Effects of education on the progression of early- versus late-stage mild cognitive impairment.

PubMed

Ye, Byoung Seok; Seo, Sang Won; Cho, Hanna; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Back, Joung Hwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, Sangyun; Han, Seol-Heui; Lee, Jae-Hong; Cheong, Hae-Kwan; Na, Duk L

2013-04-01

Highly educated participants with normal cognition show lower incidence of Alzheimer's disease (AD) than poorly educated participants, whereas longitudinal studies involving AD have reported that higher education is associated with more rapid cognitive decline. We aimed to evaluate whether highly educated amnestic mild cognitive impairment (aMCI) participants show more rapid cognitive decline than those with lower levels of education. A total of 249 aMCI patients enrolled from 31 memory clinics using the standard assessment and diagnostic processes were followed with neuropsychological evaluation (duration 17.2 ± 8.8 months). According to baseline performances on memory tests, participants were divided into early-stage aMCI (-1.5 to -1.0 standard deviation (SD)) and late-stage aMCI (below -1.5 SD) groups. Risk of AD conversion and changes in neuropsychological performances according to the level of education were evaluated. Sixty-two patients converted to AD over a mean follow-up of 1.43 years. The risk of AD conversion was higher in late-stage aMCI than early-stage aMCI. Cox proportional hazard models showed that aMCI participants, and late-stage aMCI participants in particular, with higher levels of education had a higher risk of AD conversion than those with lower levels of education. Late-stage aMCI participants with higher education showed faster cognitive decline in language, memory, and Clinical Dementia Rating Sum of Boxes (CDR-SOB) scores. On the contrary, early-stage aMCI participants with higher education showed slower cognitive decline in MMSE and CDR-SOB scores. Our findings suggest that the protective effects of education against cognitive decline remain in early-stage aMCI and disappear in late-stage aMCI.

Minimally invasive transcanal myringotomy for pediatric early stage congenital cholesteatoma.

PubMed

Jang, Chul Ho; Jung, Eun Kyung; Sung, Chung Man; Kim, Seung Beom; Kim, Young Yoon; Seong, Jong Yuap; Kang, Sung Hoon; Cho, Yong Beom

2016-11-01

Recently, minimally invasive transcanal myringotomy (MITM), which is a useful surgical technique for early stage congenital cholesteatoma (CC) in children, was introduced. The purpose of this study is to evaluate the short-term surgical results of MITM in pediatric early stage CC. We retrospectively reviewed the charts of 24 patients who underwent MITM between January 2013 and October 2015. The patients' ages ranged from 1 to 16 years (mean, 2.6 years). There were 17 male and 7 female patients. The right side (n = 13) was affected twice as often as the left side (n = 11). The most common site was the anterosuperior quadrant (15 cases). The diameter of the CC on axial computed tomography images ranged from 2.8 to 5.7 mm (mean, 3.9 mm). CCs were graded according to Potsic's system: 18 cases were classified as stage I, 3 case as stage II, and 3 cases as stage III. AllCCs except 1 were closed type. In21 patients, the tympanic membrane closed naturally without recurrence. Three patients showed small persistent dry perforation. Natural closure occurred in these patients, who were treated with paper patches. MITM is a simple, effective technique for removing an early stage CC from the middle ear, and it can minimize operative time, length of hospitalization, and postoperative morbidity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Early-stage valuation of medical devices: the role of developmental uncertainty.

PubMed

Girling, Alan; Young, Terry; Brown, Celia; Lilford, Richard

2010-08-01

At the concept stage, many uncertainties surround the commercial viability of a new medical device. These include the ultimate functionality of the device, the cost of producing it and whether, and at what price, it can be sold to a health-care provider (HCP). Simple assessments of value can be made by estimating such unknowns, but the levels of uncertainty may mean that their operational value for investment decisions is unclear. However, many decisions taken at the concept stage are reversible and will be reconsidered later before the product is brought to market. This flexibility can be exploited to enhance early-stage valuations. To develop a framework for valuing a new medical device at the concept stage that balances benefit to the HCP against commercial costs. This is done within a simplified stage-gated model of the development cycle for new products. The approach is intended to complement existing proposals for the evaluation of the commercial headroom available to new medical products. A model based on two decision gates can lead to lower bounds (underestimates) for product value that can serve to support a decision to develop the product. Quantifiable uncertainty that can be resolved before the device is brought to market will generally enhance early-stage valuations of the device, and this remains true even when some components of uncertainty cannot be fully described. Clinical trials and other evidence-gathering activities undertaken as part of the development process can contribute to early-stage estimates of value.

PTT functional recovery in early stage II PTTD after tendon balancing and calcaneal lengthening osteotomy.

PubMed

Brilhault, Jean; Noël, Vincent

2012-10-01

The decision to offer surgery for Stage II posterior tibial tendon deficiency (PTTD) is a difficult one since orthotic treatment has been documented to be a viable alternative to surgery at this stage. Taking this into consideration we limited our treatment to bony realignment by a lengthening calcaneus Evans osteotomy and tendon balancing. The goal of the study was to clinically evaluate PTT functional recovery with this procedure. The patient population included 17 feet in 13 patients. Inclusion was limited to early Stage II PTTD flatfeet with grossly intact but deficient PTT. Deficiency was assessed by the lack of hindfoot inversion during single heel rise test. The surgical procedure included an Evans calcaneal opening wedge osteotomy with triceps surae and peroneus brevis tendon lengthening. PTT function at follow up was evaluated by an independent examiner. Evaluation was performed at an average of 4 (range, 2 to 6.3) years. One case presented postoperative subtalar pain that required subtalar fusion. Every foot could perform a single heel rise with 13 feet having active inversion of the hindfoot during elevation. The results of this study provide evidence of PTT functional recovery without augmentation in early Stage II. It challenges our understanding of early Stage II PTTD as well as the surgical guidelines recommending PTT augmentation at this specific stage.

Evaluating Indicators and Life Cycle Inventories for Processes in Early Stages of Technical Readiness

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

Tan, Eric C; Smith, Raymond; Ruiz-Mercado, Gerardo

This presentation examines different methods for analyzing manufacturing processes in the early stages of technical readiness. Before developers know much detail about their processes, it is valuable to apply various assessments to evaluate their performance. One type of assessment evaluates performance indicators to describe how closely processes approach desirable objectives. Another type of assessment determines the life cycle inventories (LCI) of inputs and outputs for processes, where for a functional unit of product, the user evaluates the resources used and the releases to the environment. These results can be compared to similar processes or combined with the LCI of othermore » processes to examine up-and down-stream chemicals. The inventory also provides a listing of the up-stream chemicals, which permits study of the whole life cycle. Performance indicators are evaluated in this presentation with the U.S. Environmental Protection Agency's GREENSCOPE (Gauging Reaction Effectiveness for ENvironmental Sustainability with a multi-Objective Process Evaluator) methodology, which evaluates processes in four areas: Environment, Energy, Economics, and Efficiency. The method develops relative scores for indicators that allow comparisons across various technologies. In this contribution, two conversion pathways for producing cellulosic ethanol from biomass, via thermochemical and biochemical routes, are studied. The information developed from the indicators and LCI can be used to inform the process design and the potential life cycle effects of up- and down-stream chemicals.« less

Confidence interval estimation of the difference between two sensitivities to the early disease stage.

PubMed

Dong, Tuochuan; Kang, Le; Hutson, Alan; Xiong, Chengjie; Tian, Lili

2014-03-01

Although most of the statistical methods for diagnostic studies focus on disease processes with binary disease status, many diseases can be naturally classified into three ordinal diagnostic categories, that is normal, early stage, and fully diseased. For such diseases, the volume under the ROC surface (VUS) is the most commonly used index of diagnostic accuracy. Because the early disease stage is most likely the optimal time window for therapeutic intervention, the sensitivity to the early diseased stage has been suggested as another diagnostic measure. For the purpose of comparing the diagnostic abilities on early disease detection between two markers, it is of interest to estimate the confidence interval of the difference between sensitivities to the early diseased stage. In this paper, we present both parametric and non-parametric methods for this purpose. An extensive simulation study is carried out for a variety of settings for the purpose of evaluating and comparing the performance of the proposed methods. A real example of Alzheimer's disease (AD) is analyzed using the proposed approaches. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Psychometric evaluation of a new instrument to measure disease self-management of the early stage chronic kidney disease patients.

PubMed

Lin, Chiu-Chu; Wu, Chia-Chen; Wu, Li-Min; Chen, Hsing-Mei; Chang, Shu-Chen

2013-04-01

This study aims to develop a valid and reliable chronic kidney disease self-management instrument (CKD-SM) for assessing early stage chronic kidney disease patients' self-management behaviours. Enhancing early stage chronic kidney disease patients' self-management plays a key role in delaying the progression of chronic kidney disease. Healthcare provider understanding of early stage chronic kidney disease patients' self-management behaviours can help develop effective interventions. A valid and reliable instrument for measuring chronic kidney disease patients' self-management behaviours is needed. A cross-sectional descriptive study collected data for principal components analysis with oblique rotation. Mandarin- or Taiwanese-speaking adults with chronic kidney disease (n=252) from two medical centres and one regional hospital in Southern Taiwan completed the CKD-SM. Construct validity was evaluated by exploratory factor analysis. Internal consistency and test-retest reliability were estimated by Cronbach's alpha and Pearson correlation coefficients. Four factors were extracted and labelled self-integration, problem-solving, seeking social support and adherence to recommended regimen. The four factors accounted for 60.51% of the total variance. Each factor showed acceptable internal reliability with Cronbach's alpha from 0.77-0.92. The test-retest correlations for the CKD-SM was 0.72. The psychometric quality of the CKD-SM instrument was satisfactory. Research to conduct a confirmatory factor analysis to further validate this new instrument's construct validity is recommended. The CKD-SM instrument is useful for clinicians who wish to identify the problems with self-management among chronic kidney disease patients early. Self-management assessment will be helpful to develop intervention tailored to the needs of the chronic kidney disease population. © 2013 Blackwell Publishing Ltd.

76 FR 81430 - Small Business Investment Companies-Early Stage SBICs; Public Webinars

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... SMALL BUSINESS ADMINISTRATION 13 CFR Part 107 Small Business Investment Companies--Early Stage... Webinars regarding its proposed Early Stage Small Business Investment Companies (Early Stage SBIC) rule. The proposed Early Stage SBIC rule defines a new sub-category of small business investment companies...

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

Early stages of soldering reactions

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

Lord, R.A.; Umantsev, A.

2005-09-15

An experiment on the early stages of intermetallic compound layer growth during soldering and its theoretical analysis were conducted with the intent to study the controlling factors of the process. An experimental technique based on fast dipping and pulling of a copper coupon in liquid solder followed by optical microscopy allowed the authors to study the temporal behavior of the sample on a single micrograph. The technique should be of value for different areas of metallurgy because many experiments on crystallization may be described as the growth of a layer of intermediate phase. Comparison of the experimental results with themore » theoretical calculations allowed one to identify the kinetics of dissolution as the rate-controlling mechanism on the early stages and measure the kinetic coefficient of dissolution. A popular model of intermetallic compound layer structure coarsening is discussed.« less

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

PubMed

Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

2018-05-02

EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Couple-Focused Group Intervention for Women With Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon L.; Ostroff, Jamie S.; Winkel, Gary; Fox, Kevin; Grana, Generosa; Miller, Eric; Ross, Stephanie; Frazier, Thomas

2005-01-01

This study examined the efficacy of a couple-focused group intervention on psychological adaptation of women with early stage breast cancer and evaluated whether perceived partner unsupportive behavior or patient functional impairment moderated intervention effects. Two hundred thirty-eight women were randomly assigned to receive either 6 sessions…

Apply radiomics approach for early stage prognostic evaluation of ovarian cancer patients: a preliminary study

NASA Astrophysics Data System (ADS)

Danala, Gopichandh; Wang, Yunzhi; Thai, Theresa; Gunderson, Camille; Moxley, Katherine; Moore, Kathleen; Mannel, Robert; Liu, Hong; Zheng, Bin; Qiu, Yuchen

2017-03-01

Predicting metastatic tumor response to chemotherapy at early stage is critically important for improving efficacy of clinical trials of testing new chemotherapy drugs. However, using current response evaluation criteria in solid tumors (RECIST) guidelines only yields a limited accuracy to predict tumor response. In order to address this clinical challenge, we applied Radiomics approach to develop a new quantitative image analysis scheme, aiming to accurately assess the tumor response to new chemotherapy treatment, for the advanced ovarian cancer patients. During the experiment, a retrospective dataset containing 57 patients was assembled, each of which has two sets of CT images: pre-therapy and 4-6 week follow up CT images. A Radiomics based image analysis scheme was then applied on these images, which is composed of three steps. First, the tumors depicted on the CT images were segmented by a hybrid tumor segmentation scheme. Then, a total of 115 features were computed from the segmented tumors, which can be grouped as 1) volume based features; 2) density based features; and 3) wavelet features. Finally, an optimal feature cluster was selected based on the single feature performance and an equal-weighed fusion rule was applied to generate the final predicting score. The results demonstrated that the single feature achieved an area under the receiver operating characteristic curve (AUC) of 0.838+/-0.053. This investigation demonstrates that the Radiomic approach may have the potential in the development of high accuracy predicting model for early stage prognostic assessment of ovarian cancer patients.

Comparative evaluation of existing expendable upper stages for space shuttle

NASA Technical Reports Server (NTRS)

Weyers, V. J.; Sagerman, G. D.; Borsody, J.; Lubick, R. J.

1974-01-01

The use of existing expendable upper stages in the space shuttle during its early years of operation is evaluated. The Burner 2, Scout, Delta, Agena, Transtage, and Centaur were each studied under contract by their respective manufacturers to determine the extent and cost of the minimum modifications necessary to integrate the stage with the shuttle orbiter. A comparative economic analysis of thirty-five different families of these stages is discussed. Results show that the overall transportation system cost differences between many of the families are quite small. However, by considering several factors in addition to cost, it is possible to select one family as being representative of the capability of the minimum modification existing stage approach. The selected family meets all of the specified mission requirements during the early years of shuttle operation.

Chemical defense of early life stages of benthic marine invertebrates.

PubMed

Lindquist, Niels

2002-10-01

Accurate knowledge of factors affecting the survival of early life stages of marine invertebrates is critically important for understanding their population dynamics and the evolution of their diverse reproductive and life-history characteristics. Chemical defense is an important determinant of survival for adult stages of many sessile benthic invertebrates, yet relatively little consideration has been given to chemical defenses at the early life stages. This review examines the taxonomic breadth of early life-stage chemical defense in relation to various life-history and reproductive characteristics, as well as possible constraints on the expression of chemical defense at certain life stages. Data on the localization of defensive secondary metabolites in larvae and the fitness-related consequences of consuming even a small amount of toxic secondary metabolites underpin proposals regarding the potential for Müllerian and Batesian mimicry to occur among marine larvae. The involvement of microbial symbionts in the chemical defense of early life stages illustrates its complexity for some species. As our knowledge of chemical defenses in early life stages grows, we will be able to more rigorously examine connections among phylogeny, chemical defenses, and the evolution of reproductive and life-history characteristics among marine invertebrates.

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Evaluation of the therapeutic effect of potassium permanganate at early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus)

USDA-ARS?s Scientific Manuscript database

The efficacy of potassium permanganate (KMnO4) against early stages of an experimental acute infection of Flavobacterium columnare in channel catfish (Ictalurus punctatus) was evaluated. Fish were experimentally challenged, by waterborne exposure for 2 h to F. columnare after cutaneous abrasion, an...

Spiritual Diversity and Living with Early-Stage Dementia.

PubMed

McGee, Jocelyn Shealy; Zhao, Holly Carlson; Myers, Dennis R; Seela Eaton, Hannah

2018-01-01

Attention to spiritual diversity is necessary for the provision of culturally informed clinical care for people with early-stage dementia and their family members. In this article, an evidence-based theoretical framework for conceptualizing spiritual diversity is described in detail (Pargament, 2011). The framework is then applied to two clinical case studies of people living with early-stage dementia to elucidate the multilayered components of spiritual diversity in this population. The case studies were selected from a larger mixed-methods study on spirituality, positive psychological factors, health, and well-being in people living with early-stage dementia and their family members. To our knowledge this is the first systematic attempt to apply a theoretical framework for understanding spiritual diversity in this population. Implications for clinical practice are provided.

Selection is stronger in early-versus-late stages of divergence in a Neotropical livebearing fish.

PubMed

Ingley, Spencer J; Johnson, Jerald B

2016-03-01

How selection acts to drive trait evolution at different stages of divergence is of fundamental importance in our understanding of the origins of biodiversity. Yet, most studies have focused on a single point along an evolutionary trajectory. Here, we provide a case study evaluating the strength of divergent selection acting on life-history traits at early-versus-late stages of divergence in Brachyrhaphis fishes. We find that the difference in selection is stronger in the early-diverged population than the late-diverged population, and that trait differences acquired early are maintained over time. © 2016 The Author(s).

Occurrence of lymph node metastasis in early-stage parotid gland cancer.

PubMed

Stenner, Markus; Molls, Christoph; Luers, Jan C; Beutner, Dirk; Klussmann, Jens P; Huettenbrink, Karl-Bernd

2012-02-01

Lymph node metastasis is one of the most important factors in therapy and prognosis for patients with parotid gland cancer. Nevertheless, the extent of the primary tumor resection and the necessity of a neck dissection still is a common issue. Since little is known about lymph node metastasis in early-stage parotid gland cancer, the purpose of the present study was to evaluate the occurrence of lymph node metastases in T1 and T2 carcinomas and its impact on local control and survival. We retrospectively analyzed 70 patients with early-stage (T1 and T2) primary parotid gland cancer. All patients were treated with parotidectomy and an ipsilateral neck dissection from 1987 to 2009. Clinicopathological and survival parameters were calculated. The median follow-up time was 51.7 months. A positive pathological lymph node stage (pN+) was found in 21.4% of patients with a significant correlation to the clinical lymph node stage (cN) (p = 0.061). There were no differences in the clinical and histopathological data between pN- and pN+ patients. In 73.3% of pN+ patients, the metastases were located intraparotideal. The incidence of occult metastases (pN+/cN-) was 17.2%. Of all patients with occult metastases, 30.0% had extraparotideal lymphatic spread. A positive lymph node stage significantly indicated a poorer 5-year overall as well as 5-year disease-free survival rate compared to pN- patients (p = 0.048; p = 0.011). We propose total parotidectomy in combination with at least a level II-III selective neck dissection in any case of early-stage parotid gland cancer.

Swimming speed alteration in the early developmental stages of Paracentrotus lividus sea urchin as ecotoxicological endpoint.

PubMed

Morgana, Silvia; Gambardella, Chiara; Falugi, Carla; Pronzato, Roberto; Garaventa, Francesca; Faimali, Marco

2016-04-01

Behavioral endpoints have been used for decades to assess chemical impacts at concentrations unlikely to cause mortality. With recently developed techniques, it is possible to investigate the swimming behavior of several organisms under laboratory conditions. The aims of this study were: i) assessing for the first time the feasibility of swimming speed analysis of the early developmental stage sea urchin Paracentrotus lividus by an automatic recording system ii) investigating any Swimming Speed Alteration (SSA) on P. lividus early stages exposed to a chemical reference; iii) identifying the most suitable stage for SSA test. Results show that the swimming speed of all the developmental stages was easily recorded. The swimming speed was inhibited as a function of toxicant concentration. Pluteus were the most appropriate stage for evaluating SSA in P. lividus as ecotoxicological endpoint. Finally, swimming of sea urchin early stages represents a sensitive endpoint to be considered in ecotoxicological investigations. Copyright © 2016 Elsevier Ltd. All rights reserved.

76 FR 76907 - Small Business Investment Companies-Early Stage SBICs

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-09

... respect to geographic location. SBA's primary concern in terms of geography is to ensure that the Early... SBICs is the primary source of cash used to service their SBA debt. SBA expects that some Early Stage...--Early Stage SBICs AGENCY: U.S. Small Business Administration. ACTION: Proposed rule. SUMMARY: In this...

Treatment of Early-stage Extracranial Arteriovenous Malformations with Intralesional Interstitial Bleomycin Injection: A Pilot Study.

PubMed

Jin, Yunbo; Zou, Yun; Hua, Chen; Chen, Hui; Yang, Xi; Ma, Gang; Chang, Lei; Qiu, Yajing; Lyu, Dongze; Wang, Tianyou; Chang, Shih-Jen; Qiao, Congzhen; Luo, Chunfen; Tremp, Mathias; Lin, Xiaoxi

2018-04-01

Purpose To assess the efficacy and safety of intralesional interstitial bleomycin injection in the treatment of early-stage (Schobinger stage I or II) extracranial arteriovenous malformations (AVMs). Materials and Methods This prospective study involved 34 patients with early-stage AVMs, as defined by the Schobinger staging system. The patients received intralesional interstitial bleomycin injected at a maximum dose of 15 000 IU or 1000 IU per kilogram of body weight for children who weighed less than 15 kg per procedure for a total of 6 months (once every month). Therapeutic outcome was evaluated by the degree of devascularization at angiography and the clinical outcome 3 months after the last treatment. Further follow-up was evaluated based on further clinical outcome. Adverse events were recorded according to the Society of Interventional Radiology classification. Results Of the 34 patients with early-stage AVM, 32 (mean age, 20.5 years; 24 female [75%]) completed the study. The results showed that 27 (84.4%, 95% confidence interval [CI]: 71.1, 97.7) patients were responsive to bleomycin injection, including nine (28.1%) with a complete response. Four (12.5%) patients showed no response, and one (3.1%) patient experienced worsening 3 months after the last treatment. During further follow-up (mean follow-up time, 20.7 months; range, 5-28 months), the outcome remained stable in 31 (96.9%) of the 32 patients. A major complication, anaphylactic shock, was observed in one (3.1%, 95% CI: 0, 9.5) patient. Common minor complications included hyperpigmentation, nausea, pruritus, and bullae. Conclusion Intralesional interstitial bleomycin injection is a feasible approach for early-stage AVMs and yields safe and effective outcomes. © RSNA, 2017.

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

NASA Astrophysics Data System (ADS)

Viola, Kirsten L.; Sbarboro, James; Sureka, Ruchi; de, Mrinmoy; Bicca, Maíra A.; Wang, Jane; Vasavada, Shaleen; Satpathy, Sreyesh; Wu, Summer; Joshi, Hrushikesh; Velasco, Pauline T.; Macrenaris, Keith; Waters, E. Alex; Lu, Chang; Phan, Joseph; Lacor, Pascale; Prasad, Pottumarthi; Dravid, Vinayak P.; Klein, William L.

2015-01-01

One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.

Living with early-stage dementia: a review of qualitative studies.

PubMed

Steeman, Els; de Casterlé, Bernadette Dierckx; Godderis, Jan; Grypdonck, Mieke

2006-06-01

This paper presents a literature review whose aim was to provide better understanding of living with early-stage dementia. Even in the early stages, dementia may challenge quality of life. Research on early-stage dementia is mainly in the domain of biomedical aetiology and pathology, providing little understanding of what it means to live with dementia. Knowledge of the lived experience of having dementia is important in order to focus pro-active care towards enhancing quality of life. Qualitative research is fundamentally well suited to obtaining an insider's view of living with early-stage dementia. We performed a meta-synthesis of qualitative research findings. We searched MEDLINE, CINAHL, and PsycINFO and reviewed the papers cited in the references of pertinent articles, the references cited in a recently published book on the subjective experience of dementia, one thesis, and the journal Dementia. Thirty-three pertinent articles were identified, representing 28 separate studies and 21 different research samples. Findings were coded, grouped, compared and integrated. Living with dementia is described from the stage a person discovers the memory impairment, through the stage of being diagnosed with dementia, to that of the person's attempts to integrate the impairment into everyday life. Memory loss often threatens perceptions of security, autonomy and being a meaningful member of society. At early stages of memory loss, individuals use self-protecting and self-adjusting strategies to deal with perceived changes and threats. However, the memory impairment itself may make it difficult for an individual to deal with these changes, thereby causing frustration, uncertainty and fear. Our analysis supports the integration of proactive care into the diagnostic process, because even early-stage dementia may challenge quality of life. Moreover, this care should actively involve both the individual with dementia and their family so that both parties can adjust positively

Falls and Fall Prevention in Older Adults With Early-Stage Dementia: An Integrative Review.

PubMed

Lach, Helen W; Harrison, Barbara E; Phongphanngam, Sutthida

2017-05-01

Older adults with mild cognitive impairment (MCI) and early-stage dementia have an increased risk of falling, with risks to their health and quality of life. The purpose of the current integrative review was to evaluate evidence on fall risk and fall prevention in this population. Studies were included if they examined falls or fall risk factors in older adults with MCI or early-stage dementia, or reported interventions in this population; 40 studies met criteria. Evidence supports the increased risk of falls in individuals even in the early stages of dementia or MCI, and changes in gait, balance, and fear of falling that may be related to this increased fall risk. Interventions included exercise and multifactorial interventions that demonstrated some potential to reduce falls in this population. Few studies had strong designs to provide evidence for recommendations. Further study in this area is warranted. [Res Gerontol Nurs. 2017; 10(03):139-148.]. Copyright 2016, SLACK Incorporated.

Cognitive and Social Processes Predicting Partner Psychological Adaptation to Early Stage Breast Cancer

PubMed Central

Manne, Sharon; Ostroff, Jamie; Fox, Kevin; Grana, Generosa; Winkel, Gary

2009-01-01

Introduction The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners’ psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning-making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined. Materials and Methods Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner’s diagnosis (n= 253), nine (n = 167), and 18 months (n = 149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning-making, and general and cancer-specific distress at all time points. Results Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer-specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer-specific distress were found. Conclusions Results indicate several cognitive-social processes directly predict partner distress. However, moderator effect models in which the effects of partners’ processing depends upon whether these efforts result changes in perceptions of the cancer experience may add to the understanding of partners’ adaptation to cancer. PMID:18435865

Cognitive and social processes predicting partner psychological adaptation to early stage breast cancer.

PubMed

Manne, Sharon; Ostroff, Jamie; Fox, Kevin; Grana, Generosa; Winkel, Gary

2009-02-01

The diagnosis and subsequent treatment for early stage breast cancer is stressful for partners. Little is known about the role of cognitive and social processes predicting the longitudinal course of partners' psychosocial adaptation. This study evaluated the role of cognitive and social processing in partner psychological adaptation to early stage breast cancer, evaluating both main and moderator effect models. Moderating effects for meaning making, acceptance, and positive reappraisal on the predictive association of searching for meaning, emotional processing, and emotional expression on partner psychological distress were examined. Partners of women diagnosed with early stage breast cancer were evaluated shortly after the ill partner's diagnosis (N=253), 9 (N=167), and 18 months (N=149) later. Partners completed measures of emotional expression, emotional processing, acceptance, meaning making, and general and cancer-specific distress at all time points. Lower satisfaction with partner support predicted greater global distress, and greater use of positive reappraisal was associated with greater distress. The predicted moderator effects for found meaning on the associations between the search for meaning and cancer-specific distress were found and similar moderating effects for positive reappraisal on the associations between emotional expression and global distress and for acceptance on the association between emotional processing and cancer-specific distress were found. Results indicate several cognitive-social processes directly predict partner distress. However, moderator effect models in which the effects of partners' processing depends upon whether these efforts result in changes in perceptions of the cancer experience may add to the understanding of partners' adaptation to cancer.

Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows

EPA Science Inventory

Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows

EPA Science Inventory

Early-life stage fish can be more sensitive to chemical exposure than adult fish. Therefore, determining possible adverse outcome pathways (AOPs) for early-life stages is crucial. To determine chemical effects and/or mechanisms of action in exposed fish embryos and larvae, whole-...

Photons from the early stages of relativistic heavy-ion collisions

NASA Astrophysics Data System (ADS)

Oliva, L.; Ruggieri, M.; Plumari, S.; Scardina, F.; Peng, G. X.; Greco, V.

2017-07-01

We present results about photon-production in relativistic heavy-ion collisions. The main novelty of our study is the calculation of the contribution of the early-stage photons to the photon spectrum. The initial stage is modeled by an ensemble of classical gluon fields which decay to a quark-gluon plasma via the Schwinger mechanism, and the evolution of the system is studied by coupling classical field equations to relativistic kinetic theory; photon production is then computed by including the pertinent collision processes into the collision integral. We find that the contribution of the early-stage photons to the direct photon spectrum is substantial for pT≈2 GeV and higher, the exact value depending on the collision energy; therefore, we identify this part of the photon spectrum as the sign of the early stage. Moreover, the amount of photons produced during the early stage is not negligible with respect to those produced by a thermalized quark-gluon plasma: We support the idea that there is no dark age in relativistic heavy-ion collisions.

Urinary Biomarkers at Early ADPKD Disease Stage

PubMed Central

Petzold, Katja; Poster, Diane; Krauer, Fabienne; Spanaus, Katharina; Andreisek, Gustav; Nguyen-Kim, Thi Dan Linh; Pavik, Ivana; Ho, Thien Anh; Serra, Andreas L.; Rotar, Laura

2015-01-01

Background Autosomal dominant polycystic kidney disease (ADPKD) is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR) does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course. Methods ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), and Uromodulin (UMOD) were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16) was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR) was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV) was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results. Results In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2) the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found. Conclusion UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our

Involvement of reactive oxygen species during early stages of ectomycorrhiza establishment between Castanea sativa and Pisolithus tinctorius.

PubMed

Baptista, Paula; Martins, Anabela; Pais, Maria Salomé; Tavares, Rui M; Lino-Neto, Teresa

2007-05-01

Evidence for the participation of reactive oxygen species (ROS) and antioxidant systems in ectomycorrhizal (ECM) establishment is lacking. In this paper, we evaluated ROS production and the activities of superoxide dismutase (SOD) and catalase (CAT) during the early contact of the ECM fungus Pisolithus tinctorius with the roots of Castanea sativa (chestnut tree). Roots were placed in contact with P. tinctorius mycelia, and ROS production was evaluated by determining the levels of H(2)O(2) and O(2) (.-) during the early stages of fungal contact. Three peaks of H(2)O(2) production were detected, the first two coinciding with O(2) (.-) bursts. The first H(2)O(2) production peak coincided with an increase in SOD activity, whereas CAT activity seemed to be implicated in H(2)O(2) scavenging. P. tinctorius growth was evaluated in the presence of P. tinctorius-elicited C. sativa crude extracts prepared during the early stages of fungal contact. Differential hyphal growth that matched the H(2)O(2) production profile with a delay was detected. The result suggests that during the early stages of ECM establishment, H(2)O(2) results from an inhibition of ROS-scavenging enzymes and plays a role in signalling during symbiotic establishment.

Advancing Early Detection of Autism Spectrum Disorder by Applying an Integrated Two-Stage Screening Approach

ERIC Educational Resources Information Center

Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

2010-01-01

Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence…

Current developments in the treatment of early-stage classical Hodgkin lymphoma.

PubMed

Borchmann, Sven; von Tresckow, Bastian; Engert, Andreas

2016-09-01

After presenting the current treatment recommendations for early-stage Hodgkin lymphoma, we give an overview on recently published clinical trials in this setting. Furthermore, the potential influence of current trials on the treatment of early-stage Hodgkin lymphoma and integration of newly emerging drugs into treatment protocols will be discussed. Trials attempting treatment de-escalation and omission of radiotherapy on the basis of early interim PET-scans have been disappointing so far, but results of some large trials employing this strategy are still awaited. In contrast, a more defensive strategy of starting treatment with less aggressive doxorubicine, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy and intensifying treatment in early interim PET-positive patients has shown encouraging results. New drugs such as brentuximab vedotin and immune checkpoint inhibitors have shown promising results in relapsed and refractory Hodgkin lymphoma. Clinical trials of brentuximab vedotin in early-stage Hodgkin lymphoma have been initiated. Additionally, biomarker-based treatment de-escalation might be a possible route for future improvements. The challenge for future clinical research in early-stage Hodgkin lymphoma is to continue to cure the majority of patients with first-line treatment while reducing long-term toxicity. New strategies to achieve that goal are currently being developed and will further refine treatment of early-stage Hodgkin lymphoma.

Generic Difference Between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, Igor G.; Litvak, Maxim L.; Anfimov, Dimitrij S.; Sanin, Anton B.; Briggs, Michael S.; Paciesas, William S.; Pendleton, Geoffrey N.; Preece, Robert D.; Meegan, Charles A.

2001-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

General Differences between Early and Late Stages of BATSE Gamma-Ray Bursts

NASA Technical Reports Server (NTRS)

Mitrofanov, I. G.; Litvak, M. L.; Anfimov, D. S.; Sanin, A. B.; Briggs, M. S.; Paciesas, W. S.; Pendleton, G. N.; Preece, R. D.; Meegan, C. A.; Rose, M. Franklin (Technical Monitor)

2000-01-01

The early and late stages of gamma-ray bursts are studied in a statistical analysis of the large sample of long BATSE events. The primary peak is used as the boundary between the early and late stages of emission. Significant differences are found between the stages: the early stage is shorter, it has harder emission, and it becomes a smaller fraction of the total burst duration for burst groups of decreasing intensity.

Evaluation of the response of concurrent high dose rate intracavitary brachytherapy with external beam radiotherapy in management of early stage carcinoma cervix.

PubMed

Patidar, Arvind Kumar; Kumar, H S; Walke, Rahul V; Hirapara, Pushpendra H; Jakhar, Shankar Lal; Bardia, M R

2012-10-01

To evaluate local disease control and early complications of concomitant brachytherapy with external beam-radiotherapy in early stage carcinoma cervix. Fifty patients of early stage carcinoma cervix (FIGO-IB/IIA) were randomly divided into study group concomitant external beam irradiation (EBRT) and HDR-ICBT (intra-cavitary brachytherapy, xrt = 50 Gy/25 Fr, HDR 5.2 Gy*5 Fr) and the control group EBRT followed by HDR-ICBT (xrt = 50 Gy/25 Fr, HDR 7.5 Gy*3 Fr). Acute reactions and local disease response were compared between treatment and at 6-month follow up. Median overall treatment times were 38 and 61 days in the study and the control groups, respectively. Acute skin reactions and diarrhea were more in the study but manageable. At the completion of the study, there were 80 and 68 % complete responses, 16 and 20 % partial responses, 0 and 8 % stable diseases in the study group and the control group, respectively. Response was better in the study group but statistically insignificant. Larger number of patients and longer follow up are required to arrive at concrete conclusion.

