common or separate causes for cross-modal stimuli presented with arbitrary spatial and temporal disparities. (2) Predict the behavior in novel experiments where stimuli have different combinations of spatial, temporal, and reliability features. (3) Illustrate the dynamics of the proposed internal system. These results confirm our spatiotemporal similarity measure as a viable criterion for causal inference, and our decision-making framework as a viable mechanism for target selection, which may be used by the brain in cross-modal situations. Further, we suggest that a similar approach can be extended to other cognitive problems where working memory is a limiting factor, such

  19. Roles of frequency, attitudes, and multiple intelligence modality surrounding Electricity Content-Based Reader's Theatre

    NASA Astrophysics Data System (ADS)

    Hosier, Julie Winchester

    Integration of subjects is something elementary teachers must do to insure required objectives are covered. Science-based Reader's Theatre is one way to weave reading into science. This study examined the roles of frequency, attitudes, and Multiple Intelligence modalities surrounding Electricity Content-Based Reader's Theatre. This study used quasi-experimental, repeated measures ANOVA with time as a factor design. A convenience sample of two fifth-grade classrooms participated in the study for eighteen weeks. Five Electricity Achievement Tests were given throughout the study to assess students' growth. A Student Reader's Theatre Attitudinal Survey revealed students' attitudes before and after Electricity Content-Based Reader's Theatre treatment. The Multiple Intelligence Inventory for Kids (Faris, 2007) examined whether Multiple Intelligence modality played a role in achievement on Electricity Test 4, the post-treatment test. Analysis using repeated measures ANOVA and an independent t-test found that students in the experimental group, which practiced its student-created Electricity Content-Based Reader's Theatre skits ten times versus two times for the for control group, did significantly better on Electricity Achievement Test 4, t(76) = 3.018, p = 0.003. Dependent t-tests did not find statistically significant differences between students' attitudes about Electricity Content-Based Reader's Theatre before and after treatment. A Kruskal-Wallis test found no statistically significant difference between the various Multiple Intelligence modalities score mean ranks (x2 = 5.57, df = 2, alpha = .062). Qualitative data do, however, indicate students had strong positive feelings about Electricity Content-Based Reader's Theatre after treatment. Students indicated it to be motivating, confidence-building, and a fun way to learn about science; however, they disliked writing their own scripts. Examining the frequency, attitudes, and Multiple Intelligence modalities lead to

  20. A new methodological approach for PET implementation in radiotherapy treatment planning.

    PubMed

    Bellan, Elena; Ferretti, Alice; Capirci, Carlo; Grassetto, Gaia; Gava, Marcello; Chondrogiannis, Sotirios; Virdis, Graziella; Marzola, Maria Cristina; Massaro, Arianna; Rubello, Domenico; Nibale, Otello

    2012-05-01

    In this paper, a new methodological approach to using PET information in radiotherapy treatment planning has been discussed. Computed tomography (CT) represents the primary modality to plan personalized radiation treatment, because it provides the basic electron density map for correct dose calculation. If PET scanning is also performed it is typically coregistered with the CT study. This operation can be executed automatically by a hybrid PET/CT scanner or, if the PET and CT imaging sets have been acquired through different equipment, by a dedicated module of the radiotherapy treatment planning system. Both approaches have some disadvantages: in the first case, the bore of a PET/CT system generally used in clinical practice often does not allow the use of certain bulky devices for patient immobilization in radiotherapy, whereas in the second case the result could be affected by limitations in window/level visualization of two different image modalities, and the displayed PET volumes can appear not to be related to the actual uptake into the patient. To overcome these problems, at our centre a specific procedure has been studied and tested in 30 patients, allowing good results of precision in the target contouring to be obtained. The process consists of segmentation of the biological target volume by a dedicated PET/CT console and its export to a dedicated radiotherapy system, where an image registration between the CT images acquired by the PET/CT scanner and a large-bore CT is performed. The planning target volume is contoured only on the large-bore CT and is used for virtual simulation, to individuate permanent skin markers on the patient.

  1. Current treatment options for recurrent/metastatic head and neck cancer: a post-ASCO 2011 update and review of last year's literature.

    PubMed

    Kurzweg, T; Möckelmann, N; Laban, S; Knecht, R

    2012-10-01

    The majority of patients with a squamous cell carcinoma of the head and neck present with locally advanced tumors. The first-line treatment of locally advanced tumor stages consists of a combined modality management. Despite these aggressive protocols, many patients develop locoregional recurrences or metastasis and place particularly high demands on the interdisciplinary treatment team. Treatment with a curative intent must be differentiated from a palliative one. In addition to prior treatment, resectability, age and performance status, patient wishes must be taken into consideration in treatment planning, especially considering that most therapies offer little to no overall survival benefit. Salvage surgery, chemo- and target therapies, and reirradiation are head and neck surgeon's and radiooncologist's weapons in the fight against these strong opponents. This review focuses on publications and meeting news from last year and reviews the current status of the clinical application of each treatment modality in recurrent or metastatic head and neck cancer.

  2. Targeting aerobic glycolysis: 3-bromopyruvate as a promising anticancer drug.

    PubMed

    Cardaci, Simone; Desideri, Enrico; Ciriolo, Maria Rosa

    2012-02-01

    The Warburg effect refers to the phenomenon whereby cancer cells avidly take up glucose and produce lactic acid under aerobic conditions. Although the molecular mechanisms underlying tumor reliance on glycolysis remains not completely clear, its inhibition opens feasible therapeutic windows for cancer treatment. Indeed, several small molecules have emerged by combinatorial studies exhibiting promising anticancer activity both in vitro and in vivo, as a single agent or in combination with other therapeutic modalities. Therefore, besides reviewing the alterations of glycolysis that occur with malignant transformation, this manuscript aims at recapitulating the most effective pharmacological therapeutics of its targeting. In particular, we describe the principal mechanisms of action and the main targets of 3-bromopyruvate, an alkylating agent with impressive antitumor effects in several models of animal tumors. Moreover, we discuss the chemo-potentiating strategies that would make unparalleled the putative therapeutic efficacy of its use in clinical settings.

  3. The concept of crosstalk-directed embryological target mining and its application to essential hypertension treatment failures.

    PubMed

    Sag, Alan Alper; Sal, Oguzhan; Kilic, Yagmur; Onal, Emine Meltem; Kanbay, Mehmet

    2017-05-01

    This review aims to introduce the novel concept of embryological target mining applied to interorgan crosstalk network genesis, and applies embryological target mining to multidrug-resistant essential hypertension (a prototype, complex, undertreated, multiorgan systemic syndrome) to uncover new treatment targets and critique why existing strategies fail. Briefly, interorgan crosstalk pathways represent the next frontier for target mining in molecular medicine. This is because stereotyped stepwise organogenesis presents a unique opportunity to infer interorgan crosstalk pathways that may be crucial to discovering novel treatment targets. Insights gained from this review will be applied to patient management in a clinician-directed fashion. ©2017 Wiley Periodicals, Inc.

  4. From the Medical Board of the National Psoriasis Foundation: Treatment targets for plaque psoriasis.

    PubMed

    Armstrong, April W; Siegel, Michael P; Bagel, Jerry; Boh, Erin E; Buell, Megan; Cooper, Kevin D; Callis Duffin, Kristina; Eichenfield, Lawrence F; Garg, Amit; Gelfand, Joel M; Gottlieb, Alice B; Koo, John Y M; Korman, Neil J; Krueger, Gerald G; Lebwohl, Mark G; Leonardi, Craig L; Mandelin, Arthur M; Menter, M Alan; Merola, Joseph F; Pariser, David M; Prussick, Ronald B; Ryan, Caitriona; Shah, Kara N; Weinberg, Jeffrey M; Williams, MaryJane O U; Wu, Jashin J; Yamauchi, Paul S; Van Voorhees, Abby S

    2017-02-01

    An urgent need exists in the United States to establish treatment goals in psoriasis. We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  5. Treatment of nonconvergence of Fourier modal method arising from irregular field singularities at lossless metal-dielectric right-angle edges.

    PubMed

    Mei, Yanpeng; Liu, Haitao; Zhong, Ying

    2014-04-01

    In a recent work [J. Opt. Soc. Am. A28, 738 (2011)], Lifeng Li and Gerard Granet investigate nonconvergence cases of the Fourier modal method (FMM). They demonstrate that the nonconvergence is due to the irregular field singularities at lossless metal-dielectric right-angle edges. Here we make further investigations on the problem and find that the FMM surprisingly converges for deep sub-wavelength gratings (grating period being much smaller than the illumination wavelength). To overcome the nonconvergence for gratings that are not deep sub-wavelength, we approximately replace the lossless metal-dielectric right-angle edges by a medium with a gradually varied refraction index, so as to remove the irregular field singularities. With such treatment, convergence is observed as the region of the approximate medium approaches vanishing.

  6. Dual-modal photoacoustic and ultrasound imaging of dental implants

    NASA Astrophysics Data System (ADS)

    Lee, Donghyun; Park, Sungjo; Kim, Chulhong

    2018-02-01

    Dental implants are common method to replace decayed or broken tooth. As the implant treatment procedures varies according to the patients' jawbone, bone ridge, and sinus structure, appropriate examinations are necessary for successful treatment. Currently, radiographic examinations including periapical radiology, panoramic X-ray, and computed tomography are commonly used for diagnosing and monitoring. However, these radiographic examinations have limitations in that patients and operators are exposed to radioactivity and multiple examinations are performed during the treatment. In this study, we demonstrated photoacoustic (PA) and ultrasound (US) combined imaging of dental implant that can lower the total amount of absorbed radiation dose in dental implant treatment. An acoustic resolution PA macroscopy and a clinical PA/US system was used for dental implant imaging. The acquired dual modal PA/US imaging results support that the proposed photoacoustic imaging strategy can reduce the radiation dose rate during dental implant treatment.

  7. Protocol for a systematic review with network meta-analysis of the modalities used to deliver eHealth interventions for chronic pain.

    PubMed

    Slattery, Brian W; Haugh, Stephanie; Francis, Kady; O'Connor, Laura; Barrett, Katie; Dwyer, Christopher P; O'Higgins, Siobhan; Egan, Jonathan; McGuire, Brian E

    2017-03-03

    As eHealth interventions prove both efficacious and practical, and as they arguably overcome certain barriers encountered by traditional face-to-face treatment for chronic pain, their number has increased dramatically in recent times. However, there is a dearth of research that focuses on evaluating and comparing the different types of technology-assisted interventions. This is a protocol for a systematic review that aims to evaluate the eHealth modalities in the context of psychological and non-psychological (other than non-drug) interventions for chronic pain. We will search the Cochrane Central Register of Controlled Trials (CENTRAL: The Cochrane Library), MEDLINE, Embase and PsycINFO. Randomised controlled trials (RCTs) with more than 20 participants per trial arm that have evaluated non-drug psychological or non-psychological interventions delivered via an eHealth modality and have pain as an outcome measure will be included. Two review authors will independently extract data and assess the study suitability in accordance with the Cochrane Collaboration Risk of Bias Tool. Studies will be included if they measure at least one outcome variable in accordance with the IMMPACT guidelines (i.e. pain severity, pain interference, physical functioning, symptoms, emotional functioning, global improvement and disposition). Secondary outcomes will be measures of depression and health-related quality of life (HRQoL). A network meta-analysis will be conducted based on direct comparisons to generate indirect comparisons of modalities across treatment trials, which will return rankings for the eHealth modalities in terms of their effectiveness. Most trials that use an eHealth intervention to manage chronic pain typically use one modality. As a result, little evidence exists to support which modality type is the most effective. The current review will address this gap in the literature and compare the different eHealth modalities used for technology-assisted interventions for

  8. Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer

    DTIC Science & Technology

    2004-05-01

    AD Award Number: DAMD17-01-1-0090 TITLE: Targeted Delivery of Therapeutic Oligonucleotides for the Treatment of Prostate Cancer PRINCIPAL...independence and chemoresistance are the major obstacles in the treatment of patients with advanced prostate cancer (Denis & Murphy, 1993; Oh & Kantoff...independence and chemoresistance in prostate cancer (McDonnell et al., 1992; Colombel et al., 1993; Berchem et al., 1995; Raffo et al., 1995; Bauer et al

  9. Modal vector estimation for closely spaced frequency modes

    NASA Technical Reports Server (NTRS)

    Craig, R. R., Jr.; Chung, Y. T.; Blair, M.

    1982-01-01

    Techniques for obtaining improved modal vector estimates for systems with closely spaced frequency modes are discussed. In describing the dynamical behavior of a complex structure modal parameters are often analyzed: undamped natural frequency, mode shape, modal mass, modal stiffness and modal damping. From both an analytical standpoint and an experimental standpoint, identification of modal parameters is more difficult if the system has repeated frequencies or even closely spaced frequencies. The more complex the structure, the more likely it is to have closely spaced frequencies. This makes it difficult to determine valid mode shapes using single shaker test methods. By employing band selectable analysis (zoom) techniques and by employing Kennedy-Pancu circle fitting or some multiple degree of freedom (MDOF) curve fit procedure, the usefulness of the single shaker approach can be extended.

  10. Folic acid-functionalized up-conversion nanoparticles: toxicity studies in vivo and in vitro and targeted imaging applications

    NASA Astrophysics Data System (ADS)

    Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi

    2014-07-01

    Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a

  11. Fecal microbiota transplantation is a rescue treatment modality for refractory ulcerative colitis

    PubMed Central

    Uygun, Ahmet; Ozturk, Kadir; Demirci, Hakan; Oger, Cem; Avci, Ismail Yasar; Turker, Turker; Gulsen, Mustafa

    2017-01-01

    Abstract Background: Fecal microbial transplantation (FMT) provides to replace beneficial bacteria with more favorable microbiomes in recipient with dysbiosis. The aim of the present study was to prospectively investigate the efficacy of FMT by assessing the clinical and endoscopic response in patients with ulcerative colitis (UC) who had failed anti-inflammatory and immunosuppressive therapy. Methods: In this prospective and uncontrolled study, 30 patients with UC were included. All medications except mesalazine were stopped 4 weeks before FMT. Colonoscopy was performed both before and after FMT. To assess the efficacy of FMT, Mayo scores were calculated at week 0 and week 12. A total of 500 mL extracted fresh fecal suspension was administered into the 30 to 40 cm proximal of terminal ileum of recipients. Results: After FMT, 21 of the (70%) 30 patients showed clinical response, and 13 of the 30 (43.3%) patients achieved clinical and endoscopic remission at the week 12. Nine patients (30%) were accepted as a nonresponder at the end of the week 12. There was no significant difference among donors concerning both the rate of clinical remission and clinical response. No adverse events were observed in the majority of patients during FMT and 12 weeks follow-up. Seven patients (23.3%) experienced mild adverse events such as nausea, vomiting, abdominal pain, diarrhea, and fewer after FMT. Conclusion: FMT could be considered as a promising rescue treatment modality before surgery in patients with refractory UC. Besides, FMT also appears to be definitely safer and more tolerable than the immunosuppressive therapy in patients with UC (NCT02575040). PMID:28422836

  12. Anti-Inflammatory Targets for the Treatment of Reperfusion Injury in Stroke

    PubMed Central

    Mizuma, Atsushi; Yenari, Midori A.

    2017-01-01

    While the mainstay of acute stroke treatment includes revascularization via recombinant tissue plasminogen activator or mechanical thrombectomy, only a minority of stroke patients are eligible for treatment, as delayed treatment can lead to worsened outcome. This worsened outcome at the experimental level has been attributed to an entity known as reperfusion injury (R/I). R/I is occurred when revascularization is delayed after critical brain and vascular injury has occurred, so that when oxygenated blood is restored, ischemic damage is increased, rather than decreased. R/I can increase lesion size and also worsen blood barrier breakdown and lead to brain edema and hemorrhage. A major mechanism underlying R/I is that of poststroke inflammation. The poststroke immune response consists of the aberrant activation of glial cell, infiltration of peripheral leukocytes, and the release of damage-associated molecular pattern (DAMP) molecules elaborated by ischemic cells of the brain. Inflammatory mediators involved in this response include cytokines, chemokines, adhesion molecules, and several immune molecule effectors such as matrix metalloproteinases-9, inducible nitric oxide synthase, nitric oxide, and reactive oxygen species. Several experimental studies over the years have characterized these molecules and have shown that their inhibition improves neurological outcome. Yet, numerous clinical studies failed to demonstrate any positive outcomes in stroke patients. However, many of these clinical trials were carried out before the routine use of revascularization therapies. In this review, we cover mechanisms of inflammation involved in R/I, therapeutic targets, and relevant experimental and clinical studies, which might stimulate renewed interest in designing clinical trials to specifically target R/I. We propose that by targeting anti-inflammatory targets in R/I as a combined therapy, it may be possible to further improve outcomes from pharmacological thrombolysis or

  13. Combined modality treatment of gastric cancer

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

    Gunderson, L.L.; Hoskins, R.B.; Cohen, A.C.

    1983-07-01

    In a series of 46 patients with localized gastric cancer treated at Massachusetts General Hospital, problems with excessive acute or chronic toxicity due to combination treatment with irradiation (XRT) and chemotherapy (CT) were not seen. Forty of the 46 received combined treatment with 2 regimens: (1) irradiation plus concomitant 3 days of 5-FU followed by maintenance 5-FU or combined drugs-26 patients; (2) in the other 14 patients, the sequence of irradiation and chemotherapy was altered. A single course of combined drug chemotherapy was given prior to irradiation and 5 to 6 additional courses were administered after completion of XRT (CT-XRT-CT).more » The drug combination was initially 5-FU-BGNU but this was changed to FAM (5-FU, Adriamycin, Mitomycin C). In this series, there were no cases of septicemia or any deaths related to treatment. A 3 year survival rate of about 20% was achieved for the total group of patients and 43% in the group with resection but at high risk for later failure. Our inability to improve these numbers is undoubtedly a result of dose limitations with external beam irradiation combined with a systemic failure problem. When irradiation is combined with surgical resection of all or a majority of tumor, both survival and local control appear to be better than in the unresected patient group. Only 4 of 29 patients (14%) with curative resection, or resection but residual disease, had later evidence of failure within the irradiation field as opposed to 6 of 9 or 66% in the group with unresectable disease.« less

  14. An introduction to physical therapy modalities.

    PubMed

    Chapman, Brenda L; Liebert, Rainer B; Lininger, Monica R; Groth, Jessica J

    2007-05-01

    Timely and appropriate rehabilitation of musculoskeletal injuries is the most effective way of restoring full function and decreasing the likelihood of recurrence of the same injury. Application of specific physical therapy modalities and therapeutic exercises is based on the stages of healing. A typical physical therapy protocol progresses sequentially through the following phases: pain control, restoring range of motion, restoring strength, neuromuscular retraining, and return to full activity. The commonly used modalities reviewed here include heat, cold, ultrasound, phonophoresis, iontophoresis, and electrical stimulation. In this article we provide a basic review of physical therapy modalities.

  15. [Current strategies in the treatment of renal-cell cancer: targeted therapies].

    PubMed

    Trigo, José Manuel; Bellmunt, Joaquim

    2008-03-22

    Renal-cell carcinoma represents 95% of all renal tumours. The Von Hippel-Lindau (VHL) tumor-suppressor gene is mutated or silenced in most clear cell renal carcinomas. pVHL loss results in the stabilization of the heterodimeric transcription factor hypoxia-inducible factor (HIF) and enhanced transactivation of HIF target genes. HIF itself has been difficult to inhibit with drug-like molecules although a number of agents that indirectly inhibit HIF, including mTOR (mammalian target of rapamycin) inhibitors, have been identified. Moreover, a number of drugs have been developed that target HIF-responsive gene products, such as vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), implicated in tumor angiogenesis. Many of these targeted therapies, especially sunitinib, have demonstrated significant activity in kidney cancer clinical trials and represent a substantive advance in the treatment of this disease.

  16. Enteropeptidase: A Gene Associated with a Starvation Human Phenotype and a Novel Target for Obesity Treatment

    PubMed Central

    Braud, Sandrine; Ciufolini, Marco A.; Harosh, Itzik

    2012-01-01

    Background Obesity research focuses essentially on gene targets associated with the obese phenotype. None of these targets have yet provided a viable drug therapy. Focusing instead on genes that are involved in energy absorption and that are associated with a “human starvation phenotype”, we have identified enteropeptidase (EP), a gene associated with congenital enteropeptidase deficiency, as a novel target for obesity treatment. The advantages of this target are that the gene is expressed exclusively in the brush border of the intestine; it is peripheral and not redundant. Methodology/Principal Findings Potent and selective EP inhibitors were designed around a boroarginine or borolysine motif. Oral administration of these compounds to mice restricted the bioavailability of dietary energy, and in a long-term treatment it significantly diminished the rate of increase in body weight, despite ad libitum food intake. No adverse reactions of the type seen with lipase inhibitors, such as diarrhea or steatorrhea, were observed. This validates EP as a novel, druggable target for obesity treatment. Conclusions In vivo testing of novel boroarginine or borolysine-based EP inhibitors validates a novel approach to the treatment of obesity. PMID:23185382

  17. "US-detonated nano bombs" facilitate targeting treatment of resistant breast cancer.

    PubMed

    Shi, Jinjin; Liu, Wei; Fu, Yu; Yin, Na; Zhang, Hongling; Chang, Junbiao; Zhang, Zhenzhong

    2018-03-28

    Reversal of drug resistance and targeted therapy are the keys but remain challenging in resistant breast cancer treatment. Herein, low frequency ultrasound detonated "nano bombs" were rationally designed and used for treatment of resistant breast cancer. For the 'nano bombs', the ammunition (Doxorubicin, DOX) was loaded into the ammunition depot (hollow mesoporous TiO 2 , MTNs), and the safety device (dsDNA) was wrapped on the surface of MTNs to avoid the unexpected DOX release. We found the "US-detonated explosive" abilities of "nano bomb" MTNs (NBMTNs), including explosive generation of ROS, explosive release of DOX, US-triggered lysosome escape and mitochondrial targeting in the in vitro and in vivo studies. More importantly, the drug resistance of MCF-7/ADR cells could be reversed via the inhibition of mitochondrial energy supply approach caused by the "explosion" of NBMTNs. Furthermore, NBMTNs combined the superior chemotherapy efficacy of DOX and potent SDT efficacy in one single platform and significantly enhanced the anticancer efficacy. Our results demonstrate an approach for reversing resistance and specific targeting of tumors using 'US-detonated nano bombs'. Copyright © 2018 Elsevier B.V. All rights reserved.

  18. Targeted drug delivery nanosystems based on copolymer poly(lactide)-tocopheryl polyethylene glycol succinate for cancer treatment

    NASA Astrophysics Data System (ADS)

    Thu Ha, Phuong; Nguyen, Hoai Nam; Doan Do, Hai; Thong Phan, Quoc; Nguyet Tran Thi, Minh; Phuc Nguyen, Xuan; Nhung Hoang Thi, My; Huong Le, Mai; Nguyen, Linh Toan; Quang Bui, Thuc; Hieu Phan, Van

    2016-03-01

    Along with the development of nanotechnology, drug delivery nanosystems (DDNSs) have attracted a great deal of concern among scientists over the world, especially in cancer treatment. DDNSs not only improve water solubility of anticancer drugs but also increase therapeutic efficacy and minimize the side effects of treatment methods through targeting mechanisms including passive and active targeting. Passive targeting is based on the nano-size of drug delivery systems while active targeting is based on the specific bindings between targeting ligands attached on the drug delivery systems and the unique receptors on the cancer cell surface. In this article we present some of our results in the synthesis and testing of DDNSs prepared from copolymer poly(lactide)-tocopheryl polyethylene glycol succinate (PLA-TPGS), which carry anticancer drugs including curcumin, paclitaxel and doxorubicin. In order to increase the targeting effect to cancer cells, active targeting ligand folate was attached to the DDNSs. The results showed copolymer PLA-TPGS to be an excellent carrier for loading hydrophobic drugs (curcumin and paclitaxel). The fabricated DDNSs had a very small size (50-100 nm) and enhanced the cellular uptake and cytotoxicity of drugs. Most notably, folate-decorated paclitaxel-loaded copolymer PLA-TPGS nanoparticles (Fol/PTX/PLA-TPGS NPs) were tested on tumor-bearing nude mice. During the treatment time, Fol/PTX/PLA-TPGS NPs always exhibited the best tumor growth inhibition compared to free paclitaxel and paclitaxel-loaded copolymer PLA-TPGS nanoparticles. All results evidenced the promising potential of copolymer PLA-TPGS in fabricating targeted DDNSs for cancer treatment.

  19. Features and treatment modality of iliopsoas abscess and its outcome: a 6-year hospital-based study

    PubMed Central

    2013-01-01

    Background Percutaneous drainage (PCD) and surgical intervention are two primary treatment options for iliopsoas abscess (IPA). However, there is currently no consensus on when to use PCD or surgical intervention, especially in patients with gas-forming IPA. This study compared the characteristics of patients with gas-forming and non-gas forming IPA and their mortality rates under different treatment modalities. An algorithm for selecting appropriate treatment for IPA patients is proposed based on our findings. Methods Eighty-eight IPA patients between July 2007 and February 2013 were enrolled in this retrospective study. Patients < 18 years of age or with an incomplete course of treatment were excluded. Demographic information, clinical characteristics, and outcomes of different treatment approaches were compared between gas-forming IPA and non-gas forming IPA patients. Results Among the 88 enrolled patients, 27 (31%) had gas-forming IPA and 61 (69%) had non-gas forming IPA. The overall intra-hospital mortality rate was 25%. The gas-forming IPA group had a higher intra-hospital mortality rate (12/27, 44.0%) than the non-gas forming IPA group (10/61, 16.4%) (P < 0.001). Only 2 of the 13 patients in the gas-forming IPA group initially accepting PCD had a good outcome (success rate = 15.4%). Three of the 11 IPA patients with failed initial PCD expired, and 8 of the 11 patients with failed initial PCD accepted salvage operation, of whom 5 survived. Seven of the 8 gas-forming IPA patients accepting primary surgical intervention survived (success rate = 87.5%). Only 1 of the 6 gas-forming IPA patients who accepted antibiotics alone, without PCD or surgical intervention, survived (success rate = 16.7%). In the non-gas forming IPA group, 23 of 61 patients initially accepted PCD, which was successful in 17 patients (73.9%). The success rate of PCD was much higher in the non-gas forming group than in the gas-forming group (P <0.01). Conclusions Based on

  20. Eigenvectors phase correction in inverse modal problem

    NASA Astrophysics Data System (ADS)

    Qiao, Guandong; Rahmatalla, Salam

    2017-12-01

    The solution of the inverse modal problem for the spatial parameters of mechanical and structural systems is heavily dependent on the quality of the modal parameters obtained from the experiments. While experimental and environmental noises will always exist during modal testing, the resulting modal parameters are expected to be corrupted with different levels of noise. A novel methodology is presented in this work to mitigate the errors in the eigenvectors when solving the inverse modal problem for the spatial parameters. The phases of the eigenvector component were utilized as design variables within an optimization problem that minimizes the difference between the calculated and experimental transfer functions. The equation of motion in terms of the modal and spatial parameters was used as a constraint in the optimization problem. Constraints that reserve the positive and semi-positive definiteness and the inter-connectivity of the spatial matrices were implemented using semi-definite programming. Numerical examples utilizing noisy eigenvectors with augmented Gaussian white noise of 1%, 5%, and 10% were used to demonstrate the efficacy of the proposed method. The results showed that the proposed method is superior when compared with a known method in the literature.

  1. Transcutaneous laser treatment of leg veins.

    PubMed

    Meesters, Arne A; Pitassi, Luiza H U; Campos, Valeria; Wolkerstorfer, Albert; Dierickx, Christine C

    2014-03-01

    properties of the target structure, (2) pulse stacking and multiple pass laser treatment, (3) combination of laser therapy with sclerotherapy or radiofrequency, and (4) indocyanin green enhanced laser therapy. Future studies will have to confirm the role of these developments in the treatment of leg veins. The literature still lacks double-blind controlled clinical trials comparing the different laser modalities with each other and with sclerotherapy. Such trials should be the focus of future research.

  2. Unintended Embodiment of Concepts into Percepts: Sensory Activation Boosts Attention for Same-Modality Concepts in the Attentional Blink Paradigm

    ERIC Educational Resources Information Center

    Vermeulen, Nicolas; Mermillod, Martial; Godefroid, Jimmy; Corneille, Olivier

    2009-01-01

    This study shows that sensory priming facilitates reports of same-modality concepts in an attentional blink paradigm. Participants had to detect and report two target words (T1 and T2) presented for 53 ms each among a series of nonwords distractors at a frequency of up to 19 items per second. SOA between target words was set to 53 ms or 213 ms,…

  3. Blood glutamate grabbing does not reduce the hematoma in an intracerebral hemorrhage model but it is a safe excitotoxic treatment modality.