Early infection risk with primary versus staged Hemodialysis Reliable Outflow (HeRO) graft implantation.

PubMed

Griffin, Andrew S; Gage, Shawn M; Lawson, Jeffrey H; Kim, Charles Y

2017-01-01

This study evaluated whether the use of a staged Hemodialysis Reliable Outflow (HeRO; Merit Medical, South Jordan, Utah) implantation strategy incurs increased early infection risk compared with conventional primary HeRO implantation. A retrospective review was performed of 192 hemodialysis patients who underwent HeRO graft implantation: 105 patients underwent primary HeRO implantation in the operating room, and 87 underwent a staged implantation where a previously inserted tunneled central venous catheter was used for guidewire access for the venous outflow component. Within the staged implantation group, 32 were performed via an existing tunneled hemodialysis catheter (incidentally staged), and 55 were performed via a tunneled catheter inserted across a central venous occlusion in an interventional radiology suite specifically for HeRO implantation (intentionally staged). Early infection was defined as episodes of bacteremia or HeRO infection requiring resection ≤30 days of HeRO implantation. For staged HeRO implantations, the median interval between tunneled catheter insertion and conversion to a HeRO graft was 42 days. The overall HeRO-related infection rate ≤30 days of implantation was 8.6% for primary HeRO implantation and 2.3% for staged implantations (P = .12). The rates of early bacteremia and HeRO resection requiring surgical resection were not significantly different between groups (P = .19 and P = .065, respectively), nor were age, gender, laterality, anastomosis to an existing arteriovenous access, human immunodeficiency virus status, diabetes, steroids, chemotherapy, body mass index, or graft location. None of the patient variables, techniques, or graft-related variables correlated significantly with the early infection rate. The staged HeRO implantation strategy did not result in an increased early infection risk compared with conventional primary implantation and is thus a reasonable strategy for HeRO insertion in hemodialysis patients

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2014-07-01 2014-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... the test solution concentrations. The test terminates following 60 days of post-hatch exposure (for an... 40 Protection of Environment 32 2011-07-01 2011-07-01 false Fish early life stage toxicity test... Fish early life stage toxicity test. (a) Purpose. This guideline is intended to be used for assessing...

Screening for Frailty in Older Patients With Early-Stage Solid Tumors: A Prospective Longitudinal Evaluation of Three Different Geriatric Tools.

PubMed

Biganzoli, Laura; Mislang, Anna Rachelle; Di Donato, Samantha; Becheri, Dimitri; Biagioni, Chiara; Vitale, Stefania; Sanna, Giuseppina; Zafarana, Elena; Gabellini, Stefano; Del Monte, Francesca; Mori, Elena; Pozzessere, Daniele; Brunello, Antonella; Luciani, Andrea; Laera, Letizia; Boni, Luca; Di Leo, Angelo; Mottino, Giuseppe

2017-07-01

Frailty increases the risk of adverse health outcomes and/or dying when exposed to a stressor, and routine frailty assessment is recommended to guide treatment decision. The Balducci frailty criteria (BFC) and Fried frailty criteria (FFC) are commonly used, but these are time consuming. Vulnerable Elders Survey-13 (VES-13) score of ≥7, a simple and resource conserving function-based scoring system, may be used instead. This prospective study evaluates the performance of VES-13 in parallel with BFC and FFC, to identify frailty in elderly patients with early-stage cancer. Patients aged ≥70 years with early-stage solid tumors were classified as frail/nonfrail based on BFC (≥1 criteria), FFC (≥3 criteria), and VES-13 (score ≥ 7). All patients were assessed for functional decline and death. We evaluated 185 patients. FFC had a 17% frailty rate, whereas BFC and VES-13 both had 25%, with poor concordance seen between the three geriatric tools. FFC (hazard ratio = 1.99, p = .003) and VES-13 (hazard ratio = 2.81, p < .001) strongly discriminated for functional decline, whereas BFC (hazard ratio = 3.29, p < .001) had the highest discriminatory rate for deaths. BFC and VES-13 remained prognostic for overall survival in multivariate analysis correcting for age, tumor type, stage, and systemic treatment. A VES-13 score of ≥7 is a valuable discriminating tool for predicting functional decline or death and can be used as a frailty-screening tool among older cancer patients in centers with limited resources to conduct a comprehensive geriatric assessment. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

PubMed Central

Butler, Pamela D.; Zemon, Vance; Schechter, Isaac; Saperstein, Alice M.; Hoptman, Matthew J.; Lim, Kelvin O.; Revheim, Nadine; Silipo, Gail; Javitt, Daniel C.

2005-01-01

Background Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-d-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. Objectives To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. Design, Setting, and Participants Between-group study at an inpatient state psychiatric hospital and out-patient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. Main Outcome Measures (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. Results Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P=.001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P=.001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P=.002), which was in turn related to deficits in complex visual processing (P≤.04). Both

Financial Implication of Radioactive Iodine Therapy for Early-Stage Papillary Thyroid Cancer.

PubMed

Al-Qurayshi, Zaid; Bu Ali, Daniah; Srivastav, Sudesh; Kandil, Emad

2017-01-01

The aim of this study was to evaluate disease-specific survival and cost related to radioactive iodine therapy (RAI) utilization in patients with early-stage papillary thyroid carcinoma (PTC). This was a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER) database, 2004-2012. A total of 38,374 patients with PTC were identified. Of those, 56.3% had adjuvant RAI. RAI administration was not associated with a survival advantage in patients with PTC stage I (hazard ratio [HR] 1.26, 95% confidence interval [CI] 0.11, 14.54; p = 0.85) or stage II (HR 0.50, 95% CI 0.05, 4.88; p = 0.55). Patients with PTC stage III who underwent adjuvant RAI had an improved survival (HR 0.30, 95% CI 0.10, 0.91; p = 0.033). In 2012, RAI was used in 45.5% of patients with stage I and in 71.4% of patients with stage II. The total expenditure on adjuvant RAI for PTC stage I throughout the study period was estimated to be USD 82.3 million with an annual average of USD 9.1 (±2.0) million/year. If the decline rate in the utilization of RAI continued, the model projected that the annual expenditure would decrease by USD 0.14 million/year. There is a high prevalence of adjuvant RAI utilization for early-stage PTC that is causing financial burden on the health system with no evidence of survival benefit. © 2017 S. Karger AG, Basel.

Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows (poster)

EPA Science Inventory

Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

A Four Stage Approach to Early Childhood Intervention.

ERIC Educational Resources Information Center

Haber, Julian S.

This paper describes a model for the involvement of primary health care personnel in the identification and treatment of developmental disabilities as a part of early childhood intervention programs. The integrated multidisciplinary model is divided into four stages. During the first stage an assignment of prenatal, perinatal, and postnatal risk…

The impact of early psychosocial intervention on self-efficacy of care recipient/carer dyads living with early stage dementia - A mixed methods study.

PubMed

Stockwell-Smith, G; Moyle, W; Kellett, U

2018-05-13

To evaluate the effect of a targeted community-based psychosocial intervention on self-efficacy outcomes for care recipient/carer dyads living with early-stage dementia. There is increasing interest in the role of self-efficacy and self-management structures in determining positive outcomes for people with dementia. The assumption is that care recipient/carer dyads who receive early support to identify and adjust to dementia related changes will cope better in the long-term. An explanatory sequential mixed-method design was employed. Primarily quantitative with qualitative data providing a supportive secondary role to expand on and illuminate the quantitative findings. 88 dyads were recruited and allocated on a regional basis to an intervention or control group. Intervention group dyads received the Early Diagnosis Dyadic Intervention. Control group dyads received two information manuals. Quantitative data were collected at three time-points. Qualitative data were collected via evaluation questionnaires and semi-structured interviews. Intervention structure, content and delivery were acceptable to the dyads but few quantitative self-efficacy findings reached statistical significance. Improvements in self-efficacy were evident in the post-intervention evaluation qualitative responses where dyads expressed greater confidence in identifying and accessing community support. There is an urgent need for effective psychosocial interventions to help reduce the impact of dementia symptoms on patients, carers and society. This study makes an important contribution to our understanding of the capacity of psychosocial interventions to improve self-efficacy outcomes for care recipient/carer dyads with early-stage dementia while also illustrating the challenges associated with measuring self-efficacy in the early stages of the condition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Notch and Delta mRNAs in early-stage and mid-stage Drosophila embryos exhibit complementary patterns of protein producing potentials

PubMed Central

Shepherd, Andrew; Wesley, Uma; Wesley, Cedric

2010-01-01

Notch and Delta proteins generate Notch signaling that specifies cell fates during animal development. There is an intriguing phenomenon in Drosophila embryogenesis that has not received much attention and whose significance to embryogenesis is unknown. Notch and Delta mRNAs expressed in early-stage embryos are shorter than their counterparts in mid-stage embryos. We show here that the difference in sizes is due to mRNA 3′ processing at alternate polyadenylation sites. While the early-stage Notch mRNA has a lower protein-producing potential than the mid-stage Notch mRNA, the early-stage Delta mRNA has a higher protein-producing potential than the mid-stage Delta mRNA. Our data can explain the complementary patterns of Notch and Delta protein levels in early-stage and mid-stage embryos. Our data also raise the possibility that the manner and regulation of Notch signaling change in the course of embryogenesis and that this change is effected by 3′ UTR and mRNA 3′ processing factors. PMID:20201103

Early stage sustainability evaluation of new, nanoscale cathode materials for Li-ion batteries.

PubMed

Hischier, Roland; Kwon, Nam Hee; Brog, Jean-Pierre; Fromm, Katharina M

2018-05-07

We present results of early stage sustainability evaluation of two development strategies for new, nano-scale cathode materials for Li-ion batteries: (i) a new production pathway of existing material (LiCoO2), and (ii) a new nanomaterial (LiMnPO4). Nano-LiCoO2 was synthesized via a single source precursor route at lower temperature with a shorter reaction time, resulting in a smaller grain size and, thereby, a better diffusivity for Li-ions. Nano-LiMnPO4 was synthesized via a wet chemical method. The sustainability potential of these materials has then been investigated (at the laboratory and pilot production scales). The results show that the environmental impact of nano-LiMnPO4 is lower compared to the other examined nanomaterial by several factors, and this regardless of the indicator for the comparison. In contrast to commercial cathode materials, this new material shows, particularly on an energy and capacity basis, results in the same order of magnitude as those of lithium manganese oxide (LiMn2O4), and only slightly higher values than those for lithium iron phosphate (LiFePO4); values that are clearly lower than those for high-temperature LiCoO2. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Economic evaluation of genomic test-directed chemotherapy for early-stage lymph node-positive breast cancer.

PubMed

Hall, Peter S; McCabe, Christopher; Stein, Robert C; Cameron, David

2012-01-04

Multi-parameter genomic tests identify patients with early-stage breast cancer who are likely to derive little benefit from adjuvant chemotherapy. These tests can potentially spare patients the morbidity from unnecessary chemotherapy and reduce costs. However, the costs of the test must be balanced against the health benefits and cost savings produced. This economic evaluation compared genomic test-directed chemotherapy using the Oncotype DX 21-gene assay with chemotherapy for all eligible patients with lymph node-positive, estrogen receptor-positive early-stage breast cancer. We performed a cost-utility analysis using a state transition model to calculate expected costs and benefits over the lifetime of a cohort of women with estrogen receptor-positive lymph node-positive breast cancer from a UK perspective. Recurrence rates for Oncotype DX-selected risk groups were derived from parametric survival models fitted to data from the Southwest Oncology Group 8814 trial. The primary outcome was the incremental cost-effectiveness ratio, expressed as the cost (in 2011 GBP) per quality-adjusted life-year (QALY). Confidence in the incremental cost-effectiveness ratio was expressed as a probability of cost-effectiveness and was calculated using Monte Carlo simulation. Model parameters were varied deterministically and probabilistically in sensitivity analysis. Value of information analysis was used to rank priorities for further research. The incremental cost-effectiveness ratio for Oncotype DX-directed chemotherapy using a recurrence score cutoff of 18 was £5529 (US $8852) per QALY. The probability that test-directed chemotherapy is cost-effective was 0.61 at a willingness-to-pay threshold of £30 000 per QALY. Results were sensitive to the recurrence rate, long-term anthracycline-related cardiac toxicity, quality of life, test cost, and the time horizon. The highest priority for further research identified by value of information analysis is the recurrence rate in test

Early stages of Ostwald ripening

NASA Astrophysics Data System (ADS)

Shneidman, Vitaly A.

2013-07-01

The Becker-Döring (BD) nucleation equation is known to predict a narrow double-exponential front (DEF) in the distribution of growing particles over sizes, which is due to early transient effects. When mass conservation is included, nucleation is eventually exhausted while independent growth is replaced by ripening. Despite the enormous difference in the associated time scales, and the resulting demand on numerics, within the generalized BD model the early DEF is shown to be crucial for the selection of the unique self-similar Lifshitz-Slyozov-Wagner asymptotic regime. Being preserved till the latest stages of growth, the DEF provides a universal part of the initial conditions for the ripening problem, regardless of the mass exchange mechanism between the nucleus and the matrix.

All-optical photoacoustic imaging and detection of early-stage dental caries

NASA Astrophysics Data System (ADS)

Sampathkumar, Ashwin; Hughes, David A.; Longbottom, Chris; Kirk, Katherine J.

2015-02-01

Dental caries remain one of the most common oral diseases in the world. Current detection methods, such as dental explorer and X-ray radiography, suffer from poor sensitivity and specificity at the earliest (and reversible) stages of the disease because of the small size (< 100 microns) of early-stage lesions. We have developed a fine-resolution (480 nm), ultra-broadband (1 GHz), all-optical photoacoustic imaging (AOPAI) system to image and detect early stages of tooth decay. This AOPAI system provides a non-contact, non-invasive and non-ionizing means of detecting early-stage dental caries. Ex-vivo teeth exhibiting early-stage, white-spot lesions were imaged using AOPAI. Experimental scans targeted each early-stage lesion and a reference healthy enamel region. Photoacoustic (PA) signals were generated in the tooth using a 532-nm pulsed laser and the light-induced broadband ultrasound signal was detected at the surface of the tooth with an optical path-stabilized Michelson interferometer operating at 532 nm. The measured time-domain signal was spatially resolved and back-projected to form 2D and 3D maps of the lesion using k-wave reconstruction methods. Experimental data collected from areas of healthy and diseased enamel indicate that the lesion generated a larger PA response compared to healthy enamel. The PA-signal amplitude alone was able to detect a lesion on the surface of the tooth. However, time- reversal reconstructions of the PA scans also quantitatively depicted the depth of the lesion. 3D PA reconstruction of the diseased tooth indicated a sub-surface lesion at a depth of 0.6 mm, in addition to the surface lesion. These results suggest that our AOPAI system is well suited for rapid clinical assessment of early-stage dental caries. An overview of the AOPAI system, fine-resolution PA and histology results of diseased and healthy teeth will be presented.

Efficient harvesting methods for early-stage snake and turtle embryos.

PubMed

Matsubara, Yoshiyuki; Kuroiwa, Atsushi; Suzuki, Takayuki

2016-04-01

Reptile development is an intriguing research target for understating the unique morphogenesis of reptiles as well as the evolution of vertebrates. However, there are numerous difficulties associated with studying development in reptiles. The number of available reptile eggs is usually quite limited. In addition, the reptile embryo is tightly adhered to the eggshell, making it a challenge to isolate reptile embryos intact. Furthermore, there have been few reports describing efficient procedures for isolating intact embryos especially prior to pharyngula stage. Thus, the aim of this review is to present efficient procedures for obtaining early-stage reptilian embryos intact. We first describe the method for isolating early-stage embryos of the Japanese striped snake. This is the first detailed method for obtaining embryos prior to oviposition in oviparous snake species. Second, we describe an efficient strategy for isolating early-stage embryos of the soft-shelled turtle. © 2016 Japanese Society of Developmental Biologists.

Subcortical grey matter changes in untreated, early stage Parkinson's disease without dementia.

PubMed

Lee, Hye Mi; Kwon, Kyum-Yil; Kim, Min-Jik; Jang, Ji-Wan; Suh, Sang-Il; Koh, Seong-Beom; Kim, Ji Hyun

2014-06-01

Previous MRI studies have investigated cortical or subcortical grey matter changes in patients with Parkinson's disease (PD), yielding inconsistent findings between the studies. We therefore sought to determine whether focal cortical or subcortical grey matter changes may be present from the early disease stage. We recruited 49 untreated, early stage PD patients without dementia and 53 control subjects. Voxel-based morphometry was used to evaluate cortical grey matter changes, and automated volumetry and shape analysis were used to assess volume changes and shape deformation of the subcortical grey matter structures, respectively. Voxel-based morphometry showed neither reductions nor increases in grey matter volume in patients compared to controls. Compared to controls, PD patients had significant reductions in adjusted volumes of putamen, nucleus accumbens, and hippocampus (corrected p < 0.05). Vertex-based shape analysis showed regionally contracted area on the posterolateral and ventromedial putamen bilaterally in PD patients (corrected p < 0.05). No correlations were found between cortical and subcortical grey matter and clinical variables representing disease duration and severity. Our results suggest that untreated, early stage PD without dementia is associated with volume reduction and shape deformation of subcortical grey matter, but not with cortical grey matter reduction. Our findings of structural changes in the posterolateral putamen and ventromedial putamen/nucleus accumbens could provide neuroanatomical basis for the involvement of motor and limbic striatum, further implicating motor and non-motor symptoms in PD, respectively. Early hippocampal involvement might be related to the risk for developing dementia in PD patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

Usability of tablet computers by people with early-stage dementia.

PubMed

Lim, Fabian S; Wallace, Tim; Luszcz, Mary A; Reynolds, Karen J

2013-01-01

Tablet computers are generally associated with an intuitive interface. The adoption and use of tablet computers within the early-stage dementia context could potentially assist in daily living and provide users with a source for leisure activities and social networking. As dementia mainly affects the older adult population, it is expected that many people with dementia and even their carers do not use tablet computers as part of their everyday living. This paper explores the usability of tablet computers within the early-stage dementia context as a source of leisure for people with dementia. The main advantage of the use of tablet computers in this manner is to provide carers some reprieve from the constant care and attention often required in caring for people with dementia. Seven-day in-home trials were conducted to determine whether people with early-stage dementia were -capable of using a tablet computer independently. Twenty-one people with early-stage dementia and carer dyads participated in the trial. Feedback was gathered through questionnaires from both the person with dementia and their carer regarding the use of a tablet computer as part of their everyday living. Approximately half the participants with dementia were able to engage with and use the tablet computer independently, which proved to be helpful to their carers. No significant traits were observed to help identify those who were less likely to use a tablet computer. Carer relief was quantified by the amount of time participants with dementia spent using the device without supervision. The results and feedback from the trial provide significant insights to introducing new technology within the early-stage dementia context. Users' needs must be considered on a case-by-case basis to successfully facilitate the uptake of tablet computers in the dementia context. The trial has provided sufficient justification to further explore more uses of tablet computers in the dementia context, and not just for

Update on the Treatment of Early-Stage Triple-Negative Breast Cancer.

PubMed

Sharma, Priyanka

2018-04-14

Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared to other breast cancer subtypes. Currently, chemotherapy remains the main modality of treatment for early-stage TNBC, as there is no approved targeted therapy for this subtype. The biologic heterogeneity of TNBC has hindered the development and evaluation of novel agents, but recent advancements in subclassifying TNBC have paved the way for further investigation of more effective systemic therapies, including cytotoxic and targeted agents. TNBC is enriched for germline BRCA mutation and for somatic deficiencies in homologous recombination DNA repair, the so-called "BRCAness" phenotype. Together, germline BRCA mutations and BRCAness are promising biomarkers of susceptibility to DNA-damaging therapy. Various investigational approaches are consequently being investigated in early-stage TNBC, including immune checkpoint inhibitors, platinum compounds, PI3K pathway inhibitors, and androgen receptor inhibitors. Due to the biological diversity found within TNBC, patient selection based on molecular biomarkers could aid the design of early-phase clinical trials, ultimately accelerating the clinical application of effective new agents. TNBC is an aggressive breast cancer subtype, for which multiple targeted approaches will likely be required for patient outcomes to be substantially improved.

Surgical Staging of Early Stage Endometrial Cancer: Comparison Between Laparotomy and Laparoscopy

PubMed Central

Api, Murat; Kayatas, Semra; Boza, Aysen Telce; Nazik, Hakan; Adiguzel, Cevdet; Guzin, Kadir; Eroglu, Mustafa

2013-01-01

Background The aim of the present study was to compare the laparotomy (LT) and laparoscopy (LS) in patients who undergone surgical staging for early stage endometrium cancer. Methods Retrospective data were collected and analyzed for amount of intraoperative bleeding, complication rates, total resected and laterality specific number of lymph nodes and duration of operation in patients operated with either LT or LS. Results Seventy-nine stage I endometrium cancer patients were found to be eligible for the trial purposes: 58 (73.4%) treated by LT and 21 (26.6%) treated by LS. The number of lymph nodes was similar in LT (8.9 ± 5.3) and LS (9.2 ± 4.8) (P = 0.8). In LT group, there was no difference in the number of lymph nodes between the right and left sides (10 ± 5.8 and 8.7 ± 4.8 respectively, P = 0.19); in LS group, the number of lymph nodes resected from the right side was higher than the left side (9.8 ± 5 and 7 ± 3.5 respectively, P = 0.039). The amount of intraoperative bleeding and hospitalization period were significantly higher in LT group. Seventy-nine patients had a median follow-up of 30 months. The two groups were similar for disease-free survival (P = 0.46, log rank test). Conclusions There was no significant difference between the two methods in terms of number of total resected lymph nodes. In early stage endometrial carcinoma, LS has provided adequate staging and similar survival rates with LT. PMID:29147363

High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides.

PubMed

de Masson, Adele; O'Malley, John T; Elco, Christopher P; Garcia, Sarah S; Divito, Sherrie J; Lowry, Elizabeth L; Tawa, Marianne; Fisher, David C; Devlin, Phillip M; Teague, Jessica E; Leboeuf, Nicole R; Kirsch, Ilan R; Robins, Harlan; Clark, Rachael A; Kupper, Thomas S

2018-05-09

Mycosis fungoides (MF), the most common cutaneous T cell lymphoma (CTCL) is a malignancy of skin-tropic memory T cells. Most MF cases present as early stage (stage I A/B, limited to the skin), and these patients typically have a chronic, indolent clinical course. However, a small subset of early-stage cases develop progressive and fatal disease. Because outcomes can be so different, early identification of this high-risk population is an urgent unmet clinical need. We evaluated the use of next-generation high-throughput DNA sequencing of the T cell receptor β gene ( TCRB ) in lesional skin biopsies to predict progression and survival in a discovery cohort of 208 patients with CTCL (177 with MF) from a 15-year longitudinal observational clinical study. We compared these data to the results in an independent validation cohort of 101 CTCL patients (87 with MF). The tumor clone frequency (TCF) in lesional skin, measured by high-throughput sequencing of the TCRB gene, was an independent prognostic factor of both progression-free and overall survival in patients with CTCL and MF in particular. In early-stage patients, a TCF of >25% in the skin was a stronger predictor of progression than any other established prognostic factor (stage IB versus IA, presence of plaques, high blood lactate dehydrogenase concentration, large-cell transformation, or age). The TCF therefore may accurately predict disease progression in early-stage MF. Early identification of patients at high risk for progression could help identify candidates who may benefit from allogeneic hematopoietic stem cell transplantation before their disease becomes treatment-refractory. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Role of Chemotherapy and Targeted Therapy in Early-Stage Non-Small Cell Lung Cancer.

PubMed

Gadgeel, Shirish M

2017-01-01

On the basis of several randomized trials and meta-analyses, adjuvant chemotherapy is the accepted standard of care for certain patients with early-stage non-small cell lung cancer (NSCLC). Patients with stage II, IIIA, or large (≥ 4 cm) IB tumors are candidates for adjuvant chemotherapy. The survival improvement with adjuvant chemotherapy is approximately 5% at 5 years, though certain trials have suggested that it can be 8% to 10%. Neoadjuvant chemotherapy also has shown a survival advantage, though the volume of data with this approach is far less than that of adjuvant chemotherapy. The combination of cisplatin and vinorelbine is the most well-studied regimen, but current consensus is to use four cycles of any of the platinum-based chemotherapy regimens commonly used as front-line therapy for patients with advanced-stage NSCLC. Trials to define biomarkers that can predict benefit from adjuvant chemotherapy have not been successful, but results of other such trials are still awaited. On the basis of the benefit observed with targeted agents in patients with advanced-stage disease and driver genetic alterations in their tumors, ongoing trials are evaluating the utility of these targeted agents as adjuvant therapy. Similarly, clinical benefit observed with checkpoint inhibitors has prompted assessment of these drugs in patients with early-stage NSCLC. It is very likely, in the future, that factors other than the anatomy of the tumor will be used to select patients with early-stage NSCLC for systemic therapy and that the choice of systemic therapy will extend beyond platinum-based chemotherapy.

DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c. PROGRAM...determine the copy number gain and loss for early stage high grade ovarian cancers through IlluminaHumanOmniExpress-FFPE BeadChip system • Subtask 1 DNA

Estimation of Wheat Plant Density at Early Stages Using High Resolution Imagery

PubMed Central

Liu, Shouyang; Baret, Fred; Andrieu, Bruno; Burger, Philippe; Hemmerlé, Matthieu

2017-01-01

Crop density is a key agronomical trait used to manage wheat crops and estimate yield. Visual counting of plants in the field is currently the most common method used. However, it is tedious and time consuming. The main objective of this work is to develop a machine vision based method to automate the density survey of wheat at early stages. RGB images taken with a high resolution RGB camera are classified to identify the green pixels corresponding to the plants. Crop rows are extracted and the connected components (objects) are identified. A neural network is then trained to estimate the number of plants in the objects using the object features. The method was evaluated over three experiments showing contrasted conditions with sowing densities ranging from 100 to 600 seeds⋅m-2. Results demonstrate that the density is accurately estimated with an average relative error of 12%. The pipeline developed here provides an efficient and accurate estimate of wheat plant density at early stages. PMID:28559901

Management of Early Stage, High-Risk Endometrial Carcinoma: Preoperative and Surgical Considerations

PubMed Central

Pettigrew, Gaetan

2013-01-01

Endometrial cancer is the most common gynecologic malignancy in the developed world. Most cases are diagnosed at an early stage and have low-grade histology, portending an overall excellent prognosis. There exists a subgroup of patients with early, high-risk disease, whose management remains controversial, as current data is clouded by inclusion of early stage tumors with different high-risk features for recurrence, unstandardized protocols for surgical staging, and an evolving staging system by which we are grouping these patients. Here, we present preoperative and intraoperative considerations that should be taken into account when planning surgical management for this population of patients. PMID:23878545

New application of 18F-fluoride PET for the detection of bone remodeling in early-stage osteoarthritis of the hip.

PubMed

Kobayashi, Naomi; Inaba, Yutaka; Tateishi, Ukihide; Yukizawa, Yohei; Ike, Hiroyuki; Inoue, Tomio; Saito, Tomoyuki

2013-10-01

Recent studies have reported the acceleration of subchondral bone remodeling during the development of osteoarthritis (OA). However, it is not possible to evaluate such molecular abnormalities using conventional radiographic techniques. We have applied 18F-fluoride PET to the analysis of painful or dysplastic hips at various stages of OA and then compared this with radiographic findings and clinical findings. A consecutive series of 65 joints from 48 patients (average age, 40 years; range, 19-72 years) with a hip joint complaint or radiographic dysplastic hip were enrolled in this study. Twenty-five contralateral joints without any evidence of OA or clinical symptoms were assigned as a normal control group. Radiographic evaluations were performed on the basis of Kellgren and Lawrence grade and the minimum joint space. Clinical evaluations were performed using the grading scale for pain severity and the SUVmax was measured for each joint. The association between SUVmax and the radiographic or clinical findings was evaluated. 18F-fluoride PET shows a significantly higher uptake value for progressive-stage OA cases than for early-stage cases and also shows a significantly higher uptake value in cases with severe pain. Even in early-OA-stage patients who do not show joint space narrowing on a plain x-ray, cases with severe pain show a significantly higher uptake value. 18F-fluoride PET has great potential as an imaging method for diagnosing early-stage OA without any marked radiographic changes.

Multimodal imaging findings in 'hyper-early' stage MEWDS.

PubMed

Cahuzac, Armelle; Wolff, Benjamin; Mathis, Thibaud; Errera, Marie-Hélène; Sahel, José-Alain; Mauget-Faÿsse, Martine

2017-10-01

To describe a new stage of multiple evanescent white dot syndrome (MEWDS), occurring at a very early phase of the disease. Retrospective analysis of clinical, angiographic and tomographic findings in four patients with 'hyper-early' stage MEWDS. In four patients seen within 1 week of the onset of symptoms, fundus analysis revealed macular granity and the classic yellow-white dots, some having no corresponding hyperautofluorescent pattern. Spectral-domain optical coherence tomography (SD-OCT) showed central foveal disruption of the ellipsoid zone (EZ) and interdigitation layer with a hyper-reflective dome-shaped lesion. In two patients, fluorescein angiography (FA) revealed an intermediate hypofluorescent perimacular halo, whereas late indocyanine green angiography (ICGA) showed a hyperfluorescent halo as well as the classic MEWDS features. After a few days, the EZ disruption appeared complete on OCT and fundus autofluorescence (FAF) in all patients. Visual acuity, OCT and FAF findings had fully recovered within 3 months. We have shown a new feature of MEWDS on FAF, OCT, FA and ICGA, corresponding to a very early stage of the disease. 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/.

Unraveling Mixed Hydrate Formation: Microscopic Insights into Early Stage Behavior.

PubMed

Hall, Kyle Wm; Zhang, Zhengcai; Kusalik, Peter G

2016-12-29

The molecular-level details of mixed hydrate nucleation remain unclear despite the broad implications of this process for a variety of scientific domains. Through analysis of mixed hydrate nucleation in a prototypical CH 4 /H 2 S/H 2 O system, we demonstrate that high-level kinetic similarities between mixed hydrate systems and corresponding pure hydrate systems are not a reliable basis for estimating the composition of early stage mixed hydrate nuclei. Moreover, we show that solution compositions prior to and during nucleation are not necessarily effective proxies for the composition of early stage mixed hydrate nuclei. Rather, microscopic details, (e.g., guest-host interactions and previously neglected cage types) apparently play key roles in determining early stage behavior of mixed hydrates. This work thus provides key foundational concepts and insights for understanding mixed hydrate nucleation.

Driving behaviors in early stage dementia: a study using in-vehicle technology.

PubMed

Eby, David W; Silverstein, Nina M; Molnar, Lisa J; LeBlanc, David; Adler, Geri

2012-11-01

According to the Alzheimer's Association (2011), (1) in 8 people age 65 and older, and about one-half of people age 85 and older, have Alzheimer's disease in the United States (US). There is evidence that drivers with Alzheimer's disease and related dementias are at an increased risk for unsafe driving. Recent advances in sensor, computer, and telecommunication technologies provide a method for automatically collecting detailed, objective information about the driving performance of drivers, including those with early stage dementia. The objective of this project was to use in-vehicle technology to describe a set of driving behaviors that may be common in individuals with early stage dementia (i.e., a diagnosis of memory loss) and compare these behaviors to a group of drivers without cognitive impairment. Seventeen drivers with a diagnosis of early stage dementia, who had completed a comprehensive driving assessment and were cleared to drive, participated in the study. Participants had their vehicles instrumented with a suite of sensors and a data acquisition system, and drove 1-2 months as they would under normal circumstances. Data from the in-vehicle instrumentation were reduced and analyzed, using a set of algorithms/heuristics developed by the research team. Data from the early stage dementia group were compared to similar data from an existing dataset of 26 older drivers without dementia. The early stage dementia group was found to have significantly restricted driving space relative to the comparison group. At the same time, the early stage dementia group (which had been previously cleared by an occupational therapist as safe to drive) drove as safely as the comparison group. Few safety-related behavioral errors were found for either group. Wayfinding problems were rare among both groups, but the early stage dementia group was significantly more likely to get lost. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of Early-Age Concrete Compressive Strength with Ultrasonic Sensors.

PubMed

Yoon, Hyejin; Kim, Young Jin; Kim, Hee Seok; Kang, Jun Won; Koh, Hyun-Moo

2017-08-07

Surface wave velocity measurement of concrete using ultrasonic sensors requires testing on only one side of a member. Thus, it is applicable to concrete cast inside a form and is often used to detect flaws and evaluate the compressive strength of hardened concrete. Predicting the in situ concrete strength at a very early stage inside the form helps with determining the appropriate form removal time and reducing construction time and costs. In this paper, the feasibility of using surface wave velocities to predict the strength of in situ concrete inside the form at a very early stage was evaluated. Ultrasonic sensors were used to measure a series of surface waves for concrete inside a form in the first 24 h after placement. A continuous wavelet transform was used to compute the travel time of the propagating surface waves. The cylindrical compressive strength and penetration resistance tests were also performed during the test period. Four mixtures and five curing temperatures were used for the specimens. The surface wave velocity was confirmed to be applicable to estimating the concrete strength at a very early age in wall-like elements. An empirical formula is proposed for evaluating the early-age compressive strength of concrete considering the 95% prediction intervals.