    PubMed

    da Silva-Candal, Andrés; Vieites-Prado, Alba; Gutiérrez-Fernández, María; Rey, Ramón I; Argibay, Bárbara; Mirelman, David; Sobrino, Tomás; Rodríguez-Frutos, Berta; Castillo, José; Campos, Francisco

    2015-07-01

    Recent studies have shown that blood glutamate grabbing is an effective strategy to reduce the excitotoxic effect of extracellular glutamate released during ischemic brain injury. The purpose of the study was to investigate the effect of two of the most efficient blood glutamate grabbers (oxaloacetate and recombinant glutamate oxaloacetate transaminase 1: rGOT1) in a rat model of intracerebral hemorrhage (ICH). Intracerebral hemorrhage was produced by injecting collagenase into the basal ganglia. Three treatment groups were developed: a control group treated with saline, a group treated with oxaloacetate, and a final group treated with human rGOT1. Treatments were given 1 hour after hemorrhage. Hematoma volume (analyzed by magnetic resonance imaging (MRI)), neurologic deficit, and blood glutamate and GOT levels were quantified over a period of 14 days after surgery. The results observed showed that the treatments used induced a significant reduction of blood glutamate levels; however, they did not reduce the hematoma, nor did they improve the neurologic deficit. In the present experimental study, we have shown that this novel therapeutic strategy is not effective in case of ICH pathology. More importantly, these findings suggest that blood glutamate grabbers are a safe treatment modality that can be given in cases of suspected ischemic stroke without previous neuroimaging.

  4. New diagnostic modalities in the diagnosis of heart failure.

    PubMed Central

    Mitchell, Judith E.; Palta, Sanjeev

    2004-01-01

    Heart failure (HF) is the one cardiovascular disease that is increasing in prevalence in the United States. As the population continues to age, the incidence will certainly be amplified. However, some studies have shown that HF is correctly diagnosed initially in only 50% of affected patients. Despite the use of history, physical examination, echocardiogram, and chest x-ray, the percentage of correct initial diagnosis of HF is low. Recognizing the symptoms of HF decompensations is often problematic because other diagnoses can mimic them. There are two new diagnostic modalities that offer promise in improving HF diagnostic accuracy and identifying early HF decompensations. These diagnostic modalities include tests utilizing impedance cardiography and the B-type natriuretic peptide assay. They have the potential of increasing the accuracy of HF diagnosis and guide pharmacological treatment in the inpatient and outpatient settings. They may also assist in the recognition (or prediction) of acute HF decompensations. Images Figure 2 PMID:15586645

  5. Computational selection of antibody-drug conjugate targets for breast cancer

    PubMed Central

    Fauteux, François; Hill, Jennifer J.; Jaramillo, Maria L.; Pan, Youlian; Phan, Sieu; Famili, Fazel; O'Connor-McCourt, Maureen

    2016-01-01

    The selection of therapeutic targets is a critical aspect of antibody-drug conjugate research and development. In this study, we applied computational methods to select candidate targets overexpressed in three major breast cancer subtypes as compared with a range of vital organs and tissues. Microarray data corresponding to over 8,000 tissue samples were collected from the public domain. Breast cancer samples were classified into molecular subtypes using an iterative ensemble approach combining six classification algorithms and three feature selection techniques, including a novel kernel density-based method. This feature selection method was used in conjunction with differential expression and subcellular localization information to assemble a primary list of targets. A total of 50 cell membrane targets were identified, including one target for which an antibody-drug conjugate is in clinical use, and six targets for which antibody-drug conjugates are in clinical trials for the treatment of breast cancer and other solid tumors. In addition, 50 extracellular proteins were identified as potential targets for non-internalizing strategies and alternative modalities. Candidate targets linked with the epithelial-to-mesenchymal transition were identified by analyzing differential gene expression in epithelial and mesenchymal tumor-derived cell lines. Overall, these results show that mining human gene expression data has the power to select and prioritize breast cancer antibody-drug conjugate targets, and the potential to lead to new and more effective cancer therapeutics. PMID:26700623

  6. [Alternative treatments for interstitial cystitis].

    PubMed

    Gamé, X; Bart, S; Castel-Lacanal, E; De Sèze, M; Karsenty, G; Labat, J-J; Rigaud, J; Scheiber-Nogueira, M C; Ruffion, A

    2009-06-01

    Interstitial cystitis is the first cause of bladder pain. In case of failure of the usual treatments, several other modalities have been proposed. These therapeutic modalities are posterior sacral root neuromodulation, posterior tibial nerve stimulation, vanilloid agent intravesical instillation, intradetrusor botulinum toxin injections and surgery. A certain efficiency of each of these treatments in the interstitial cystitis has been reported. However, the evaluation of these treatments is limited and the level of evidence is too low to propose these treatments in routine.

  7. Comparison of HELIX TWT Simulation Using 2-D PIC (Magic), 2-D Modal (Gator), and 1-D Modal (Christine) Methods

    DTIC Science & Technology

    1998-05-01

    Mission Research Corporation MRC/WDC-R-424 COMPARISON OF HELIX TWT SIMULATION USING 2-D PIC ( MAGIC ), 2-D MODAL (GATOR), AND 1-D MODAL (CHRISTINE...BRILLOUIN RUN 9 3.4 OUTLIER ELECTRON EFFECT IN GATOR 12 3.5 EMISSION CONDITION AND NONLAMINAR FLOW IN MAGIC 12 3.6 RADIAL SHEAR 13 SECTION 4. PPM B...Simulation using 2-D PIC ( MAGIC ), 2-D Modal (GATOR) and 1-D Modal (CHRISTINE) methods * D.N. Smithe(a), H. Freund(b), T. M. Antonsen Jr.,(b)’(c), E

  8. [Spatial-temporal analysis and clinical findings of gait: comparison of two modalities of treatment in children with cerebral palsy-spastic hemiplegia. Preliminary report].

    PubMed

    Arellano-Martínez, Irma Tamara; Rodríguez-Reyes, Gerardo; Quiñones-Uriostegui, Ivet; Arellano-Saldaña, María Elena

    2013-01-01

    Cerebral palsy is the most common cause of disability among children. Parent's main concerns are the acquisition and improvement of gait. The aim of this study was to compare long term results of the effect of two modalities of gait training. Quantitative measurement of gait and clinical assessment of the gross motor function classification system and Modified Ashworth Scale were perfomed in 14 patients with Cerebral palsy -spastic hemiplegia and randomizedly assigned into two groups of treatment: the first one using a driven gait orthosis (Lokomat(®)) and the second a gait training a long a rail inside a hydrotherapy tank. Measurements and assessments, above described, were performed immediately and one year after the treatment concluded. Significant change was observed in the gross motor function classification system from II to I among children (p=0.042) and a positive correlation between the shape functional of the march and the gross motor function classification system (r = 0.54, p = 0.042). Patients on the Lokomat(®) training improved on gait symmetry over patients on the conventional therapy (p = 0.05). A year after, this intervention showed tendency to kept the gait patterns only on patients treated with the Lokomat(®) Benefit obtained with either modality was evident for both groups. However, residual effects observed on the Lokomat group, either in clinical assessment or gait parameters, were more promising than in the conventional therapy. Due to the size of the sample used in this study the results are not conclusive and more research must be done on this subject in long term time horizon.

  9. Modal-Power-Based Haptic Motion Recognition

    NASA Astrophysics Data System (ADS)

    Kasahara, Yusuke; Shimono, Tomoyuki; Kuwahara, Hiroaki; Sato, Masataka; Ohnishi, Kouhei

    Motion recognition based on sensory information is important for providing assistance to human using robots. Several studies have been carried out on motion recognition based on image information. However, in the motion of humans contact with an object can not be evaluated precisely by image-based recognition. This is because the considering force information is very important for describing contact motion. In this paper, a modal-power-based haptic motion recognition is proposed; modal power is considered to reveal information on both position and force. Modal power is considered to be one of the defining features of human motion. A motion recognition algorithm based on linear discriminant analysis is proposed to distinguish between similar motions. Haptic information is extracted using a bilateral master-slave system. Then, the observed motion is decomposed in terms of primitive functions in a modal space. The experimental results show the effectiveness of the proposed method.

  10. DOTAM derivatives as active cartilage-targeting drug carriers for the treatment of osteoarthritis.

    PubMed

    Hu, Hai-Yu; Lim, Ngee-Han; Ding-Pfennigdorff, Danping; Saas, Joachim; Wendt, K Ulrich; Ritzeler, Olaf; Nagase, Hideaki; Plettenburg, Oliver; Schultz, Carsten; Nazare, Marc

    2015-03-18

    Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.

  11. TARGETED SEQUENTIAL DESIGN FOR TARGETED LEARNING INFERENCE OF THE OPTIMAL TREATMENT RULE AND ITS MEAN REWARD.

    PubMed

    Chambaz, Antoine; Zheng, Wenjing; van der Laan, Mark J

    2017-01-01

    This article studies the targeted sequential inference of an optimal treatment rule (TR) and its mean reward in the non-exceptional case, i.e. , assuming that there is no stratum of the baseline covariates where treatment is neither beneficial nor harmful, and under a companion margin assumption. Our pivotal estimator, whose definition hinges on the targeted minimum loss estimation (TMLE) principle, actually infers the mean reward under the current estimate of the optimal TR. This data-adaptive statistical parameter is worthy of interest on its own. Our main result is a central limit theorem which enables the construction of confidence intervals on both mean rewards under the current estimate of the optimal TR and under the optimal TR itself. The asymptotic variance of the estimator takes the form of the variance of an efficient influence curve at a limiting distribution, allowing to discuss the efficiency of inference. As a by product, we also derive confidence intervals on two cumulated pseudo-regrets, a key notion in the study of bandits problems. A simulation study illustrates the procedure. One of the corner-stones of the theoretical study is a new maximal inequality for martingales with respect to the uniform entropy integral.

  12. Temperature distribution in target tumor tissue and photothermal tissue destruction during laser immunotherapy

    NASA Astrophysics Data System (ADS)

    Doughty, Austin; Hasanjee, Aamr; Pettitt, Alex; Silk, Kegan; Liu, Hong; Chen, Wei R.; Zhou, Feifan

    2016-03-01

    Laser Immunotherapy is a novel cancer treatment modality that has seen much success in treating many different types of cancer, both in animal studies and in clinical trials. The treatment consists of the synergistic interaction between photothermal laser irradiation and the local injection of an immunoadjuvant. As a result of the therapy, the host immune system launches a systemic antitumor response. The photothermal effect induced by the laser irradiation has multiple effects at different temperature elevations which are all required for optimal response. Therefore, determining the temperature distribution in the target tumor during the laser irradiation in laser immunotherapy is crucial to facilitate the treatment of cancers. To investigate the temperature distribution in the target tumor, female Wistar Furth rats were injected with metastatic mammary tumor cells and, upon sufficient tumor growth, underwent laser irradiation and were monitored using thermocouples connected to locally-inserted needle probes and infrared thermography. From the study, we determined that the maximum central tumor temperature was higher for tumors of less volume. Additionally, we determined that the temperature near the edge of the tumor as measured with a thermocouple had a strong correlation with the maximum temperature value in the infrared camera measurement.

  13. Visually augmented targeted combination light therapy for acne vulgaris: a case report.

    PubMed

    Yazdi, Alireza; Lyons, Colin-William; Roberts, Niamh

    2017-10-31

    Acne vulgaris is a common skin disease. Pharmacological modalities for treatment are proven to be efficacious but have limitations. Light therapy for acne vulgaris has shown promise in previous studies. This case report and its accompanying images show how a novel approach of visually augmented high fluence light therapy has been used to good effect. A 26-year-old Caucasian woman with acne vulgaris resistant to treatment with topical therapy underwent three sessions of combination potassium titanyl phosphate laser (532 nm)/neodymium-doped: yttrium aluminum garnet laser (1064 nm) light therapy with visually augmented narrow spot size and high fluence. A 73% reduction in total inflammatory lesions was evident 6 months after the initial treatment. This case report illustrates that there may be utility in this novel approach of narrow spot size, magnification-assisted, high fluence targeted combination laser therapy for inflammatory acne.

  14. Outcomes of targeted treatment for vesicoureteral reflux in children with nonneurogenic lower urinary tract dysfunction.

    PubMed

    Fast, Angela M; Nees, Shannon N; Van Batavia, Jason P; Combs, Andrew J; Glassberg, Kenneth I

    2013-09-01

    There is a known association between nonneurogenic lower urinary tract conditions and vesicoureteral reflux. Whether reflux is secondary to the lower urinary tract condition or coincidental is controversial. We determined the rate of reflux resolution in patients with lower urinary tract dysfunction using targeted treatment for the underlying condition. Patients diagnosed and treated for a lower urinary tract condition who had concomitant vesicoureteral reflux at or near the time of diagnosis were included. Patients underwent targeted treatment and antibiotic prophylaxis, and reflux was monitored with voiding cystourethrography or videourodynamics. Vesicoureteral reflux was identified in 58 ureters in 36 females and 5 males with a mean age of 6.2 years. After a mean of 3.1 years of treatment reflux resolved with targeted treatment in 26 of 58 ureters (45%). All of these patients had a history of urinary tract infections before starting targeted treatment. Resolution rates of vesicoureteral reflux were similar for all reflux grades. Resolution or significant improvement of reflux was greater in the ureters of patients with dysfunctional voiding (70%) compared to those with idiopathic detrusor overactivity disorder (38%) or detrusor underutilization (40%). Vesicoureteral reflux associated with lower urinary tract conditions resolved with targeted treatment and antibiotic prophylaxis in 45% of ureters. Unlike the resolution rates reported in patients with reflux without a coexisting lower urinary tract condition, we found that there were no differences in resolution rates among grades I to V reflux in patients with lower urinary tract conditions. Patients with dysfunctional voiding had the most improvement and greatest resolution of reflux. Additionally grade V reflux resolved in some patients. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  15. Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities

    PubMed Central

    Santangelo, Valerio

    2018-01-01

    Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010) to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory) in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory) in one spatial location. The analysis of the independent components (ICs) revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS) and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF) and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC). The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among brain networks

  16. Large-Scale Brain Networks Supporting Divided Attention across Spatial Locations and Sensory Modalities.

    PubMed

    Santangelo, Valerio

    2018-01-01

    Higher-order cognitive processes were shown to rely on the interplay between large-scale neural networks. However, brain networks involved with the capability to split attentional resource over multiple spatial locations and multiple stimuli or sensory modalities have been largely unexplored to date. Here I re-analyzed data from Santangelo et al. (2010) to explore the causal interactions between large-scale brain networks during divided attention. During fMRI scanning, participants monitored streams of visual and/or auditory stimuli in one or two spatial locations for detection of occasional targets. This design allowed comparing a condition in which participants monitored one stimulus/modality (either visual or auditory) in two spatial locations vs. a condition in which participants monitored two stimuli/modalities (both visual and auditory) in one spatial location. The analysis of the independent components (ICs) revealed that dividing attentional resources across two spatial locations necessitated a brain network involving the left ventro- and dorso-lateral prefrontal cortex plus the posterior parietal cortex, including the intraparietal sulcus (IPS) and the angular gyrus, bilaterally. The analysis of Granger causality highlighted that the activity of lateral prefrontal regions were predictive of the activity of all of the posteriors parietal nodes. By contrast, dividing attention across two sensory modalities necessitated a brain network including nodes belonging to the dorsal frontoparietal network, i.e., the bilateral frontal eye-fields (FEF) and IPS, plus nodes belonging to the salience network, i.e., the anterior cingulated cortex and the left and right anterior insular cortex (aIC). The analysis of Granger causality highlights a tight interdependence between the dorsal frontoparietal and salience nodes in trials requiring divided attention between different sensory modalities. The current findings therefore highlighted a dissociation among brain networks

  17. Targeting oncogenic Myc as a strategy for cancer treatment.

    PubMed

    Chen, Hui; Liu, Hudan; Qing, Guoliang

    2018-01-01

    The MYC family oncogene is deregulated in >50% of human cancers, and this deregulation is frequently associated with poor prognosis and unfavorable patient survival. Myc has a central role in almost every aspect of the oncogenic process, orchestrating proliferation, apoptosis, differentiation, and metabolism. Although Myc inhibition would be a powerful approach for the treatment of many types of cancers, direct targeting of Myc has been a challenge for decades owing to its "undruggable" protein structure. Hence, alternatives to Myc blockade have been widely explored to achieve desirable anti-tumor effects, including Myc/Max complex disruption, MYC transcription and/or translation inhibition, and Myc destabilization as well as the synthetic lethality associated with Myc overexpression. In this review, we summarize the latest advances in targeting oncogenic Myc, particularly for cancer therapeutic purposes.

  18. Response Modality Variations Affect Determinations of Children's Learning Styles.

    ERIC Educational Resources Information Center

    Janowitz, Jeffrey M.

    The Swassing-Barbe Modality Index (SBMI) uses visual, auditory, and tactile inputs, but only reconstructed output, to measure children's modality strengths. In this experiment, the SBMI's three input modalities were crossed with two output modalities (spoken and drawn) in addition to the reconstructed standard to result in nine treatment…

  19. Inflammation and Immune Regulation as Potential Drug Targets in Antidepressant Treatment

    PubMed Central

    Schmidt, Frank M.; Kirkby, Kenneth C.; Lichtblau, Nicole

    2016-01-01

    Growing evidence supports a mutual relationship between inflammation and major depression. A variety of mechanisms are outlined, indicating how inflammation may be involved in the pathogenesis, course and treatment of major depression. In particular, this review addresses 1) inflammatory cytokines as markers of depression and potential predictors of treatment response, 2) findings that cytokines interact with antidepressants and non-pharmacological antidepressive therapies, such as electroconvulsive therapy, deep brain stimulation and physical activity, 3) the influence of cytokines on the cytochrome (CYP) p450-system and drug efflux transporters, and 4) how cascades of inflammation might serve as antidepressant drug targets. A number of clinical trials have focused on agents with immunmodulatory properties in the treatment of depression, of which this review covers nonsteroidal anti-inflammatory drugs (NSAIDs), cytokine inhibitors, ketamine, polyunsaturated fatty acids, statins and curcumin. A perspective is also provided on possible future immune targets for antidepressant therapy, such as toll-like receptor-inhibitors, glycogen synthase kinase-3 inhibitors, oleanolic acid analogs and minocycline. Concluding from the available data, markers of inflammation may become relevant factors for more personalised planning and prediction of response of antidepressant treatment strategies. Agents with anti-inflammatory properties have the potential to serve as clinically relevant antidepressants. Further studies are required to better define and identify subgroups of patients responsive to inflammatory agents as well as to define optimal time points for treatment onset and duration. PMID:26769225

  20. Different patterns of modality dominance across development.

    PubMed

    Barnhart, Wesley R; Rivera, Samuel; Robinson, Christopher W

    2018-01-01

    The present study sought to better understand how children, young adults, and older adults attend and respond to multisensory information. In Experiment 1, young adults were presented with two spoken words, two pictures, or two word-picture pairings and they had to determine if the two stimuli/pairings were exactly the same or different. Pairing the words and pictures together slowed down visual but not auditory response times and delayed the latency of first fixations, both of which are consistent with a proposed mechanism underlying auditory dominance. Experiment 2 examined the development of modality dominance in children, young adults, and older adults. Cross-modal presentation attenuated visual accuracy and slowed down visual response times in children, whereas older adults showed the opposite pattern, with cross-modal presentation attenuating auditory accuracy and slowing down auditory response times. Cross-modal presentation also delayed first fixations in children and young adults. Mechanisms underlying modality dominance and multisensory processing are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Multilayer modal actuator-based piezoelectric transformers.

    PubMed

    Huang, Yao-Tien; Wu, Wen-Jong; Wang, Yen-Chieh; Lee, Chih-Kung

    2007-02-01

    An innovative, multilayer piezoelectric transformer equipped with a full modal filtering input electrode is reported herein. This modal-shaped electrode, based on the orthogonal property of structural vibration modes, is characterized by full modal filtering to ensure that only the desired vibration mode is excited during operation. The newly developed piezoelectric transformer is comprised of three layers: a multilayered input layer, an insulation layer, and a single output layer. The electrode shape of the input layer is derived from its structural vibration modal shape, which takes advantage of the orthogonal property of the vibration modes to achieve a full modal filtering effect. The insulation layer possesses two functions: first, to couple the mechanical vibration energy between the input and output, and second, to provide electrical insulation between the two layers. To meet the two functions, a low temperature, co-fired ceramic (LTCC) was used to provide the high mechanical rigidity and high electrical insulation. It can be shown that this newly developed piezoelectric transformer has the advantage of possessing a more efficient energy transfer and a wider optimal working frequency range when compared to traditional piezoelectric transformers. A multilayer piezoelectric, transformer-based inverter applicable for use in LCD monitors or portable displays is presented as well.

  2. Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

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

    Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.

    2010-09-15

    Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences inmore » radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to

  3. Molecular targets in urothelial cancer: detection, treatment, and animal models of bladder cancer

    PubMed Central

    Smolensky, Dmitriy; Rathore, Kusum; Cekanova, Maria

    2016-01-01

    Bladder cancer remains one of the most expensive cancers to treat in the United States due to the length of required treatment and degree of recurrence. In order to treat bladder cancer more effectively, targeted therapies are being investigated. In order to use targeted therapy in a patient, it is important to provide a genetic background of the patient. Recent advances in genome sequencing, as well as transcriptome analysis, have identified major pathway components altered in bladder cancer. The purpose of this review is to provide a broad background on bladder cancer, including its causes, diagnosis, stages, treatments, animal models, as well as signaling pathways in bladder cancer. The major focus is given to the PI3K/AKT pathway, p53/pRb signaling pathways, and the histone modification machinery. Because several promising immunological therapies are also emerging in the treatment of bladder cancer, focus is also given on general activation of the immune system for the treatment of bladder cancer. PMID:27784990

  4. IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

    DTIC Science & Technology

    2014-02-01

    DRP-1: Treatment of Malignant Pleural Effusion with ZD6474, a Novel VEGFR and EGFR TK Inhibitor (PI and co-PI: Roy Herbst, M.D., Ph.D., Carlos...Jimenez, M.D.) Recurrent malignant pleural effusion is a debilitating clinical problem that requires palliation with repeated therapeutic...thoracentesis or pleurodesis (Putnam, J Surg Clin North Am 2002). Malignant pleural effusions have been associated with high levels of VEGF. Treatment with a

  5. Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

    PubMed

    Rahman, Wahida; Dickenson, Anthony H

    2015-06-01

    Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics. Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy. Somatosensory phenotyping of chronic pain patients, as a surrogate of putative pain generating mechanisms, may predict patient response to treatment. Identification of new targets will inform and guide future research, aiding the development of more effective analgesics. Future clinical trial designs should implement sensory phenotyping of patients, as an inclusion or stratification criterion, in order to establish an individualized, mechanism-based treatment of osteoarthritis pain.

  6. Awareness of Prostate Cancer and Screening Modalities Among Long Island Men.

    PubMed

    Leonard, James A; Wells, Jenna B; Brandler, Ethan S

    2017-03-01

    Despite advances in prostate cancer (PC) treatment and outcomes, it remains one of the most commonly diagnosed cancers and the second leading cause of cancer mortality in men. Furthermore, there exist little data about patient awareness of PC and the frequency of screening. Adult men (470) presenting to the emergency department at a tertiary care center (Stony Brook University) between 2014 and 2015 were surveyed orally for their perceived risk of PC, awareness of PC and screening modalities, and screening history. In a population that mirrors the racial demographics of the United States, it was observed that significant disparities in awareness of PC exist among several populations including those at greatest risk. This study revealed an important opportunity for education on PC and screening modalities among the population of men at risk.

  7. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

    PubMed Central

    Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

    2016-01-01

    Objective To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). Background TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Methods Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. Results API costs per kg were $347–$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128–$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Conclusions Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID:26817636

  8. Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment.

    PubMed

    Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

    2016-01-27

    To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  9. Cortical reorganization in postlingually deaf cochlear implant users: Intra-modal and cross-modal considerations.

    PubMed

    Stropahl, Maren; Chen, Ling-Chia; Debener, Stefan

    2017-01-01

    With the advances of cochlear implant (CI) technology, many deaf individuals can partially regain their hearing ability. However, there is a large variation in the level of recovery. Cortical changes induced by hearing deprivation and restoration with CIs have been thought to contribute to this variation. The current review aims to identify these cortical changes in postlingually deaf CI users and discusses their maladaptive or adaptive relationship to the CI outcome. Overall, intra-modal and cross-modal reorganization patterns have been identified in postlingually deaf CI users in visual and in auditory cortex. Even though cross-modal activation in auditory cortex is considered as maladaptive for speech recovery in CI users, a similar activation relates positively to lip reading skills. Furthermore, cross-modal activation of the visual cortex seems to be adaptive for speech recognition. Currently available evidence points to an involvement of further brain areas and suggests that a focus on the reversal of visual take-over of the auditory cortex may be too limited. Future investigations should consider expanded cortical as well as multi-sensory processing and capture different hierarchical processing steps. Furthermore, prospective longitudinal designs are needed to track the dynamics of cortical plasticity that takes place before and after implantation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  10. Modal Parameter Identification and Numerical Simulation for Self-anchored Suspension Bridges Based on Ambient Vibration

    NASA Astrophysics Data System (ADS)

    Liu, Bing; Sun, Li Guo

    2018-06-01

    This paper chooses the Nanjing-Hangzhou high speed overbridge, a self-anchored suspension bridge, as the research target, trying to identify the dynamic characteristic parameters of the bridge by using the peak-picking method to analyze the velocity response data under ambient excitation collected by 7 vibration pickup sensors set on the bridge deck. The ABAQUS is used to set up a three-dimensional finite element model for the full bridge and amends the finite element model of the suspension bridge based on the identified modal parameter, and suspender force picked by the PDV100 laser vibrometer. The study shows that the modal parameter can well be identified by analyzing the bridge vibration velocity collected by 7 survey points. The identified modal parameter and measured suspender force can be used as the basis of the amendment of the finite element model of the suspension bridge. The amended model can truthfully reflect the structural physical features and it can also be the benchmark model for the long-term health monitoring and condition assessment of the bridge.

  11. The Next Generation of Targeted Molecules for the Treatment of Chronic Lymphocytic Leukemia.

    PubMed

    Jeyakumar, Deepa; O'Brien, Susan

    2016-11-15

    With the recent approval of several new targeted therapies for chronic lymphocytic leukemia (CLL), there are now multiple options for its treatment. Inhibitors of Bruton tyrosine kinase (with ibrutinib being the first-in-class US Food and Drug Administration-approved agent) and phosphoinositide 3-kinase (with idelalisib as the first-in-class approved agent) are promising because they are generally well tolerated and highly effective against this malignancy. These agents may be particularly important in the treatment of older patients who are less able to tolerate the myelosuppression (and subsequent infections) associated with chemoimmunotherapy. As a class of medications, B-cell receptor inhibitors have some unique side effects, including redistribution lymphocytosis. Toxicities associated specifically with ibrutinib include increased risk for bleeding and atrial fibrillation. Idelalisib also has some unique toxicities: transaminitis, colitis, and pneumonitis. Targeted therapies recently approved for use in CLL include the novel anti-CD20 monoclonal antibodies obinutuzumab and ofatumumab, and the B-cell lymphoma 2 inhibitor venetoclax. This article describes the clinical data that led to approval of these B-cell receptor inhibitors for the treatment of CLL, and highlights newer agents in clinical development that target the same kinases as the currently available therapies.

  12. Recruitment and treatment practices for help-seeking "prodromal" patients.

    PubMed

    McGlashan, Thomas H; Addington, Jean; Cannon, Tyrone; Heinimaa, Markus; McGorry, Patrick; O'Brien, Mary; Penn, David; Perkins, Diana; Salokangas, Raimo K R; Walsh, Barbara; Woods, Scott W; Yung, Alison

    2007-05-01

    The prodrome of psychosis has become a target for early identification and for treatments that address both symptoms and risk for future psychosis. Interest and activity in this realm is now worldwide. Clinical trials with rigorous methodology have only just begun, making treatment guidelines premature. Despite the sparse evidence base, treatments are currently applied to patients in the new prodromal clinics, usually treatments developed for established psychosis and modified for the prodromal phase. This communication will describe representative samplings of how treatment-seeking prodromal patients are currently recruited and treated in prodromal clinics worldwide. Recruitment includes how prodromal patients are sought, initially evaluated, apprised of their high-risk status, and informed of the risks and benefits of prodromal treatments and how their mental state is monitored over time. The treatment modalities offered (and described) include engagement, supportive therapy, case management, stress management, cognitive behavioral treatment, family-based treatment, antipsychotic pharmacotherapy, and non-antipsychotic pharmacotherapy. References for details are noted.

  13. Current status of the use of modalities in wound care: electrical stimulation and ultrasound therapy.

    PubMed

    Ennis, William J; Lee, Claudia; Plummer, Malgorzata; Meneses, Patricio

    2011-01-01

    Wound healing is a complex pathway that requires cells, an appropriate biochemical environment (i.e., cytokines, chemokines), an extracellular matrix, perfusion, and the application of both macrostrain and microstrain. The process is both biochemically complex and energy dependent. Healing can be assisted in difficult cases through the use of physical modalities. In the current literature, there is much debate over which treatment modality, dosage level, and timing is optimal. The mechanism of action for both electrical stimulation and ultrasound are reviewed along with possible clinical applications for the plastic surgeon.