Evaluation of Early-Age Concrete Compressive Strength with Ultrasonic Sensors

PubMed Central

Yoon, Hyejin; Kim, Young Jin; Kim, Hee Seok; Kang, Jun Won; Koh, Hyun-Moo

2017-01-01

Surface wave velocity measurement of concrete using ultrasonic sensors requires testing on only one side of a member. Thus, it is applicable to concrete cast inside a form and is often used to detect flaws and evaluate the compressive strength of hardened concrete. Predicting the in situ concrete strength at a very early stage inside the form helps with determining the appropriate form removal time and reducing construction time and costs. In this paper, the feasibility of using surface wave velocities to predict the strength of in situ concrete inside the form at a very early stage was evaluated. Ultrasonic sensors were used to measure a series of surface waves for concrete inside a form in the first 24 h after placement. A continuous wavelet transform was used to compute the travel time of the propagating surface waves. The cylindrical compressive strength and penetration resistance tests were also performed during the test period. Four mixtures and five curing temperatures were used for the specimens. The surface wave velocity was confirmed to be applicable to estimating the concrete strength at a very early age in wall-like elements. An empirical formula is proposed for evaluating the early-age compressive strength of concrete considering the 95% prediction intervals. PMID:28783128

Stage is a prognostic factor for surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status has been implemented.

PubMed

Eskiizmir, G; Ozgur, E; Karaca, G; Temiz, P; Yanar, N Hacioglu; Ozyurt, B Cengiz

2017-10-01

To determine the locoregional control and survival rates (in terms of risk factors) of patients who underwent surgical resection of early-stage lip cancer and for whom a 'wait and see' policy in terms of neck status had been implemented. The sociodemographic data, tumour stage, tumour characteristics and histopathological features of 41 patients with early-stage lip cancer were evaluated. Factors predictive of survival and locoregional recurrence were analysed. The five-year overall survival and disease-free survival rates were determined, and the prognostic risk factors were compared. The mean follow-up period was 60.5 months (range, 4-92 months). Age, sex, tumour stage, tumour thickness and volume, and perineural involvement were not predictive of locoregional recurrence or survival. Pathological tumour stage (T1 vs T2) was a prognostic factor for both five-year overall survival (87.3 vs 65.6 per cent, p = 0.042) and disease-free survival (88.6 vs 65.6 per cent, p = 0.037). Tumour stage was clearly a major factor affecting the prognosis of surgically treated patients with early-stage lip cancer for whom a 'wait and see' policy in terms of neck status had been implemented.

Bioaccumulation of lipophilic substances in fish early life stages

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

Petersen, G.I.; Kristensen, P.

1998-07-01

Accumulation of {sup 14}C-labeled polycyclic aromatic hydrocarbons, naphthalene, phenanthrene, pyrene, and benzo(a)pyrene and polychlorinated biphenyl (PCB) congeners PCB 31 and PCB 105 with a log octanol/water partition coefficient (K{sub ow}) range from 3.37 to 6.5 was investigated in eggs and larvae of zebra fish (Brachydanio rerio), and in larvae of cod (Gadus morhua), herring (Clupea harengus), and turbot (Scophthalmus maximus). Significant differences in the uptake and elimination rate constants between eggs and larvae of zebra fish were seen. The low rate of uptake and the lower elimination rate of eggs did, however, lead to bioconcentration factors (BCFs) comparable to thosemore » for larvae. As biotransformation of xenobiotics in embryonic and larval stages was indicated to be insignificant compared to juvenile/adult stages, body burdens of readily biotransformed chemicals may be higher in fish early life stages. Because weight and lipid content did not differ much between the investigated species, the main reason for the variability in BCFs between marine species and freshwater species was considered to be caused by differences in exposure temperatures that affect the degree of biotransformation. Due to the smaller size of larvae and thus an increased total surface of the membranes per unit fish weight, steady-state conditions were reached at a faster r/ate in early life stages than in juvenile/adult life stages. The lipid-normalized bioconcentration factors (BCF{sub L}) were linearly related to K{sub ow} but BCF{sub L} was, in general, higher than K{sub ow}, indicating that octanol is not a suitable surrogate for fish lipids. Differences in bioconcentration kinetics between larvae and juvenile/adult life stages are considered to be the main reason for the higher sensitivity, with respect to external effect concentrations, generally obtained for early life stages of fish.« less

HMGCR inhibits the early stage of PCV2 infection, while PKC enhances the infection at the late stage.

PubMed

Ma, Teng; Chen, Xinrong; Ouyang, Hongsheng; Liu, Xiaohui; Ouyang, Ting; Peng, Zhiyuan; Yang, Xin; Chen, Fuwang; Pang, Daxin; Bai, Jieying; Ren, Linzhu

2017-02-02

Porcine circovirus type 2 (PCV2) is the smallest DNA virus, which causes porcine circovirus diseases and porcine circovirus-associated diseases (PCVD/PCVAD). Due the small size of viral genomic DNA, PCV2 replication predominantly relies on the host factors. In this study, effects of PKC and HMGCR on PCV2 infection were evaluated using real time PCR and western blot. We found that PKC and HMGCR participated in different stages of PCV2 infection. HMGCR works on the early stage of the infection to inhibit the virus infection, while PKC enhances the infection at the late stage. Furthermore, PKC enhances PCV2 replication by activating JNK1/2 and inactivating HMGCR via regulating phosphorylation of these two proteins, while HMGCR can suppress phosphorylation of JNK1/2. The results in the present study will provide new sights in the pathogenesis of PCV2 infection, as well as interactions between host factors during PCV2 infection. Copyright © 2016 Elsevier B.V. All rights reserved.

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | FNLCR Staging

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective. For some time, the national lab’s Nanotechno

Regional brain activity during early-stage intense romantic love predicted relationship outcomes after 40 months: an fMRI assessment.

PubMed

Xu, Xiaomeng; Brown, Lucy; Aron, Arthur; Cao, Guikang; Feng, Tingyong; Acevedo, Bianca; Weng, Xuchu

2012-09-20

Early-stage romantic love is associated with activation in reward and motivation systems of the brain. Can these localized activations, or others, predict long-term relationship stability? We contacted participants from a previous fMRI study of early-stage love by Xu et al. [34] after 40 months from initial assessments. We compared brain activation during the initial assessment at early-stage love for those who were still together at 40 months and those who were apart, and surveyed those still together about their relationship happiness and commitment at 40 months. Six participants who were still with their partners at 40 months (compared to six who had broken up) showed less activation during early-stage love in the medial orbitofrontal cortex, right subcallosal cingulate and right accumbens, regions implicated in long-term love and relationship satisfaction [1,2]. These regions of deactivation at the early stage of love were also negatively correlated with relationship happiness scores collected at 40 months. Other areas involved were the caudate tail, and temporal and parietal lobes. These data are preliminary evidence that neural responses in the early stages of romantic love can predict relationship stability and quality up to 40 months later in the relationship. The brain regions involved suggest that forebrain reward functions may be predictive for relationship stability, as well as regions involved in social evaluation, emotional regulation, and mood. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort

PubMed Central

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-01-01

Study Objectives: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Methods: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. Results: 8.2% of participants had mild CKD (stage 1–2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m2 with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30–60 mL/min/1.73 m2). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Conclusions: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. Citation: Ogna A, Forni Ogna V, Haba Rubio J, Tobback N, Andries D, Preisig M, Tafti M, Vollenweider P, Waeber G, Marques-Vidal P, Heinzer R. Sleep characteristics in early stages of chronic kidney disease in the HypnoLaus cohort. SLEEP 2016;39(4):945–953. PMID:26715230

10 CFR 51.50 - Environmental report-construction permit, early site permit, or combined license stage.

Code of Federal Regulations, 2011 CFR

2011-01-01

... costs of the proposed action or an evaluation of alternative energy sources. (3) For other than light... 10 Energy 2 2011-01-01 2011-01-01 false Environmental report-construction permit, early site permit, or combined license stage. 51.50 Section 51.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED...

10 CFR 51.50 - Environmental report-construction permit, early site permit, or combined license stage.

Code of Federal Regulations, 2013 CFR

2013-01-01

... costs of the proposed action or an evaluation of alternative energy sources. (3) For other than light... 10 Energy 2 2013-01-01 2013-01-01 false Environmental report-construction permit, early site permit, or combined license stage. 51.50 Section 51.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED...

10 CFR 51.50 - Environmental report-construction permit, early site permit, or combined license stage.

Code of Federal Regulations, 2010 CFR

2010-01-01

... costs of the proposed action or an evaluation of alternative energy sources. (3) For other than light... 10 Energy 2 2010-01-01 2010-01-01 false Environmental report-construction permit, early site permit, or combined license stage. 51.50 Section 51.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED...

10 CFR 51.50 - Environmental report-construction permit, early site permit, or combined license stage.

Code of Federal Regulations, 2014 CFR

2014-01-01

... costs of the proposed action or an evaluation of alternative energy sources. (3) For other than light... 10 Energy 2 2014-01-01 2014-01-01 false Environmental report-construction permit, early site permit, or combined license stage. 51.50 Section 51.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED...

10 CFR 51.50 - Environmental report-construction permit, early site permit, or combined license stage.

Code of Federal Regulations, 2012 CFR

2012-01-01

... costs of the proposed action or an evaluation of alternative energy sources. (3) For other than light... 10 Energy 2 2012-01-01 2012-01-01 false Environmental report-construction permit, early site permit, or combined license stage. 51.50 Section 51.50 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED...

Recurrence of Early Stage Colon Cancer Predicted by Expression Pattern of Circulating microRNAs

PubMed Central

Shivapurkar, Narayan; Weiner, Louis M.; Marshall, John L.; Madhavan, Subha; Deslattes Mays, Anne; Juhl, Hartmut; Wellstein, Anton

2014-01-01

Systemic treatment of patients with early-stage cancers attempts to eradicate occult metastatic disease to prevent recurrence and increased morbidity. However, prediction of recurrence from an analysis of the primary tumor is limited because disseminated cancer cells only represent a small subset of the primary lesion. Here we analyze the expression of circulating microRNAs (miRs) in serum obtained pre-surgically from patients with early stage colorectal cancers. Groups of five patients with and without disease recurrence were used to identify an informative panel of circulating miRs using quantitative PCR of genome-wide miR expression as well as a set of published candidate miRs. A panel of six informative miRs (miR-15a, mir-103, miR-148a, miR-320a, miR-451, miR-596) was derived from this analysis and evaluated in a separate validation set of thirty patients. Hierarchical clustering of the expression levels of these six circulating miRs and Kaplan-Meier analysis showed that the risk of disease recurrence of early stage colon cancer can be predicted by this panel of miRs that are measurable in the circulation at the time of diagnosis (P = 0.0026; Hazard Ratio 5.4; 95% CI of 1.9 to 15). PMID:24400111

The early stages of duplicate gene evolution

PubMed Central

Moore, Richard C.; Purugganan, Michael D.

2003-01-01

Gene duplications are one of the primary driving forces in the evolution of genomes and genetic systems. Gene duplicates account for 8–20% of the genes in eukaryotic genomes, and the rates of gene duplication are estimated at between 0.2% and 2% per gene per million years. Duplicate genes are believed to be a major mechanism for the establishment of new gene functions and the generation of evolutionary novelty, yet very little is known about the early stages of the evolution of duplicated gene pairs. It is unclear, for example, to what extent selection, rather than neutral genetic drift, drives the fixation and early evolution of duplicate loci. Analysis of recently duplicated genes in the Arabidopsis thaliana genome reveals significantly reduced species-wide levels of nucleotide polymorphisms in the progenitor and/or duplicate gene copies, suggesting that selective sweeps accompany the initial stages of the evolution of these duplicated gene pairs. Our results support recent theoretical work that indicates that fates of duplicate gene pairs may be determined in the initial phases of duplicate gene evolution and that positive selection plays a prominent role in the evolutionary dynamics of the very early histories of duplicate nuclear genes. PMID:14671323

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

PubMed

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

2016-01-01

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

Fibroblast growth factor 23, iron and inflammation - are they related in early stages of chronic kidney disease?

PubMed

Lukaszyk, Ewelina; Lukaszyk, Mateusz; Koc-Zorawska, Ewa; Bodzenta-Lukaszyk, Anna; Malyszko, Jolanta

2017-06-01

Fibroblast growth factor 23 (FGF-23) levels are elevated in impaired renal function. Inflammation and iron are potential regulators of FGF-23. The aim of the study was to evaluate the association between FGF-23 concentration, novel iron status biomarkers and inflammatory parameters among patients with early stages of chronic kidney disease (CKD). The study population included 84 patients with CKD in the early stage. Serum hemoglobin, fibrinogen, creatinine, iron, transferrin saturation and ferritin levels were measured using standard laboratory methods. Commercially available kits were used to measure: intact FGF-23, hepcidin, soluble transferrin receptor (sTfR), interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hsCRP). In patients with CKD no differences in FGF-23 concentration according to iron status were observed. Lower iron concentration was associated with higher concentrations of hsCRP, IL-6 and fibrinogen. In univariate and multivariate analysis FGF-23 correlated with fibrinogen ( r = -0.23, p < 0.05) and eGFR ( r = -0.36, p < 0.05). FGF-23 is affected by kidney function and fibrinogen but not iron status parameters in the early stages of CKD. Our data are paving the way for further studies on the role of FGF-23 in iron metabolism, especially in early stages of CKD.

Early stage response problem for post-disaster incidents

NASA Astrophysics Data System (ADS)

Kim, Sungwoo; Shin, Youngchul; Lee, Gyu M.; Moon, Ilkyeong

2018-07-01

Research on evacuation plans for reducing damages and casualties has been conducted to advise defenders against threats. However, despite the attention given to the research in the past, emergency response management, designed to neutralize hazards, has been undermined since planners frequently fail to apprehend the complexities and contexts of the emergency situation. Therefore, this study considers a response problem with unique characteristics for the duration of the emergency. An early stage response problem is identified to find the optimal routing and scheduling plan for responders to prevent further hazards. Due to the complexity of the proposed mathematical model, two algorithms are developed. Data from a high-rise building, called Central City in Seoul, Korea, are used to evaluate the algorithms. Results show that the proposed algorithms can procure near-optimal solutions within a reasonable time.

[Aging affects early stage direction selectivity of MT cells in rhesus monkeys].

PubMed

Liang, Zhen; Chen, Yue-Ming; Meng, Xue; Wang, Yi; Zhou, Bao-Zhuo; Xie, Ying-Ying; He, Wen-Sheng

2012-10-01

The middle temporal area (MT/V5) plays an important role in motion processing. Neurons in this area have a strongly selective response to the moving direction of objects and as such, the selectivity of MT neurons was proposed to be a neural mechanism for the perception of motion. Our previous studies have found degradation in direction selectivity of MT neurons in old monkeys, but this direction selectivity was calculated during the whole response time and the results were not able to uncover the mechanism of motion perception over a time course. Furthermore, experiments have found that direction selectivity was enhanced by attention at a later stage. Therefore, the response should be excluded in experiments with anesthesia. To further characterize the neural mechanism over a time course, we investigated the age-related changes of direction selectivity in the early stage by comparing the proportions of direction selective MT cells in old and young macaque monkeys using in vivo single-cell recording techniques. Our results show that the proportion of early-stage-direction-selective cells is lower in old monkeys than in young monkeys, and that the early stage direction bias (esDB) of old MT cells decreased relative to young MT cells. Furthermore, the proportion of MT cells having strong early stage direction selectivity in old monkeys was decreased. Accordingly, the functional degradation in the early stage of MT cells may mediate perceptual declines of old primates in visual motion tasks.

Endoscopic ultrasound staging for early esophageal cancer: Are we denying patients neoadjuvant chemo-radiation?

PubMed

Luu, Carrie; Amaral, Marisa; Klapman, Jason; Harris, Cynthia; Almhanna, Khaldoun; Hoffe, Sarah; Frakes, Jessica; Pimiento, Jose M; Fontaine, Jacques P

2017-12-14

To evaluate the accuracy of endoscopic ultrasound (EUS) in early esophageal cancer (EC) performed in a high-volume tertiary cancer center. A retrospective review of patients undergoing esophagectomy was performed and patients with cT1N0 and cT2N0 esophageal cancer by EUS were evaluated. Patient demographics, tumor characteristics, and treatment were reviewed. EUS staging was compared to surgical pathology to determine accuracy of EUS. Descriptive statistics was used to describe the cohort. Student's t test and Fisher's exact test or χ 2 test was used to compare variables. Logistic regression analysis was used to determine if clinical variables such as tumor location and tumor histology were associated with EUS accuracy. Between 2000 and 2015, 139 patients with clinical stageIorIIA esophageal cancer undergoing esophagectomy were identified. There were 25 (18%) female and 114 (82%) male patients. The tumor location included the middle third of the esophagus in 11 (8%) and lower third and gastroesophageal junction in 128 (92%) patients. Ninety-three percent of patients had adenocarcinoma. Preoperative EUS matched the final surgical pathology in 73/139 patients for a concordance rate of 53%. Twenty-nine patients (21%) were under-staged by EUS; of those, 19 (14%) had unrecognized nodal disease. Positron emission tomography (PET) was used in addition to EUS for clinical staging in 62/139 patients. Occult nodal disease was only found in 4 of 62 patients (6%) in whom both EUS and PET were negative for nodal involvement. EUS is less accurate in early EC and endoscopic mucosal resection might be useful in certain settings. The addition of PET to EUS improves staging accuracy.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Large-scale Metabolomic Analysis Reveals Potential Biomarkers for Early Stage Coronary Atherosclerosis.

PubMed

Gao, Xueqin; Ke, Chaofu; Liu, Haixia; Liu, Wei; Li, Kang; Yu, Bo; Sun, Meng

2017-09-18

Coronary atherosclerosis (CAS) is the pathogenesis of coronary heart disease, which is a prevalent and chronic life-threatening disease. Initially, this disease is not always detected until a patient presents with seriously vascular occlusion. Therefore, new biomarkers for appropriate and timely diagnosis of early CAS is needed for screening to initiate therapy on time. In this study, we used an untargeted metabolomics approach to identify potential biomarkers that could enable highly sensitive and specific CAS detection. Score plots from partial least-squares discriminant analysis clearly separated early-stage CAS patients from controls. Meanwhile, the levels of 24 metabolites increased greatly and those of 18 metabolites decreased markedly in early CAS patients compared with the controls, which suggested significant metabolic dysfunction in phospholipid, sphingolipid, and fatty acid metabolism in the patients. Furthermore, binary logistic regression showed that nine metabolites could be used as a combinatorial biomarker to distinguish early-stage CAS patients from controls. The panel of nine metabolites was then tested with an independent cohort of samples, which also yielded satisfactory diagnostic accuracy (AUC = 0.890). In conclusion, our findings provide insight into the pathological mechanism of early-stage CAS and also supply a combinatorial biomarker to aid clinical diagnosis of early-stage CAS.

Robotic-Assisted Thoracic Surgery for Early-Stage Lung Cancer: A Review.

PubMed

Brooks, Paula

2015-07-01

This review evaluates the benefits and disadvantages associated with the use of robotic-assisted technology in performing lobectomies in patients with early-stage lung cancer. The author conducted a literature search of Ovid®, MEDLINE®, PubMed®, and CINAHL® for articles published from 2005 to 2013. Search criteria included key terms such as robot, robotic, robotic-assisted lobectomy, and lung cancer. Of 922 articles, the author included a total of 12 research-based published studies in the analysis and incorporated the findings into an evidence table. Results showed that robotic-assisted lobectomies are feasible safe procedures for patients with stage 1A or 1B lung cancer; however, there is a steep learning curve and long-term randomized studies evaluating robotic-assisted lobectomy and conventional posterolateral thoracotomy or video-assisted thoracic lobectomy are needed. For patient safety, perioperative nurses should be aware of the length of time and experience required to perform these procedures, the costs, techniques, benefits, and disadvantages. Copyright © 2015 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia

PubMed Central

2014-01-01

Background Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Results Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Conclusions Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low

Selection occurs within linear fruit and during the early stages of reproduction in Robinia pseudoacacia.

PubMed

Yuan, Cun-Quan; Sun, Yu-Han; Li, Yun-Fei; Zhao, Ke-Qi; Hu, Rui-Yang; Li, Yun

2014-03-21

Pollen donor compositions differ during the early stages of reproduction due to various selection mechanisms. In addition, ovules linearly ordered within a fruit have different probabilities of reaching maturity. Few attempts, however, have been made to directly examine the magnitude and timing of selection, as well as the mechanisms during early life stages and within fruit. Robinia pseudoacacia, which contains linear fruit and non-random ovule maturation and abortion patterns, has been used to study the viability of selection within fruit and during the early stages of reproduction. To examine changes in the pollen donor composition during the early stages of reproduction and of progeny originating from different positions within fruit, paternity analyses were performed for three early life stages (aborted seeds, mature seeds and seedlings) in the insect-pollinated tree R. pseudoacacia. Selection resulted in an overall decrease in the level of surviving selfed progeny at each life stage. The greatest change was observed between the aborted seed stage and mature seed stage, indicative of inbreeding depression (the reduced fitness of a given population that occurs when related individual breeding was responsible for early selection). A selective advantage was detected among paternal trees. Within fruits, the distal ends showed higher outcrossing rates than the basal ends, indicative of selection based on the order of seeds within the fruit. Our results suggest that selection exists both within linear fruit and during the early stages of reproduction, and that this selection can affect male reproductive success during the early life stages. This indicates that tree species with mixed-mating systems may have evolved pollen selection mechanisms to increase the fitness of progeny and adjust the population genetic composition. The early selection that we detected suggests that inbreeding depression caused the high abortion rate and low seed set in R. pseudoacacia.

In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.

PubMed

Hellbach, Katharina; Yaroshenko, Andre; Meinel, Felix G; Yildirim, Ali Ö; Conlon, Thomas M; Bech, Martin; Mueller, Mark; Velroyen, Astrid; Notohamiprodjo, Mike; Bamberg, Fabian; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz

2015-07-01

The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema. Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images. Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher

Association of Marital Status With T Stage at Presentation and Management of Early-Stage Melanoma.

PubMed

Sharon, Cimarron E; Sinnamon, Andrew J; Ming, Michael E; Chu, Emily Y; Fraker, Douglas L; Karakousis, Giorgos C

2018-05-01

Early detection of melanoma is associated with improved patient outcomes. Data suggest that spouses or partners may facilitate detection of melanoma before the onset of regional and distant metastases. Less well known is the influence of marital status on the detection of early clinically localized melanoma. To evaluate the association between marital status and T stage at the time of presentation with early-stage melanoma and the decision for sentinel lymph node biopsy (SLNB) in appropriate patients. This retrospective, population-based study used the Surveillance, Epidemiology, and End Results database of 18 population-based registered cancer institutes. Patients with cutaneous melanoma who were at least 18 years of age and without evidence of regional or distant metastases and presented from January 1, 2010, through December 31, 2014, were identified for the study. Data were analyzed from September 27 to December 5, 2017. Marital status, categorized as married, never married, divorced, or widowed. Clinical T stage at presentation and performance of SLNB for lesions with Breslow thickness greater than 1 mm. A total of 52 063 patients were identified (58.8% men and 41.2% women; median age, 64 years; interquartile range, 52-75 years). Among married patients, 16 603 (45.7%) presented with T1a disease, compared with 3253 never married patients (43.0%), 1422 divorced patients (39.0%), and 1461 widowed patients (32.2%) (P < .001). Conversely, 428 widowed patients (9.4%) presented with T4b disease compared with 1188 married patients (3.3%) (P < .001). The association between marital status and higher T stage at presentation remained significant among never married (odds ratio [OR], 1.32; 95% CI, 1.26-1.39; P < .001), divorced (OR, 1.38; 95% CI, 1.30-1.47; P < .001), and widowed (OR, 1.70; 95% CI, 1.60-1.81; P < .001) patients after adjustment for various socioeconomic and patient factors. Independent of T stage and other patient factors, married

Urine biomarkers in the early stages of diseases: current status and perspective.

PubMed

Jing, Jian; Gao, Youhe

2018-02-01

As a noninvasive and easily available biological fluid, the urine is becoming an important source for disease biomarker study. Change is essential for the usefulness of a biomarker. Without homeostasis mechanisms, urine can accommodate more changes, especially in the early stages of diseases. In this review, we summarize current status and discuss perspectives on the discovery of urine biomarkers in the early stages of diseases. We emphasize the advantages of urine biomarkers compared to plasma biomarkers for the diagnosis of diseases at early stages, propose a urine biomarker research roadmap, and highlight a novel membrane storage technique that enables large-scale urine sample collection and storage efficiently and economically. It is anticipated that urine biomarker studies will greatly promote early diagnosis, prevention, treatment, and prognosis of a variety of diseases, and provide strong support for translational and precision medicine.

Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

PubMed Central

Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

2013-01-01

Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

Thermographic evaluation of early melanoma within the vascularized skin using combined non-Newtonian blood flow and bioheat models.

PubMed

Bhowmik, Arka; Repaka, Ramjee; Mishra, Subhash C

2014-10-01

A theoretical study on vascularized skin model to predict the thermal evaluation criteria of early melanoma using the dynamic thermal imaging technique is presented in this article. Thermographic evaluation of melanoma has been carried out during the thermal recovery of skin from undercooled condition. During thermal recovery, the skin has been exposed to natural convection, radiation, and evaporation. The thermal responses of melanoma have been evaluated by integrating the bioheat model for multi-layered skin with the momentum as well as energy conservation equations for blood flow. Differential changes in the surface thermal response of various melanoma stages except that of the early stage have been determined. It has been predicted that the thermal response due to subsurface blood flow overpowers the response of early melanoma. Hence, the study suggests that the quantification of early melanoma diagnosis using thermography has not reached a matured stage yet. Therefore, the study presents a systematic analysis of various intermediate melanoma stages to determine the thermal evaluation criteria of early melanoma. The comprehensive modeling effort made in this work supports the prediction of the disease outcome and relates the thermal response with the variation in patho-physiological, thermal and geometrical parameters. Copyright © 2014 Elsevier Ltd. All rights reserved.

Poor prognosis of uterine serous carcinoma compared with grade 3 endometrioid carcinoma in early stage patients.

PubMed

Park, Ji Young; Nam, Joo-Hyun; Kim, Young-Tak; Kim, Yong-Man; Kim, Jong-Hyeok; Kim, Dae-Yeon; Sohn, Insuk; Lee, Shin-Wha; Sung, Chang Ohk; Kim, Kyu-Rae

2013-03-01

Difference in prognosis between grade 3 endometrioid carcinoma (G3EC) of the endometrium and uterine serous carcinoma (USC) is controversial. In this study, we further evaluated the difference in prognosis, if any, between G3EC (n = 61) and USC (n = 47) on a total of 565 patients with endometrial cancer. In addition, meta-analysis was performed using data from seven previous publications (n = 8,637) and from the Asan Medical Center (n = 108). Regarding the cases from our institution, USC tended to occur in older patients (≥65 years) than G3EC (P = 0.011). Deep myometrial invasion (more than or equal to half) was more frequently identified in G3EC (36/61, 59.0 %) than in USC (17/47, 36.2 %) (P = 0.021). Between patients with early stage G3EC and USC (stages I and II), there were no significant differences in any clinicopathological parameter, but there was a significant difference in overall survival (P = 0.017) that was not found in advanced stage (P = 0.588). USC was an independent prognostic factor for poor overall survival (hazard ratio, 6.125; P = 0.030) in early stage patients. In the meta-analysis on 5-year survival in patients with early stage cancers, which also included our study results, a higher relative risk (1.92, 95 % CI 1.62-2.27) was demonstrated in USC than in G3EC (P < 0.001). In conclusion, our study reveals that USC is associated with a poorer prognosis compared with G3EC, only in patients with early stage carcinoma, suggesting that different treatment strategies should be considered according to the histologic type in order to improve treatment outcome.

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PubMed Central

Terry, Kathryn L.; Schock, Helena; Fortner, Renée T.; Hüsing, Anika; Fichorova, Raina N.; Yamamoto, Hidemi S.; Vitonis, Allison F.; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J.; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J.; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C.; Gunter, Marc J.; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf

2016-01-01

Purpose About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases. PMID:27060155

3-Nitrotyrosine and glutathione antioxidant system in patients in the early and late stages of bipolar disorder

PubMed Central

Andreazza, Ana Cristina; Kapczinski, Flavio; Kauer-Sant’Anna, Marcia; Walz, Julio C.; Bond, David J.; Gonçalves, Carlos A.; Young, L. Trevor; Yatham, Lakshmi N.

2009-01-01

Background There has been an increasing interest in the role of oxidative stress in the pathophysiology of bipolar disorder. To explore this further, we evaluated the activity of glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST), as well as 3-nitrotyrosine levels and carbonyl content in patients in the early (within 3 years of illness onset) and late (a minimum of 10 years of illness) stages of bipolar disorder. Methods We matched 30 patients in the early stage and 30 patients in the late stage of bipolar disorder, diagnosed according to DSM-IV criteria, with 60 healthy controls (30 matched for each group of patients). We measured symptomatic status using the Hamilton Rating Scale for Depression and the Young Mania Rating Scale. Results We found a significant increase in 3-nitrotyrosine levels among patients in the early (p < 0.010) and late (p < 0.010) stages of bipolar disorder. The activity of GR and GST was increased only among patients in the late stage of illness. Glutathione peroxidase activity and carbonyl content did not differ among the groups. Limitations Limitations of our study include its cross-sectional design, which did not allow us to examine direct causative mechanisms or the effects of progression of illness, and the potential environmental bias introduced by comparing patient groups recruited from different regions of the world. Conclusion Our data indicate a possible tyrosine nitration-induced damage in patients with bipolar disorder that is present from the early stage of illness. Our data also indicate that patients in the late stage of illness demonstrate enhanced activity of GR and GST, which could suggest the involvement of a compensatory system in bipolar disorder. PMID:19568477

Upper stage technology evaluation studies

NASA Technical Reports Server (NTRS)

1972-01-01

Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

Radiographic and functional results in the treatment of early stages of Charcot neuroarthropathy with a walker boot and immediate weight bearing.

PubMed

Parisi, Maria Candida Ribeiro; Godoy-Santos, Alexandre Leme; Ortiz, Rafael Trevisan; Sposeto, Rafael Barban; Sakaki, Marcos Hideyo; Nery, Marcia; Fernandes, Tulio Diniz

2013-01-01

One of the most common gold standards for the treatment of Charcot neuroarthropathy (CN) in the early Eichenholtz stages I and II is immobilization with the total contact casting and lower limb offloading. However, the total amount of offloading is still debatable. This study evaluates the clinical and radiographic findings in the treatment of early stages of CN (Eichenholtz stages I and II) with a walker boot and immediate total weight-bearing status. Twenty-two patients with type 2 diabetes mellitus (DM) and CN of Eichenholtz stages I and II were selected for non-operative treatment. All patients were educated about their condition, and full weight bearing was allowed as tolerated. Patients were monitored on a fortnightly basis in the earlier stages, with clinical examination, temperature measurement, and standardized weight-bearing radiographs. Their American Orthopedic Foot and Ankle Society (AOFAS) scores were determined before and after the treatment protocol. No cutaneous ulcerations or infections were observed in the evaluated cases. The mean measured angles at the beginning and end of the study, although showing relative increase, did not present a statistically significant difference (p > 0.05). Mean AOFAS scores showed a statistically significant improvement by the end of the study (p < 0.005). The treatment of early stages of CN (Eichenholtz stages I and II) with emphasis on walker boot and immediate weight bearing has shown a good functional outcome, non-progressive deformity on radiographic assessment, and promising results as a safe treatment option.

Critical Dysphagia is Common in Parkinson Disease and Occurs Even in Early Stages: A Prospective Cohort Study.

PubMed

Pflug, Christina; Bihler, Moritz; Emich, Katharina; Niessen, Almut; Nienstedt, Julie Cläre; Flügel, Till; Koseki, Jana-Christiane; Plaetke, Rosemarie; Hidding, Ute; Gerloff, Christian; Buhmann, Carsten

2018-02-01

To assess the prevalence of dysphagia and its typical findings in unselected "real-world" Parkinson patients using an objective gold-standard method. This was a prospective, controlled, cross-sectional study conducted in 119 consecutive Parkinson patients of all stages independent of subjective dysphagia. Patients and 32 controls were clinically and endoscopically examined by flexible endoscopic evaluation of swallowing (FEES) to evaluate the deglutition with regard to three consistencies (water, biscuit, and bread). Typical findings of dysphagia like penetration and aspiration, residues, and leakage were assessed. Dysphagia was common in Parkinson patients and occurred in all, even early, disease stages. Only 5% (6/119) of patients showed a completely unremarkable deglutition. Aspiration was seen in 25% (30/119) of patients and always related to water. Residues occurred in 93% (111/119), most commonly for bread. Leakage was much less frequent and was found in only 3-18%, depending on consistency. In a significant fraction of patients, objective dysphagia was not subjectively perceived. A total of 16% of asymptomatic patients suffered from critical aspiration. Significant swallowing deficiencies already occurred in early disease. Aspiration was found in 4 of 20 (20%) patients with disease duration of less than 2 years. Seven of 57 patients (12%) with Hoehn and Yahr stage 2 suffered from severe aspiration. Given the high frequency of critical aspiration in Parkinson disease, these patients should be evaluated early for dysphagia to avoid complications and recommend an adequate therapy. FEES is a simple, cost efficient, minimally invasive method that is ideally suited for this purpose.

Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

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

Fort, D.J.; Stover, E.L.

1995-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased inmore » each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Early two-stage double opposing Z-plasty or one-stage push-back palatoplasty?: comparisons in maxillary development and speech outcome at 4 years of age.