  14. Imaging modalities for the in vivo surveillance of mesenchymal stromal cells.

    PubMed

    Hossain, Mohammad Ayaz; Chowdhury, Tina; Bagul, Atul

    2015-11-01

    Bone marrow stromal cells exist as mesenchymal stromal cells (MSCs) and have the capacity to differentiate into multiple tissue types when subjected to appropriate culture conditions. This property of MSCs creates therapeutic opportunities in regenerative medicine for the treatment of damage to neural, cardiac and musculoskeletal tissues or acute kidney injury. The prerequisite for successful cell therapy is delivery of cells to the target tissue. Assessment of therapeutic outcomes utilize traditional methods to examine cell function of MSC populations involving routine biochemical or histological analysis for cell proliferation, protein synthesis and gene expression. However, these methods do not provide sufficient spatial and temporal information. In vivo surveillance of MSC migration to the site of interest can be performed through a variety of imaging modalities such as the use of radiolabelling, fluc protein expression bioluminescence imaging and paramagnetic nanoparticle magnetic resonance imaging. This review will outline the current methods of in vivo surveillance of exogenously administered MSCs in regenerative medicine while addressing potential technological developments. Furthermore, nanoparticles and microparticles for cellular labelling have shown that migration of MSCs can be spatially and temporally monitored. In vivo surveillance therefore permits time-stratified assessment in animal models without disruption of the target organ. In vivo tracking of MSCs is non-invasive, repeatable and non-toxic. Despite the excitement that nanoparticles for tracking MSCs offer, delivery methods are difficult because of the challenges with imaging three-dimensional systems. The current advances and growth in MSC research, is likely to provide a wealth of evidence overcoming these issues. Copyright © 2014 John Wiley & Sons, Ltd.

  15. Treatment Patterns and Burden of Illness in Patients Initiating Targeted Therapy or Chemotherapy for Pancreatic Neuroendocrine Tumors.

    PubMed

    Broder, Michael S; Chang, Eunice; Reddy, Sheila R; Neary, Maureen P

    2017-08-01

    The aim of this study was to characterize treatment patterns and burden of pancreatic neuroendocrine tumors (PNET). Using 2 claims databases, we identified patients with PNET initiating targeted therapy (everolimus, sunitinib) or chemotherapy from 2009 to 2012. The first targeted/cytotoxic therapy was considered index treatment. Treatment patterns were graphically evaluated from index treatment initiation until enrollment or study end, whichever occurred first. Disease burden was examined by index group for first follow-up year. In treatment pattern analyses (582 newly treated patients with PNET), 72.2% received chemotherapy index treatment, 16.2% everolimus, and 11.7% received sunitinib. Median index treatment duration was 242, 146, and 126 days for everolimus, sunitinib, and cytotoxics (P < 0.01). Sunitinib initiators switched most often followed by everolimus and cytotoxic initiators. In disease burden analyses, 338 patients met inclusion criteria, with mean age of 54.5 (standard deviation, 9.9) years, 45.6% were female, and there were no significant between-group differences. Targeted therapy initiators had more prior somatostatin analog use versus cytotoxics (53.4% vs 25.1%, P < 0.001); 72.5% had comorbidities after treatment initiation; 42.9% had 1 or more inpatient hospitalization; and 47.9% had 1 or more emergency department visit. Pancreatic neuroendocrine tumor treatment patterns varied; cytotoxics were more often used as early therapy than targeted agents, but for less time. Patients had high health care utilization, irrespective of treatment, potentially from burdensome symptoms and comorbidities.

  16. Body System Effects of a Multi-Modal Training Program Targeting Chronic, Motor Complete Thoracic Spinal Cord Injury.

    PubMed

    Gant, Katie L; Nagle, Kathleen G; Cowan, Rachel E; Field-Fote, Edelle C; Nash, Mark S; Kressler, Jochen; Thomas, Christine K; Castellanos, Mabelin; Widerström-Noga, Eva; Anderson, Kimberly D

    2018-02-01

    The safety and efficacy of pharmacological and cellular transplantation strategies are currently being evaluated in people with spinal cord injury (SCI). In studies of people with chronic SCIs, it is thought that functional recovery will be best achieved when drug or cell therapies are combined with rehabilitation protocols. However, any functional recovery attributed to the therapy may be confounded by the conditioned state of the body and by training-induced effects on neuroplasticity. For this reason, we sought to investigate the effects of a multi-modal training program on several body systems. The training program included body-weight-supported treadmill training for locomotion, circuit resistance training for upper body conditioning, functional electrical stimulation for activation of sublesional muscles, and wheelchair skills training for overall mobility. Eight participants with chronic, thoracic-level, motor-complete SCI completed the 12-week training program. After 12 weeks, upper extremity muscular strength improved significantly for all participants, and some participants experienced improvements in function, which may be explained by increased strength. Neurological function did not change. Changes in pain and spasticity were highly variable between participants. This is the first demonstration of the effect of this combination of four training modalities. However, balancing participant and study-site burden with capturing meaningful outcome measures is also an important consideration.

  17. 40 CFR 1033.520 - Alternative ramped modal cycles.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Following the completion of the third test phase of the applicable ramped modal cycle, conduct the post... POLLUTION CONTROLS CONTROL OF EMISSIONS FROM LOCOMOTIVES Test Procedures § 1033.520 Alternative ramped modal... locomotive notch settings. Ramped modal cycles combine multiple test modes of a discrete-mode steady-state...

  18. Cortisol increase in empathic stress is modulated by emotional closeness and observation modality.

    PubMed

    Engert, Veronika; Plessow, Franziska; Miller, Robert; Kirschbaum, Clemens; Singer, Tania

    2014-07-01

    Stress disorders are among the most commonly occurring of all mental disorders. In this context, the question arises whether the stress inevitably unfolding around us has the potential to "contaminate" and compromise us. In the current multi-center study, we investigate the existence of such empathic stress (defined as a full-blown physiological stress response that arises solely by observing a target undergo a stressful situation), and whether empathic stress permeates to the core of the stress system, the hypothalamic-pituitary-adrenal (HPA) axis. Additionally, we investigate whether empathic stress responses may be modulated by the familiarity between observer and target (partners vs. strangers), the modality of observation (real-life vs. virtual) and observer sex (female vs. male). Participants were tested in dyads, paired with a loved one or a stranger of the opposite sex. While the target of the dyad (n=151) was exposed to a psychosocial stressor, the observer (n=211) watched through a one-way mirror or via live video transmission. Overall, 26% of the observers displayed physiologically significant cortisol increases. This empathic stress was more pronounced in intimate observer-target dyads (40%) and during the real-life representation of the stressor (30%). Empathic stress was further modulated by interindividual differences in empathy measures. Despite the higher prevalence of empathic stress in the partner and real-life observation conditions, significant cortisol responses also emerged in strangers (10%) and the virtual observation modality (24%). The occurrence of empathic stress down to the level of HPA-axis activation, in some cases even in total strangers and when only virtually witnessing another's distress, may have important implications for the development of stress-related diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. EGFR-targeted gelatin nanoparticles for systemic administration of gemcitabine in an orthotopic pancreatic cancer model.

    PubMed

    Singh, Amit; Xu, Jing; Mattheolabakis, George; Amiji, Mansoor

    2016-04-01

    In this study, we have formulated redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a targeted vector for systemic delivery of gemcitabine therapy in pancreatic cancer. The gelatin nanoparticles were formed by ethanol-induced desolvation process to encapsulate the bound drug. The surface of the nanoparticles was decorated either with poly(ethylene glycol) (PEG) chains to impart enhanced circulation time or with EGFR targeting peptide to confer target specificity. Our in vitro studies in Panc-1 human pancreatic ductal adenocarcinoma cells confirm that gemcitabine encapsulated in EGFR-targeted gelatin nanoparticles, released through disulfide bond cleavage, had a significantly improved cytotoxic profile. Further, the in vivo anticancer activity was evaluated in an orthotopic pancreatic adenocarcinoma tumor bearing SCID beige mice, which confirmed that EGFR-targeted gelatin nanoparticles could efficiently deliver gemcitabine to the tumor leading to higher therapeutic benefit as compared to the drug in solution. The treatment of pancreatic cancer remains unsatisfactory, with an average 5-year survival of less than 5%. New treatment modalities are thus urgently needed. In this study, the authors presented their formulation of redox-responsive epidermal growth factor receptor (EGFR)-targeted type B gelatin nanoparticles as a carrier for gemcitabine. In-vitro and in-vivo experiments showed encouraging results. It is hoped that the findings would provide a novel and alternative drug delivery platform for the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Beta-lactamase targeted enzyme activatable photosensitizers for antimicrobial PDT

    NASA Astrophysics Data System (ADS)

    Zheng, Xiang; Verma, Sarika; Sallum, Ulysses W.; Hasan, Tayyaba

    2009-06-01

    Photodynamic therapy (PDT) as a treatment modality for infectious disease has shown promise. However, most of the antimicrobial photosensitizers (PS) non-preferentially accumulate in both bacteria and host tissues, causing host tissue phototoxicity during treatment. We have developed a new antimicrobial PDT strategy which exploits beta-lactam resistance mechanism, one of the major drug-resistance bacteria evolved, to achieve enhanced target specificity with limited host damage. Our strategy comprises a prodrug construct with a PS and a quencher linked by beta-lactam ring, resulting in a diminished phototoxicity. This construct, beta-lactamase enzyme-activated-photosensitizer (beta-LEAP), can only be activated in the presence of both light and bacteria, and remains inactive elsewhere such as mammalian tissue. Beta-LEAP construct had shown specific cleavage by purified beta-lactamase and by beta-lactamase over-expressing methicillin resistant Staphylococcus aureus (MRSA). Specific photodynamic toxicity was observed towards MRSA, while dark and light toxicity were equivalent to reference strains. The prodrug design, synthesis and photophysical properties will be discussed.

  1. Novel immunotherapy and treatment modality for severe food allergies.

    PubMed

    Nagakura, Ken-Ichi; Sato, Sakura; Yanagida, Noriyuki; Ebisawa, Motohiro

    2017-06-01

    In recent years, many studies on oral immunotherapy (OIT) have been conducted; however, few have focused on severe food allergies. The purpose of this review was to assess the efficacy and safety of oral immunotherapies for patients with severe food allergy. We reviewed multiple immunotherapy reports published within a few years or reports focusing on severe food allergies. We also investigated recent studies on OIT and novel food allergy management. Immunotherapies targeting low-dose antigen exposure and oral food challenges using low-dose target volumes may be safer than conventional OIT. It is necessary to consider which immunotherapy regimen is appropriate based on allergy severity of the patient.

  2. Allosteric Modulators for the Treatment of Schizophrenia: Targeting Glutamatergic Networks

    PubMed Central

    Menniti, Frank S.; Lindsley, Craig W.; Conn, P. Jeffrey; Pandit, Jayvardhan; Zagouras, Panayiotis; Volkmann, Robert A.

    2013-01-01

    Schizophrenia is a highly debilitating mental disorder which afflicts approximately 1% of the global population. Cognitive and negative deficits account for the lifelong disability associated with schizophrenia, whose symptoms are not effectively addressed by current treatments. New medicines are needed to treat these aspects of the disease. Neurodevelopmental, neuropathological, genetic, and behavioral pharmacological data indicate that schizophrenia stems from a dysfunction of glutamate synaptic transmission, particularly in frontal cortical networks. A number of novel pre- and postsynaptic mechanisms affecting glutamatergic synaptic transmission have emerged as viable targets for schizophrenia. While developing orthosteric glutamatergic agents for these targets has proven extremely difficult, targeting allosteric sites of these targets has emerged as a promising alternative. From a medicinal chemistry perspective, allosteric sites provide an opportunity of finding agents with better drug-like properties and greater target specificity. Furthermore, allosteric modulators are better suited to maintaining the highly precise temporal and spatial aspects of glutamatergic synaptic transmission. Herein, we review neuropathological and genomic/genetic evidence underscoring the importance of glutamate synaptic dysfunction in the etiology of schizophrenia and make a case for allosteric targets for therapeutic intervention. We review progress in identifying allosteric modulators of AMPA receptors, NMDA receptors, and metabotropic glutamate receptors, all with the aim of restoring physiological glutamatergic synaptic transmission. Challenges remain given the complexity of schizophrenia and the difficulty in studying cognition in animals and humans. Nonetheless, important compounds have emerged from these efforts and promising preclinical and variable clinical validation has been achieved. PMID:23409764

  3. Multifunctional targeted liposomal drug delivery for efficient glioblastoma treatment

    PubMed Central

    Belhadj, Zakia; Zhan, Changyou; Ying, Man; Wei, Xiaoli; Xie, Cao; Yan, Zhiqiang; Lu, Weiyue

    2017-01-01

    Glioblastoma multiforme (GBM) has been considered to be the most malignant brain tumors. Due to the existence of various barriers including the blood–brain barrier (BBB) and blood–brain tumor barrier (BBTB) greatly hinder the accumulation and deep penetration of chemotherapeutics, the treatment of glioma remains to be the most challenging task in clinic. In order to circumvent these hurdles, we developed a multifunctional liposomal glioma-targeted drug delivery system (c(RGDyK)/pHA-LS) modified with cyclic RGD (c(RGDyK)) and p-hydroxybenzoic acid (pHA) in which c(RGDyK) could target integrin αvβ3 overexpressed on the BBTB and glioma cells and pHA could target dopamine receptors on the BBB. In vitro, c(RGDyK)/pHA-LS could target glioblastoma cells (U87), brain capillary endothelial cells (bEnd.3) and umbilical vein endothelial cells (HUVECs) through a comprehensive pathway. Besides, c(RGDyK)/pHA-LS could also increase the cytotoxicity of doxorubicin encapsulated in liposomes on glioblastoma cells, and was able to penetrate inside the glioma spheroids after traversing the in vitro BBB and BBTB. In vivo, we demonstrated the targeting ability of c(RGDyK)/pHA-LS to intracranial glioma. As expected, c(RGDyK)/pHA-LS/DOX showed a median survival time of 35 days, which was 2.31-, 1.76- and 1.5-fold higher than that of LS/DOX, c(RGDyK)-LS/DOX, and pHA-LS/DOX, respectively. The findings here suggested that the multifunctional glioma-targeted drug delivery system modified with both c(RGDyK) and pHA displayed strong antiglioma efficiency in vitro and in vivo, representing a promising platform for glioma therapy. PMID:28978003

  4. Modality and risk management for orthodontic extrusion procedures in interdisciplinary treatment for generating proper bone and tissue contours for the planned implant: a case report.

    PubMed

    Maeda, Sachiko; Sasaki, Takeshi

    2015-12-01

    In adult interdisciplinary treatments with using dental implants, limited orthodontic treatment, especially orthodontic extrusion (OE), offers many benefits by both correcting teeth alignment and by contributing to the regeneration of periodontal tissues. However, orthodontic procedures carry some risks and unpredictabilities that might compromise tooth and/or periodontal tissue health. Especially in complex cases, it is difficult to decide which orthodontic treatment modalities should be combined, in what sequences they should be applied, and what their force systems and treatment times are.To achieve optimum results, some cases require two or more OEs to the same site being carried out at different times while taking the treatment effects into consideration. Such staged OE offers minimum intervention and maximum efficiency. In this case report, OE was first applied for orthodontic extraction. After bone regeneration followed by an implant placement and another surgical operation, a second OE was applied to align the inclination of an adjacent tooth. As a result, a predictable prognosis of implants as well as greatly improved esthetics and periodontal tissue health were achieved.

  5. Novel drug target identification for the treatment of dementia using multi-relational association mining.

    PubMed

    Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

    2015-07-08

    Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

  6. Novel drug target identification for the treatment of dementia using multi-relational association mining

    PubMed Central

    Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

    2015-01-01

    Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. PMID:26154857

  7. Veterans in substance abuse treatment program self-initiate box gardening as a stress reducing therapeutic modality.

    PubMed

    Lehmann, Lauren P; Detweiler, Jonna G; Detweiler, Mark B

    2018-02-01

    To assess the experiences of a veteran initiated horticultural therapy garden during their 28-day inpatient Substance Abuse Residential Rehabilitation Treatment Program (SARRTP). Retrospective study. Veterans Affairs Medical Center (VAMC), Salem, Virginia, USA INTERVENTIONS: Group interviews with veterans from the last SARRTP classes and individual interviews with VAMC greenhouse staff in summer of 2016. Time spent in garden, frequency of garden visits, types of passive and active garden activities, words describing the veterans' emotional reactions to utilizing the garden. In 3 summer months of 2016, 50 percent of the 56 veterans interviewed visited and interacted with the gardens during their free time. Frequency of visits generally varied from 3 times weekly to 1-2 times a day. Amount of time in the garden varied from 10min to 2h. The veterans engaged in active and/or passive gardening activities during their garden visits. The veterans reported feeling "calm", "serene", and "refreshed" during garden visitation and after leaving the garden. Although data was secured only at the end of the 2016 growing season, interviews of the inpatient veterans revealed that they used their own initiative and resources to continue the horticulture therapy program for 2 successive growing years after the original pilot project ended in 2014. These non-interventionist, therapeutic garden projects suggest the role of autonomy and patient initiative in recovery programs for veterans attending VAMC treatment programs and they also suggest the value of horticulture therapy as a meaningful evidence- based therapeutic modality for veterans. Published by Elsevier Ltd.

  8. Modulation of Myostatin/Hepatocyte Growth Factor Balance by Different Hemodialysis Modalities.

    PubMed

    Esposito, Pasquale; La Porta, Edoardo; Calatroni, Marta; Grignano, Maria Antonietta; Milanesi, Samantha; Verzola, Daniela; Battaglia, Yuri; Gregorini, Marilena; Libetta, Carmelo; Garibotto, Giacomo; Rampino, Teresa

    2017-01-01

    Background. In this study we investigated the relevance of myostatin and Hepatocyte Growth Factor (HGF) in patients undergoing hemodialysis HD and the influence of different HD modalities on their levels. Methods. We performed a prospective crossover study in which HD patients were randomized to undergo 3-month treatment periods with bicarbonate hemodialysis (BHD) followed by online hemodiafiltration (HDF). Clinical data, laboratory parameters, and myostatin and HGF serum levels were collected and compared. Results. Ten patients and six controls (C) were evaluated. In any experimental condition myostatin and HGF levels were higher in HD than in C. At enrollment and after BHD there were not significant correlations, whereas at the end of the HDF treatment period myostatin and HGF were inversely correlated ( r   -0.65, p < 0.05), myostatin serum levels inversely correlated with transferrin ( r   -0.73, p < 0.05), and HGF levels that resulted positively correlated with BMI ( r 0.67, p < 0.05). Moving from BHD to HDF, clinical and laboratory parameters were unchanged, as well as serum HGF, whereas myostatin levels significantly decreased (6.3 ± 4.1 versus 4.3 ± 3.1 ng/ml, p < 0.05). Conclusions. Modulation of myostatin levels and myostatin/HGF balance by the use of different HD modalities might represent a novel approach to the prevention and treatment of HD-related muscle wasting syndrome.

  9. The metaphysics of quantum mechanics: Modal interpretations

    NASA Astrophysics Data System (ADS)

    Gluck, Stuart Murray

    2004-11-01

    This dissertation begins with the argument that a preferred way of doing metaphysics is through philosophy of physics. An understanding of quantum physics is vital to answering questions such as: What counts as an individual object in physical ontology? Is the universe fundamentally indeterministic? Are indiscernibles identical? This study explores how the various modal interpretations of quantum mechanics answer these sorts of questions; modal accounts are one of the two classes of interpretations along with so-called collapse accounts. This study suggests a new alternative within the class of modal views that yields a more plausible ontology, one in which the Principle of the Identity of Indisceribles is necessarily true. Next, it shows that modal interpretations can consistently deny that the universe must be fundamentally indeterministic so long as they accept certain other metaphysical commitments: either a perfect initial distribution of states in the universe or some form of primitive dispositional properties. Finally, the study sketches out a future research project for modal interpretations based on developing quantified quantum logic.

  10. The therapeutic effectiveness of using visual art modalities with the bereaved: a systematic review

    PubMed Central

    Gramling, Sandra E

    2018-01-01

    Bereaved individuals are increasingly considered at risk for negative psychological and physiological outcomes. Visual art modalities are often incorporated into grief therapy interventions, and clinical application of art therapy techniques with the bereaved has been widely documented. Although clinicians and recipients of these interventions advocate for their helpfulness in adapting to bereavement, research investigating the efficacy of visual art modalities has produced equivocal results and has not yet been synthesized to establish empirical support across settings. Accordingly, this review critically evaluates the existent literature on the effectiveness of visual art modalities with the bereaved and offers suggestions for future avenues of research. A total of 27 studies were included in the current review. Meta-analysis was not possible because of clinical heterogeneity and insufficient comparable data on outcome measures across studies. A narrative synthesis reports that therapeutic application of visual art modalities was associated with positive changes such as continuing bonds with the deceased and meaning making. Modest and conflicting preliminary evidence was found to support treatment effectiveness in alleviating negative grief symptoms such as general distress, functional impairment, and symptoms of depression and anxiety. PMID:29440940

  11. The therapeutic effectiveness of using visual art modalities with the bereaved: a systematic review.

    PubMed

    Weiskittle, Rachel E; Gramling, Sandra E

    2018-01-01

    Bereaved individuals are increasingly considered at risk for negative psychological and physiological outcomes. Visual art modalities are often incorporated into grief therapy interventions, and clinical application of art therapy techniques with the bereaved has been widely documented. Although clinicians and recipients of these interventions advocate for their helpfulness in adapting to bereavement, research investigating the efficacy of visual art modalities has produced equivocal results and has not yet been synthesized to establish empirical support across settings. Accordingly, this review critically evaluates the existent literature on the effectiveness of visual art modalities with the bereaved and offers suggestions for future avenues of research. A total of 27 studies were included in the current review. Meta-analysis was not possible because of clinical heterogeneity and insufficient comparable data on outcome measures across studies. A narrative synthesis reports that therapeutic application of visual art modalities was associated with positive changes such as continuing bonds with the deceased and meaning making. Modest and conflicting preliminary evidence was found to support treatment effectiveness in alleviating negative grief symptoms such as general distress, functional impairment, and symptoms of depression and anxiety.

  12. A study of the radiobiological modeling of the conformal radiation therapy in cancer treatment

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil Prasad

    Cancer is one of the leading causes of mortalities in the world. The precise diagnosis of the disease helps the patients to select the appropriate modality of the treatments such as surgery, chemotherapy and radiation therapy. The physics of X-radiation and the advanced imaging technologies such as positron emission tomography (PET) and computed tomography (CT) plays an important role in the efficient diagnosis and therapeutic treatments in cancer. However, the accuracy of the measurements of the metabolic target volumes (MTVs) in the PET/CT dual-imaging modality is always limited. Similarly the external beam radiation therapy (XRT) such as 3D conformal radiotherapy (3DCRT) and intensity modulated radiation therapy (IMRT) is the most common modality in the radiotherapy treatment. These treatments are simulated and evaluated using the XRT plans and the standard methodologies in the commercial planning system. However, the normal organs are always susceptible to the radiation toxicity in these treatments due to lack of knowledge of the appropriate radiobiological models to estimate the clinical outcomes. We explored several methodologies to estimate MTVs by reviewing various techniques of the target volume delineation using the static phantoms in the PET scans. The review suggests that the more precise and practical method of delineating PET MTV should be an intermediate volume between the volume coverage for the standardized uptake value (SUV; 2.5) of glucose and the 50% (40%) threshold of the maximum SUV for the smaller (larger) volume delineations in the radiotherapy applications. Similarly various types of optimal XRT plans were designed using the CT and PET/CT scans for the treatment of various types of cancer patients. The qualities of these plans were assessed using the universal plan-indices. The dose-volume criteria were also examined in the targets and organs by analyzing the conventional dose-volume histograms (DVHs). The biological models such as tumor

  13. Picosecond 532-nm neodymium-doped yttrium aluminum garnet laser-a promising modality for the management of verrucous epidermal nevi.

    PubMed

    Levi, Assi; Amitai, Dan Ben; Mimouni, Daniel; Leshem, Yael A; Arzi, Ofir; Lapidoth, Moshe

    2018-04-01

    The verrucous epidermal nevus (VEN) is the most common type of epidermal nevi. As lesions can be disfiguring, treatment is often sought. Many therapeutic approaches have been reported, with variable efficacy and safety. Picosecond (PS) lasers are novel laser devices designated to target small chromophores. A side effect of these lasers is blistering due to epidermal-dermal separation. We aimed to harness this side effect of the PS lasers to treat patients with VEN. The purpose of this study was to report our experience treating VEN using a PS 532-nm laser. We present a retrospective case series of six patients with large VEN who were treated using a PS 532-nm laser (2-6 treatments, 8-10 weeks apart). Response in clinical photographs was assessed by two independent dermatologists and graded on a scale of 0 (exacerbation) to 4 (76-100% improvement). Patient satisfaction was recorded on a scale of 1-5. All patients demonstrated significant improvement. Average improvement was 3.7 on the quartile scale of improvement. Patient satisfaction rate averaged 4.7. The PS 532-nm laser is a promising novel modality for the treatment of large VEN.

  14. State-Targeted Funding and Technical Assistance to Increase Access to Medication Treatment for Opioid Use Disorder.

    PubMed

    Abraham, Amanda J; Andrews, Christina M; Grogan, Colleen M; Pollack, Harold A; D'Aunno, Thomas; Humphreys, Keith; Friedmann, Peter D

    2018-04-01

    As the United States grapples with an opioid epidemic, expanding access to effective treatment for opioid use disorder is a major public health priority. Identifying effective policy tools that can be used to expand access to care is critically important. This article examines the relationship between state-targeted funding and technical assistance and adoption of three medications for treating opioid use disorder: oral naltrexone, injectable naltrexone, and buprenorphine. This study draws from the 2013-2014 wave of the National Drug Abuse Treatment System Survey, a nationally representative, longitudinal study of substance use disorder treatment programs. The sample includes data from 695 treatment programs (85.5% response rate) and representatives from single-state agencies in 49 states and Washington, D.C. (98% response rate). Logistic regression was used to examine the relationships of single-state agency targeted funding and technical assistance to availability of opioid use disorder medications among treatment programs. State-targeted funding was associated with increased program-level adoption of oral naltrexone (adjusted odds ratio [AOR]=3.14, 95% confidence interval [CI]=1.49-6.60, p=.004) and buprenorphine (AOR=2.47, 95% CI=1.31-4.67, p=.006). Buprenorphine adoption was also correlated with state technical assistance to support medication provision (AOR=1.18, 95% CI=1.00-1.39, p=.049). State-targeted funding for medications may be a viable policy lever for increasing access to opioid use disorder medications. Given the historically low rates of opioid use disorder medication adoption in treatment programs, single-state agency targeted funding is a potentially important tool to reduce mortality and morbidity associated with opioid disorders and misuse.

  15. Optical Quality and Threshold Target Identification and Military Target Task Performance after Advanced Keratorefractive Surgery

    DTIC Science & Technology

    2013-05-01

    and Sensors Directorate. • Study participants and physicians select treatment: PRK or LASIK . WFG vs . WFO treatment modality is randomized. The...to undergo wavefront-guided (WFG) photorefractive keratectomy ( PRK ), WFG laser in situ keratomileusis ( LASIK ), wavefront optimized (WFO) PRK or WFO...TERMS Military, Refractive Surgery, PRK , LASIK , Night Vision, Wavefront Optimized, Wavefront Guided, Visual Performance, Quality of Vision, Outcomes

  16. Verifying different-modality properties for concepts produces switching costs.

    PubMed

    Pecher, Diane; Zeelenberg, René; Barsalou, Lawrence W

    2003-03-01

    According to perceptual symbol systems, sensorimotor simulations underlie the representation of concepts. It follows that sensorimotor phenomena should arise in conceptual processing. Previous studies have shown that switching from one modality to another during perceptual processing incurs a processing cost. If perceptual simulation underlies conceptual processing, then verifying the properties of concepts should exhibit a switching cost as well. For example, verifying a property in the auditory modality (e.g., BLENDER-loud) should be slower after verifying a property in a different modality (e.g., CRANBERRIES-tart) than after verifying a property in the same modality (e.g., LEAVES-rustling). Only words were presented to subjects, and there were no instructions to use imagery. Nevertheless, switching modalities incurred a cost, analogous to the cost of switching modalities in perception. A second experiment showed that this effect was not due to associative priming between properties in the same modality. These results support the hypothesis that perceptual simulation underlies conceptual processing.

  17. Semantic control and modality: an input processing deficit in aphasia leading to deregulated semantic cognition in a single modality.

    PubMed

    Thompson, Hannah E; Jefferies, Elizabeth

    2013-08-01

    Research suggests that semantic memory deficits can occur in at least three ways. Patients can (1) show amodal degradation of concepts within the semantic store itself, such as in semantic dementia (SD), (2) have difficulty in controlling activation within the semantic system and accessing appropriate knowledge in line with current goals or context, as in semantic aphasia (SA) and (3) experience a semantic deficit in only one modality following degraded input from sensory cortex. Patients with SA show deficits of semantic control and access across word and picture tasks, consistent with the view that their problems arise from impaired modality-general control processes. However, there are a few reports in the literature of patients with semantic access problems restricted to auditory-verbal materials, who show decreasing ability to retrieve concepts from words when they are presented repeatedly with closely related distractors. These patients challenge the notion that semantic control processes are modality-general and suggest instead a separation of 'access' to auditory-verbal and non-verbal semantic systems. We had the rare opportunity to study such a case in detail. Our aims were to examine the effect of manipulations of control demands in auditory-verbal semantic, non-verbal semantic and non-semantic tasks, allowing us to assess whether such cases always show semantic control/access impairments that follow a modality-specific pattern, or whether there are alternative explanations. Our findings revealed: (1) deficits on executive tasks, unrelated to semantic demands, which were more evident in the auditory modality than the visual modality; (2) deficits in executively-demanding semantic tasks which were accentuated in the auditory-verbal domain compared with the visual modality, but still present on non-verbal tasks, and (3) a coupling between comprehension and executive control requirements, in that mild impairment on single word comprehension was greatly

  18. Evidence-based Peer Review for Radiation Therapy - Updated Review of the Literature with a Focus on Tumour Subsite and Treatment Modality.