PubMed

Yamanishi, Tadashi; Nishio, Juntaro; Sako, Michiyo; Kohara, Hiroshi; Hirano, Yoshiko; Yamanishi, Yukiko; Adachi, Tadafumi; Miya, Shigenori; Mukai, Takao

2011-02-01

Determining the optimal timing and procedure of palatal surgery for children with cleft lip and palate has long raised a major controversy. An early two-stage palatoplasty protocol has been a recent trend in an attempt to obtain preferable maxillary growth without compromising adequate speech development. In this study, we aim to address whether the resulting maxillofacial growth and speech development obtained by an early 2-stage palatoplasty protocol are better than those obtained by conventional 1-stage push-back palatoplasty. Seventy-two nonsyndromic children with complete unilateral cleft lip and palate were enrolled in this study. They were divided into 2 groups: 30 children, who were treated with early 2-stage palatoplasty, in which soft palate closure was performed using a modified Furlow's procedure at 12 months of age and hard palate closure was performed at 18 months of age (Early Tow Stage [ETS] group: 22 boys, 8 girls), and 42 children, who underwent 1-stage Wardill-Kilner push-back palatoplasty at 12 months of age (Push Back [PB] group: 31 boys, 11 girls). Cephalometric analysis for maxillofacial growth and assessments of speech development were performed for each child at 4 years of age. The ETS group showed a lager maxillary length than the PB group [anterior nasal spine (ANS)-ptm': ETS, 46.7 ± 2.0 mm; PB, 43.6 ± 2.3 mm]. The ANS in the ETS group was positioned more anteriorly than that in the PB group (N'-ANS: ETS, 2.5 ± 1.8 mm; PB, 0.26 ± 2.5 mm), whereas the posterior edge of the maxilla positioned anteroposteiorly was comparable between the 2 groups. The anterior facial height was significantly greater in the ETS group than in the PB group (N-N': ETS, 43.3 ± 2.9 mm; PB, 40.1 ± 2.3 mm, S-S': ETS, 29.7 ± 3.2 mm; PB, 31.0 ± 3.2 mm). No statistically significant differences were observed in the incidence of either velopharyngeal incompetence or articulation errors between the 2 groups at 4 years of age. Our results show that the early 2

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma.

PubMed

Najjar, Raymond P; Sharma, Sourabh; Atalay, Eray; Rukmini, Annadata V; Sun, Christopher; Lock, Jing Zhan; Baskaran, Mani; Perera, Shamira A; Husain, Rahat; Lamoureux, Ecosse; Gooley, Joshua J; Aung, Tin; Milea, Dan

2018-03-21

To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. Cross-sectional study. Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm 2 /s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in

Multimodal imaging evaluation in staging of rectal cancer

PubMed Central

Heo, Suk Hee; Kim, Jin Woong; Shin, Sang Soo; Jeong, Yong Yeon; Kang, Heoung-Keun

2014-01-01

Rectal cancer is a common cancer and a major cause of mortality in Western countries. Accurate staging is essential for determining the optimal treatment strategies and planning appropriate surgical procedures to control rectal cancer. Endorectal ultrasonography (EUS) is suitable for assessing the extent of tumor invasion, particularly in early-stage or superficial rectal cancer cases. In advanced cases with distant metastases, computed tomography (CT) is the primary approach used to evaluate the disease. Magnetic resonance imaging (MRI) is often used to assess preoperative staging and the circumferential resection margin involvement, which assists in evaluating a patient’s risk of recurrence and their optimal therapeutic strategy. Positron emission tomography (PET)-CT may be useful in detecting occult synchronous tumors or metastases at the time of initial presentation. Restaging after neoadjuvant chemoradiotherapy (CRT) remains a challenge with all modalities because it is difficult to reliably differentiate between the tumor mass and other radiation-induced changes in the images. EUS does not appear to have a useful role in post-therapeutic response assessments. Although CT is most commonly used to evaluate treatment responses, its utility for identifying and following-up metastatic lesions is limited. Preoperative high-resolution MRI in combination with diffusion-weighted imaging, and/or PET-CT could provide valuable prognostic information for rectal cancer patients with locally advanced disease receiving preoperative CRT. Based on these results, we conclude that a combination of multimodal imaging methods should be used to precisely assess the restaging of rectal cancer following CRT. PMID:24764662

Association of medial meniscal extrusion with medial tibial osteophyte distance detected by T2 mapping MRI in patients with early-stage knee osteoarthritis.

PubMed

Hada, Shinnosuke; Ishijima, Muneaki; Kaneko, Haruka; Kinoshita, Mayuko; Liu, Lizu; Sadatsuki, Ryo; Futami, Ippei; Yusup, Anwajan; Takamura, Tomohiro; Arita, Hitoshi; Shiozawa, Jun; Aoki, Takako; Takazawa, Yuji; Ikeda, Hiroshi; Aoki, Shigeki; Kurosawa, Hisashi; Okada, Yasunori; Kaneko, Kazuo

2017-09-12

Medial meniscal extrusion (MME) is associated with progression of medial knee osteoarthritis (OA), but no or little information is available for relationships between MME and osteophytes, which are found in cartilage and bone parts. Because of the limitation in detectability of the cartilage part of osteophytes by radiography or conventional magnetic resonance imaging (MRI), the rate of development and size of osteophytes appear to have been underestimated. Because T2 mapping MRI may enable us to evaluate the cartilage part of osteophytes, we aimed to examine the association between MME and OA-related changes, including osteophytes, by using conventional and T2 mapping MRI. Patients with early-stage knee OA (n = 50) were examined. MRI-detected OA-related changes, in addition to MME, were evaluated according to the Whole-Organ Magnetic Resonance Imaging Score. T2 values of the medial meniscus and osteophytes were measured on T2 mapping images. Osteophytes surgically removed from patients with end-stage knee OA were histologically analyzed and compared with findings derived by radiography and MRI. Medial side osteophytes were detected by T2 mapping MRI in 98% of patients with early-stage knee OA, although the detection rate was 48% by conventional MRI and 40% by radiography. Among the OA-related changes, medial tibial osteophyte distance was most closely associated with MME, as determined by multiple logistic regression analysis, in the patients with early-stage knee OA (β = 0.711, p < 0.001). T2 values of the medial meniscus were directly correlated with MME in patients with early-stage knee OA, who showed ≥ 3 mm of MME (r = 0.58, p = 0.003). The accuracy of osteophyte evaluation by T2 mapping MRI was confirmed by histological analysis of the osteophytes removed from patients with end-stage knee OA. Our study demonstrates that medial tibial osteophyte evaluated by T2 mapping MRI is frequently observed in the patients with early-stage knee

Effects of genistein on early-stage cutaneous wound healing

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

Park, Eunkyo; Lee, Seung Min; Jung, In-Kyung

2011-07-08

Highlights: {yields} We examine the effect of genistein on cutaneous wound healing. {yields} Genistein enhanced wound closure during the early stage of wound healing. {yields} These genistein effects on wound closure were induced by reduction of oxidative stress through increasing antioxidant capacity and modulation of pro-inflammatory cytokine expression. -- Abstract: Wound healing occurs in three sequential phases: hemostasis and inflammation, proliferation, and remodeling. Inflammation, the earliest phase, is considered a critical period for wound healing because immune cells remove damaged tissues, foreign debris, and remaining dead tissue. Wound healing would be delayed without inflammation, and this phase is affected bymore » antioxidation capacity. Therefore, we hypothesized that genistein, which has an antioxidant effect, might modulate the wound healing process by altering the inflammatory response. After three days of acclimation, mice were divided into three groups: control, 0.025% genistein, and 0.1% genistein. After two weeks of an experimental diet, skin wounds were induced. Wounded skin areas were imaged, and the healing rate calculated. To measure lipid peroxidation, antioxidant enzyme expression and activity, and pro-inflammatory cytokine expression, skin and liver tissues were harvested at 12, 24, 48, and 72 h. Genistein did not affect body weight. The rate of wound closure in mice fed genistein was significantly faster than in the control group during the early stage of wound healing, especially in first three days. Cu, Zn-SOD and Mn-SOD expression in wound skin tissue in the 0.1% genistein group was lower than in the control group. However, CAT expression did not differ among groups. We also found that genistein modulated NF-{kappa}B and TNF-{alpha} expression during the early stage of wound healing. The genistein group had significantly lower hepatic lipid peroxidation and higher SOD, CAT, and GPx activities than the control group. These

Sleep Characteristics in Early Stages of Chronic Kidney Disease in the HypnoLaus Cohort.

PubMed

Ogna, Adam; Forni Ogna, Valentina; Haba Rubio, José; Tobback, Nadia; Andries, Dana; Preisig, Martin; Tafti, Mehdi; Vollenweider, Peter; Waeber, Gerard; Marques-Vidal, Pedro; Heinzer, Raphaël

2016-04-01

To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function. © 2016 Associated Professional Sleep Societies, LLC.

Folding of Polymer Chains in Early Stage of Crystallization

NASA Astrophysics Data System (ADS)

Yuan, Shichen; Miyoshi, Toshikazu

Understanding the structural formation of long polymer chains in the early stage of crystallization is one of the long-standing problems in polymer science. Using solid state NMR, we investigated chain trajectory of isotactic polypropylene in the mesomorphic nano-domains formed via rapid and deep quenching. Comparison of experimental and simulated 13C-13C Double Quantum (DQ) buildup curves demonstrated that instead of random re-entry models and solidification models, individual chains in the mesomorphic form iPP adopt adjacent reentry sequences with an average folding number of = 3-4 (assuming an adjacent re-entry fraction of of 100%) during mesomorphic formation process via nucleation and growth in the early stage. This work was financially supported by the National Science Foundation (Grant DMR-1105829 and 1408855) and startup funds from the UA.

Is knowledge translation adequate? A quality assurance study of staging investigations in early stage breast cancer patients.

PubMed

Han, Dolly; Hogeveen, Sophie; Sweet Goldstein, Miriam; George, Ralph; Brezden-Masley, Christine; Hoch, Jeffrey; Haq, Rashida; Simmons, Christine E

2012-02-01

After primary surgery, patients diagnosed with early stage breast cancer undergo radiological investigations based on pathologic stage of disease to rule out distant metastases. Published guidelines can aid clinicians in determining which tests are appropriate based on stage of disease. We wished to assess the consistency of radiological staging in an academic community oncology setting with standard guidelines and to determine the overall impact of non-adherence to these guidelines. A retrospective cohort study was conducted for new breast cancer patients seen at a single institution between January 2009 and April 2010. Patients were included if initial diagnosis and primary surgery was at this institution. Pathologic stage and radiological tests completed were recorded. A literature review was performed and the results were compared with those from this study to determine overall adherence rates. Subsequently, a cost analysis was performed to determine the financial impact at this centre. 231 patients met eligibility criteria for inclusion in this study. A large proportion of patients were over-staged with 129 patients (55%) undergoing unnecessary investigations according to guidelines. Specifically, 59% of stage I patients and 58% of stage II patients were over-investigated. Distant metastases at the time of diagnosis were found in three patients, all of whom had stage III disease (1.3%). The literature reviewed revealed similar non-adherence rates in other centres. The estimated cost of such non-adherence is in the range of $78 (CDN) per new early stage breast cancer patient seen at this centre. This oncology centre has a low adherence to practice guidelines for staging investigations in breast cancer patients, with 55% of patients undergoing unnecessary tests. Very few patients had metastases at diagnosis, and all had pathological stage III disease. Efforts may need to focus on improving knowledge translation across clinical oncology settings to increase

Radiation therapy in early-stage invasive breast cancer.

PubMed

Lin, Ray; Tripuraneni, Prabhakar

2011-06-01

The treatment of breast cancer involves a multi-disciplinary approach with radiation therapy playing a key role. Breast-conserving surgery has been an option for women with early-stage breast cancer for over two decades now. Multiple randomized trials now have demonstrated the efficacy of breast-conserving surgery followed by radiation therapy. With the advancements in breast imaging and the successful campaign for early detection of breast cancer, more women today are found to have early-stage small breast cancers. Patient factors (breast size, tumor location, history of prior radiation therapy, preexisting conditions such as collagen vascular disease, age, having prosthetically augmented breasts), pathological factors (margin status, tumor size, presence of extensive intraductal component requiring multiple surgical excisions), as well as patient preference are all taken into consideration prior to surgical management of breast cancer. Whole-breast fractionated radiation therapy between 5 and 7 weeks is considered as the standard of care treatment following breast-conserving surgery. However, new radiation treatment strategies have been developed in recent years to provide alternatives to the conventional 5-7 week whole-breast radiation therapy for some patients. Accelerated partial breast radiation therapy (APBI) was introduced because the frequency of breast recurrences outside of the surgical cavity has been shown to be low. This technique allows treatments to be delivered quicker (usually 1 week, twice daily) to a limited volume. Often times, this treatment involves the use of a brachytherapy applicator to be placed into the surgical cavity following breast-conserving surgery. Accelerated hypofractionated whole-breast irradiation may be another faster way to deliver radiation therapy following breast-conserving surgery. This journal article reviews the role of radiation therapy in women with early-stage breast cancer addressing patient selection in breast

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

PubMed

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C; Gunter, Marc J; Merritt, Melissa A; Riboli, Elio; Cramer, Daniel W; Kaaks, Rudolf

2016-09-15

About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542. ©2016 American Association for Cancer Research.

Liquid biopsy for early stage lung cancer.

PubMed

Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

2018-04-01

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

Low-Dose Consolidation Radiation Therapy for Early Stage Unfavorable Hodgkin Lymphoma

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

Torok, Jordan A., E-mail: jordan.torok@dm.duke.edu; Wu, Yuan; Prosnitz, Leonard R.

Purpose: The German Hodgkin Study Group (GHSG) trial HD11 established 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and 30 Gy of radiation therapy (RT) as a standard for early stage (I, II), unfavorable Hodgkin lymphoma (HL). Additional cycles of ABVD may allow for a reduction in RT dose and improved toxicity profile. Methods and Materials: Patients treated with combined modality therapy at the Duke Cancer Institute for early stage, unfavorable HL by GHSG criteria from 1994 to 2012 were included. Patients who did not undergo post-chemotherapy functional imaging (positron emission tomography or gallium imaging) or who failed to achievemore » a complete response were excluded. Clinical outcomes were estimated using the Kaplan-Meier method. Late effects were also evaluated. Results: A total of 90 patients met inclusion criteria for analysis. Median follow-up was 5 years. Chemotherapy consisted primarily of ABVD (88%) with a median number of 6 cycles. The median dose of consolidation RT was 23.4 Gy. Four patients had relapses, 2 of which were in-field. Ten-year progression-free survival (PFS) and overall survival (OS) were 93% (95% confidence interval [CI]: 0.82-0.97) and 98% (95% CI: 0.92-0.99), respectively. For the subset of patients (n=46) who received 5 to 6 cycles of chemotherapy and ≤24 Gy, the 10-year PFS and OS values were 88% (95% CI: 70%-96%) and 98% (95% CI: 85% - 99%), respectively. The most common late effect was hypothyroidism (20%) with no cardiac complications. Seven secondary malignancies were diagnosed, with only 1 arising within the RT field. Conclusions: Lower doses of RT may be sufficient when combined with more than 4 cycles of ABVD for early stage, unfavorable HL and may result in a more favorable toxicity profile than 4 cycles of ABVD and 30 Gy of RT.« less

Development of an early-stage toll revenue estimation model.

DOT National Transportation Integrated Search

2012-05-01

With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

Efficient embryonic culture method for the Japanese striped snake, Elaphe quadrivirgata, and its early developmental stages.

PubMed

Matsubara, Yoshiyuki; Sakai, Atsushi; Kuroiwa, Atsushi; Suzuki, Takayuki

2014-10-01

The morphogenesis of snake embryos is an elusive yet fascinating research target for developmental biologists. However, few data exist on development of early snake embryo due to limited availability of pregnant snakes, and the need to harvest early stage embryos directly from pregnant snakes before oviposition without knowing the date of fertilization. We established an ex vivo culture method for early snake embryos using the Japanese striped snake, Elaphe quadrivirgata. This method, which we named "sausage-style (SS) culture", allows us to harvest snake embryos at specific stages for each experiment. Using this SS culture system, we calculated somite formation rate at early stages before oviposition. The average somite formation rate between 6/7 and 12/13 somite stages was 145.9 min, between 60/70 and 80/91 somite stages 42.4 min, and between 113-115 and 126/127 somite stages 71 min. Thus, somite formation rate that we observed during early snake embryogenesis was changed over time. We also describe a developmental staging series for E. quadrivirgata. This is the first report of a developmental series of early snake embryogenesis prior to oviposition by full-color images with high-resolution. We propose that the SS culture system is an easy method for treating early snake embryos ex vivo. © 2014 The Authors Development, Growth & Differentiation © 2014 Japanese Society of Developmental Biologists.

Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

PubMed Central

Abbosh, Christopher; Birkbak, Nicolai J.; Wilson, Gareth A.; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D.; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Quinn, Anne Marie; Crosbie, Phil; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-sellers, Melanie; Prakash, Vineet; Lester, Jason; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S.; Van Loo, Peter; Dive, Caroline; Lin, Jimmy; Rabinowitz, Matthew; Aerts, Hugo JWL; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G.; Swanton, Charles

2017-01-01

Summary The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies PMID:28445469

Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.

PubMed

Abbosh, Christopher; Birkbak, Nicolai J; Wilson, Gareth A; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Marie Quinn, Anne; Crosbie, Phil A; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean A; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-Sellers, Melanie; Prakash, Vineet; Lester, Jason F; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S; Van Loo, Peter; Dive, Caroline; Lin, C Jimmy; Rabinowitz, Matthew; Aerts, Hugo J W L; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G; Swanton, Charles

2017-04-26

The early detection of relapse following primary surgery for non-small-cell lung cancer and the characterization of emerging subclones, which seed metastatic sites, might offer new therapeutic approaches for limiting tumour recurrence. The ability to track the evolutionary dynamics of early-stage lung cancer non-invasively in circulating tumour DNA (ctDNA) has not yet been demonstrated. Here we use a tumour-specific phylogenetic approach to profile the ctDNA of the first 100 TRACERx (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy (Rx)) study participants, including one patient who was also recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and analyse the tumour-volume detection limit. Through blinded profiling of postoperative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients who are very likely to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastasis, providing a new approach for ctDNA-driven therapeutic studies.

Sentinel Lymph Node (SLN) laparoscopic assessment early stage in endometrial cancer.

PubMed

Gargiulo, T; Giusti, M; Bottero, A; Leo, L; Brokaj, L; Armellino, F; Palladin, L

2003-06-01

The aim of the study was to demonstrate the validity of sentinel lymph node (SLN) detection after injection of radioactive isotope and patent blue dye in patients affected by early stage endometrial cancer. The second purpose was to compare radioactive isotope and patent blue dye migration. Between September 2000 and May 2001, 11 patients with endometrial cancer FIGO stage Ib (n=10) and IIa (n=1) underwent laparoscopic SLN detection during laparoscopic assisted vaginal hysterectomy with bilateral salpingo-oophorectomy and pelvic bilateral systematic lymphadenectomy. Radioactive isotope injection was performed 24 ours before surgery and blue dye injection was performed just before surgery in the cervix at 3, 6, 9 and 12 hours. A 350 mm laparoscopic gamma-scintiprobe MR 100 type 11, (99m)Tc setted (Pol.Hi.Tech.), was used intraoperatively for detecting SLN. Seventeen SLN were detected at lymphoscintigraphy (6 bilateral and 5 monolateral). At laparoscopic surgery the same locations were found belonging at internal iliac lymph nodes (the so called "Leveuf-Godard" area, lateral to the inferior vescical artery, ventral to the origin of uterine artery and medial or caudal to the external iliac vein). Fourteen SLN were negative at histological analysis and only 3 positive for micrometastasis (mean SLN sections = 60. All the other pelvic lymph nodes were negative at histological analysis. The same SLN locations detected with g-scintiprobe were observed during laparoscopy after patent blue dye injection. If the sensitivity of the assessment of SLN is confirmed to be 100%, this laparoscopic approach could change the management of early stage endometrial cancer. The clinical validity of this technique must be evaluated prospectively.

Signatures of unfolding in the early stages of protein denaturation

NASA Astrophysics Data System (ADS)

Gray, Harry B.; Winkler, Jay R.; Kozak, John J.

2012-04-01

A comparative study of the early stages of unfolding of five proteins: cyt c, c-b 562, cyt c‧, azurin, and lysozyme is reported. From crystallographic data, helical regions and intervening non-helical (or 'turning') regions are identified in each. Exploiting a previously introduced geometrical model, the paper describes quantitatively the stepwise extension of a polypeptide chain subject to the geometrical constraint that the spatial relationship among the residues of each triplet is fixed by native-state crystallographic data. Despite differences among the above-cited proteins, remarkable universality of behavior is found in the early stages of unfolding. At the very earliest stages, internal residues in each helical region have a common unfolding history; the terminal residues, however, are extraordinarily sensitive to structural perturbations. Residues in non-helical sections of the polypeptide unfold after residues in the internal helical regions, but with increasing steric perturbation playing a dominant role in advancing denaturation.

Elevated levels of circulating IL-7 and IL-15 in patients with early stage prostate cancer

PubMed Central

2011-01-01

Background Chronic inflammation has been suggested to favour prostate cancer (PCA) development. Interleukins (IL) represent essential inflammation mediators. IL-2, IL-7, IL-15 and IL-21, sharing a common receptor γ chain (c-γ), control T lymphocyte homeostasis and proliferation and play major roles in regulating cancer-immune system interactions. We evaluated local IL-2, IL-7, IL-15 and IL-21 gene expression in prostate tissues from patients with early stage PCA or benign prostatic hyperplasia (BPH). As control, we used IL-6 gene, encoding an IL involved in PCA progression. IL-6, IL-7 and IL-15 titres were also measured in patients' sera. Methods Eighty patients with BPH and 79 with early (1 to 2c) stage PCA were enrolled. Gene expression in prostate tissues was analyzed by quantitative real-time PCR (qRT-PCR). Serum IL concentrations and acute phase protein titres were evaluated by ELISA. Mann-Whitney, Wilcoxon and χ2 tests were used to compare IL gene expression and serum titers in the two groups of patients. Receiver operating characteristic (ROC) curves were constructed to evaluate the possibility to distinguish sera from different groups of patients based on IL titers. Results IL-2 and IL-21 gene expression was comparably detectable, with low frequency and at low extents, in PCA and BPH tissues. In contrast, IL-6, IL-7 and IL-15 genes were expressed more frequently (p < 0.0001, p = 0.0047 and p = 0.0085, respectively) and to significantly higher extents (p = 0.0051, p = 0.0310 and p = 0.0205, respectively) in early stage PCA than in BPH tissues. Corresponding proteins could be detected to significantly higher amounts in sera from patients with localized PCA, than in those from patients with BPH (p = 0.0153, p = 0.0174 and p = 0.0064, respectively). Analysis of ROC curves indicates that IL-7 (p = 0.0039), but not IL-6 (p = 0.2938) or IL-15 (p = 0.1804) titres were able to distinguish sera from patients with malignancy from those from patients with benign

Lock-in thermal imaging for the early-stage detection of cutaneous melanoma: a feasibility study.

PubMed

Bonmarin, Mathias; Le Gal, Frédérique-Anne

2014-04-01

This paper theoretically evaluates lock-in thermal imaging for the early-stage detection of cutaneous melanoma. Lock-in thermal imaging is based on the periodic thermal excitation of the specimen under test. Resulting surface temperature oscillations are recorded with an infrared camera and allow the detection of variations of the sample's thermophysical properties under the surface. In this paper, the steady-state and transient skin surface temperatures are numerically derived for a different stage of development of the melanoma lesion using a two-dimensional axisymmetric multilayer heat-transfer model. The transient skin surface temperature signals are demodulated according to the digital lock-in principle to compute both a phase and an amplitude image of the lesions. The phase image can be advantageously used to accurately detect cutaneous melanoma at an early stage of development while the maximal phase shift can give precious information about the lesion invasion depth. The ability of lock-in thermal imaging to suppress disturbing subcutaneous thermal signals is demonstrated. The method is compared with the previously proposed pulse-based approaches, and the influence of the modulation frequency is further discussed. Copyright © 2014 Elsevier Ltd. All rights reserved.

Numerical insights into the early stages of nanoscale electrodeposition: nanocluster surface diffusion and aggregative growth.

PubMed

Mamme, Mesfin Haile; Köhn, Christoph; Deconinck, Johan; Ustarroz, Jon

2018-04-19

Fundamental understanding of the early stages of electrodeposition at the nanoscale is key to address the challenges in a wide range of applications. Despite having been studied for decades, a comprehensive understanding of the whole process is still out of reach. In this work, we introduce a novel modelling approach that couples a finite element method (FEM) with a random walk algorithm, to study the early stages of nanocluster formation, aggregation and growth, during electrochemical deposition. This approach takes into account not only electrochemical kinetics and transport of active species, but also the surface diffusion and aggregation of adatoms and small nanoclusters. The simulation results reveal that the relative surface mobility of the nanoclusters compared to that of the adatoms plays a crucial role in the early growth stages. The number of clusters, their size and their size dispersion are influenced more significantly by nanocluster mobility than by the applied overpotential itself. Increasing the overpotential results in shorter induction times and leads to aggregation prevalence at shorter times. A higher mobility results in longer induction times, a delayed transition from nucleation to aggregation prevalence, and as a consequence, a larger surface coverage of smaller clusters with a smaller size dispersion. As a consequence, it is shown that a classical first-order nucleation kinetics equation cannot describe the evolution of the number of clusters with time, N(t), in potentiostatic electrodeposition. Instead, a more accurate representation of N(t) is provided. We show that an evaluation of N(t), which neglects the effect of nanocluster mobility and aggregation, can induce errors of several orders of magnitude in the determination of nucleation rate constants. These findings are extremely important towards evaluating the elementary electrodeposition processes, considering not only adatoms, but also nanoclusters as building blocks.

Central Pain Processing in Early-Stage Parkinson's Disease: A Laser Pain fMRI Study

PubMed Central

Petschow, Christine; Scheef, Lukas; Paus, Sebastian; Zimmermann, Nadine; Schild, Hans H.; Klockgether, Thomas; Boecker, Henning

2016-01-01

Background & Objective Pain is a common non-motor symptom in Parkinson’s disease. As dopaminergic dysfunction is suggested to affect intrinsic nociceptive processing, this study was designed to characterize laser-induced pain processing in early-stage Parkinson’s disease patients in the dopaminergic OFF state, using a multimodal experimental approach at behavioral, autonomic, imaging levels. Methods 13 right-handed early-stage Parkinson’s disease patients without cognitive or sensory impairment were investigated OFF medication, along with 13 age-matched healthy control subjects. Measurements included warmth perception thresholds, heat pain thresholds, and central pain processing with event-related functional magnetic resonance imaging (erfMRI) during laser-induced pain stimulation at lower (E = 440 mJ) and higher (E = 640 mJ) target energies. Additionally, electrodermal activity was characterized during delivery of 60 randomized pain stimuli ranging from 440 mJ to 640 mJ, along with evaluation of subjective pain ratings on a visual analogue scale. Results No significant differences in warmth perception thresholds, heat pain thresholds, electrodermal activity and subjective pain ratings were found between Parkinson’s disease patients and controls, and erfMRI revealed a generally comparable activation pattern induced by laser-pain stimuli in brain areas belonging to the central pain matrix. However, relatively reduced deactivation was found in Parkinson’s disease patients in posterior regions of the default mode network, notably the precuneus and the posterior cingulate cortex. Conclusion Our data during pain processing extend previous findings suggesting default mode network dysfunction in Parkinson’s disease. On the other hand, they argue against a genuine pain-specific processing abnormality in early-stage Parkinson’s disease. Future studies are now required using similar multimodal experimental designs to examine pain processing in more advanced

Primary Surgery vs Radiotherapy for Early Stage Oral Cavity Cancer.

PubMed

Ellis, Mark A; Graboyes, Evan M; Wahlquist, Amy E; Neskey, David M; Kaczmar, John M; Schopper, Heather K; Sharma, Anand K; Morgan, Patrick F; Nguyen, Shaun A; Day, Terry A

2018-04-01

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

EPA Science Inventory

Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

Early-Stage Capital Cost Estimation of Biorefinery Processes: A Comparative Study of Heuristic Techniques.

PubMed

Tsagkari, Mirela; Couturier, Jean-Luc; Kokossis, Antonis; Dubois, Jean-Luc

2016-09-08

Biorefineries offer a promising alternative to fossil-based processing industries and have undergone rapid development in recent years. Limited financial resources and stringent company budgets necessitate quick capital estimation of pioneering biorefinery projects at the early stages of their conception to screen process alternatives, decide on project viability, and allocate resources to the most promising cases. Biorefineries are capital-intensive projects that involve state-of-the-art technologies for which there is no prior experience or sufficient historical data. This work reviews existing rapid cost estimation practices, which can be used by researchers with no previous cost estimating experience. It also comprises a comparative study of six cost methods on three well-documented biorefinery processes to evaluate their accuracy and precision. The results illustrate discrepancies among the methods because their extrapolation on biorefinery data often violates inherent assumptions. This study recommends the most appropriate rapid cost methods and urges the development of an improved early-stage capital cost estimation tool suitable for biorefinery processes. © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2014 CFR

2014-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

13 CFR 107.1181 - Interest reserve requirements for Early Stage SBICs.

Code of Federal Regulations, 2013 CFR

2013-01-01

...) Binding unfunded commitments from your Institutional Investors that cannot be called for any purpose other... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Interest reserve requirements for... Rules for Leverage Issued by An Early Stage Sbic § 107.1181 Interest reserve requirements for Early...

Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

PubMed

Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

2014-07-01

Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adjuvant (post-surgery) chemotherapy for early stage epithelial ovarian cancer

PubMed Central

Winter-Roach, Brett A; Kitchener, Henry C; Lawrie, Theresa A

2014-01-01

Background Epithelial ovarian cancer is diagnosed in 4500 women in the UK each year of whom 1700 will ultimately die of their disease.Of all cases 10% to 15% are diagnosed early when there is still a good possibility of cure. The treatment of early stage disease involves surgery to remove disease often followed by chemotherapy. The largest clinical trials of this adjuvant therapy show an overall survival (OS) advantage with adjuvant platinum-based chemotherapy but the precise role of this treatment in subgroups of women with differing prognoses needs to be defined. Objectives To systematically review the evidence for adjuvant chemotherapy in early stage epithelial ovarian cancer to determine firstly whether there is a survival advantage of this treatment over the policy of observation following surgery with chemotherapy reserved for treatment of disease recurrence, and secondly to determine if clinical subgroups of differing prognosis based on histological sub-type, or completeness of surgical staging, have more or less to gain from chemotherapy following initial surgery. Search methods We performed an electronic search using the Cochrane Gynaecological Cancer Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL 2011, Issue 3), MEDLINE (1948 to Aug week 5, 2011) and EMBASE (1980 to week 36, 2011). We developed the search strategy using free-text and medical subject headings (MESH). Selection criteria We selected randomised clinical trials that met the inclusion criteria set out based on the populations, interventions, comparisons and outcome measures. Data collection and analysis Two review authors independently extracted data and assessed trial quality. Disagreements were resolved by discussion with a third review author. We performed random-effects meta-analyses and subgroup analyses. Main results Five randomised controlled trials (RCTs), enrolling 1277 women, with a median follow-up of 46 to 121 months, met the inclusion criteria. Four

Susceptibility of early life stages of Xenopus laevis to cadmium

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

Herkovits, J.; Perez-Coll, C.S.; Cardellini, P.

1997-02-01

The susceptibility of Xenopus laevis to cadmium during different stages of development was evaluated by exposing embryos to cadmium concentrations ranging from 0.1 to 10 mg Cd{sup 2+}/L for 24, 48, and 72 h and assessing lethality and malformations. Susceptibility increased from the two blastomeres stage (stage 2) to stage 40, in which the 24-h LC100 was 1.13 mg Cd{sup 2+}/L, and resistance increased from this stage onward. Malformations occurred at all developmental stages evaluated, the most common being reduced size, incurvated axis, underdeveloped or abnormally developed fin, microcephaly, and microphtalmy. Scanning electron microscopy revealed changes in the ectodermal surfacemore » ranging from slightly vaulted cells to a severe reduction in the number of ciliated cells as the concentration of cadmium increased. The intraspecific variation evaluated in embryos (from four sets of parents) at seven developmental stages, expressed as the coefficient of variation of the LC100, ranged from 10 to 112% and reflects the capacity of Xenopus laevis to adapt to changing environmental conditions at different embryonic stages.« less

Management of low-risk early-stage cervical cancer: Should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?

PubMed Central

Ramirez, Pedro T.; Pareja, Rene; Rendón, Gabriel J.; Millan, Carlos; Frumovitz, Michael; Schmeler, Kathleen M.

2014-01-01

The standard treatment for women with early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer. Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm, stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical cancer. PMID:24041877

[An unexpected stage of alkalosis in the dynamics of the early posthemorrhagic period].

PubMed

Beliaev, A V

2000-01-01

A study was made on acid-base metabolism in early posthemorrhagic period as exemplified by examination of patients presenting with gastrointestinal hemorrhage. It has been ascertained that hemorrhage is accompanied by a mixed variant of the acid-base state (ABS) deviation, namely metabolic lactate-acidosis and respiratory alkalosis. In the time-related course of posthemorrhagic period such deviations persist in patients with lethal outcome; with the disease running a favourable course the above deviations are found to return to normal quite soon. The development of complications leads to staging in ABC, its stages being as follows: stage I--the initial stage, stage II--persisting metabolic acidosis and respiratory alkalosis, stage III--alkalosis, stage IV--normalization, with stage III of ABS being encouraged by hypocapnia caused by function disorders of the lungs in early posthemorrhagic period, normalization of cell metabolism, increase in the rate of urination as a reflection of the third earlier identified stage of water metabolism, with the H+ excretion in the urine at the previous level. The identified ABS stage III threatens coming trouble, being accompanied by metabolic deviations together with a risk of function disorder of the myocardium.