    PubMed

    Huo, M; Gorayski, P; Poulsen, M; Thompson, K; Pinkham, M B

    2017-10-01

    Technological advances in radiation therapy permit steep dose gradients from the target to spare normal tissue, but increase the risk of geographic miss. Suboptimal target delineation adversely affects clinical outcomes. Prospective peer review is a method for quality assurance of oncologists' radiotherapy plans. Published surveys suggest it is widely implemented. However, it may not be feasible to review every case before commencement of radiation therapy in all departments. The rate of plan changes following peer review of cases without a specific subsite or modality is typically around 10%. Stereotactic body radiation therapy, head and neck, gynaecological, gastrointestinal, haematological and lung cases are associated with higher rates of change of around 25%. These cases could thus be prioritised for peer review. Other factors may limit peer review efficacy including organisational culture, time constraints and the physical environment in which sessions are held. Recommendations for peer review endorsed by the American Society for Radiation Oncology were made available in 2013, but a number of relevant studies have been published since. Here we review and update the literature, and provide an updated suggestion for the implementation of peer review to serve as an adjunct to published guidelines. This may help practitioners evaluate their current processes and maximise the utility and effectiveness of peer review sessions. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  19. Modal Analysis of Space-rocket Equipment Components

    NASA Astrophysics Data System (ADS)

    Igolkin, A. A.; Safin, A. I.; Prokofiev, A. B.

    2018-01-01

    In order to prevent vibration damage an analysis of natural frequencies and mode shapes of elements of rocket and space technology should be developed. This paper discusses technique of modal analysis on the example of the carrier platform. Modal analysis was performed by using mathematical modeling and laser vibrometer. Experimental data was clarified by using Test.Lab software. As a result of modal analysis amplitude-frequency response of carrier platform was obtained and the parameters of the elasticity was clarified.

  20. Pre-Motor Response Time Benefits in Multi-Modal Displays

    DTIC Science & Technology

    2013-11-12

    when animals are presented with stimuli from two sensory modalities as compared with stimulation from only one modality. The combinations of two...modality attention and orientation behaviors (see also Wallace, Meredith, & Stein, 609 !998). Multi-modal stimulation in the world is not always...perceptually when the stimuli are congruent. In another study, Craig (2006) had participants judge the direction of apparent motion by stimulating

  1. 3D multi-scale FCN with random modality voxel dropout learning for Intervertebral Disc Localization and Segmentation from Multi-modality MR Images.

    PubMed

    Li, Xiaomeng; Dou, Qi; Chen, Hao; Fu, Chi-Wing; Qi, Xiaojuan; Belavý, Daniel L; Armbrecht, Gabriele; Felsenberg, Dieter; Zheng, Guoyan; Heng, Pheng-Ann

    2018-04-01

    Intervertebral discs (IVDs) are small joints that lie between adjacent vertebrae. The localization and segmentation of IVDs are important for spine disease diagnosis and measurement quantification. However, manual annotation is time-consuming and error-prone with limited reproducibility, particularly for volumetric data. In this work, our goal is to develop an automatic and accurate method based on fully convolutional networks (FCN) for the localization and segmentation of IVDs from multi-modality 3D MR data. Compared with single modality data, multi-modality MR images provide complementary contextual information, which contributes to better recognition performance. However, how to effectively integrate such multi-modality information to generate accurate segmentation results remains to be further explored. In this paper, we present a novel multi-scale and modality dropout learning framework to locate and segment IVDs from four-modality MR images. First, we design a 3D multi-scale context fully convolutional network, which processes the input data in multiple scales of context and then merges the high-level features to enhance the representation capability of the network for handling the scale variation of anatomical structures. Second, to harness the complementary information from different modalities, we present a random modality voxel dropout strategy which alleviates the co-adaption issue and increases the discriminative capability of the network. Our method achieved the 1st place in the MICCAI challenge on automatic localization and segmentation of IVDs from multi-modality MR images, with a mean segmentation Dice coefficient of 91.2% and a mean localization error of 0.62 mm. We further conduct extensive experiments on the extended dataset to validate our method. We demonstrate that the proposed modality dropout strategy with multi-modality images as contextual information improved the segmentation accuracy significantly. Furthermore, experiments conducted on

  2. SU-C-BRE-01: 3D Conformal Micro Irradiation Results of Four Treatment Sites for Preclinical Small Animal and Clinical Treatment Plans

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

    Price, S; Yaddanapudi, S; Rangaraj, D

    Purpose: Small animal irradiation can provide preclinical insights necessary for clinical advancement. In order to provide clinically relevant data, these small animal irradiations must be designed such that the treatment methods and results are comparable to clinical protocols, regardless of variations in treatment size and modality. Methods: Small animal treatments for four treatment sites (brain, liver, lung and spine) were investigated, accounting for change in treatment energy and target size. Up to five orthovoltage (300kVp) beams were used in the preclinical treatments, using circular, square, and conformal tungsten apertures, based on the treatment site. Treatments were delivered using the imagemore » guided micro irradiator (microIGRT). The plans were delivered to a mouse sized phantom and dose measurements in axial and coronal planes were performed using radiochromic film. The results of the clinical and preclinical protocols were characterized in terms of conformality number, CTV coverage, dose nonuniformity ratio, and organ at risk sparing. Results: Preclinical small animal treatment conformality was within 1–16% of clinical results for all treatment sites. The volume of the CTV receiving 100% of the prescription dose was typically within 10% of clinical values. The dose non-uniformity was consistently higher for preclinical treatments compared to clinical treatments, indicating hot spots in the target. The ratios of the mean dose in the target to the mean dose in an organ at risk were comparable if not better for preclinical versus clinical treatments. Finally, QUANTEC dose constraints were applied and the recommended morbidity limits were satisfied in each small animal treatment site. Conclusion: We have shown that for four treatment sites, preclinical 3D conformal small animal treatments can be clinically comparable if clinical protocols are followed. Using clinical protocols as the standard, preclinical irradiation methods can be altered and

  3. Risk-Based Treatment Targets for Onsite Non-Potable Water ...

    EPA Pesticide Factsheets

    This presentation presents risk-based enteric pathogen log reduction targets for non-potable and potable uses of a variety of alternative source waters (i.e., municipal wastewater, locally-collected greywater, rainwater, and stormwater). A probabilistic, forward Quantitative Microbial Risk Assessment (QMRA) was used to derive the pathogen log10 reduction targets (LRTs) that corresponded with an infection risk of either 10-4 per person per year (ppy) or 10-2 ppy. The QMRA accounted for variation in pathogen concentration and sporadic pathogen occurrence (when data were available) in source waters for reference pathogens Rotavirus, Adenovirus, Norovirus, Campylobacter spp., Salmonella spp., Giardia spp., and Cryptosporidium spp.. Non-potable uses included indoor use (for toilet flushing and clothes washing) with accidental ingestion of treated non-potable water (or cross connection with potable water), and unrestricted irrigation for outdoor use. Various exposure scenarios captured the uncertainty from key inputs, i.e., the pathogen concentration in source water; the volume of water ingested; and for the indoor use, the frequency of and the fraction of the population exposed to accidental ingestion. Both potable and non-potable uses required pathogen treatment for the selected waters and the LRT was generally greater for potable use than nonpotable indoor use and unrestricted irrigation. The difference in treatment requirements among source waters was driven by th

  4. Comparison of Sexual Function and Hormonal Parameters Between Mood Stabilizer Treatment Modalities in Bipolar Disorder

    PubMed Central

    KESEBİR, Sermin; TOPRAK, Burak; BAYKARAN, Burak; HARİRİ, Aytül; BİLİCİ, Mustafa

    2014-01-01

    Introduction The aim of this study was to determine the differences between lithium and atypical antipsychotics (quetiapine and olanzapine) with regard to their effects on sexual functions and hormonal variables and to assess the findings in term of gender differences, in patients with bipolar disorder. Method 28 female and 29 male patients diagnosed as having bipolar disorder type I according to the DSM-IV, using lithium or quetiapine and quetiapine+lithium or olanzapine and olanzapine+lithium were evaluated consecutively. Being in remission period and given informed consent were set as inclusion criteria in these cases. Interviews with the patients were carried out using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) and SKIP-TURK. Sexual functions and satisfaction were evaluated with the Arizona Sexual Experiences Scale (ASEX) and the Golombok Rust Inventory of Sexual Satisfaction (GRISS). Blood samples of the patients were taken in order to determine prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and free testosterone (T) levels. Results GRISS scores in male patients were higher than in female patients (p=.001). The number of manic, depressive and total episodes, and functionality levels were similar between the treatment groups, both in female and male patients. No differences were found between treatment modalities in terms of hormone levels both in female and male patients. Among females, ASEX scores of the patients treated with lithium monotherapy were less than the ones treated with quetiapine and olanzapine. Among patients with quetiapine monotherapy, GRISS scores in male patients were higher than in female patients. Conclusion There are some evidences showing gender-based differences in the side effects of atypical antipsychotic drugs. Future studies with a specific focus on this topic are needed in order to have a better understanding of the basic mechanisms of gender differences

  5. Cost-effectiveness of secondary screening modalities for hypertension.

    PubMed

    Wang, Y Claire; Koval, Alisa M; Nakamura, Miyabi; Newman, Jonathan D; Schwartz, Joseph E; Stone, Patricia W

    2013-02-01

    Clinic-based blood pressure (CBP) has been the default approach for the diagnosis of hypertension, but patients may be misclassified because of masked hypertension (false negative) or 'white coat' hypertension (false positive). The incorporation of other diagnostic modalities, such as home blood pressure monitoring (HBPM) and ambulatory blood pressure monitoring (ABPM), holds promise to improve diagnostic accuracy and subsequent treatment decisions. We reviewed the literature on the costs and cost-effectiveness of adding HBPM and ABPM to routine blood pressure screening in adults. We excluded letters, editorials, and studies of pregnant and/or pre-eclamptic patients, children, and patients with specific conditions (e.g. diabetes). We identified 14 original, English language studies that included cost outcomes and compared two or more modalities. ABPM was found to be cost saving for diagnostic confirmation following an elevated CBP in six studies. Three of four studies found that adding HBPM to an elevated CBP was also cost-effective. Existing evidence supports the cost-effectiveness of incorporating HBPM or ABPM after an initial CBP-based diagnosis of hypertension. Future research should focus on their implementation in clinical practice, long-term economic values, and potential roles in identifying masked hypertension.

  6. Radical Cystectomy Compared to Combined Modality Treatment for Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

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

    Vashistha, Vishal; Wang, Hanzhang; Mazzone, Andrew

    Purpose: To perform a comprehensive comparison of overall survival (OS), disease-specific survival (DSS), progression-free survival (PFS), and treatment-related complications between radical cystectomy (RC) and combined modality treatment (CMT—radiation therapy, concurrent chemotherapy, and maximal transurethral resection of bladder tumor) in the setting of muscle-invasive bladder cancer. Methods and Materials: We searched 7 databases (PubMed, Scopus, EMBASE, Proquest, CINAHL, and (ClinicalTrials.gov)) for randomized, controlled trials and prospective and retrospective studies directly comparing RC with CMT from database inception to March 2016. We conducted meta-analyses evaluating OS, DSS, and PFS with hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Nineteen studies evaluating 12,380 subjects weremore » selected. For the 8 studies encompassing 9554 subjects eligible for meta-analyses, we found no difference in OS at 5 years (HR 0.96, favoring CMT, 95% CI 0.72-1.29; P=.778) or 10 years (HR 1.02, favoring cystectomy, 95% CI 0.73-1.42; P=.905). No difference was observed in DSS at 5 years (HR 0.83, favoring radiation, 95% CI 0.54-1.28; P=.390) or 10 years (HR 1.17, favoring cystectomy, 95% CI 0.89-1.55; P=.264), or PFS at 10 years (HR 0.85, favoring CMT, 95% CI 0.43-1.67; P=.639). The cystectomy arms had higher rates of early major complications, whereas rates of minor complications were similar between the 2 treatments. Conclusion: Current meta-analysis reveals no differences in OS, DSS, or PFS between RC and CMT. Further randomized, controlled trials are necessary to identify the optimal treatment for specific patients.« less

  7. Dynamic modal estimation using instrumental variables

    NASA Technical Reports Server (NTRS)

    Salzwedel, H.

    1980-01-01

    A method to determine the modes of dynamical systems is described. The inputs and outputs of a system are Fourier transformed and averaged to reduce the error level. An instrumental variable method that estimates modal parameters from multiple correlations between responses of single input, multiple output systems is applied to estimate aircraft, spacecraft, and off-shore platform modal parameters.

  8. Current and future medical treatments for patients with acromegaly.

    PubMed

    Maffezzoni, Filippo; Formenti, Anna Maria; Mazziotti, Gherardo; Frara, Stefano; Giustina, Andrea

    2016-08-01

    Acromegaly is a relatively rare condition of growth hormone (GH) excess associated with significant morbidity and, when left untreated, high mortality. Therapy for acromegaly is targeted at decreasing GH and insulin-like growth hormone 1 levels, ameliorating patients' symptoms and decreasing any local compressive effects of the pituitary adenoma. The therapeutic options for acromegaly include surgery, medical therapies (such as dopamine agonists, somatostatin receptor ligands and the GH receptor antagonist pegvisomant) and radiotherapy. However, despite all these treatments option, approximately 50% of patients are not adequately controlled. In this paper, the authors discuss: 1) efficacy and safety of current medical therapy 2) the efficacy and safety of the new multireceptor-targeted somatostatin ligand pasireotide 3) medical treatments currently under clinical investigation (oral octreotide, ITF2984, ATL1103), and 4) preliminary data on the use of new injectable and transdermal/transmucosal formulations of octreotide. This expert opinion supports the need for new therapeutic agents and modalities for patients with acromegaly.