Disruption of Smad-dependent signaling for growth of GST-P-positive lesions from the early stage in a rat two-stage hepatocarcinogenesis model

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

Ichimura, Ryohei, E-mail: red0828@hotmail.co.j; Mizukami, Sayaka, E-mail: non_sugar_life@hotmail.co.j; Takahashi, Miwa, E-mail: mtakahashi@nihs.go.j

2010-08-01

To clarify the involvement of signaling of transforming growth factor (TGF)-{beta} during the hepatocarcinogenesis, the immunohistochemical distribution of related molecules was analyzed in relation with liver cell lesions expressing glutathione S-transferase placental form (GST-P) during liver tumor promotion by fenbendazole, phenobarbital, piperonyl butoxide, or thioacetamide, using rats. Our study focused on early-stage promotion (6 weeks after starting promotion) and late-stage promotion (57 weeks after starting promotion). With regard to Smad-dependent signaling, cytoplasmic accumulation of phosphorylated Smad (phospho-Smad)-2/3 - identified as Smad3 by later immunoblot analysis - increased in the subpopulation of GST-P{sup +} foci, while Smad4, a nuclear transporter ofmore » Smad2/3, decreased during early-stage promotion. By late-stage promotion, GST-P{sup +} lesions lacking phospho-Smad2/3 had increased in accordance with lesion development from foci to carcinomas, while Smad4 largely disappeared in most proliferative lesions. With regard to Smad-independent mitogen-activated protein kinases, GST-P{sup +} foci that co-expressed phospho-p38 mitogen-activated protein kinase increased during early-stage promotion; however, p38-downstream phospho-activating transcriptional factor (ATF)-2, ATF3, and phospho-c-Myc, were inversely downregulated without relation to promotion. By late-stage promotion, proliferative lesions downregulated phospho-ATF2 and phospho-c-Myc along with lesion development, as with downregulation of phospho-p38 in all lesions. These results suggest that from the early stages, carcinogenic processes were facilitated by disruption of tumor suppressor functions of Smad-dependent signaling, while Smad-independent activation of p38 was an early-stage phenomenon. GST-P{sup -} foci induced by promotion with agonists of peroxisome proliferator-activated receptor-{alpha} did not change Smad expression, suggesting an aberration in the Smad

To Stay or to Go? Narratives of Early-Stage Sociologists about Persisting in Academia

ERIC Educational Resources Information Center

Wöhrer, Veronika

2014-01-01

Based on analyses of life course questionnaires, semi-structured qualitative interviews and focus group interviews carried out with early-stage sociologists over a period of 8 years, this paper presents analyzes of continuity and change in the decisions made by early-stage researchers in regard to their work and careers. The longitudinal approach…

Fertility sparing surgery in early stage epithelial ovarian cancer

PubMed Central

Martinelli, Fabio; Lorusso, Domenica; Haeusler, Edward; Carcangiu, Marialuisa; Raspagliesi, Francesco

2014-01-01

Objective Fertility sparing surgery (FSS) is a strategy often considered in young patients with early epithelial ovarian cancer. We investigated the role and the outcomes of FSS in eEOC patients who underwent comprehensive surgery. Methods From January 2003 to January 2011, 24 patients underwent fertility sparing surgery. Eighteen were one-to-one matched and balanced for stage, histologic type and grading with a group of patients who underwent radical comprehensive staging (n=18). Demographics, surgical procedures, morbidities, pathologic findings, recurrence-rate, pregnancy-rate and correlations with disease-free survival were assessed. Results A total of 36 patients had a complete surgical staging including lymphadenectomy and were therefore analyzed. Seven patients experienced a recurrence: four (22%) in the fertility sparing surgery group and three (16%) in the control group (p=not significant). Sites of recurrence were: residual ovary (two), abdominal wall and peritoneal carcinomatosis in the fertility sparing surgery group; pelvic (two) and abdominal wall in the control group. Recurrences in the fertility sparing surgery group appeared earlier (mean, 10.3 months) than in radical comprehensive staging group (mean, 53.3 months) p<0.001. Disease-free survival were comparable between the two groups (p=0.422). No deaths were reported. All the patients in fertility sparing surgery group recovered a regular period. Thirteen out of 18 (72.2%) attempted to have a pregnancy. Five (38%) achieved a spontaneous pregnancy with a full term delivery. Conclusion Fertility sparing surgery in early epithelial ovarian cancer submitted to a comprehensive surgical staging could be considered safe with oncological results comparable to radical surgery group. PMID:25142621

In vivo laser confocal microscopy findings of radial keratoneuritis in patients with early stage Acanthamoeba keratitis.

PubMed

Kobayashi, Akira; Yokogawa, Hideaki; Yamazaki, Natsuko; Ishibashi, Yasuhisa; Oikawa, Yosaburo; Tokoro, Masaharu; Sugiyama, Kazuhisa

2013-07-01

To investigate in vivo corneal changes of keratoneuritis in early stage Acanthamoeba keratitis (AK) using in vivo laser confocal microscopy. Single-center, prospective, clinical study. Thirteen eyes (12 patients; 5 men and 7 women; mean age ± standard deviation, 22.3 ± 4.2 years) with keratoneuritis resulting from early stage AK were included in this study. In vivo laser confocal microscopy was performed, paying special attention to keratoneuritis. Selected confocal images of corneal layers were evaluated qualitatively for shape and degree of light reflection of abnormal cells and deposits. In all patients, Acanthamoeba cysts were observed clearly in the basal epithelial cell layer as highly reflective round particles with a diameter of 10 to 20 μm. Bowman's layer infiltration of Acanthamoeba cysts was observed in only 1 case, and no cases showed stromal or nerve infiltration of Acanthamoeba cysts. In the stroma, all cases showed highly reflective activated keratocytes forming a honeycomb pattern; these changes were significant around the keratoneuritis. Infiltration of inflammatory cells, possibly polymorphonuclear cells, was observed along with keratocyte bodies in all cases. Numerous highly reflective spindle-shaped materials were observed around the keratoneuritis. Most notably, highly reflective patchy lesions were observed around the keratoneuritis in 11 cases (84.6%). Inflammatory cells also were observed in the endothelial cell layer in 4 cases (30.8%). In vivo laser confocal microscopy identified consistent corneal abnormalities around keratoneuritis in early stage AK patients, of which highly reflective patchy lesions may be characteristic of keratoneuritis. Further morphologic studies of corneas with early stage AK in a larger number of patients may elucidate the clinical significance of radial keratoneuritis and may help us to understand the interaction between Acanthamoeba organisms and host corneal cells or nerves. Copyright © 2013 American

SPIRIT advance care planning intervention in early stage dementias: An NIH stage I behavioral intervention development trial.

PubMed

Song, Mi-Kyung; Ward, Sandra E; Hepburn, Kenneth; Paul, Sudeshna; Shah, Raj C; Morhardt, Darby J

2018-06-02

People in the early stages of Alzheimer's disease and related dementias (ADRD) are encouraged to engage in advance care planning (ACP) while they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions with the surrogate. In this NIH Stage I behavioral intervention development trial, we will adapt and test an efficacious ACP intervention, SPIRIT (Sharing Patient's Illness Representation to Increase Trust), with people with mild dementia and their surrogates to promote open, honest discussions while such discussions about end-of-life care are possible. We will first adapt SPIRIT (in person) to target people with mild dementia and their surrogates through a process of modification-pretesting-refinement using stakeholders (persons with mild dementia, family caregivers, and clinicians) and experts, including adapting the delivery mode to interactive web-based videoconference format (SPIRIT-remote). Then in a 3-group RCT with 120 patient-surrogate dyads, we will evaluate the feasibility and acceptability of SPIRIT in-person and SPIRIT remote, and preliminary efficacy of SPIRIT compared to usual care on preparedness outcomes for end-of-life decision making (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) shortly after the intervention. This Stage I research of SPIRIT will generate valuable insights regarding how to improve ACP for people with mild dementia who will progress to an advanced stage of the disease in the foreseeable future. ClinicalTrials.gov NCT03311711, Registered 10/12/2017. Copyright © 2018. Published by Elsevier Inc.

Treatment of Early Stage Endometrial Cancer by Transumbilical Laparoendoscopic Single-Site Surgery Versus Traditional Laparoscopic Surgery

PubMed Central

Cai, Hui-hua; Liu, Mu-biao; He, Yuan-li

2016-01-01

Abstract To compare the outcomes of transumbilical laparoendoscopic single-site surgery (TU-LESS) versus traditional laparoscopic surgery (TLS) for early stage endometrial cancer (EC). We retrospectively reviewed the medical records of patients with early stage EC who were surgically treated by TU-LESS or TLS between 2011 and 2014 in a tertiary care teaching hospital. We identified 18 EC patients who underwent TU-LESS. Propensity score matching was used to match this group with 18 EC patients who underwent TLS. All patients underwent laparoscopic-assisted vaginal hysterectomy, bilateral salpingo-oophorectomy, and systematic pelvic lymphadenectomy by TU-LESS or TLS without conversion to laparoscopy or laparotomy. Number of pelvic lymph nodes retrieved, operative time and estimated blood loss were comparable between 2 groups. Satisfaction values of the cosmetic outcome evaluated by the patient at day 30 after surgery were significantly higher in TU-LESS group than that in TLS group (9.6 ± 0.8 vs 7.5 ± 0.7, P < 0.001), while there was no statistical difference in postoperative complications within 30 days after surgery, postoperative hospital stay, and hospital cost. For the surgical management of early stage EC, TU-LESS may be a feasible alternative approach to TLS, with comparable short-term surgical outcomes and superior cosmetic outcome. Future large-scale prospective studies are needed to identify these benefits. PMID:27057851

[Results after distraction arthroplasty according to Bufalini and Perugia in early stages of trapeziometacarpal osteoarthritis].

PubMed

Fatzer, Lukas; Soleman, E; Sanchez, T

2015-02-01

A distraction arthroplasty of the trapeziometacarpal joint was introduced by Bufalini and Perugia for the treatment of the early stages of carpometacarpal osteoarthritis. Our retrospective study presents the results of this technique. Thereby, a tendon graft anchored to the distal second metacarpal is fixed at the base of the first metacarpal, keeping it in distraction. 10 distraction arthroplasties were performed in 9 patients with carpometacarpal osteoarthritis stage I and II of the thumb after unsuccessful conservative therapy. In 2 cases, which were excluded from our study, trapeziectomy had to be performed because of persisting pain. Patient satisfaction, pain measurement, range of motion, and tip, key and grip strength were evaluated at a follow-up of 46.5 (29-63) months in the remaining 7 patients (8 operations overall). Strengh measurement was taken in an absolute value and compared to the opposite side. Thumb range of motion was measured with the combined flexion-opposition of the thumb with the Kapandij index and also the angle of abduction of the metacarpal I to metacarpal II. Assessment included a DASH score evaluation and an X-ray control. All of the 7 evaluated patients were satisfied with the operation results. Compared to the opposite side, patients achieved 80.1% (5.9 kg±1.1 kg) of key pinch strength, 86.3% (4.8 kg±0.9 kg) of oppositional tip pinch strength, and 86.1% (23.1 kg±4.8 kg) of grip strength. In combined flexion and opposition a Kapandij index of 8.5 (94.4%) compared to 9 on the opposite side was achieved. Thumb radial abduction was 48.2°±2.8°, compared to 51.0°±2.9° on the contralateral hand. At follow-up, the mean DASH score was 17.8 (±10.0). Radiological control showed no progression of carpometacarpal osteoarthritis of the thumb. The collected data after distraction arthroplasty according to Bufalini and Perugia confirm the efficacy of the technique in the early stage of carpometacarpal osteoarthritis of the

[Treatment of non-small cell lung carcinoma in early stages].

PubMed

Meneses, José Carlos; Avila Martínez, Régulo J; Ponce, Santiago; Zuluaga, Mauricio; Bartolomé, Adela; Gámez, Pablo

2013-12-01

Treatment of lung carcinoma is multidisciplinary. There are different therapeutic strategies available, although surgery shows the best results in those patients with lung carcinoma in early stages. Other options such as stereotactic radiation therapy are relegated to patients with small tumors and poor cardiopulmonary reserve or to those who reject surgery. Adjuvant chemotherapy is not justified in patients with stage i of the disease and so double adjuvant chemotherapy should be considered. This adjuvant chemotherapy should be based on cisplatin after surgery in those patients with stages ii and IIIA. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Good daily habits during the early stages of life determine success throughout life.

PubMed

Kohyama, Jun

2016-01-01

This paper assesses hypothesis that sufficient sleep duration and proper circadian rhythms during the early stages of life are indispensable to a successful life. Successful life was defined according to the famous cohort studies of Mischel's and Dunedin. To assess the hypothesis, neuronal elements presumably affecting early daily habits and successful life are reviewed. The effect of sufficient sleep duration and proper circadian rhythms during early stages of life on the development of the prefrontal cortex has been found to be the key issue to verify the hypothesis. Socioeconomic status is found to be another issue to be studied.

Nurses' experiences using a nursing information system: early stage of technology implementation.

PubMed

Lee, Ting-Ting

2007-01-01

Adoption of information technology in nursing practice has become a trend in healthcare. The impact of this technology on users has been widely studied, but little attention has been given to its influence at the beginning stage of implementation. Knowing the barriers to adopting technology could shorten this transition stage and minimize its negative influences. The purpose of this study was to explore nurses' experiences in the early stage of implementing a nursing information system. Focus groups were used to collect data at a medical center in Taiwan. The results showed that nurses had problems with the system's content design, had insufficient training, were concerned about data security, were stressed by added work, and experienced poor interdisciplinary cooperation. To smooth this beginning stage, the author recommends involving nurses early in the system design, providing sufficient training in keyboard entry skills, redesigning workflow, and improving interdisciplinary communication.

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review.

PubMed

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83-0.98, P=0.01; RR =0.84, 95% CI: 0.75-0.95, P=0.004; RR =0.77, 95% CI: 0.60-0.98, P=0.04; and RR =0.70, 95% CI: 0.52-0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88-0.98, P=0.003; RR =0.84, 95% CI

Radiofrequency ablation versus resection for Barcelona clinic liver cancer very early/early stage hepatocellular carcinoma: a systematic review

PubMed Central

He, Zhen-Xin; Xiang, Pu; Gong, Jian-Ping; Cheng, Nan-Sheng; Zhang, Wei

2016-01-01

Aim To compare the long-term survival outcomes of radiofrequency ablation and liver resection for single very early/early stage hepatocellular carcinoma (HCC). Methods The Cochrane Library (Issue 3, 2015), Embase (1974 to March 15, 2015), PubMed (1950 to March 15, 2015), Web of Science (1900 to March 15, 2015), and Chinese Biomedical Literature Database (1978 to March 15, 2015) were searched to identify relevant trials. Only trials that compared radiofrequency ablation and liver resection for single very early stage (≤2 cm) or early stage (≤3 cm) HCC according to the Barcelona clinic liver cancer (BCLC) staging system were considered for inclusion in this review. The primary outcomes that we analyzed were the 3-year and 5-year overall survival (OS) rates, and the secondary outcomes that we analyzed were the 3-year and 5-year disease-free survival (DFS) rates. Review Manager 5.3 was used to perform a cumulative meta-analysis. Possible publication bias was examined using a funnel plot. A random-effects model was applied to summarize the various outcomes. Results Six studies involving 947 patients were identified that compared radiofrequency ablation (n=528) to liver resection (n=419) for single BCLC very early HCC. In these six studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were significantly lower in the radiofrequency ablation group than in the liver resection group (risk ratio [RR] =0.90, 95% confidence interval [CI]: 0.83–0.98, P=0.01; RR =0.84, 95% CI: 0.75–0.95, P=0.004; RR =0.77, 95% CI: 0.60–0.98, P=0.04; and RR =0.70, 95% CI: 0.52–0.94, P=0.02, respectively). Ten studies involving 2,501 patients were identified that compared radiofrequency ablation (n=1,476) to liver resection (n=1,025) for single BCLC early HCC. In these ten studies, the rates of 3-year OS, 5-year OS, 3-year DFS, and 5-year DFS were also significantly lower in the radiofrequency ablation group than in the liver resection group (RR =0.93, 95% CI: 0.88–0

Characteristics of Early Stages of Corrosion Fatigue in Aircraft Skin

DOT National Transportation Integrated Search

1996-02-01

SRI International is conducting research to characterize and quantitatively describe the early stages of corrosion fatigue in the fuselage skin of commercial aircraft. Specific objectives are to gain an improved deterministic understanding of the tra...

Effect of low-level copper and pentachlorophenol exposure on various early life stages of Xenopus laevis

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

Fort, D.J.; Stover, E.L.

1996-12-31

An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis, was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorphenol, from 0 d to 4 d (standard Frog Embryo Teratogenesis Assay--Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in eachmore » successive time period. Longer-term exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5 {micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.« less

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index

PubMed Central

Hacker, Mallory L.; Turchan, Maxim; Molinari, Anna L.; Currie, Amanda D.

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50–75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT (n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t-tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group (p > 0.05). BMI change over two years was not different between the groups (p = 0.62, ODT = −0.89; DBS+ODT = −0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152). PMID:28676842

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson's Disease Is Not Associated with Increased Body Mass Index.

PubMed

Millan, Sarah H; Hacker, Mallory L; Turchan, Maxim; Molinari, Anna L; Currie, Amanda D; Charles, David

2017-01-01

Previous studies suggest that deep brain stimulation of the subthalamic nucleus (STN-DBS) for Parkinson's disease (PD) leads to weight gain. This study analyzes changes in body mass index (BMI) in 29 subjects from a prospective, single-blind trial of DBS in early stage PD (age 50-75, Hoehn & Yahr stage II off medication, treated with antiparkinsonian medications for ≥6 months but <4 years, and without a history of motor fluctuations, dyskinesias, or dementia). Subjects were randomized to DBS plus optimal drug therapy (DBS+ODT; n = 15) or ODT ( n = 14) and followed for 24 months. Weight and height were recorded at baseline and each follow-up visit and used to calculate BMI. BMIs were compared within and between groups using nonparametric t -tests. Mean BMI at baseline was 29.7 in the ODT group and 32.3 in the DBS+ODT group ( p > 0.05). BMI change over two years was not different between the groups ( p = 0.62, ODT = -0.89; DBS+ODT = -0.17). This study suggests that STN-DBS is not associated with weight gain in subjects with early stage PD. This finding will be tested in an upcoming FDA-approved phase III multicenter, randomized, double-blind, placebo-controlled, pivotal clinical trial evaluating DBS in early stage PD (ClinicalTrials.gov identifier NCT00282152).

Sentinel lymph node navigation surgery for early stage gastric cancer.

PubMed

Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

2014-05-21

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient's quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation.

Sentinel lymph node navigation surgery for early stage gastric cancer

PubMed Central

Mitsumori, Norio; Nimura, Hiroshi; Takahashi, Naoto; Kawamura, Masahiko; Aoki, Hiroaki; Shida, Atsuo; Omura, Nobuo; Yanaga, Katsuhiko

2014-01-01

We attempted to evaluate the history of sentinel node navigation surgery (SNNS), technical aspects, tracers, and clinical applications of SNNS using Infrared Ray Electronic Endoscopes (IREE) combined with Indocyanine Green (ICG). The sentinel lymph node (SLN) is defined as a first lymph node (LN) which receives cancer cells from a primary tumor. Reports on clinical application of SNNS for gastric cancers started to appear since early 2000s. Two prospective multicenter trials of SNNS for gastric cancer have also been accomplished in Japan. Kitagawa et al reported that the endoscopic dual (dye and radioisotope) tracer method for SN biopsy was confirmed acceptable and effective when applied to the early-stage gastric cancer (EGC). We have previously reported the usefulness of SNNS in gastrointestinal cancer using ICG as a tracer, combined with IREE (Olympus Optical, Tokyo, Japan) to detect SLN. LN metastasis rate of EGC is low. Hence, clinical application of SNNS for EGC might lead us to avoid unnecessary LN dissection, which could preserve the patient’s quality of life after operation. The most ideal method of SNNS should allow secure and accurate detection of SLN, and real time observation of lymphatic flow during operation. PMID:24914329

Identification of Owl Monkey CD4 Receptors Broadly Compatible with Early-Stage HIV-1 Isolates

PubMed Central

Meyerson, Nicholas R.; Sharma, Amit; Wilkerson, Gregory K.

2015-01-01

ABSTRACT Most HIV-1 variants isolated from early-stage human infections do not use nonhuman primate versions of the CD4 receptor for cellular entry, or they do so poorly. We and others have previously shown that CD4 has experienced strong natural selection over the course of primate speciation, but it is unclear whether this selection has influenced the functional characteristics of CD4 as an HIV-1 receptor. Surprisingly, we find that selection on CD4 has been most intense in the New World monkeys, animals that have never been found to harbor lentiviruses related to HIV-1. Based on this, we sampled CD4 genetic diversity within populations of individuals from seven different species, including five species of New World monkeys. We found that some, but not all, CD4 alleles found in Spix's owl monkeys (Aotus vociferans) encode functional receptors for early-stage human HIV-1 isolates representing all of the major group M clades (A, B, C, and D). However, only some isolates of HIV-1 subtype C can use the CD4 receptor encoded by permissive Spix's owl monkey alleles. We characterized the prevalence of functional CD4 alleles in a colony of captive Spix's owl monkeys and found that 88% of surveyed individuals are homozygous for permissive CD4 alleles, which encode an asparagine at position 39 of the receptor. We found that the CD4 receptors encoded by two other species of owl monkeys (Aotus azarae and Aotus nancymaae) also serve as functional entry receptors for early-stage isolates of HIV-1. IMPORTANCE Nonhuman primates, particularly macaques, are used for preclinical evaluation of HIV-1 vaccine candidates. However, a significant limitation of the macaque model is the fact that most circulating HIV-1 variants cannot use the macaque CD4 receptor to enter cells and have to be adapted to these species. This is particularly true for viral variants from early stages of infection, which represent the most relevant vaccine targets. In this study, we found that some individuals

A Four-Stage Method for Developing Early Interventions for Alcohol among Aboriginal Adolescents

ERIC Educational Resources Information Center

Mushquash, Christopher J.; Comeau, M. Nancy; McLeod, Brian D.; Stewart, Sherry H.

2010-01-01

This paper details a four-stage methodology for developing early alcohol interventions for at-risk Aboriginal youth. Stage 1 was an integrative approach to Aboriginal education that upholds Aboriginal traditional wisdom supporting respectful relationships to the Creator, to the land and to each other. Stage 2 used quantitative methods to…

Succession Influences Wild Bees in a Temperate Forest Landscape: The Value of Early Successional Stages in Naturally Regenerated and Planted Forests

PubMed Central

Taki, Hisatomo; Okochi, Isamu; Okabe, Kimiko; Inoue, Takenari; Goto, Hideaki; Matsumura, Takeshi; Makino, Shun'ichi

2013-01-01

In many temperate terrestrial forest ecosystems, both natural human disturbances drive the reestablishment of forests. Succession in plant communities, in addition to reforestation following the creation of open sites through harvesting or natural disturbances, can affect forest faunal assemblages. Wild bees perform an important ecosystem function in human-altered and natural or seminatural ecosystems, as they are essential pollinators for both crops and wild flowering plants. To maintain high abundance and species richness for pollination services, it is important to conserve and create seminatural and natural land cover with optimal successional stages for wild bees. We examined the effects of forest succession on wild bees. In particular, we evaluated the importance of early successional stages for bees, which has been suspected but not previously demonstrated. A range of successional stages, between 1 and 178 years old, were examined in naturally regenerated and planted forests. In total 4465 wild bee individuals, representing 113 species, were captured. Results for total bees, solitary bees, and cleptoparasitic bees in both naturally regenerated and planted conifer forests indicated a higher abundance and species richness in the early successional stages. However, higher abundance and species richness of social bees in naturally regenerated forest were observed as the successional stages progressed, whereas the abundance of social bees in conifer planted forest showed a concave-shaped relationship when plotted. The results suggest that early successional stages of both naturally regenerated and conifer planted forest maintain a high abundance and species richness of solitary bees and their cleptoparasitic bees, although social bees respond differently in the early successional stages. This may imply that, in some cases, active forest stand management policies, such as the clear-cutting of planted forests for timber production, would create early successional

Succession influences wild bees in a temperate forest landscape: the value of early successional stages in naturally regenerated and planted forests.

PubMed

Taki, Hisatomo; Okochi, Isamu; Okabe, Kimiko; Inoue, Takenari; Goto, Hideaki; Matsumura, Takeshi; Makino, Shun'ichi

2013-01-01

In many temperate terrestrial forest ecosystems, both natural human disturbances drive the reestablishment of forests. Succession in plant communities, in addition to reforestation following the creation of open sites through harvesting or natural disturbances, can affect forest faunal assemblages. Wild bees perform an important ecosystem function in human-altered and natural or seminatural ecosystems, as they are essential pollinators for both crops and wild flowering plants. To maintain high abundance and species richness for pollination services, it is important to conserve and create seminatural and natural land cover with optimal successional stages for wild bees. We examined the effects of forest succession on wild bees. In particular, we evaluated the importance of early successional stages for bees, which has been suspected but not previously demonstrated. A range of successional stages, between 1 and 178 years old, were examined in naturally regenerated and planted forests. In total 4465 wild bee individuals, representing 113 species, were captured. Results for total bees, solitary bees, and cleptoparasitic bees in both naturally regenerated and planted conifer forests indicated a higher abundance and species richness in the early successional stages. However, higher abundance and species richness of social bees in naturally regenerated forest were observed as the successional stages progressed, whereas the abundance of social bees in conifer planted forest showed a concave-shaped relationship when plotted. The results suggest that early successional stages of both naturally regenerated and conifer planted forest maintain a high abundance and species richness of solitary bees and their cleptoparasitic bees, although social bees respond differently in the early successional stages. This may imply that, in some cases, active forest stand management policies, such as the clear-cutting of planted forests for timber production, would create early successional

Long-term outcomes in patients with early stage nodular lymphocyte-predominant Hodgkin's lymphoma treated with radiotherapy.

PubMed

Solanki, Abhishek A; LeMieux, Melissa Horoschak; Chiu, Brian C-H; Mahmood, Usama; Hasan, Yasmin; Koshy, Matthew

2013-01-01

Radiation therapy (RT) is commonly used as definitive treatment for early-stage nodular lymphocyte-predominant Hodgkin's lymphoma (NLPHL). We evaluated the cause-specific survival (CSS), overall survival (OS), and second malignancy (SM) rates in patients with early-stage NLPHL treated with RT. Patients with stage I-II NLPHL between 1988 and 2009 who underwent RT were selected from the Surveillance, Epidemiology and End Results database. Univariate analysis (UVA) for CSS and Os was performed using the Kaplan-Meier method and included age, gender, involved site, year of diagnosis, presence of B-symptoms, and extranodal involvement (ENI). Multivariable analysis (MVA) was performed using Cox Proportional Hazards modeling and included the above clinical variables. SM were classified as RT-related or non-RT-related. Freedom from SM and freedom from RT-related SM were determined using the Kaplan-Meier method. The study cohort included 469 patients. Median age was 37 years. The most common involved sites were the head and neck (36%), axilla/arm (26%), and multiple lymph node regions (18%). Sixty-eight percent had stage I disease, 70% were male, 4% had ENI, and 7% had B-symptoms. Median follow-up was 6 years. Ten-year CSS and Os were 98% and 88%, respectively. On UVA, none of the covariates was associated with CSS. Increasing age (p<0.01) and female gender (p<0.01) were associated with worse Os. On MVA, older age (p<0.01), female gender (p=0.04), multiple regions of involvement (p=0.03), stage I disease (p=0.02), and presence of B-symptoms (p=0.02) were associated with worse Os. Ten-year freedom from SM and freedom from RT-related SM were 89% and 99%, respectively. This is the largest series to evaluate the outcomes of stage I-II NLPHL patients treated with RT and found that this patient population has an excellent long-term prognosis and a low rate of RT-related second malignancies.

Stage-specific differences in secretory profile of mesenchymal stromal cells (MSCs) subjected to early- vs late-stage OA synovial fluid.

PubMed

Gómez-Aristizábal, A; Sharma, A; Bakooshli, M A; Kapoor, M; Gilbert, P M; Viswanathan, S; Gandhi, R

2017-05-01

Although, mesenchymal stromal cells (MSCs) are being clinically investigated for their use in osteoarthritis (OA), it is unclear whether their postulated therapeutic properties are equally effective in the early- and late-stages of OA. In this study we investigated MSC cytokine secretion post-exposure to synovial fluid (SF), obtained from early- vs late-stage knee OA patients to justify a potential patient stratification strategy to maximize MSC-mediated treatment effects. Subjects were recruited and categorized into early- [Kellgren-Lawrence (KL) grade I/II, n = 12] and late-stage (KL-III/IV, n = 12) knee OA groups. SF samples were obtained, and their proteome was tested using multiplex assays, after 3-days culture, with and without MSCs. SFs cultured without MSCs were used as a baseline to identify MSC-secreted factors into SFs cultured with MSCs. Linear mixed-effect models and non-parametric tests were used to identify alterations in the MSC secretome during exposure to OA SF (3-days). MSCs cultured for 3-days in 0.5% fetal bovine serum (FBS)-supplemented medium were used to compare SF results with culture medium. Following exposure to OA SF, the MSC secretome contained proteins that are involved in tissue repair, angiogenesis, chemotaxis, matrix remodeling and the clotting process. However, chemokine (C-X-C motif) ligand-8 (CXCL8; chemoattractant), interleukin-6 (IL6) and chemokine (C-C motif) ligand 2 (CCL2) were elevated in the MSC-secretome in response to early- vs late-stage OA SF. Early- vs late-stage OA SF samples elicit a differential MSC secretome response, arguing for stratification of OA patients to maximize MSC-mediated therapeutic effects. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Driving in Early-Stage Alzheimer's Disease: An Integrative Review of the Literature.

PubMed

Davis, Rebecca L; Ohman, Jennifer M

2017-03-01

One of the most difficult decisions for individuals with Alzheimer's disease (AD) is when to stop driving. Because driving is a fundamental activity linked to socialization, independent functioning, and well-being, making the decision to stop driving is not easy. Cognitive decline in older adults can lead to getting lost while driving, difficulty detecting and avoiding hazards, as well as increased errors while driving due to compromised judgment and difficulty in making decisions. The purpose of the current literature review was to synthesize evidence regarding how individuals with early-stage AD, their families, and providers make determinations about driving safety, interventions to increase driving safety, and methods to assist cessation and coping for individuals with early-stage AD. The evidence shows that changes in driving ability start early and progress throughout the trajectory of AD. Some individuals with mild cognitive impairment or early-stage AD may be safe to drive for a period of time. Support groups aimed at helping with the transition have been shown to be helpful for individuals who stop driving. Research and practice must support interventions to help individuals maintain safety while driving, as well as cope with driving cessation. [Res Gerontol Nurs. 2017; 10(2):86-100.]. Copyright 2016, SLACK Incorporated.

Using the 21-gene assay to guide adjuvant chemotherapy decision-making in early-stage breast cancer: a cost-effectiveness evaluation in the German setting.

PubMed

Blohmer, J U; Rezai, M; Kümmel, S; Kühn, T; Warm, M; Friedrichs, K; Benkow, A; Valentine, W J; Eiermann, W

2013-01-01

The 21-gene assay (Oncotype DX Breast Cancer Test (Genomic Health Inc., Redwood City, CA)) is a well validated test that predicts the likelihood of adjuvant chemotherapy benefit and the 10-year risk of distant recurrence in patients with ER+, HER2- early-stage breast cancer. The aim of this analysis was to evaluate the cost-effectiveness of using the assay to inform adjuvant chemotherapy decisions in Germany. A Markov model was developed to make long-term projections of distant recurrence, survival, quality-adjusted life expectancy, and direct costs for patients with ER+, HER2-, node-negative, or up to 3 node-positive early-stage breast cancer. Scenarios using conventional diagnostic procedures or the 21-gene assay to inform treatment recommendations for adjuvant chemotherapy were modeled based on a prospective, multi-center trial in 366 patients. Transition probabilities and risk adjustment were based on published landmark trials. Costs (2011 Euros (€)) were estimated from a sick fund perspective based on resource use in patients receiving chemotherapy. Future costs and clinical benefits were discounted at 3% annually. The 21-gene assay was projected to increase mean life expectancy by 0.06 years and quality-adjusted life expectancy by 0.06 quality-adjusted life years (QALYs) compared with current clinical practice over a 30-year time horizon. Clinical benefits were driven by optimized allocation of adjuvant chemotherapy. Costs from a healthcare payer perspective were lower with the 21-gene assay by ∼€561 vs standard of care. Probabilistic sensitivity analysis indicated that there was an 87% probability that the 21-gene assay would be dominant (cost and life saving) to standard of care. Country-specific data on the risk of distant recurrence and quality-of-life were not available. Guiding decision-making on adjuvant chemotherapy using the 21-gene assay was projected to improve survival, quality-adjusted life expectancy, and be cost saving vs the current

Improved early outcome for end-stage dilated cardiomyopathy in children.

PubMed

McMahon, Anne-Marie; van Doorn, Carin; Burch, Michael; Whitmore, Pauline; Neligan, Sophie; Rees, Philip; Radley-Smith, Rosemary; Goldman, Allan; Brown, Katherine; Cohen, Gordon; Tsang, Victor; Elliott, Martin; de Leval, Marc R

2003-12-01

To review the impact of management changes on the early outcomes of end-stage dilated cardiomyopathy in children. We conducted a retrospective study of all consecutive children with end-stage dilated cardiomyopathy who received hospital treatment since 1992. Over the past 3 years the following management changes were made: (1) more aggressive use of mechanical cardiac assistance; (2) high priority listing for transplantation; and (3) ABO incompatible transplants for infants. Outcomes for 46 patients admitted between 1992 and 1999 (group I) were compared with 53 patients between 2000 and March 2003 (group II). In group I, 12 (26%) patients received mechanical support with recovery in 3 and transplantation in 5 (1 died). In group II, 19 (36%) patients received extracorporeal membrane oxygenation, with recovery in 5 and transplantation in 12 (all survived). The use of mechanical assistance was associated with high morbidity related to bleeding, end-organ failure, and long-term mechanical ventilation. Five patients in group II received ABO incompatible transplants and all survived. There have been no episodes of rejection or need for increased immunosuppressive therapy. Hospital mortality has been significantly reduced (group I, 37% vs group II, 11%; P <.05). Recent refinements in the management of end-stage dilated cardiomyopathy in children have significantly reduced early mortality. Identification of markers of early myocardial recovery and development of mechanical devices for longer term and more physiologic support are essential to achieve further improvements in outcome.

Following iron speciation in the early stages of magnetite magnetosome biomineralization

DOE PAGES

Firlar, Emre; Perez-Gonzalez, Teresa; Olszewska, Agata; ...

2016-02-26

Understanding magnetosome magnetite biomineralization is of fundamental interest to devising the strategies for bioinspired synthesis of magnetic materials at the nanoscale. Thus, we investigated the early stages of magnetosome formation in this work and correlated the size and emergent crystallinity of magnetosome nanoparticles with the changes in chemical environment of iron and oxygen by utilizing advanced analytical electron microscopy techniques. We observed that magnetosomes in the early stages of biomineralization with the sizes of 5–10 nm were amorphous, with a majority of iron present as Fe 3+, indicative of ferric hydroxide. The magnetosomes with intermediate sizes showed partially crystalline structuremore » with a majority of iron present as Fe 3+ and trace amounts of Fe 2+. The fully maturated magnetosomes were indexed to magnetite. Furthermore, our approach provides spatially resolved structural and chemical information of individual magnetosomes with different particle sizes, attributed to magnetosomes at different stages of biomineralization.« less

French Multicenter Study Evaluating the Risk of Lymph Node Metastases in Early-Stage Endometrial Cancer: Contribution of a Risk Scoring System.

PubMed

Bendifallah, Sofiane; Canlorbe, Geoffroy; Arsène, Emmanuelle; Collinet, Pierre; Huguet, Florence; Coutant, Charles; Hudry, Delphine; Graesslin, Olivier; Raimond, Emilie; Touboul, Cyril; Daraï, Emile; Ballester, Marcos

2015-08-01

This study was designed to develop a risk scoring system (RSS) for predicting lymph node (LN) metastases in patients with early-stage endometrial cancer (EC). Data of 457 patients with early-stage EC who received primary surgical treatment between January 2001 and December 2012 were abstracted from a prospective, multicentre database (training set). A risk model based on factors impacting LN metastases was developed. To assess the discrimination of the RSS, both internal by the bootstrap approach and external validation (validation set) were adopted. Overall the LN metastasis rate was 11.8 % (54/457). LN metastases were associated with five variables: age ≥60 years, histological grade 3 and/or type 2, primary tumor diameter ≥1.5 cm, depth of myometrial invasion ≥50 %, and the positive lymphovascular space involvement status. These variables were included in the RSS and assigned scores ranging from 0 to 9. The discrimination of the RSS was 0.81 [95 % confidence interval (CI) 0.78-0.84] in the training set. The area under the curve of the receiver-operating characteristics for predicting LN metastases after internal and external validation was 0.80 (95 % CI 0.77-0.83) and 0.85 (95 % CI 0.81-0.89), respectively. A total score of 6 points corresponded to the optimal threshold of the RSS with a rate of LN metastases of 7.5 % (29/385) and 34.7 % (25/72) for low-risk (≤6 points) and high-risk patients (>6 points), respectively. At this threshold, the diagnostic accuracy was 83 %. This RSS could be useful in clinical practice to determine which patients with early-stage EC should benefit from secondary surgical staging including complete lymphadenectomy.

Early stages of figure-ground segregation during perception of the face-vase.

PubMed

Pitts, Michael A; Martínez, Antígona; Brewer, James B; Hillyard, Steven A

2011-04-01

The temporal sequence of neural processes supporting figure-ground perception was investigated by recording ERPs associated with subjects' perceptions of the face-vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects' figure-ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ∼ 150-200 msec) when that region was perceived as figure versus background. These components likely reflect an early "border ownership" stage, and a subsequent "figure-ground segregation" stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure-ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure-ground perception, each which are subject to modifications by selective attention.

Two-Stage Categorization in Brand Extension Evaluation: Electrophysiological Time Course Evidence

PubMed Central

Wang, Xiaoyi

2014-01-01

A brand name can be considered a mental category. Similarity-based categorization theory has been used to explain how consumers judge a new product as a member of a known brand, a process called brand extension evaluation. This study was an event-related potential study conducted in two experiments. The study found a two-stage categorization process reflected by the P2 and N400 components in brand extension evaluation. In experiment 1, a prime–probe paradigm was presented in a pair consisting of a brand name and a product name in three conditions, i.e., in-category extension, similar-category extension, and out-of-category extension. Although the task was unrelated to brand extension evaluation, P2 distinguished out-of-category extensions from similar-category and in-category ones, and N400 distinguished similar-category extensions from in-category ones. In experiment 2, a prime–probe paradigm with a related task was used, in which product names included subcategory and major-category product names. The N400 elicited by subcategory products was more significantly negative than that elicited by major-category products, with no salient difference in P2. We speculated that P2 could reflect the early low-level and similarity-based processing in the first stage, whereas N400 could reflect the late analytic and category-based processing in the second stage. PMID:25438152

Toxicity of naproxen sodium and its mixture with tramadol hydrochloride on fish early life stages.

PubMed

Sehonova, Pavla; Plhalova, Lucie; Blahova, Jana; Doubkova, Veronika; Prokes, Miroslav; Tichy, Frantisek; Fiorino, Emma; Faggio, Caterina; Svobodova, Zdenka

2017-12-01

Pharmaceuticals occur in water bodies as a consequence of their incomplete removal during waste water treatment processes. The occurence of pharmaceuticals in surface waters as well as their possible impact on aquatic vertebrates have received considerable attention in recent years. However, there is still a lack of informations on the chronic effects of widely used drugs as well as their possible mixture toxicity on non-target aquatic vertebrates as well as their possible mixture toxicity. The aim of this study was to assess the effects of naproxen sodium on early life stages of fish and evaluate its mixture toxicity with tramadol hydrochloride, which was assessed in our earlier study as a single substance. Two embryo-larval toxicity tests with common carp (Cyprinus carpio) were performed according to the OECD guideline 210 (Fish, Early-life Stage Toxicity Test) in order to assess the subchronic toxicity of naproxen sodium and tramadol hydrochlorid-naproxen sodium mixture at the concentrations of 10; 50; 100 and 200 μg/L. These experiments were conducted for 32 days. The subchronic exposure to naproxen sodium and naproxen sodium and tramadol hydrochloride mixture had a strong effect on the early life stages of common carp. Hatching, developmental rate, morphology, histopathology and, in the case of the naproxen sodium and tramadol hydrochloride mixture, mortality were influenced. The bioindicators of oxidative stress were also influenced. The LOEC was determined at 10 μg/L for both naproxen sodium and naproxen sodium and tramadol hydrochloride mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Laminarin improves developmental competence of porcine early stage embryos by inhibiting oxidative stress.

PubMed

Jiang, Hao; Liang, Shuang; Yao, Xue-Rui; Jin, Yong-Xun; Shen, Xing-Hui; Yuan, Bao; Zhang, Jia-Bao; Kim, Nam-Hyung

2018-04-23

Laminarin (LMA), a β-glucan mixture with good biocompatibility, improves the growth performance and immune response when used as food additives and nutraceuticals. The aim of the present research was to explore the effects of LMA on porcine early stage embryo development, as well as the underlying mechanisms. The results showed that the developmental competence of porcine early stage embryos was dramatically improved after LMA supplementation during the in vitro culture period. The presence of 20 μg/mL LMA during the in vitro culture period significantly improved cleavage rate, blastocyst formation rates, hatching rate, and total cell number in the blastocyst compared to that in the control group. Notably, LMA attenuated the intracellular reactive oxygen species generation induced by H 2 O 2 . Furthermore, LMA not only increased intracellular glutathione levels, but also ameliorated mitochondrial membrane potential. In addition, the expression of a zygotic genome activation related gene (YAP1), pluripotency-related genes (OCT4, NANOG, and SOX2), and hatching-related genes (COX2, GATA4, and ITGA5) were up-regulated following LMA supplementation during porcine early stage embryo development. These results demonstrate that LMA has beneficial effects on the development of porcine early stage embryos via regulation of oxidative stress. This evidence provides a novel method for embryo development improvement associated with exposure to LMA. Copyright © 2018 Elsevier Inc. All rights reserved.

Recognition of early stage thigmotaxis in Morris water maze test with convolutional neural network.

PubMed

Higaki, Akinori; Mogi, Masaki; Iwanami, Jun; Min, Li-Juan; Bai, Hui-Yu; Shan, Bao-Shuai; Kan-No, Harumi; Ikeda, Shuntaro; Higaki, Jitsuo; Horiuchi, Masatsugu

2018-01-01

The Morris water maze test (MWM) is a useful tool to evaluate rodents' spatial learning and memory, but the outcome is susceptible to various experimental conditions. Thigmotaxis is a commonly observed behavioral pattern which is thought to be related to anxiety or fear. This behavior is associated with prolonged escape latency, but the impact of its frequency in the early stage on the final outcome is not clearly understood. We analyzed swim path trajectories in male C57BL/6 mice with or without bilateral common carotid artery stenosis (BCAS) treatment. There was no significant difference in the frequencies of particular types of trajectories according to ischemic brain surgery. The mouse groups with thigmotaxis showed significantly prolonged escape latency and lower cognitive score on day 5 compared to those without thigmotaxis. As the next step, we made a convolutional neural network (CNN) model to recognize the swim path trajectories. Our model could distinguish thigmotaxis from other trajectories with 96% accuracy and specificity as high as 0.98. These results suggest that thigmotaxis in the early training stage is a predictive factor for impaired performance in MWM, and machine learning can detect such behavior easily and automatically.

Strong correlation between early stage atherosclerosis and electromechanical coupling of aorta

NASA Astrophysics Data System (ADS)

Liu, X. Y.; Yan, F.; Niu, L. L.; Chen, Q. N.; Zheng, H. R.; Li, J. Y.

2016-03-01

Atherosclerosis is the underlying cause of cardiovascular diseases that are responsible for many deaths in the world, and the early diagnosis of atherosclerosis is highly desirable. The existing imaging methods, however, are not capable of detecting the early stage of atherosclerosis development due to their limited spatial resolution. Using piezoresponse force microscopy (PFM), we show that the piezoelectric response of an aortic wall increases as atherosclerosis advances, while the stiffness of the aorta shows a less evident correlation with atherosclerosis. Furthermore, we show that there is strong correlation between the coercive electric field necessary to switch the polarity of the artery and the development of atherosclerosis. Thus by measuring the electromechanical coupling of the aortic wall, it is possible to probe atherosclerosis at the early stage of its development, not only improving the spatial resolution by orders of magnitude, but also providing comprehensive quantitative information on the biomechanical properties of the artery.

Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

PubMed

Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

2013-06-01

Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

PubMed Central

Wu, Chia-Chou; Lin, Chih-Lung; Chen, Ting-Shou

2015-01-01

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID:26366411

Developmental rate and behavior of early life stages of bighead carp and silver carp

USGS Publications Warehouse

Chapman, Duane C.; George, Amy E.

2011-01-01

The early life stages of Asian carp are well described by Yi and others (1988), but since these descriptions are represented by line drawings based only on live individuals and lacked temperature controls, further information on developmental time and stages is of use to expand understanding of early life stages of these species. Bighead carp and silver carp were cultured under two different temperature treatments to the one-chamber gas bladder stage, and a photographic guide is provided for bighead carp and silver carp embryonic and larval development, including notes about egg morphology and larval swimming behavior. Preliminary information on developmental time and hourly thermal units for each stage is also provided. Both carp species developed faster under warmer conditions. Developmental stages and behaviors are generally consistent with earlier works with the exception that strong vertical swimming immediately after hatching was documented in this report.

Early-\\x90stage Electrical Breakdown involving Tunneling

NASA Astrophysics Data System (ADS)

Hjalmarson, Harold; Moore, Chris; Schultz, Peter; Bussman, Ezra; Scrymgeour, David; Hopkins, Matt

The early stage of electrical breakdown from a surface is assumed to involve field emission. In real-world applications, the electrical field is often assumed to be increased by geometrical effects. In addition to these enhancement effects, contamination by adsorbates can lead to reductions in the effective work functions. To develop a physics-based understanding beyond the use of these empirical effects, the field emission currents at early times are being computed and measured. The calculations involve a solution of the Boltzmann equation, and the measurements involve a scanning tunneling microscope. Early results from this collaborative theoretical-experimental project will be described in this presentation. The presentation will focus on results for an ideal system with an absence of geometrical effects. Sandia National Laboratories is a multi-mission laboratory managed and operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration under contract DE-AC04-94AL85000.

Stereotactic body radiotherapy for operable early-stage non-small cell lung cancer.

PubMed

Eriguchi, Takahisa; Takeda, Atsuya; Sanuki, Naoko; Tsurugai, Yuichiro; Aoki, Yousuke; Oku, Yohei; Hara, Yu; Akiba, Takeshi; Shigematsu, Naoyuki

2017-07-01

To analyze outcomes of stereotactic body radiotherapy (SBRT) for operable patients with early-stage non-small cell lung cancer (NSCLC) and to evaluate factors associated with outcomes. We retrospectively analyzed operable patients with NSCLC, staged as cT1-2N0M0, treated with SBRT between 2006 and 2015. Both biopsy-proven and clinically diagnosed NSCLC were included. Local control and survival rates were calculated and compared between subsets of patients. We investigated factors associated with outcomes. We identified 88 operable patients among 661 patients with cT1-2N0M0 NSCLC. The median age was 79 years (range: 55-88). The median follow-up time after SBRT was 40 months (range: 4-121). Fifty-nine patients had been pathologically diagnosed and the other 29 had been clinically diagnosed as having NSCLC. Local control, cause-specific survival (CSS) and overall survival (OS) at 3 years were 91%, 97% and 90% for T1, and 100%, 82% and 74% for T2, respectively. The CSS and OS at 3 years were 100% and 100% for GGO and 83% and 59% for solid tumors, respectively (p=0.005). On univariate analysis, age and T stage were significantly associated with CSS, and age, the Charlson Comorbidity Index (CCI), and opacity were significantly associated with OS. On multivariate analysis, age and CCI were significantly associated with OS. As for toxicities, Grades 0, 1, 2 and 3 radiation pneumonitis occurred in 37.5%, 47.7%, 13.6% and 1.1% of patients, respectively. No Grade 4 or 5 radiation pneumonitis occurred, and no other toxicities of Grade 2 or above were observed. Outcomes of SBRT for operable early stage NSCLC were as good as previous SBRT and surgery studies. Further investigation for selecting good SBRT candidates is warranted in high-risk operable patients. Copyright © 2017 Elsevier B.V. All rights reserved.

Subthalamic Nucleus Deep Brain Stimulation in Early Stage Parkinson’s Disease

PubMed Central

Charles, David; Konrad, Peter E.; Neimat, Joseph S.; Molinari, Anna L.; Tramontana, Michael G.; Finder, Stuart G.; Gill, Chandler E.; Bliton, Mark J.; Kao, Chris C.; Phibbs, Fenna T.; Hedera, Peter; Salomon, Ronald M.; Cannard, Kevin R.; Wang, Lily; Song, Yanna; Davis, Thomas L.

2014-01-01

Background Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson’s disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Methods Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50–75, on medication ≥ 6 months but < 4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n=15) or DBS+ODT (n=15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. Results As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. The DBS+ODT group took less medication at all time points, and this reached maximum difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS+ODT group suffered serious adverse events; remaining adverse events were mild or transient. Conclusions This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. PMID:24768120

Amygdalohippocampal MR volume measurements in the early stages of Alzheimer disease

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

Lehericy, S.; Baulac, M.; Chiras, J.

1994-05-01

To evaluate the accuracy of hippocampal and amygdala volume measurements in diagnosing patients in the early stages of Alzheimer disease. Measurements of the hippocampal formation, amygdala, amygdalohippocampal complex (the two measurements summed), caudate nucleus, and ventricles, normalized for total intracranial volume, were obtained on coronal sections (1.5 T, 400/13 [repetition time/echo time], 5 mm) of 13 patients in the mild (minimental status {ge} 21) and five patients in the moderate stages of Alzheimer disease (10 < minimental status < 21), and eight age-matched control subjects. For patients with a minimental status score of 21 or greater, atrophy was significant formore » the amygdala and hippocampal formation (-36% and -25% for amygdala/total intracranial volume and hippocampal formation/total intracranial volume, respectively), but not for the caudate nucleus. No significant ventricular enlargement was found. For patients with a minimental status score less than 21, atrophy was more severe in all structures studied (amygdala/total intracranial volume -40%; hippocampal formation/total intracranial volume, -45%; caudate nucleus/total intracranial volume, -21%), and ventricles were enlarged (63%). No overlap was found between Alzheimer disease and control values for the amygdalohippocampal volume, even in the mild stages of the disease. In Alzheimer disease patients, hippocampal formation volumes correlated with the minimental status. Hippocampal and amygdala atrophy is marked and significant in the mild stages of Alzheimer disease. Volumetric measurements of the amygdala and the amygdalohippocampal complex appear more accurate than those of the hippocampal formation alone in distinguishing patients with Alzheimer disease. 46 refs., 8 figs., 2 tabs.« less

The Impact of Radiation Oncologists on the Early Adoption of Hypofractionated Radiation Therapy for Early-Stage Breast Cancer.

PubMed

Boero, Isabel J; Gillespie, Erin F; Hou, Jiayi; Paravati, Anthony J; Kim, Ellen; Einck, John P; Yashar, Catheryn; Mell, Loren K; Murphy, James D

2017-03-01

Despite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer. We identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy. Among the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P<.05). The individual radiation oncologist strongly influenced the likelihood of a patient

Early Stages of the Evolution of Life: a Cybernetic Approach

NASA Astrophysics Data System (ADS)

Melkikh, Alexey V.; Seleznev, Vladimir D.

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Early stages of the evolution of life: a cybernetic approach.

PubMed

Melkikh, Alexey V; Seleznev, Vladimir D

2008-08-01

Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

Dual odontogenic origins develop at the early stage of rat maxillary incisor development.

PubMed

Kriangkrai, Rungarun; Iseki, Sachiko; Eto, Kazuhiro; Chareonvit, Suconta

2006-03-01

Developmental process of rat maxillary incisor has been studied through histological analysis and investigation of tooth-related gene expression patterns at initial tooth development. The tooth-related genes studied here are fibroblast growth factor-8 (Fgf-8), pituitary homeobox gene-2 (Pitx-2), sonic hedgehog (Shh), muscle segment homeobox-1 (Msx-1), paired box-9 (Pax-9) and bone morphogenetic protein-4 (Bmp-4). The genes are expressed in oral epithelium and/or ectomesenchyme at the stage of epithelial thickening to the early bud stage of tooth development. Both the histological observation and tooth-related gene expression patterns during early stage of maxillary incisor development demonstrate that dual odontogenic origins aligned medio-laterally in the medial nasal process develop, subsequently only single functional maxillary incisor dental placode forms. The cascade of tooth-related gene expression patterns in rat maxillary incisor studied here is quite similar to those of the previous studies in mouse mandibular molar, even though the origins of oral epithelium and ectomesenchyme involved in development of maxillary incisor and mandibular molar are different. Thus, we conclude that maxillary incisor and mandibular molar share a similar signaling control of Fgf-8, Pitx-2, Shh, Msx-1, Pax-9 and Bmp-4 genes at the stage of oral epithelial thickening to the early bud stage of tooth development.

Early Stages of Figure–Ground Segregation during Perception of the Face–Vase

PubMed Central

Pitts, Michael A.; Martínez, Antígona; Brewer, James B.; Hillyard, Steven A.

2011-01-01

The temporal sequence of neural processes supporting figure–ground perception was investigated by recording ERPs associated with subjects’ perceptions of the face–vase figure. In Experiment 1, subjects continuously reported whether they perceived the face or the vase as the foreground figure by pressing one of two buttons. Each button press triggered a probe flash to the face region, the vase region, or the borders between the two. The N170/vertex positive potential (VPP) component of the ERP elicited by probes to the face region was larger when subjects perceived the faces as figure. Preceding the N170/VPP, two additional components were identified. First, when the borders were probed, ERPs differed in amplitude as early as 110 msec after probe onset depending on subjects’ figure–ground perceptions. Second, when the face or vase regions were probed, ERPs were more positive (at ~150–200 msec) when that region was perceived as figure versus background. These components likely reflect an early “border ownership” stage, and a subsequent “figure–ground segregation” stage of processing. To explore the influence of attention on these stages of processing, two additional experiments were conducted. In Experiment 2, subjects selectively attended to the face or vase region, and the same early ERP components were again produced. In Experiment 3, subjects performed an identical selective attention task, but on a display lacking distinctive figure–ground borders, and neither of the early components were produced. Results from these experiments suggest sequential stages of processing underlying figure–ground perception, each which are subject to modifications by selective attention. PMID:20146604

Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

PubMed

Louie, Raphael J; Tonneson, Jennifer E; Gowarty, Minda; Goodney, Philip P; Barth, Richard J; Rosenkranz, Kari M

2015-11-01

Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

Early-stage aeolian protodune development and migration

NASA Astrophysics Data System (ADS)

Nield, J. M.; Baddock, M. C.; Wiggs, G.

2017-12-01

Early-stage bedforms, or protodunes, can be observed to form on sandy beaches, desert gravels or superimposed on the surfaces of larger dunes and can develop topography of 0.1 m or more over several hours. These protodunes are the precursors to embryo and eventually mature dunes, and so it is important to understand how feedbacks between flow, transport and form contribute to this development sequence. Whilst theory and conceptual models have offered some explanation for protodune existence and development, we know surprisingly little about how these bedforms initiate and migrate because it is difficult to measure small changes in form (millimetres; seconds) on highly active surfaces of limited topographic expression. Here, we employ terrestrial laser scanning (TLS) to measure morphological change at the high frequency and spatial resolution (sub-millimetre) required to gain new insights into protodune behaviour. Along with TLS derived saltation and surface moisture, additional sediment flux and windspeed measurements help to elucidate how the protodune topography interacts with airflow and sand transport. We focus on a number of coastal bedforms in various development stages including a 0.06 m high protodune which grew vertically by 0.005 m in two hours with the switch from erosion to deposition identified to occur at a point 0.07 m upwind of the crest. This growth was associated with a reduction in time-averaged sediment flux of 18% over the crestal region. We also observed a decline in lower stoss slope steepness (by 3°) and a steepening of the lee slope, indicating a reshaping of initial protodune form towards the morphology of a more mature dune. Our findings highlight the crucial role of form-flow feedbacks, even on very small bedforms, in driving early-stage bedform growth and development, and show how the use of high resolution TLS to measure both surface topography and grains moving above the surface, can offer new insights into a long standing deficiency

Funding opportunities for investigators in the early stages of career development.

PubMed

Sumandea, C Amelia; Balke, C William

2009-03-10

Many sources of advice and guidance are available to the early career investigator. Generally, mentors serve as the primary source of information, although program and review officers are the most underutilized resources. This article organizes these opportunities to enable early career investigators to plot a rational trajectory for career success. A list of the major agencies that provide grant support for early career investigators is included. In addition, funding opportunities are organized on the basis of the stage in career development pathway and the type of terminal degree.

Assessment of the quality of medical care among patients with early stage prostate cancer undergoing expectant management in the United States.

PubMed

Ritchey, Jamie; Gay, E Greer; Spencer, Benjamin A; Miller, David C; Wallner, Lauren P; Stewart, Andrew K; Dunn, Rodney L; Litwin, Mark S; Wei, John T

2012-09-01

Given the increased attention to the quality and cost of medical care, the Institute of Medicine and Centers for Medicare and Medicaid Services have called for performance measurement and reporting. The clinical management of prostate cancer has been outlined, yet is not intended to describe quality prostate cancer care. Therefore, RAND researchers developed quality indicators for early stage prostate cancer. The ACoS (American College of Surgeons) used these indicators to perform the first national assessment to our knowledge of the quality of care among men with early stage prostate cancer undergoing expectant management. Information from medical records was abstracted for evidence of compliance with the RAND indicators (structure and process). Weighted and stratified proportions were calculated to assess indicator compliance. Logistic regression models were fit and evaluated by hospital type and patient factors. A weighted and stratified total of 13,876 early stage prostate cancer cases on expectant management in 2000 to 2001 were investigated. Compliance with structural indicators was high (greater than 80%) and compliance with process indicators varied (19% to 87%). Differences in process indicators were observed from models by hospital type and comorbid conditions, but not for age, race or insurance status. Using the RAND quality indicators this study revealed several process areas for quality improvement among men with early stage prostate cancer on expectant management in the United States. Efforts to improve the quality of early stage prostate cancer care need to move beyond the paradigm of age, race and insurance status. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Flexibility in Early Stage Design of U. S. Navy Ships: An Analysis of Options

DTIC Science & Technology

2011-01-01

Flexibility in Early Stage Design of US Navy Ships: An Analysis of Options by Jonathan Page B.S., Systems Engineering, US Naval Academy, 2002...8217C/ v = (;!;!: ;: Pat Hale Director, Systems Design and Ma~ement Fellows Program E~i_yfering.S~~pivi~i~ Acceptedby...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Flexibility in Early Stage Design of U. S. Navy Ships: An

Morphological and histomorphological structures of testes and ovaries in early developmental stages of the silkworm, Bombyx mori.

PubMed

Sakai, Hiroki; Kirino, Yohei; Katsuma, Susumu; Aoki, Fugaku; Suzuki, Masataka G

2016-01-01

The gonad develops as a testis in male or an ovary in female. In the silkworm, B. mori , little is known about testis and ovary in the embryonic stages and early larval stages. In this study, we performed morphological and histomorphological observations of ovaries and testes from the late embryonic stage to the 1st instar larval stage. Results obtained with lack of accurate information on sex of examined individuals may be misleading, thus we performed phenotypic observations of gonads by utilizing sex-limited strain that enables us to easily discriminate female embryos from male ones based on those egg colors. In testis, four testicular follicles were clearly observed in the testis at the first instar larval stage, and boundary layers were formed between the testicular follicles. At the late embryonic stage, the testis consisted of four testicular follicles, while the boundary layers were still obscure. In ovary, four ovarioles were easily recognizable in the ovary at the first instar larval stage, and boundary layers were formed between the ovarioles. However, in the late embryonic stage, it was quite difficult to identify four ovarioles. Morphological characteristics were almost similar between testis and ovary in early developmental stages. Our present study demonstrates that the most reliable difference between testis and ovary in early developmental stages is the attaching point of the duct. Formation and development of the duct may be sensitive to the sex-determining signal and display sexual dimorphism in early embryonic stages.

Socioeconomic position and surgery for early-stage non-small-cell lung cancer: A population-based study in Denmark.

PubMed

Kærgaard Starr, Laila; Osler, Merete; Steding-Jessen, Marianne; Lidegaard Frederiksen, Birgitte; Jakobsen, Erik; Østerlind, Kell; Schüz, Joachim; Johansen, Christoffer; Oksbjerg Dalton, Susanne

2013-03-01

To examine possible associations between socioeconomic position and surgical treatment of patients with early-stage non-small-cell lung cancer (NSCLC). In a register-based clinical cohort study, patients with early-stage (stages I-IIIa) NSCLC were identified in the Danish Lung Cancer Register 2001-2008 (date of diagnosis, histology, stage, and treatment), the Central Population Register (vital status), the Integrated Database for Labour Market Research (socioeconomic position), and the Danish Hospital Discharge Register (comorbidity). Logistic regression analyses were performed overall and separately for stages I, II and IIIa. Of the 5538 eligible patients with stages I-IIIa NSCLC diagnosed 2001-2008, 53% underwent surgery. Higher stage, older age, being female and diagnosis early in the study period were associated with higher odds for not receiving surgery. Low disposable income was associated with greater odds for no surgery in stage I and stage II patients as was living alone for stage I patients. Comorbidity, a short diagnostic interval and small diagnostic volume were all associated with higher odds for not undergoing surgery; but these factors did not appear to explain the association with income or living alone for early-stage NSCLC patients. Early-stage NSCLC patients with low income or who live alone are less likely to undergo surgery than those with a high income or who live with a partner, even after control for possible explanatory factors. Thus, even in a health care system with free, equal access to health services, disadvantaged groups are less likely to receive surgery for lung cancer. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Metamorphic density controls on early-stage subduction dynamics

NASA Astrophysics Data System (ADS)

Duesterhoeft, Erik; Oberhänsli, Roland; Bousquet, Romain

2013-04-01

Subduction is primarily driven by the densification of the downgoing oceanic slab, due to dynamic P-T-fields in subduction zones. It is crucial to unravel slab densification induced by metamorphic reactions to understand the influence on plate dynamics. By analyzing the density and metamorphic structure of subduction zones, we may gain knowledge about the driving, metamorphic processes in a subduction zone like the eclogitization (i.e., the transformation of a MORB to an eclogite), the breakdown of hydrous minerals and the release of fluid or the generation of partial melts. We have therefore developed a 2D subduction zone model down to 250 km that is based on thermodynamic equilibrium assemblage computations. Our model computes the "metamorphic density" of rocks as a function of pressure, temperature and chemical composition using the Theriak-Domino software package at different time stages. We have used this model to investigate how the hydration, dehydration, partial melting and fractionation processes of rocks all influence the metamorphic density and greatly depend on the temperature field within subduction systems. These processes are commonly neglected by other approaches (e.g., gravitational or thermomechanical in nature) reproducing the density distribution within this tectonic setting. The process of eclogitization is assumed as being important to subduction dynamics, based on the very high density (3.6 g/cm3) of eclogitic rocks. The eclogitization in a MORB-type crust is possible only if the rock reaches the garnet phase stability field. This process is primarily temperature driven. Our model demonstrates that the initiation of eclogitization of the slab is not the only significant process that makes the descending slab denser and is responsible for the slab pull force. Indeed, our results show that the densification of the downgoing lithospheric mantle (due to an increase of pressure) starts in the early subduction stage and makes a significant

Dyadic Intervention for Family Caregivers and Care Receivers in Early-Stage Dementia

ERIC Educational Resources Information Center

Whitlatch, Carol J.; Judge, Katherine; Zarit, Steven H.; Femia, Elia

2006-01-01

Purpose: The Early Diagnosis Dyadic Intervention (EDDI) program provides a structured, time-limited protocol of one-on-one and dyadic counseling for family caregivers and care receivers who are in the early stages of dementia. The goals and procedures of EDDI are based on previous research suggesting that dyads would benefit from an intervention…

[Effects of the association of sulbutiamine with an acetylcholinesterase inhibitor in early stage and moderate Alzheimer disease].

PubMed

Ollat, H; Laurent, B; Bakchine, S; Michel, B-F; Touchon, J; Dubois, B

2007-01-01

The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.

Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

EPA Science Inventory

Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

Lernpunkt Deutsch--Stage 1.

ERIC Educational Resources Information Center

Theil, Elvira

1997-01-01

Evaluates the first stage of "Lernpunkt Deutsch," a new three-stage German course designed for upper elementary and early secondary school. Describes the publisher's package of materials and the appropriateness of the course, utility of the different package elements, format of the materials, and assesses whether the course provides pedagogically…

Role of chemotherapy and targeted therapy in early-stage non-small cell lung cancer.

PubMed

Nagasaka, Misako; Gadgeel, Shirish M

2018-01-01

Adjuvant platinum based chemotherapy is accepted as standard of care in stage II and III non-small cell lung cancer (NSCLC) patients and is often considered in patients with stage IB disease who have tumors ≥ 4 cm. The survival advantage is modest with approximately 5% at 5 years. Areas covered: This review article presents relevant data regarding chemotherapy use in the perioperative setting for early stage NSCLC. A literature search was performed utilizing PubMed as well as clinical trial.gov. Randomized phase III studies in this setting including adjuvant and neoadjuvant use of chemotherapy as well as ongoing trials on targeted therapy and immunotherapy are also discussed. Expert commentary: With increasing utilization of screening computed tomography scans, it is possible that the percentage of early stage NSCLC patients will increase in the coming years. Benefits of adjuvant chemotherapy in early stage NSCLC patients remain modest. There is a need to better define patients most likely to derive survival benefit from adjuvant therapy and spare patients who do not need adjuvant chemotherapy due to the toxicity of such therapy. Trials for adjuvant targeted therapy, including adjuvant EGFR-TKI trials and trials of immunotherapy drugs are ongoing and will define the role of these agents as adjuvant therapy.

Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

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

Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

2016-04-01

Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

New features of triacylglycerol biosynthetic pathways of peanut seeds in early developmental stages.

PubMed

Yu, Mingli; Liu, Fengzhen; Zhu, Weiwei; Sun, Meihong; Liu, Jiang; Li, Xinzheng

2015-11-01

The peanut (Arachis hypogaea L.) is one of the three most important oil crops in the world due to its high average oil content (50 %). To reveal the biosynthetic pathways of seed oil in the early developmental stages of peanut pods with the goal of improving the oil quality, we presented a method combining deep sequencing analysis of the peanut pod transcriptome and quantitative real-time PCR (RT-PCR) verification of seed oil-related genes. From the sequencing data, approximately 1500 lipid metabolism-associated Unigenes were identified. The RT-PCR results quantified the different expression patterns of these triacylglycerol (TAG) synthesis-related genes in the early developmental stages of peanut pods. Based on these results and analysis, we proposed a novel construct of the metabolic pathways involved in the biosynthesis of TAG, including the Kennedy pathway, acyl-CoA-independent pathway and proposed monoacylglycerol pathway. It showed that the biosynthetic pathways of TAG in the early developmental stages of peanut pods were much more complicated than a simple, unidirectional, linear pathway.