  9. Marine natural products for multi-targeted cancer treatment: A future insight.

    PubMed

    Kumar, Maushmi S; Adki, Kaveri M

    2018-05-30

    Cancer is world's second largest alarming disease, which involves abnormal cell growth and have potential to spread to other parts of the body. Most of the available anticancer drugs are designed to act on specific targets by altering the activity of involved transporters and genes. As cancer cells exhibit complex cellular machinery, the regeneration of cancer tissues and chemo resistance towards the therapy has been the main obstacle in cancer treatment. This fact encourages the researchers to explore the multitargeted use of existing medicines to overcome the shortcomings of chemotherapy for alternative and safer treatment strategies. Recent developments in genomics-proteomics and an understanding of the molecular pharmacology of cancer have also challenged researchers to come up with target-based drugs. The literature supports the evidence of natural compounds exhibiting antioxidant, antimitotic, anti-inflammatory, antibiotic as well as anticancer activity. In this review, we have selected marine sponges as a prolific source of bioactive compounds which can be explored for their possible use in cancer and have tried to link their role in cancer pathway. To prove this, we revisited the literature for the selection of cancer genes for the multitargeted use of existing drugs and natural products. We used Cytoscape network analysis and Search tool for retrieval of interacting genes/ proteins (STRING) to study the possible interactions to show the links between the antioxidants, antibiotics, anti-inflammatory and antimitotic agents and their targets for their possible use in cancer. We included total 78 pathways, their genes and natural compounds from the above four pharmacological classes used in cancer treatment for multitargeted approach. Based on the Cytoscape network analysis results, we shortlist 22 genes based on their average shortest path length connecting one node to all other nodes in a network. These selected genes are CDKN2A, FH, VHL, STK11, SUFU, RB1

  10. KIFC1: a promising chemotherapy target for cancer treatment?

    PubMed

    Xiao, Yu-Xi; Yang, Wan-Xi

    2016-07-26

    The kinesin motor KIFC1 has been suggested as a potential chemotherapy target due to its critical role in clustering of the multiple centrosomes found in cancer cells. In this regard, KIFC1 seems to be non-essential in normal somatic cells which usually possess only two centrosomes. Moreover, KIFC1 is also found to initiatively drive tumor malignancy and metastasis by stabilizing a certain degree of genetic instability, delaying cell cycle and protecting cancer cell surviving signals. However, that KIFC1 also plays roles in other specific cell types complicates the question of whether it is a promising chemotherapy target for cancer treatment. For example, KIFC1 is found functionally significant in vesicular and organelle trafficking, spermiogenesis, oocyte development, embryo gestation and double-strand DNA transportation. In this review we summarize a recent collection of information so as to provide a generalized picture of ideas and mechanisms against and in favor of KIFC1 as a chemotherapy target. And we also drew the conclusion that KIFC1 is a promising chemotherapy target for some types of cancers, because the side-effects of inhibiting KIFC1 mentioned in this review are theoretically easy to avoid, while KIFC1 is functionally indispensable during mitosis and malignancy of multi-centrosome cancer cells. Further investigations of how KIFC1 is regulated throughout the mitosis in cancer cells are needed for the understanding of the pathways where KIFC1 is involved and for further exploitation of indirect KIFC1 inhibitors.

  11. Current siRNA Targets in the Prevention and Treatment of Intimal Hyperplasia

    PubMed Central

    Pradhan-Nabzdyk, Leena; Huang, Chenyu; LoGerfo, Frank W.; Nabzdyk, Christoph S.

    2014-01-01

    Intimal hyperplasia (IH) is the leading cause of late vein and prosthetic bypass graft failure. Injury at the time of graft implantation leading to the activation of endothelial cells and dedifferentiation of vascular smooth muscle cells to a synthetic phenotype are known causes of IH. Prior attempts to develop therapy to mitigate these cellular changes to prevent IH and graft failure have failed. Small interfering RNA (siRNA) mediated targeted gene silencing is a promising tool to prevent IH. Several studies have been performed in this direction to target genes that are involved in IH. In this review we discuss siRNA targets that are being investigated for prevention and treatment of IH. PMID:25227753

  12. A comparison of three different physiotherapy modalities used in the physiotherapy of burns.

    PubMed

    Sar, Zübeyir; Polat, Mine Gülden; Özgül, Bahar; Aydoğdu, Onur; Camcoğlu, Burcu; Acar, Ahmet Hakan; Yurdalan, Saadet Ufuk

    2013-01-01

    The present study compared the effectiveness of matrix rhythm therapy, ultrasound treatment (UT), laser treatment (LT) used in the physiotherapy of burns. The study was conducted at the Wound and Burn Healing Center, Dr. Lütfi Kırdar Kartal Education and Research Hospital (Turkey) from June 2009 to January 2012. The case series comprised 39 individuals with second- and third-degree upper-limb burns, whose burn traumas ended approximately 1 to 3 months previously. Participants were separated into three groups: matrix rhythm treatment (MRT), UT and LT; each group was also applied a treatment protocol including whirlpool and exercise. Pain, range of motion (ROM), muscular strength, skin elasticity, and sensory functions were evaluated before and after the treatment. Pressure sense and passive ROM were higher in the MRT group than in the LT group (P < .05). Pain was lower in the LT group than in the UT group, and passive ROM was higher in the UT group than the in LT group (P < .05). Active ROM was found to increase in all treatment groups, whereas passive ROM increased only in the MRT and UT groups; pressure sense increased only in the MRT group, and pain decreased only in the LT group (P < .05). MRT was found to be more effective in the restoration of sensory functions than LT, whereas LT was more effective in reducing pain than UT. No significant difference was observed in terms of skin elasticity according to the results of three treatment modalities. It is suggested that further research with more cases should be conducted to examine the long-term effect of treatment modalities.

  13. Dual-modality imaging of function and physiology

    NASA Astrophysics Data System (ADS)

    Hasegawa, Bruce H.; Iwata, Koji; Wong, Kenneth H.; Wu, Max C.; Da Silva, Angela; Tang, Hamilton R.; Barber, William C.; Hwang, Andrew B.; Sakdinawat, Anne E.

    2002-04-01

    Dual-modality imaging is a technique where computed tomography or magnetic resonance imaging is combined with positron emission tomography or single-photon computed tomography to acquire structural and functional images with an integrated system. The data are acquired during a single procedure with the patient on a table viewed by both detectors to facilitate correlation between the structural and function images. The resulting data can be useful for localization for more specific diagnosis of disease. In addition, the anatomical information can be used to compensate the correlated radionuclide data for physical perturbations such as photon attenuation, scatter radiation, and partial volume errors. Thus, dual-modality imaging provides a priori information that can be used to improve both the visual quality and the quantitative accuracy of the radionuclide images. Dual-modality imaging systems also are being developed for biological research that involves small animals. The small-animal dual-modality systems offer advantages for measurements that currently are performed invasively using autoradiography and tissue sampling. By acquiring the required data noninvasively, dual-modality imaging has the potential to allow serial studies in a single animal, to perform measurements with fewer animals, and to improve the statistical quality of the data.

  14. Modal Filtering for Control of Flexible Aircraft

    NASA Technical Reports Server (NTRS)

    Suh, Peter M.; Mavris, Dimitri N.

    2013-01-01

    Modal regulators and deformation trackers are designed for an open-loop fluttering wing model. The regulators are designed with modal coordinate and accelerometer inputs respectively. The modal coordinates are estimated with simulated fiber optics. The robust stability of the closed-loop systems is compared in a structured singular-value vector analysis. Performance is evaluated and compared in a gust alleviation and flutter suppression simulation. For the same wing and flight condition two wing-shape-tracking control architectures are presented, which achieve deformation control at any point on the wing.

  15. Learning Across Senses: Cross-Modal Effects in Multisensory Statistical Learning

    PubMed Central

    Mitchel, Aaron D.; Weiss, Daniel J.

    2014-01-01

    It is currently unknown whether statistical learning is supported by modality-general or modality-specific mechanisms. One issue within this debate concerns the independence of learning in one modality from learning in other modalities. In the present study, the authors examined the extent to which statistical learning across modalities is independent by simultaneously presenting learners with auditory and visual streams. After establishing baseline rates of learning for each stream independently, they systematically varied the amount of audiovisual correspondence across 3 experiments. They found that learners were able to segment both streams successfully only when the boundaries of the audio and visual triplets were in alignment. This pattern of results suggests that learners are able to extract multiple statistical regularities across modalities provided that there is some degree of cross-modal coherence. They discuss the implications of their results in light of recent claims that multisensory statistical learning is guided by modality-independent mechanisms. PMID:21574745

  16. Output-only modal dynamic identification of frames by a refined FDD algorithm at seismic input and high damping

    NASA Astrophysics Data System (ADS)

    Pioldi, Fabio; Ferrari, Rosalba; Rizzi, Egidio

    2016-02-01

    The present paper deals with the seismic modal dynamic identification of frame structures by a refined Frequency Domain Decomposition (rFDD) algorithm, autonomously formulated and implemented within MATLAB. First, the output-only identification technique is outlined analytically and then employed to characterize all modal properties. Synthetic response signals generated prior to the dynamic identification are adopted as input channels, in view of assessing a necessary condition for the procedure's efficiency. Initially, the algorithm is verified on canonical input from random excitation. Then, modal identification has been attempted successfully at given seismic input, taken as base excitation, including both strong motion data and single and multiple input ground motions. Rather than different attempts investigating the role of seismic response signals in the Time Domain, this paper considers the identification analysis in the Frequency Domain. Results turn-out very much consistent with the target values, with quite limited errors in the modal estimates, including for the damping ratios, ranging from values in the order of 1% to 10%. Either seismic excitation and high values of damping, resulting critical also in case of well-spaced modes, shall not fulfill traditional FFD assumptions: this shows the consistency of the developed algorithm. Through original strategies and arrangements, the paper shows that a comprehensive rFDD modal dynamic identification of frames at seismic input is feasible, also at concomitant high damping.

  17. The effects of stimulus modality and task integrality: Predicting dual-task performance and workload from single-task levels

    NASA Technical Reports Server (NTRS)

    Hart, S. G.; Shively, R. J.; Vidulich, M. A.; Miller, R. C.

    1986-01-01

    The influence of stimulus modality and task difficulty on workload and performance was investigated. The goal was to quantify the cost (in terms of response time and experienced workload) incurred when essentially serial task components shared common elements (e.g., the response to one initiated the other) which could be accomplished in parallel. The experimental tasks were based on the Fittsberg paradigm; the solution to a SternBERG-type memory task determines which of two identical FITTS targets are acquired. Previous research suggested that such functionally integrated dual tasks are performed with substantially less workload and faster response times than would be predicted by suming single-task components when both are presented in the same stimulus modality (visual). The physical integration of task elements was varied (although their functional relationship remained the same) to determine whether dual-task facilitation would persist if task components were presented in different sensory modalities. Again, it was found that the cost of performing the two-stage task was considerably less than the sum of component single-task levels when both were presented visually. Less facilitation was found when task elements were presented in different sensory modalities. These results suggest the importance of distinguishing between concurrent tasks that complete for limited resources from those that beneficially share common resources when selecting the stimulus modalities for information displays.

  18. cRGD-installed docetaxel-loaded mertansine prodrug micelles: redox-triggered ratiometric dual drug release and targeted synergistic treatment of B16F10 melanoma

    NASA Astrophysics Data System (ADS)

    Zhong, Ping; Qiu, Min; Zhang, Jian; Sun, Huanli; Cheng, Ru; Deng, Chao; Meng, Fenghua; Zhong, Zhiyuan

    2017-07-01

    Combinatorial chemotherapy, which has emerged as a promising treatment modality for intractable cancers, is challenged by a lack of tumor-targeting, robust and ratiometric dual drug release systems. Here, docetaxel-loaded cRGD peptide-decorated redox-activable micellar mertansine prodrug (DTX-cRGD-MMP) was developed for targeted and synergistic treatment of B16F10 melanoma-bearing C57BL/6 mice. DTX-cRGD-MMP exhibited a small size of ca. 49 nm, high DTX and DM1 loading, low drug leakage under physiological conditions, with rapid release of both DTX and DM1 under a cytoplasmic reductive environment. Notably, MTT and flow cytometry assays showed that DTX-cRGD-MMP brought about a synergistic antitumor effect to B16F10 cancer cells, with a combination index of 0.37 and an IC50 over 3- and 13-fold lower than cRGD-MMP (w/o DTX) and DTX-cRGD-Ms (w/o DM1) controls, respectively. In vivo studies revealed that DTX-cRGD-MMP had a long circulation time and a markedly improved accumulation in the B16F10 tumor compared with the non-targeting DTX-MMP control (9.15 versus 3.13% ID/g at 12 h post-injection). Interestingly, mice treated with DTX-cRGD-MMP showed almost complete growth inhibition of B16F10 melanoma, with tumor inhibition efficacy following an order of DTX-cRGD-MMP > DTX-MMP (w/o cRGD) > cRGD-MMP (w/o DTX) > DTX-cRGD-Ms (w/o DM1) > free DTX. Consequently, DTX-cRGD-MMP significantly improved the survival rates of B16F10 melanoma-bearing mice. Importantly, DTX-cRGD-MMP caused little adverse effects as revealed by mice body weights and histological analyses. The combination of two mitotic inhibitors, DTX and DM1, appears to be an interesting approach for effective cancer therapy.

  19. Application of molecular targeted therapies in the treatment of head and neck squamous cell carcinoma.

    PubMed

    Kozakiewicz, Paulina; Grzybowska-Szatkowska, Ludmiła

    2018-05-01

    Despite the development of standard therapies, including surgery, radiotherapy and chemotherapy, survival rates for head and neck squamous cell carcinoma (HNSCC) have not changed significantly over the past three decades. Complete recovery is achieved in <50% of patients. The treatment of advanced HNSCC frequently requires multimodality therapy and involves significant toxicity. The promising, novel treatment option for patients with HNSCC is molecular-targeted therapies. The best known targeted therapies include: Epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab, panitumumab, zalutumumab and nimotuzumab), EGFR tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib, afatinib and dacomitinib), vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) or vascular endothelial growth factor receptor (VEGFR) inhibitors (sorafenib, sunitinib and vandetanib) and inhibitors of phosphatidylinositol 3-kinase/serine/threonine-specific protein kinase/mammalian target of rapamycin. There are also various inhibitors of other pathways and targets, which are promising and require evaluation in further studies.

  20. Investigative modalities in infectious keratitis.

    PubMed

    Gupta, Noopur; Tandon, Radhika

    2008-01-01

    Standard recommended guidelines for diagnosis of infectious keratitis do exist. Based on an extensive Medline literature search, the various investigative modalities available for aiding the diagnosis of microbial keratitis have been reviewed and described briefly. Preferred practice patterns have been outlined and the importance of routine pre-treatment cultures in the primary management of infectious keratitis has been highlighted. Corneal scraping, tear samples and corneal biopsy are few of the specimens needed to carry out the investigative procedures for diagnosis and for initiating therapy in cases of microbial keratitis. In bacterial, fungal and amoebic keratitis, microscopic examination of smears is essential for rapid diagnosis. Potassium hydroxide (KOH) wet mount, Gram's stain and Giemsa stain are widely used and are important for clinicians to start empirical therapy before microbial culture results are available. The usefulness of performing corneal cultures in all cases of suspected infectious keratitis has been well established. In cases of suspected viral keratitis, therapy can be initiated on clinical judgment alone. If a viral culture is needed, scrapings should directly be inoculated into the viral transport media. In vivo confocal microscopy is a useful adjunct to slit lamp bio-microscopy for supplementing diagnosis in most cases and establishing early diagnosis in many cases of non-responding fungal and amoebic keratitis. This is a non-invasive, high resolution technique which allows rapid detection of Acanthamoeba cysts and trophozoites and fungal hyphae in the cornea long before laboratory cultures give conclusive results. Other new modalities for detection of microbial keratitis include molecular diagnostic techniques like polymerase chain reaction, and genetic finger printing by pulsed field gel electrophoresis.