Volumetric modulated arc radiotherapy sparing the thyroid gland for early-stage glottic cancer: A dosimetrical analysis.

PubMed

Kim, Eun Seok; Yeo, Seung-Gu

2014-06-01

Previous studies on advanced radiotherapy (RT) techniques for early stage glottic cancer have focused on sparing the carotid artery. However, the aim of the present study was to evaluate the dosimetric advantages of volumetric modulated arc therapy (VMAT) in terms of sparing the thyroid gland in early-stage glottic cancer patients. In total, 15 cT1N0M0 glottic cancer patients treated with definitive RT using VMAT were selected, and for dosimetric comparison, a conventional RT plan comprising opposed-lateral wedged fields was generated for each patient. The carotid artery, thyroid gland and spinal cord were considered organs at risk. The prescription dose was 63 Gy at 2.25 Gy per fraction. For the thyroid gland and carotid artery, all compared parameters were significantly lower with VMAT compared with conventional RT. For the thyroid gland, the median reduction rates of the mean dose (D mean ), the volume receiving ≥30% of the prescription dose (V 30 ) and the V 50 were 32.6, 40.9 and 46.0%, respectively. The D mean was 14.7±2.6 Gy when using VMAT compared with 22.2±3.9 Gy when using conventional RT. The differences between the techniques in terms of planning target volume coverage and dose homogeneity were not significant. When considering a recent normal tissue complication probability model, which indicated the mean thyroid gland dose as the most significant predictor of radiation-induced hypothyroidism, the dosimetric advantage shown in this study may be valuable in reducing hypothyroidism following RT for early stage glottic cancer patients.

Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

PubMed Central

Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

2014-01-01

Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

Metabolomic Markers of Altered Nucleotide Metabolism in Early Stage Adenocarcinoma

PubMed Central

Wikoff, William R.; Grapov, Dmitry; Fahrmann, Johannes F.; DeFelice, Brian; Rom, William; Pass, Harvey; Kim, Kyoungmi; Nguyen, UyenThao; Taylor, Sandra L.; Kelly, Karen; Fiehn, Oliver; Miyamoto, Suzanne

2015-01-01

Adenocarcinoma, a type of non-small-cell lung cancer (NSCLC), is the most frequently diagnosed lung cancer and the leading cause of lung cancer mortality in the United States. It is well documented that biochemical changes occur early in the transition from normal to cancer cells, but the extent to which these alterations affect tumorigenesis in adenocarcinoma remains largely unknown. Herein we describe the application of mass spectrometry and multivariate statistical analysis in one of the largest biomarker research studies to date aimed at distinguishing metabolic differences between malignant and non-malignant lung tissue. Gas chromatography time-of-flight mass spectrometry was used to measure 462 metabolites in 39 malignant and non-malignant lung tissue pairs from current or former smokers with early stage (Stage IA–IB) adenocarcinoma. Statistical mixed effects models, orthogonal partial least squares discriminant analysis and network integration, were used to identify key cancer-associated metabolic perturbations in adenocarcinoma compared to non-malignant tissue. Cancer-associated biochemical alterations were characterized by: 1) decreased glucose levels, consistent with the Warburg effect, 2) changes in cellular redox status highlighted by elevations in cysteine and antioxidants, alpha- and gamma-tocopherol, 3) elevations in nucleotide metabolites 5,6-dihydrouracil and xanthine suggestive of increased dihydropyrimidine dehydrogenase and xanthine oxidoreductase activity, 4) increased 5'-deoxy-5'-methylthioadenosine levels indicative of reduced purine salvage and increased de novo purine synthesis and 5) coordinated elevations in glutamate and UDP-N-acetylglucosamine suggesting increased protein glycosylation. The present study revealed distinct metabolic perturbations associated with early stage lung adenocarcinoma which may provide candidate molecular targets for personalizing therapeutic interventions and treatment efficacy monitoring. PMID:25657018

Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure

PubMed Central

Oh, Kook-Hwan; Hwang, Young-Hwan; Cho, Jung-Hwa; Kim, Mira; Ju, Kyung Don; Joo, Kwon Wook; Kim, Dong Ki; Kim, Yon Su; Ahn, Curie

2012-01-01

Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID:22323864

Practice Patterns of Radiation Field Design for Sentinel Lymph Node-Positive Early-Stage Breast Cancer.

PubMed

Azghadi, Soheila; Daly, Megan; Mayadev, Jyoti

2016-10-01

Recent randomized trials have led to decreased use of completion axillary lymph node dissection (ALND) in early-stage breast cancer patients with a positive sentinel lymph node (SLN), causing controversy surrounding radiotherapy coverage of the axilla. We investigated the practice variation among radiation oncologists for regional nodal coverage for clinicopathologic scenarios and evaluated axillary field design decision-making processes. A customized, web-based questionnaire was e-mailed to 983 community (n = 617) and academic (n = 366) radiation oncologists with a breast cancer subspecialty practicing in the United States. The survey consisted of 18 multiple-choice questions evaluating general clinical preferences surrounding radiation therapy (RT) field design for patients with early-stage breast cancer and a positive SLN. Seven case scenarios were developed to investigate the field design in the setting of specific clinical and pathologic risk factors. Nodal coverage was classified as standard tangents (STs), high tangents (HTs), STs and a supraclavicular field (SCF), or STs and full axillary coverage (AX). A total of 145 evaluable responses were collected, with a response rate of 15.0%. Of the respondents, 12 (8.3%) reported using completion ALND for patients with 1 to 3 positive SLNs without extracapsular extension (ECE) and 66 (45.5%) performed ALND with 1 to 3 positive SLNs with ECE. For micrometastatic SLNs, with no lymphovascular system invasion, 115 (87.1%) used STs or HTs. The use of neoadjuvant chemotherapy (NAC) influenced RT field design for patients with a positive SLN without ECE, with 64 (48.5%) using STs and SCF or STs and AX treatment without NAC and 94 (70.7%) using SCF and AX after NAC. With macrometastatic SLN involvement, most respondents preferred SCF (45.27%) and AX (45.66%). In contrast, for micrometastatic involvement, HTs (43.61%) were frequently chosen. Forty (27.8%) reported using online predictive nomograms to predict further

Tau PET binding distinguishes patients with early-stage posterior cortical atrophy from amnestic Alzheimer disease dementia

PubMed Central

Day, Gregory S.; Gordon, Brian A.; Jackson, Kelley; Christensen, Jon J.; Ponisio, Maria Rosana; Su, Yi; Ances, Beau M; Benzinger, Tammie L.S.; Morris, John C.

2017-01-01

Background Flortaucipir (tau) PET binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Methods Flortaucipir and florbetapir (β-amyloid) PET-imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxel-wise level, controlling for age. Results PCA patients (median age-at-onset, 59 [51–61] years) were younger at symptom-onset than similarly-staged individuals with amnestic AD (75 [60–85] years) or CN controls (73 [61–90] years; p=0.002). Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Conclusions and Relevance Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype. PMID:28394771

Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia.

PubMed

Day, Gregory S; Gordon, Brian A; Jackson, Kelley; Christensen, Jon J; Rosana Ponisio, Maria; Su, Yi; Ances, Beau M; Benzinger, Tammie L S; Morris, John C

2017-01-01

Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease. Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age. PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients. Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

[Working memory for music in patients with mild cognitive impairment and early stage Alzheimer's disease].

PubMed

Kerer, Manuela; Marksteiner, Josef; Hinterhuber, Hartmann; Mazzola, Guerino; Kemmler, Georg; Bliem, Harald R; Weiss, Elisabeth M

2013-01-01

A variety of studies demonstrated that some forms of memory for music are spared in dementia, but only few studies have investigated patients with early stages of dementia. In this pilot-study we tested working memory for music in patients with mild cognitive impairment (MCI) and early stage Alzheimer's disease (AD) with a newly created test. The test probed working memory using 7 gradually elongated tone-lines and 6 chords which were each followed by 3 similar items and 1 identical item. The participants of the study, namely 10 patients with MCI, 10 patients with early stage AD and 23 healthy subjects were instructed to select the identical tone-line or chord. Subjects with MCI and early AD showed significantly reduced performance than controls in most of the presented tasks. In recognizing chords MCI- participants surprisingly showed an unimpaired performance. The gradual increase of the impairment during the preclinical phase of AD seems to spare this special ability in MCI.

Involvement of Clostridium botulinum ATCC 3502 Sigma Factor K in Early-Stage Sporulation

PubMed Central

Kirk, David G.; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu

2012-01-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σK is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods. PMID:22544236

Involvement of Clostridium botulinum ATCC 3502 sigma factor K in early-stage sporulation.

PubMed

Kirk, David G; Dahlsten, Elias; Zhang, Zhen; Korkeala, Hannu; Lindström, Miia

2012-07-01

A key survival mechanism of Clostridium botulinum, the notorious neurotoxic food pathogen, is the ability to form heat-resistant spores. While the genetic mechanisms of sporulation are well understood in the model organism Bacillus subtilis, nothing is known about these mechanisms in C. botulinum. Using the ClosTron gene-knockout tool, sigK, encoding late-stage (stage IV) sporulation sigma factor K in B. subtilis, was disrupted in C. botulinum ATCC 3502 to produce two different mutants with distinct insertion sites and orientations. Both mutants were unable to form spores, and their elongated cell morphology suggested that the sporulation pathway was blocked at an early stage. In contrast, sigK-complemented mutants sporulated successfully. Quantitative real-time PCR analysis of sigK in the parent strain revealed expression at the late log growth phase in the parent strain. Analysis of spo0A, encoding the sporulation master switch, in the sigK mutant and the parent showed significantly reduced relative levels of spo0A expression in the sigK mutant compared to the parent strain. Similarly, sigF showed significantly lower relative transcription levels in the sigK mutant than the parent strain, suggesting that the sporulation pathway was blocked in the sigK mutant at an early stage. We conclude that σ(K) is essential for early-stage sporulation in C. botulinum ATCC 3502, rather than being involved in late-stage sporulation, as reported for the sporulation model organism B. subtilis. Understanding the sporulation mechanism of C. botulinum provides keys to control the public health risks that the spores of this dangerous pathogen cause through foods.

Anxiety after completion of treatment for early-stage breast cancer: a systematic review to identify candidate predictors and evaluate multivariable model development.

PubMed

Harris, Jenny; Cornelius, Victoria; Ream, Emma; Cheevers, Katy; Armes, Jo

2017-07-01

The purpose of this review was to identify potential candidate predictors of anxiety in women with early-stage breast cancer (BC) after adjuvant treatments and evaluate methodological development of existing multivariable models to inform the future development of a predictive risk stratification model (PRSM). Databases (MEDLINE, Web of Science, CINAHL, CENTRAL and PsycINFO) were searched from inception to November 2015. Eligible studies were prospective, recruited women with stage 0-3 BC, used a validated anxiety outcome ≥3 months post-treatment completion and used multivariable prediction models. Internationally accepted quality standards were used to assess predictive risk of bias and strength of evidence. Seven studies were identified: five were observational cohorts and two secondary analyses of RCTs. Variability of measurement and selective reporting precluded meta-analysis. Twenty-one candidate predictors were identified in total. Younger age and previous mental health problems were identified as risk factors in ≥3 studies. Clinical variables (e.g. treatment, tumour grade) were not identified as predictors in any studies. No studies adhered to all quality standards. Pre-existing vulnerability to mental health problems and younger age increased the risk of anxiety after completion of treatment for BC survivors, but there was no evidence that chemotherapy was a predictor. Multiple predictors were identified but many lacked reproducibility or were not measured across studies, and inadequate reporting did not allow full evaluation of the multivariable models. The use of quality standards in the development of PRSM within supportive cancer care would improve model quality and performance, thereby allowing professionals to better target support for patients.

Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer.

PubMed

Lampaki, Sofia; Lazaridis, George; Zarogoulidis, Konstantinos; Kioumis, Ioannis; Papaiwannou, Antonis; Tsirgogianni, Katerina; Karavergou, Anastasia; Tsiouda, Theodora; Karavasilis, Vasilis; Yarmus, Lonny; Darwiche, Kaid; Freitag, Lutz; Sakkas, Antonios; Kantzeli, Angeliki; Baka, Sofia; Hohenforst-Schmidt, Wolfgang; Zarogoulidis, Paul

2015-01-01

Historical, the non-small cell lung cancer (NSCLC) was as a united disease entity and the chemotherapy to the metastatic cancer had limited results. Recent studies for the metastatic non-small cell lung cancer led to the ascertainment that the NSCLC does not constitute exclusively a disease entity, but different neoplasms guided from different molecular paths, different biological behavior and at extension requires different confrontation. Thus the new direction for the therapeutic approach of NSCLC is henceforth the most individualized approach based on the activated molecular paths of tumor. Distinct subtypes of NSCLC are driven by a specific genetic alteration, like EGFR, ALK, ROS1 or BRAF mutations, and these genetic alterations are sensitized to the inhibition of specific oncogenic pathways. The benefit from the use of tyrosine kinase inhibitors in patients with EGFR mutations it was confirmed by six randomized studies of phase III that investigated the role of gefitinib, erlotinib and afatinib. In these studies the response rates vary in the impressive percentages from 55% to 86% and were connected with a remarkable median progression free survival of approximately 8 to 13 months, and with better quality of life compared to that of chemotherapy. In early stages NSCLC is needed the individualization of systemic treatment in order to reduce toxicity that is observed in the classic chemotherapy and to impact outcome. The role of EGFR TKI's has been evaluated in the adjuvant chemotherapy in early stage resected NSCLC. The data from these studies suggest that adjuvant TKI therapy might not increase the overall survival, but delay the recurrences. Prospective trials restricted to EGFR or ALK driven NSCLC subsets potentially offering the opportunity for a definitive answer in early disease adjuvant setting (ALCHEMIST) or as induction treatment before stage III chemo-radiotherapy (RTOG 1210/Alliance 31101), are ongoing. Ongoing prospective trials may offer the

Collaboration with Pharma Will Introduce Nanotechnologies in Early Stage Drug Development | Poster

Cancer.gov

The Frederick National Lab has begun to assist several major pharmaceutical companies in adopting nanotechnologies in early stage drug development, when the approach is most efficient and cost-effective.

Axillary radiotherapy in conservative surgery for early-stage breast cancer (stage I and II).

PubMed

García Novoa, Alejandra; Acea Nebril, Benigno; Díaz, Inma; Builes Ramírez, Sergio; Varela, Cristina; Cereijo, Carmen; Mosquera Oses, Joaquín; López Calviño, Beatriz; Seoane Pillado, María Teresa

2016-01-01

Several clinical studies analyze axillary treatment in women with early-stage breast cancer because of changes in the indication for axillary lymph node dissection. The aim of the study is to analyze the impact of axillary radiotherapy in disease-free and overall survival in women with early breast cancer treated with lumpectomy. Retrospective study in women with initial stages of breast carcinoma treated by lumpectomy. A comparative analysis of high-risk women with axillary lymph node involvement who received axillary radiotherapy with the group of women with low risk without radiotherapy was performed. Logistic regression was used to determine factors influencing survival and lymphedema onset. A total of 541 women were included in the study: 384 patients (71%) without axillary lymph node involvement and 157 women (29%) with 1-3 axillary lymph node involvement. Patients with axillary radiotherapy had a higher number of metastatic lymph node compared to non-irradiated (1.6±0.7 vs. 1.4±0.6, P=.02). The group of women with axillary lymph node involvement and radiotherapy showed an overall and disease-free survival at 10 years similar to that obtained in patients without irradiation (89.7% and 77.2%, respectively). 3 lymph nodes involved multiplied by more than 7 times the risk of death (HR=7.20; 95% CI: 1.36 to 38.12). The multivariate analysis showed axillary lymph node dissection as the only variable associated with the development of lymphedema. The incidence of axillary relapse on stage I and II breast cancer is rare. In these patients axillary radiotherapy does not improve overall survival, but contributes to regional control in those patients with risk factors. Copyright © 2016 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

Effect of a decision aid with patient narratives in reducing decisional conflict in choice for surgery among early-stage breast cancer patients: A three-arm randomized controlled trial.

PubMed

Osaka, Wakako; Nakayama, Kazuhiro

2017-03-01

We aimed to evaluate the effect of a decision aid (DA) with patient narratives on decisional conflict in surgery choice for Japanese women with early-stage breast cancer. Two hundred ten women with early-stage breast cancer were randomly assigned to an intervention or control group. Groups 1 and 2 received standard information and a DA, with or without patient narratives, and Group 3 received standard information (control) before surgery choice. At baseline, post-intervention (Time 2), and 1 month after surgery (Time 3), we evaluated decisional conflict as the primary outcome using a decisional conflict scale (DCS). Sidak corrections for multiple comparisons in analysis of covariate were used to compare Time 2 and Time 3 DCS mean scores between each pair of groups. At Time 3, decisional conflict was significantly reduced for Group 1 vs control (P=0.021, Cohen's d =0.26) and Group 2 vs control (P=0.008, Cohen's d=0.40). The DAs with and without patient narratives are equivalently effective at reducing postoperative decisional conflict in Japanese women with early-stage breast cancer. The DAs with and without patient narratives can be used in clinical practice for women with early-stage breast cancer. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A case of urinary retention in the early stages of herpes simplex virus type-1 encephalitis.

PubMed

Fukuoka, Takuya; Nakazato, Yoshihiko; Miyake, Akifumi; Tamura, Naotoshi; Araki, Nobuo; Yamamoto, Toshimasa

2017-06-01

A 70-year-old man developed urinary retention in the early stages of herpes simplex virus (HSV) type-1 encephalitis. A nerve conduction study suggested latent myeloradiculitis. This is the first report of human herpes simplex virus-1 encephalitis followed by urinary retention at early stage from the onset like the Elsberg syndrome. Although relatively few similar cases have been reported, we consider that urinary retention is common in HSV-1 encephalitis, in which disturbances of consciousness usually require bladder catheterization from the onset. We further emphasize that urinary retention may occasionally occur in early stages of HSV-1 encephalitis, with a significant possibility of recovery. Copyright © 2017. Published by Elsevier B.V.

Structural neuroimaging across early-stage psychosis: Aberrations in neurobiological trajectories and implications for the staging model.

PubMed

Bartholomeusz, Cali F; Cropley, Vanessa L; Wannan, Cassandra; Di Biase, Maria; McGorry, Patrick D; Pantelis, Christos

2017-05-01

This review critically examines the structural neuroimaging evidence in psychotic illness, with a focus on longitudinal imaging across the first-episode psychosis and ultra-high-risk of psychosis illness stages. A thorough search of the literature involving specifically longitudinal neuroimaging in early illness stages of psychosis was conducted. The evidence supporting abnormalities in brain morphology and altered neurodevelopmental trajectories is discussed in the context of a clinical staging model. In general, grey matter (and, to a lesser extent, white matter) declines across multiple frontal, temporal (especially superior regions), insular and parietal regions during the first episode of psychosis, which has a steeper trajectory than that of age-matched healthy counterparts. Although the ultra-high-risk of psychosis literature is considerably mixed, evidence indicates that certain volumetric structural aberrations predate psychotic illness onset (e.g. prefrontal cortex thinning), while other abnormalities present in ultra-high-risk of psychosis populations are potentially non-psychosis-specific (e.g. hippocampal volume reductions). We highlight the advantages of longitudinal designs, discuss the implications such studies have on clinical staging and provide directions for future research.

Frustration Sculpts the Early Stages of Protein Folding.

PubMed

Di Silvio, Eva; Brunori, Maurizio; Gianni, Stefano

2015-09-07

The funneled energy landscape theory implies that protein structures are minimally frustrated. Yet, because of the divergent demands between folding and function, regions of frustrated patterns are present at the active site of proteins. To understand the effects of such local frustration in dictating the energy landscape of proteins, here we compare the folding mechanisms of the two alternative spliced forms of a PDZ domain (PDZ2 and PDZ2as) that share a nearly identical sequence and structure, while displaying different frustration patterns. The analysis, based on the kinetic characterization of a large number of site-directed mutants, reveals that although the late stages for folding are very robust and biased by native topology, the early stages are more malleable and dominated by local frustration. The results are briefly discussed in the context of the energy-landscape theory. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Treatment of early-stage Hodgkin lymphoma.

PubMed

Engert, Andreas; Raemaekers, John

2016-07-01

Hodgkin lymphoma (HL) has become one of the best curable malignancies today. This is particularly true for patients with early-stage disease. Today, most patients in this risk group are treated with a combination of chemotherapy followed by small-field radiotherapy. More recent clinical trials such as the German Hodgkin Study Group (GHSG) HD10 study demonstrated, that even two cycles of ABVD followed by 20 Gy involved-field radiation therapy (IF-RT) are sufficient and result in more than 90% of patients being cured. The current treatment for early unfavorable patients is either four cycles of ABVD plus 30 Gy IF-RT or two cycles of BEACOPPbaseline followed by two cycles of ABVD plus IF-RT. Here, the European Organization for Research and Treatment of Cancer (EORTC) demonstrated that in positron emission tomography (PET)-positive patients after two cycles of ABVD, treatment switched to two cycles of BEACOPPbaseline plus radiotherapy results in significantly improved outcomes. Other aspects including attempts to further reduce intensity of treatment will be discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Restricted T cell receptor repertoire in CLL-like monoclonal B cell lymphocytosis and early stage CLL.

PubMed

Blanco, Gonzalo; Vardi, Anna; Puiggros, Anna; Gómez-Llonín, Andrea; Muro, Manuel; Rodríguez-Rivera, María; Stalika, Evangelia; Abella, Eugenia; Gimeno, Eva; López-Sánchez, Manuela; Senín, Alicia; Calvo, Xavier; Abrisqueta, Pau; Bosch, Francesc; Ferrer, Ana; Stamatopoulos, Kostas; Espinet, Blanca

2018-01-01

Analysis of the T cell receptor (TR) repertoire of chronic lymphocytic leukemia-like monoclonal B cell lymphocytosis (CLL-like MBL) and early stage CLL is relevant for understanding the dynamic interaction of expanded B cell clones with bystander T cells. Here we profiled the T cell receptor β chain (TRB) repertoire of the CD4 + and CD8 + T cell fractions from 16 CLL-like MBL and 13 untreated, Binet stage A/Rai stage 0 CLL patients using subcloning analysis followed by Sanger sequencing. The T cell subpopulations of both MBL and early stage CLL harbored restricted TRB gene repertoire, with CD4 + T cell clonal expansions whose frequency followed the numerical increase of clonal B cells. Longitudinal analysis in MBL cases revealed clonal persistence, alluding to persistent antigen stimulation. In addition, the identification of shared clonotypes among different MBL/early stage CLL cases pointed towards selection of the T cell clones by common antigenic elements. T cell clonotypes previously described in viral infections and immune disorders were also detected. Altogether, our findings evidence that antigen-mediated TR restriction occurs early in clonal evolution leading to CLL and may further increase together with B cell clonal expansion, possibly suggesting that the T cell selecting antigens are tumor-related.

Sentinel lymph node biopsy in the management of early-stage cervical carcinoma.

PubMed

Diaz, John P; Gemignani, Mary L; Pandit-Taskar, Neeta; Park, Kay J; Murray, Melissa P; Chi, Dennis S; Sonoda, Yukio; Barakat, Richard R; Abu-Rustum, Nadeem R

2011-03-01

We aimed to determine the sentinel lymph node detection rates, accuracy in predicting the status of lymph node metastasis, and if pathologic ultrastaging improves the detection of micrometastases and isolated tumor cells at the time of primary surgery for cervical cancer. A prospective, non-randomized study of women with early-stage (FIGO stage IA1 with lymphovascular space involvement--IIA) cervical carcinoma was conducted from June 2003 to August 2009. All patients underwent an intraoperative intracervical blue dye injection. Patients who underwent a preoperative lymphoscintigraphy received a 99m Tc sulfur colloid injection in addition. All patients underwent sentinel lymph node (SLN) identification followed by a complete pelvic node and parametrial dissection. SLN were evaluated using our institutional protocol that included pathologic ultrastaging. SLN mapping was successful in 77 (95%) of 81 patients. A total of 316 SLN were identified, with a median of 3 SLN per patient (range, 0-10 SLN). The majority (85%) of SLN were located at three main sites: the external iliac (35%); internal iliac (30%); and obturator (20%). Positive lymph nodes (LN) were identified in 26 (32%) patients, including 21 patients with positive SLN. Fifteen of 21 patients (71%) had SLN metastasis detected on routine processing. SLN ultrastaging detected metastasis in an additional 6/21 patients (29%). Two patients had grossly positive LN at exploration, and mapping was abandoned. Three of 26 (12%) patients had successful SLN mapping; however, the SLN failed to identify the metastatic LN. Of these 3 false negative cases, 2 patients had a metastatic parametrial node as the only positive LN with multiple negative pelvic nodes including negative SLN. One patient with stage IA1 disease and lymphovascular invasion had unilateral SLN mapping and a metastatic common iliac LN identified on completion lymphadenectomy of the contralateral side that did not map. The 4 (5%) patients with unsuccessful

Stimuli-disassembling gold nanoclusters for diagnosis of early stage oral cancer by optical coherence tomography

NASA Astrophysics Data System (ADS)

Kim, Chang Soo; Ingato, Dominique; Wilder-Smith, Petra; Chen, Zhongping; Kwon, Young Jik

2018-01-01

A key design consideration in developing contrast agents is obtaining distinct, multiple signal changes in diseased tissue. Plasmonic gold nanoparticles (Au NPs) have been developed as contrast agents due to their strong surface plasmon resonance (SPR). This study aims to demonstrate that stimuli-responsive plasmonic Au nanoclusters (Au NCs) can be used as a contrast agent for optical coherence tomography (OCT) in detecting early-stage cancer. Au NPs were clustered via acid-cleavable linkers to synthesize Au NCs that disassemble under mildly acidic conditions into individual Au NPs, simultaneously diminishing SPR effect (quantified by scattering intensity) and increasing Brownian motion (quantified by Doppler variance). The acid-triggered morphological and accompanying optico-physical property changes of the acid-disassembling Au NCs were confirmed by TEM, DLS, UV/Vis, and OCT. Stimuli-responsive Au NCs were applied in a hamster check pouch model carrying early-stage squamous carcinoma tissue. The tissue was visualized by OCT imaging, which showed reduced scattering intensity and increased Doppler variance in the dysplastic tissue. This study demonstrates the promise of diagnosing early-stage cancer using molecularly programmable, inorganic nanomaterial-based contrast agents that are capable of generating multiple, stimuli-triggered diagnostic signals in early-stage cancer.[Figure not available: see fulltext.

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

PubMed Central

Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

2015-01-01

Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

PubMed

Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

2015-01-01

Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

40 CFR 797.1600 - Fish early life stage toxicity test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... dilution water or the test solution. (4) “Control” an exposure of test organisms to dilution water only or... (treatment) concentrations of a test substance and one control are required to conduct an early life stage... trays or cups for each test concentration and control (i.e., 30 per embryo cup with 2 replicates); (C...

Accuracy of repeated measurements of late-night salivary cortisol to screen for early-stage recurrence of Cushing's disease following pituitary surgery.

PubMed

Danet-Lamasou, Marie; Asselineau, Julien; Perez, Paul; Vivot, Alexandre; Nunes, Marie-Laure; Loiseau, Hugues; San-Galli, François; Cherifi-Gatta, Blandine; Corcuff, Jean-Benoît; Tabarin, Antoine

2015-02-01

The performance of late-night salivary cortisol (LNSC) to accurately screen for postoperative recurrence of Cushing's disease (CD) at an early stage is unknown. The aim of this study was to compare the accuracy of multiple sampling strategies to suggest the optimal number of LNSC samples needed for diagnosing post-surgical recurrences of CD at an early stage. Retrospective analysis in a single centre. Thirty-six patients in surgical remission of CD had successive measurements of LNSC, defined as 'sequences', using a locally modified RIA assay as part of long-term follow-up (69·2 ± 10·6 months). Patients underwent an extensive biochemical evaluation within 3 months before or after a sequence of saliva sampling and were classified as being in remission or in early-stage recurrence. The accuracy of three diagnostic strategies combining two, three or four LNSC results from a sequence was estimated using areas under the ROC curves (AUC), sensitivity, specificity and predictive values. Forty-four sequences of LNSC measurements were available. Fifty-two percent of sequences were performed during early-stage recurrence. The intrasequence variability of LNSC was higher during recurrence than during remission (medians of SDs: 2·1 vs 0·5 nm; P < 0·0001). AUCs from ROC curves ranged from 0·93 to 0·96 depending on the strategy. For 90% sensitivities, the best specificities (92·9% and 90·9%) were achieved by strategies taking into account three or four measurements summarized either by their mean or their maximum value. Increase in LNSC concentration is an early abnormality during post-surgical recurrence of CD. However, due to a major within-patient variability of LNSC from 1 day to another, a screening strategy using three or four samples collected on successive days may be recommended to detect early-stage recurrence of CD with a high accuracy. © 2014 John Wiley & Sons Ltd.

Evaluating the Stage Learning Hypothesis.

ERIC Educational Resources Information Center

Thomas, Hoben

1980-01-01

A procedure for evaluating the Genevan stage learning hypothesis is illustrated by analyzing Inhelder, Sinclair, and Bovet's guided learning experiments (in "Learning and the Development of Cognition." Cambridge: Harvard University Press, 1974). (Author/MP)

Loss of corticospinal tract integrity in early MS disease stages

PubMed Central

Neumann, Jens; Kaufmann, Jörn; Heidel, Jan; Stadler, Erhard; Sweeney-Reed, Catherine; Sailer, Michael; Schreiber, Stefanie

2017-01-01

Objective: We investigated corticospinal tract (CST) integrity in the absence of white matter (WM) lesions using diffusion tensor imaging (DTI) in early MS disease stages. Methods: Our study comprised 19 patients with clinically isolated syndrome (CIS), 11 patients with relapsing-remitting MS (RRMS), and 32 age- and sex-matched healthy controls, for whom MRI measures of CST integrity (fractional anisotropy [FA], mean diffusivity [MD]), T1- and T2-based lesion load, and brain volumes were available. The mean (SD) disease duration was 3.5 (2.1) months, and disability score was low (median Expanded Disability Status Scale 1.5) at the time of the study. Results: Patients with CIS and RRMS had significantly lower CST FA and higher CST MD values compared with controls. These findings were present, irrespective of whether WM lesions affected the CST. However, no group differences in the overall gray or WM volume were identified. Conclusions: In early MS disease stages, CST integrity is already affected in the absence of WM lesions or brain atrophy. PMID:28959706

Dosimetric and Clinical Outcomes With Intensity Modulated Radiation Therapy After Chemotherapy for Patients With Early-Stage Diffuse Large B-cell Lymphoma of Waldeyer Ring

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

Xu, Yong-Gang; Qi, Shu-Nan; Wang, Shu-Lian

Purpose: To assess the dosimetric benefit, prognosis, and toxicity of intensity modulated radiation therapy (IMRT) for early-stage, diffuse large B-cell lymphoma of Waldeyer ring (WR-DLBCL). Methods and Materials: Sixty-one patients with early-stage WR-DLBCL who received chemotherapy followed by IMRT were retrospectively reviewed. Dosimetric parameters for the target volume and critical normal structures were evaluated, and survival was calculated. Linear regression analysis was used to assess the effect of the mean dose (D{sub mean}) to the parotid glands on xerostomia. Results: The median conformity index and homogeneity index of the planning target volume (PTV) were 0.83 and 0.90, respectively, demonstrating verymore » good coverage of the target volume. The mean dose to the parotid glands was 24.9 Gy. The 5-year overall survival (OS), progression-free survival (PFS), and locoregional control (LRC) were 94.7%, 93.1%, and 98.3%, respectively. Early and late toxicities were mild, and no patient experienced late grade ≥3 toxicities. The D{sub mean} to the parotid glands had a linear correlation with late grade ≥2 xerostomia. Conclusions: IMRT after chemotherapy can provide excellent dose conformity and achieve favorable survival and LRC with mild toxicities in patients with early-stage WR-DLBCL. Dose constraints for the parotid glands should be limited to <24 Gy for early-stage WR-DLBCL.« less

Stage 2 DBPR Operational Evaluation Report

EPA Pesticide Factsheets

A completed copy of the Stage 2 DBPR Operational Evaluation Report must be sent to EPA Region 8 no later than 90 days after being notified of the analytical results that indicate an operational evaluation level has been exceeded.

Management of Early- and Late-Stage Rheumatoid Arthritis: Are Physiotherapy Students' Intended Behaviours Consistent with Canadian Best Practice Guidelines?

PubMed Central

Lineker, Sydney C.; Hallett, Christina; Tumber, Jake; Fernando, Nalin; Hul, Magdalena

2012-01-01

ABSTRACT Purpose: This study examined whether physiotherapy students in a problem-based learning (PBL) curriculum intend to implement best practices for management of clients with rheumatoid arthritis (RA). Method: Physiotherapy students (n=49) completed a subsection of the ACREU Primary Care Survey to evaluate the concordance between intended behaviours and Canadian best practices for early- and late-stage RA, before and after completing the relevant PBL content. Changes in scores were assessed using McNemar's test for dependent proportions. Results: Most students indicated that they would recommend treatments or referrals for physiotherapy/exercise, education, and occupational therapy or joint protection pre- and post-PBL (>83% and >95%, respectively). Post-PBL, more students recommended referral to a rheumatologist and disease-modifying anti-rheumatic drugs (DMARDs) for both early and late RA; however, the increase was significant only for early RA (p=0.013 and 0.031 for referral to rheumatologist and DMARDs, respectively). More students recommended psychosocial support at both stages of RA post-PBL (early RA: p<0.001; late RA: p=0.031). Although more students recommended DMARDs post-PBL, only 8 students in total made this recommendation (16%), and fewer students considered use of non-steroidal anti-inflammatory drugs. Most students (94%) did not recommend referral to a surgeon for early or late RA. Conclusion: Intended behaviour of physiotherapy students was more consistent with Canadian best practice guidelines for managing clients with early- and late-stage RA following the PBL curriculum. Further study is required to determine whether the students were less aware of best practices related to pharmacologic interventions and timely referral to appropriate specialists, or whether they considered these issues to be outside their scope of practice. PMID:23729962

Adjuvant therapy in early-stage non-small cell lung cancer.

PubMed

Serke, Monika

2010-01-01

Evidence clearly supports adjuvant chemotherapy following resection in patients with stage II or III non-small cell lung cancer (NSCLC). Based on 3 landmark studies, adjuvant chemotherapy has become standard in completely resected NSCLC stage II and IIIA. Survival benefit from adjuvant chemotherapy is estimated to be between 3% and 15%, depending on stage. Treatment should include 4 cycles of platinum-based combination chemotherapy. There is uncertainty about chemotherapy prescription in those patients with resected stage IB NSCLC, as the risk of recurrence is lower in early NSCLC and the magnitude of benefit of adjuvant therapy is proportional to the risk of relapse according to stage. Postoperative radiotherapy (PORT) should not be used for stage I or II NSCLC, and remains controversial in resected stage IIIA (N2) disease. All positive adjuvant trials have utilized a cisplatin-based regimen, usually in combination with vinorelbine, and this should be considered the standard approach. Prognostic factors to select patients who will benefit from adjuvant therapy in general or from platinum-based chemotherapy are under discussion, but not yet established. In future we hope to optimize treatment convenience for the patients by using other combinations with the hope of better efficacy results. Work is currently under way to identify prognostic factors which in future may help to identify patients who are most likely to benefit from chemotherapy. Copyright 2010 S. Karger AG, Basel.

Gd-EOB-DTPA-enhanced magnetic resonance imaging and alpha-fetoprotein predict prognosis of early-stage hepatocellular carcinoma.

PubMed

Yamashita, Taro; Kitao, Azusa; Matsui, Osamu; Hayashi, Takehiro; Nio, Kouki; Kondo, Mitsumasa; Ohno, Naoki; Miyati, Tosiaki; Okada, Hikari; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Nakanuma, Yasuni; Takamura, Hiroyuki; Ohta, Tetsuo; Nakamoto, Yasunari; Yamamoto, Masakazu; Takayama, Tadatoshi; Arii, Shigeki; Wang, XinWei; Kaneko, Shuichi

2014-11-01

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in ∼15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n=70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n=109). This noninvasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. © 2014 by the American Association for the Study of Liver Diseases.

Gd-EOB-DTPA-enhanced Magnetic Resonance Imaging and Alpha-fetoprotein Predict Prognosis of Early-Stage Hepatocellular Carcinoma

PubMed Central

Yamashita, Taro; Kitao, Azusa; Matsui, Osamu; Hayashi, Takehiro; Nio, Kouki; Kondo, Mitsumasa; Ohno, Naoki; Miyati, Tosiaki; Okada, Hikari; Yamashita, Tatsuya; Mizukoshi, Eishiro; Honda, Masao; Nakanuma, Yasuni; Takamura, Hiroyuki; Ohta, Tetsuo; Nakamoto, Yasunari; Yamamoto, Masakazu; Takayama, Tadatoshi; Arii, Shigeki; Wang, Xin Wei; Kaneko, Shuichi

2014-01-01

The survival of patients with hepatocellular carcinoma (HCC) is often individually different even after surgery for early-stage tumors. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) has been introduced recently to evaluate hepatic lesions with regard to vascularity and the activity of the organic anion transporter OATP1B3. Here, we report that Gd-EOB-DTPA-enhanced MRI (EOB-MRI) in combination with serum alpha-fetoprotein (AFP) status reflects the stem/maturational status of HCC with distinct biology and prognostic information. Gd-EOB-DTPA uptake in the hepatobiliary phase was observed in approximately 15% of HCCs. This uptake correlated with low serum AFP levels, maintenance of hepatocyte function with the up-regulation of OATP1B3 and HNF4A expression, and good prognosis. By contrast, HCC showing reduced Gd-EOB-DTPA uptake with high serum AFP levels was associated with poor prognosis and the activation of the oncogene FOXM1. Knockdown of HNF4A in HCC cells showing Gd-EOB-DTPA uptake resulted in the increased expression of AFP and FOXM1 and the loss of OATP1B3 expression accompanied by morphological changes, enhanced tumorigenesis, and loss of Gd-EOB-DTPA uptake in vivo. HCC classification based on EOB-MRI and serum AFP levels predicted overall survival in a single-institution cohort (n = 70), and its prognostic utility was validated independently in a multi-institution cohort of early-stage HCCs (n = 109). Conclusion: This non-invasive classification system is molecularly based on the stem/maturation status of HCCs and can be incorporated into current staging practices to improve management algorithms, especially in the early stage of disease. PMID:24700365

Clinical characteristics of early-stage osteonecrosis of the ankle and treatment outcomes.

PubMed

Issa, Kimona; Naziri, Qais; Kapadia, Bhaveen H; Lamm, Bradley M; Jones, Lynne C; Mont, Michael A

2014-05-07

The purposes of this study were to describe the clinical manifestations of osteonecrosis involving the distal tibia and talus, to identify risk factors associated with the disease, and to evaluate the efficacy of percutaneous drilling for the treatment of ankles with early-stage symptomatic osteonecrosis. One hundred and one ankles in seventy-three patients with symptomatic osteonecrosis of the talus and/or distal tibia treated with percutaneous drilling were identified. There were eighty-one ankles in fifty-nine patients treated only at our institution and twenty ankles in fourteen patients with a failed prior core decompression at outside institutions. The parameters evaluated included demographics, disease characteristics, clinical outcomes including the American Orthopaedic Foot & Ankle Society score, Short-Form-36 scores, University of California Los Angeles activity scores, and visual analog scale pain scores, and radiographic outcomes at a mean follow-up duration of five years (range, two to nine years). Eighty-five ankles had isolated talus osteonecrosis, eleven ankles had involvement of the distal tibia and talus, and five ankles had isolated distal tibial disease. Twenty-nine patients (40%) had initially presented with symptomatic osteonecrosis of another joint, most commonly the knee (37%), the hip (29%), and the shoulder (25%). The most common identifiable risk factors included chronic corticosteroid use (49.3%), alcohol abuse (35.6%), tobacco use (29%), and hypertension (20.5%). Overall, 83% of ankles did not demonstrate further disease progression after the procedure. There were significant improvements (p < 0.05) in clinical and patient-reported outcomes after surgical treatment. The presence of human immunodeficiency virus and sickle cell disease was associated with a higher odds ratio of disease progression to joint collapse. Osteonecrosis of the distal tibia and talus was usually part of multifocal disease, and concurrent knee osteonecrosis was

Quantitative nuclear histomorphometry predicts oncotype DX risk categories for early stage ER+ breast cancer.

PubMed

Whitney, Jon; Corredor, German; Janowczyk, Andrew; Ganesan, Shridar; Doyle, Scott; Tomaszewski, John; Feldman, Michael; Gilmore, Hannah; Madabhushi, Anant

2018-05-30

Gene-expression companion diagnostic tests, such as the Oncotype DX test, assess the risk of early stage Estrogen receptor (ER) positive (+) breast cancers, and guide clinicians in the decision of whether or not to use chemotherapy. However, these tests are typically expensive, time consuming, and tissue-destructive. In this paper, we evaluate the ability of computer-extracted nuclear morphology features from routine hematoxylin and eosin (H&E) stained images of 178 early stage ER+ breast cancer patients to predict corresponding risk categories derived using the Oncotype DX test. A total of 216 features corresponding to the nuclear shape and architecture categories from each of the pathologic images were extracted and four feature selection schemes: Ranksum, Principal Component Analysis with Variable Importance on Projection (PCA-VIP), Maximum-Relevance, Minimum Redundancy Mutual Information Difference (MRMR MID), and Maximum-Relevance, Minimum Redundancy - Mutual Information Quotient (MRMR MIQ), were employed to identify the most discriminating features. These features were employed to train 4 machine learning classifiers: Random Forest, Neural Network, Support Vector Machine, and Linear Discriminant Analysis, via 3-fold cross validation. The four sets of risk categories, and the top Area Under the receiver operating characteristic Curve (AUC) machine classifier performances were: 1) Low ODx and Low mBR grade vs. High ODx and High mBR grade (Low-Low vs. High-High) (AUC = 0.83), 2) Low ODx vs. High ODx (AUC = 0.72), 3) Low ODx vs. Intermediate and High ODx (AUC = 0.58), and 4) Low and Intermediate ODx vs. High ODx (AUC = 0.65). Trained models were tested independent validation set of 53 cases which comprised of Low and High ODx risk, and demonstrated per-patient accuracies ranging from 75 to 86%. Our results suggest that computerized image analysis of digitized H&E pathology images of early stage ER+ breast cancer might be able predict the

[Surgical treatment for incisions fat colliquation or infections at early stage after operation of lumbar disc herniation].

PubMed

Guan, Ting-Jin; Zheng, Liang-Guo; Sun, Peng; Li, Xing-Xue

2014-05-01

To explore the reason, key diagnosic point and therapeutic method of the incisions fat colliquation or infections at early stage after operation of lumbar disc herniation. From July 2007 to May 2012, clinical data of 11 patients with incision fat liquefaction or early infection after lumbar discectomy were retrospectively analyzed. There were 5 males and 6 females with an average age of 43.1 years, and the mean time of incisions fat colliquation or infection was 5 days and a half after operation. The main clinical features included local wound pain aggravating, fervescence, fresh seepage in the wound, and blood inflammatory index increased, etc. The wound could heal at the first treatment stage or not was an evaluation standard of curative effect. All patients were followed up with an average period of 21 months. The wounds of 10 cases healed at the first stage without recurrence and complications. In 1 case infected by staphylococcus aureus, distal part of the wound present local red, swelling and with wave motion at 2 months after operation, staphylococcus aureus infection was confirmed after puncture and bacterial culture, and 1 thrum was found after local incision. The wound healed after change dressings for 1 week, without recurrence after followed up for 13 months. Preventing the risk factors before operation, minimizing invasive technique during operation reasonable antibiotics application for the lumbar operation reguiring placement objects, and correctly handling with wound after operation could prevent and reduce the incidence of incisions fat liquefaction or infection after operation of lumbar disc herniation. For incision fat liquefaction or infection, early diagnosis, debridement, VSD negative pressure irrigation and drainage, to choosing sensitive antibiotics according to the results of drug sensitivity, may contribute to wound early healing and decrease complication.

CTNNB1 (beta-catenin) mutation identifies low grade, early stage endometrial cancer patients at increased risk of recurrence.

PubMed

Kurnit, Katherine C; Kim, Grace N; Fellman, Bryan M; Urbauer, Diana L; Mills, Gordon B; Zhang, Wei; Broaddus, Russell R

2017-07-01

Although the majority of low grade, early stage endometrial cancer patients will have good survival outcomes with surgery alone, those patients who do recur tend to do poorly. Optimal identification of the subset of patients who are at high risk of recurrence and would benefit from adjuvant treatment has been difficult. The purpose of this study was to evaluate the impact of somatic tumor mutation on survival outcomes in this patient population. For this study, low grade was defined as endometrioid FIGO grades 1 or 2, while early stage was defined as endometrioid stages I or II (disease confined to the uterus). Next-generation sequencing was performed using panels comprised of 46-200 genes. Recurrence-free and overall survival was compared across gene mutational status in both univariate and multivariate analyses. In all, 342 patients were identified, 245 of which had endometrioid histology. For grades 1-2, stages I-II endometrioid endometrial cancer patients, age (HR 1.07, 95% CI 1.03-1.10), CTNNB1 mutation (HR 5.97, 95% CI 2.69-13.21), and TP53 mutation (HR 4.07, 95% CI 1.57-10.54) were associated with worse recurrence-free survival on multivariate analysis. When considering endometrioid tumors of all grades and stages, CTNNB1 mutant tumors were associated with significantly higher rates of grades 1-2 disease, lower rates of deep myometrial invasion, and lower rates of lymphatic/vascular space invasion. When both TP53 and CTNNB1 mutations were considered, presence of either TP53 mutation or CTNNB1 mutation remained a statistically significant predictor of recurrence-free survival on multivariate analysis and was associated with a more precise confidence interval (HR 4.69, 95% CI 2.38-9.24). Thus, mutational analysis of a 2 gene panel of CTNNB1 and TP53 can help to identify a subset of low grade, early stage endometrial cancer patients who are at high risk of recurrence.

Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

PubMed

Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

2016-06-01

The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

"A palliative end-stage COPD patient does not exist": a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD.

PubMed

Scheerens, Charlotte; Deliens, Luc; Van Belle, Simon; Joos, Guy; Pype, Peter; Chambaere, Kenneth

2018-06-20

Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD.

Organophosphorus pesticides effect on early stages of the axolotl Ambystoma mexicanum (Amphibia: Caudata).

PubMed

Robles-Mendoza, C; García-Basilio, C; Cram-Heydrich, S; Hernández-Quiroz, M; Vanegas-Pérez, C

2009-02-01

Ambystoma mexicanum is an endemic salamander of Xochimilco, a wetland of the basin of Mexico valley. Nowadays, axolotl populations are decreasing due environmental stressors. Particularly, studies about organophosphorus pesticides (OPPs; i.e. chlorpyrifos and malathion) toxicity are of great importance due to their intensive use in agricultural activities in Xochimilco. Thus, the aim of this study was to evaluate under controlled conditions the toxicity of chlorpyrifos (CPF) and malathion (MLT) on embryos and larvae (stage 44 and 54) of A. mexicanum. Embryos and larvae were exposure 96h from 0.5 to 3mg CPFL(-1) and from 10 to 30mg MLTL(-1) in independent tests. Embryos at the end of this period were maintained 9d without pesticide in order to identify possible recuperation. Differences obtained in mortality, hatching success, development, morphological abnormalities, behaviour and activity, suggest that toxicity of CPF and MLT differs in embryos and larval stages. Embryos were less sensitive to OPPs acute exposure than axolotl larvae; additionally, toxicity of CPF in larval stages was greater than MLT. On the other hand, data obtained in axolotl embryos during the period of recuperation to CPF in particular as delay and inhibition of development, malformations and success of hatching, indicated that these responses turned out more sensitive than mortality. This study allowed to identify the toxicological potential of OPPs on early developmental stages of A. mexicanum and it is a valuable contribution for the future management of the axolotl wild population.

Assessments of plasma ghrelin levels in the early stages of parkinson's disease.

PubMed

Song, Ning; Wang, Weiwei; Jia, Fengjv; Du, Xixun; Xie, Anmu; He, Qing; Shen, Xiaoli; Zhang, Jing; Rogers, Jack T; Xie, Junxia; Jiang, Hong

2017-10-01

Gastrointestinal symptoms are early events in Parkinson's disease (PD). The gastrointestinal hormone ghrelin was neuroprotective in the nigrostriatal dopamine system. The objective of this study was to assess ghrelin levels in the early stages of PD. Plasma was collected in the fasting state in 291 PD patients in stages 1-3 and 303 age- and sex-matched healthy controls. Additional samples were taken in the glucose response test to assess nutrition-related ghrelin levels in 20 PD patients and 20 healthy controls. The enzyme-linked immunosorbent assay was used to measure total and active plasma ghrelin levels. We reported that total and active plasma ghrelin levels were decreased in PD, although there was no difference across progressive PD stages. Postprandial ghrelin suppression and preprandial peak responses were both attenuated in PD. Plasma ghrelin levels were decreased in PD; however, this event might be irrelevant to PD progression. Ghrelin responses to meals were also impaired in PD. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Practice Patterns and Long-Term Survival for Early-Stage Rectal Cancer

PubMed Central

Stitzenberg, Karyn B.; Sanoff, Hanna K.; Penn, Dolly C.; Meyers, Michael O.; Tepper, Joel E.

2013-01-01

Purpose Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. Methods All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. Results LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Conclusion Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE. PMID:24166526

Practice patterns and long-term survival for early-stage rectal cancer.

PubMed

Stitzenberg, Karyn B; Sanoff, Hanna K; Penn, Dolly C; Meyers, Michael O; Tepper, Joel E

2013-12-01

Standard of care treatment for most stage I rectal cancers is total mesorectal excision (TME). Given the morbidity associated with TME, local excision (LE) for early-stage rectal cancer has been explored. This study examines practice patterns and overall survival (OS) for early-stage rectal cancer. All patients in the National Cancer Data Base diagnosed with rectal cancer from 1998 to 2010 were initially included. Use of LE versus proctectomy and use of adjuvant radiation therapy were compared over time. Adjusted Cox proportional hazards models were used to compare OS based on treatment. LE was used to treat 46.5% of patients with T1 and 16.8% with T2 tumors. Use of LE increased steadily over time (P < .001). LE was most commonly used for women, black patients, very old patients, those without private health insurance, those with well-differentiated tumors, and those with T1 tumors. Proctectomy was associated with higher rates of tumor-free surgical margins compared with LE (95% v 76%; P < .001). Adjuvant radiation therapy use decreased over time independent of surgical procedure or T stage. For T2N0 disease, patients treated with LE alone had significantly poorer adjusted OS than those treated with proctectomy alone or multimodality therapy. Guideline-concordant adoption of LE for treatment of low-risk stage I rectal cancer is increasing. However, use of LE is also increasing for higher-risk rectal cancers that do not meet guideline criteria for LE. Treatment with LE alone is associated with poorer long-term OS. Additional studies are warranted to understand the factors driving increased use of LE.

Comparison between the story recall test and the word-list learning test in Korean patients with mild cognitive impairment and early stage of Alzheimer's disease.

PubMed

Baek, Min Jae; Kim, Hyun Jung; Kim, Sangyun

2012-01-01

Among verbal memory tests, two that are commonly used to measure the ability of verbal memory function in cognitive impairment are story recall tests and word-list learning tests. However, research is limited regarding which test might be more sensitive in discriminating between normal cognitive aging and patients with Alzheimer's disease (AD) in the Korean population. The purpose of the current study was to compare the word-list learning test (Seoul Verbal Learning Test; SVLT) and the story recall test (Korean Story Recall Test; KSRT) to determine which test is more sensitive in discriminating between individuals with normal cognitive aging and patients with mild cognitive impairment (MCI) and early stage of AD in Korea. A total of 53 healthy adults, 127 patients with MCI, and 72 patients with early stage of AD participated in this study. The receiver-operating characteristic (ROC) curve and area under the curve (AUC) were evaluated to compare these two tests. The results showed that the AUC of the SVLT was significantly larger than the AUC of the KSRT in all three groups (healthy adults vs. MCI and early stage of AD; healthy adults vs. MCI; healthy adults vs. early stage of AD). However, in comparison of patients with MCI and early stage of AD, the AUC of SVLT and the AUC of KSRT were not significant. The word-list learning test is a more useful tool for examining verbal memory function for older adults in Korea than the story recall test.

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers.

PubMed

Hequet, Delphine; Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna's assay information on physicians' adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians' opinion on the test results and the patients' degree of anxiety, difficulties with therapy and quality of life. Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64%) patients and Luminal B in 70 (36

Prospective, multicenter French study evaluating the clinical impact of the Breast Cancer Intrinsic Subtype-Prosigna® Test in the management of early-stage breast cancers

PubMed Central

Callens, Céline; Gentien, David; Albaud, Benoit; Mouret-Reynier, Marie-Ange; Dubot, Coraline; Cottu, Paul; Huchon, Cyrille; Zilberman, Sonia; Berseneff, Helene; Foa, Cyril; Salmon, Rémy; Roulot, Aurélie; Lerebours, Florence; Salomon, Anne; Ghali, Nadeem; Morel, Pascale; Li, Qianyi; Cayre, Anne; Guinebretière, Jean-Marc; Hornberger, John; Penault-Llorca, Frédérique; Rouzier, Roman

2017-01-01

Purpose The Prosigna® breast cancer prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The primary objective of this multicenter study was to evaluate the impact of Prosigna’s assay information on physicians’ adjuvant treatment decisions in patients with early-stage breast cancer. Secondary objectives were to assess confidence of practitioners in their therapeutic recommendations before and after the added information provided by the Prosigna assay; and to evaluate the emotional state of patients before and after the Prosigna test results. Methods Consecutive patients with invasive early-stage breast cancer were enrolled in a prospective, observational, multicenter study carried out in 8 hospitals in France. The Prosigna test was carried out on surgical specimens using the nCounter® Analysis System located at the Institut Curie. Both before and after receiving the Prosigna test results, physicians completed treatment confidence questionnaires and patients completed questionnaires concerning their state of anxiety, the difficulties felt in face of the therapy and quality of life. Information was also collected at 6 months regarding the physicians’ opinion on the test results and the patients’ degree of anxiety, difficulties with therapy and quality of life. Results Between March 2015 and January 2016, 8 study centers in France consecutively enrolled 210 postmenopausal women with estrogen receptor (ER) positive, human epidermal growth hormone-2 (HER-2) negative, and node negative tumors, either stage 1 or stage 2. Intrinsic tumor subtypes as assessed by the Prosigna test were 114 (58.2%) Luminal A, 79 (40.3%) Luminal B, 1 (0.5%) HER-2 enriched (HER-2E), and 2 (1.0%) basal-like. Before receiving the Prosigna test results, physicians categorized tumor subtypes based on immunohistochemistry (IHC) as Luminal A in 126 (64

Ameliorative effect of the cinnamon oil from Cinnamomum zeylanicum upon early stage diabetic nephropathy.

PubMed

Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul

2010-03-01

The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg. (c) Georg Thieme Verlag KG Stuttgart . New York.

An automatic early stage alveolar-bone-resorption evaluation method on digital dental panoramic radiographs

NASA Astrophysics Data System (ADS)

Zhang, Min; Katsumata, Akitoshi; Muramatsu, Chisako; Hara, Takeshi; Suzuki, Hiroki; Fujita, Hiroshi

2014-03-01

Periodontal disease is a kind of typical dental diseases, which affects many adults. The presence of alveolar bone resorption, which can be observed from dental panoramic radiographs, is one of the most important signs of the progression of periodontal disease. Automatically evaluating alveolar-bone resorption is of important clinic meaning in dental radiology. The purpose of this study was to propose a novel system for automated alveolar-bone-resorption evaluation from digital dental panoramic radiographs for the first time. The proposed system enables visualization and quantitative evaluation of alveolar bone resorption degree surrounding the teeth. It has the following procedures: (1) pre-processing for a test image; (2) detection of tooth root apices with Gabor filter and curve fitting for the root apex line; (3) detection of features related with alveolar bone by using image phase congruency map and template matching and curving fitting for the alveolar line; (4) detection of occlusion line with selected Gabor filter; (5) finally, evaluation of the quantitative alveolar-bone-resorption degree in the area surrounding teeth by simply computing the average ratio of the height of the alveolar bone and the height of the teeth. The proposed scheme was applied to 30 patient cases of digital panoramic radiographs, with alveolar bone resorption of different stages. Our initial trial on these test cases indicates that the quantitative evaluation results are correlated with the alveolar-boneresorption degree, although the performance still needs further improvement. Therefore it has potential clinical practicability.

Theoretical evaluation of burns to the human respiratory tract due to inhalation of hot gas in the early stage of fires.

PubMed

Lv, Yong-Gang; Liu, Jing; Zhang, Jun

2006-06-01

A transient two-dimensional mathematical model for heat and water vapor transport across the respiratory tract of human body was established and applied to predict the thermal impact of inhaled hot gas to the nasal tissues during the early stage of fires. Influences of individual's physiological status and environment variables were comprehensively investigated through numerical calculations. Burn evaluation was performed using the classical Henriques model to predict the time for thermal injury to occur. It was shown that decreasing the air velocity and increasing the respiratory rate is helpful to minimize the burn over the respiratory tract. The effect of relative humidity of surrounding dry hot air could be ignored in predicting burns for short duration exposures. Due to evaporation cooling on the mucousal membrane, the burn often occurs at certain positions underneath the skin of the tract near the inlet of the respiratory tract. Most of the tissues near the surface suffer injury immediately after exposure to fire, while in the deeper tissues, serious damage occurs after a relatively longer time period. The method presented in this paper may suggest a valuable approach to theoretically evaluate the injury of hot air to the human respiratory tract under various fire situations.

Early stage of weathering of medieval-like potash-lime model glass: evaluation of key factors.

PubMed

Gentaz, Lucile; Lombardo, Tiziana; Loisel, Claudine; Chabas, Anne; Vallotto, Marta

2011-02-01

Throughout history, a consequent part of the medieval stained glass windows have been lost, mostly because of deliberate or accidental mechanic destruction during war or revolution, but, in some cases, did not withstand the test of time simply because of their low durability. Indeed, the glasses that remain nowadays are for many in a poor state of conservation and are heavily deteriorated. Under general exposure conditions, stained glass windows undergo different kinds of weathering processes that modify their optical properties, chemistry, and structure: congruent dissolution, leaching, and particle deposition (the combination of those two leading together to the formation of neocrystallisations and eventually crusts). Previous research has studied the weathering forms and the mechanisms from which they are originated, some others identified the main environmental parameters responsible for the deterioration and highlighted that both intrinsic (glass composition) and extrinsic (environmental parameters) factors influence glass degradation. Nevertheless, a clear quantification of the impact of the different deterioration extrinsic factors has not been performed. By analysing the results obtained with model glass (durable and nondurable) exposed in the field, this paper proposes a simple mathematical computation evaluating the contribution of the different weathering factors for the early stages of exposure of the stained glasses. In the case of non durable glass, water runoff was identified as the main factor inducing the leaching (83.4 ± 2.6% contribution), followed by gas (6.4 ± 1.5%) and particle deposition (6.8 ± 2.2%) and adsorbed water (3.4 ± 0.6%). Moreover, it was shown that the extrinsic stimuli superimposes with the impact of glass composition to the weathering. Those results show that the role played by dry deposition, even if less important than that of the wet deposition, cannot be neglected.

Sentinel lymph node biopsy in early-stage cervical cancer: utility of intraoperative versus postoperative assessment.

PubMed

Fader, A Nickles; Edwards, R P; Cost, M; Kanbour-Shakir, A; Kelley, J L; Schwartz, B; Sukumvanich, P; Comerci, J; Sumkin, J; Elishaev, E; Rohan, L Cencia

2008-10-01

To determine the diagnostic accuracy of sentinel lymph node (SLN) detection using lymphoscintigraphy, intraoperative blue dye, and radiocolloid in patients with early-stage cervical cancer. Intra-cervical injection of technetium-99 sulfur colloid and lymphoscintigraphy were performed preoperatively. Isosulfan blue was injected intra-cervically immediately prior to surgery. SLNs were excised and examined intraoperatively (imprint cytology and frozen section) and postoperatively (H and E histology and immunohistochemistry (IHC) for cytokeratin). Thirty eight patients were evaluable. Laparoscopy and laparotomy were performed in 28.9% and 71.1%, respectively. Subjects had squamous cell carcinoma (n=26), adenocarcinoma (n=10) or adenosquamous (n=2) histologies. 55.3% had cervical tumors <2 cm. The overall SLN detection rate was 92.1%. The external iliac region just distal to the common iliac bifurcation was the most common SLN location. A mean of 2.1 SLNs were detected per patient with bilateral SLNs observed in 47.4%. On final pathology, metastatic nodal disease was identified in 15.7% of patients. Of these, 83.3% were detected in the SLNs. Sensitivity of SLN detection of metastasis was 100% for patients with cervical tumors <2 cm. However intraoperative evaluation by imprint cytology and frozen section correctly identified lymph node metastasis in only 33.3%. SLN detection is feasible and accurately reflects pelvic nodal basin status when performed in early-stage cervical cancer patients. However, while current intraoperative pathology techniques for assessing nodal metastases reliably detect metastases larger than 2 mm, they lack sufficient sensitivity to detect micrometastasis and isolated tumor cells.

[Long-term, tumor-free survival after radiotherapy combining hepatectomy-Whipple en bloc and orthotopic liver transplantation for early-stage hilar cholangiocarcinoma].

PubMed

Wu, You-min; Johlin, Frederick C; Rayhill, Stephen C; Jensen, Chris S; Jin, Xie; Mitros, Frank A

2009-08-01

To report the experience in surveillance and early detection of cholangiocarcinoma (CC) and in using en bloc total hepatectomy-pancreaticoduodenectomy-orthotopic liver transplantation (OLT-Whipple) to achieve complete eradication of early-stage CC complicating primary sclerosing cholangitis (PSC). Asymptomatic PSC patients underwent surveillance using endoscopic ultrasound and endoscopic retrograde cholangiopancreatography (ERCP) with multilevel brushings for cytological evaluation. Patients diagnosed with CC were treated with combined extra-beam radiotherapy, lesion-focused brachytherapy, and OLT-Whipple. Between January 1988 and February 2001, 42 of 119 PSC patients were followed according to the surveillance protocol. CC was detected in 8 patients, 6 of whom underwent OLT-Whipple. Of those 6 patients, 4 had stage I CC, and 2 had stage II CC. All 6 OLT-Whipple patients received combined external-beam and brachytherapy radiotherapy. The median time from diagnosis to OLT-Whipple was 144 days. One patient died 55 months post-transplant of an unrelated cause, without tumor recurrence. The other 5 were well without recurrence at 79, 82, 108, 128, 129 and 145 months. For patients with PSC, ERCP surveillance cytology and intralumenal endoscopic ultrasound examination allow for early detection of CC. Broad and lesion-focused radiotherapy combined with OLT-Whipple to remove the biliary epithelium en bloc offers promising long-term, tumor-free survival. All patients tolerated this extensive surgery well with good quality of life following surgery and recovery. These findings support consideration of the complete excision of an intact biliary tree via OLT-Whipple in patients with early-stage hilar CC complicating PSC.

Therapeutic efficacy of three hyaluronic acid formulations in young and middle-aged patients with early-stage meniscal injuries

PubMed Central

Dernek, Bahar; Kesiktas, Fatma Nur; Duymus, Tahir Mutlu; Diracoglu, Demirhan; Aksoy, Cihan

2017-01-01

[Purpose] To investigate and compare the efficacy of three hyaluronic acid formulations in patients with early-stage meniscal injuries. [Subjects and Methods] Male and female patients who were admitted to our clinic between January 2013 and December 2013, diagnosed with early-stage meniscus lesions of the knee, and given a hyaluronic acid treatment were included in this retrospective study. Patients were categorized into 3 groups according to their treatments: MONOVISC, OSTENIL PLUS, or ORTHOVISC. Scores from a Visual Analog Scale and the Western Ontario and McMaster Universities Arthritis Index were evaluated at baseline and one, three, and six months after baseline. [Results] A total of 55 patients were included in this study. Most of the patients were female (55%), and the mean age of the patients was 42.4 (± 8.1) years. Based on the pre- and post-injection data, there was significant reductions both in the Visual Analog Scale score and the Western Ontario and McMaster Universities Arthritis Index score after the injections for all groups. According to intergroup comparisons, no significant difference was observed in terms of efficacy. [Conclusion] Three hyaluronic acid formulations produced a similar efficacy in patients with meniscal injuries, and further studies are needed to evaluate long-term results. PMID:28744035

Distal Predominance of Electrodiagnostic Abnormalities in Early Stage Amyotrophic Lateral Sclerosis.

PubMed

Shayya, Luay; Babu, Suma; Pioro, Erik P; Li, Jianbo; Li, Yuebing

2018-05-09

We compare the electrodiagnostic (EDX) yield of limb muscles in revealing lower motor neuron (LMN) dysfunction by electromyography (EMG) in early stage amyotrophic lateral sclerosis (ALS). Single-site retrospective review Results: This study includes 122 consecutive patients with possible ALS as defined by revised El Escorial Criteria. Distal limb muscles show more frequent EMG abnormalities than proximal muscles. EDX yield is higher in the limb where weakness begins and when clinical signs of LMN dysfunction are evident. Adoption of Awaji criteria increases the yield of EMG positive segments significantly in the cervical (p<0.0005) and lumbosacral regions (P<0.0001), and upgrades 19 patients into probable and 1 patient into definite categories. Electromyographic abnormalities are distal limb-predominant in early stage ALS. A redefinition of an EDX-positive cervical or lumbosacral segment, with an emphasis on distal limb muscles, may result in an earlier ALS diagnosis. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Stage Separation CFD Tool Development and Evaluation

NASA Technical Reports Server (NTRS)

Droege, Alan; Gomez, Reynaldo; Wang, Ten-See

2002-01-01

This viewgraph presentation evaluates CFD (Computational Fluid Dynamics) tools for solving stage separation problems. The demonstration and validation of the tools is for a second generation RLV (Reusable Launch Vehicle) stage separation. The flow solvers are: Cart3D; Overflow/Overflow-D; Unic.

Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

PubMed

Schneider, Lon S

2014-03-01

The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

Association Between Increased Vascular Density and Loss of Protective RAS in Early-Stage NPDR

NASA Technical Reports Server (NTRS)

Radhakrishnan, Krishnan; Raghunandan, Sneha; Vyas, Ruchi J.; Vu, Amanda C.; Bryant, Douglas; Yaqian, Duan; Knecht, Brenda E.; Grant, Maria B.; Chalam, K . V.; Parsons-Wingerter, Patricia

2016-01-01

Our hypothesis predicts that retinal blood vessels increase in density during early-stage progression to moderate nonproliferative diabetic retinopathy (NPDR). The prevailing paradigm of NPDR progression is that vessels drop out prior to abnormal, vision-impairing regrowth at late-stage proliferative diabetic retinopathy (DR). However, surprising results for our previous preliminary study 1 with NASA's VESsel GENeration Analysis (VESGEN) software showed that vessels proliferated considerably during moderate NPDR compared to drop out at both mild and severe NPDR. Validation of our hypothesis will support development of successful early-stage regenerative therapies such as vascular repair by circulating angiogenic cells (CACs). The renin-angiotensin system (RAS)is implicated in the pathogenesis of DR and in the function of CACs, a critical bone marrow-derived population that is instrumental in vascular repair.

Speech acoustic markers of early stage and prodromal Huntington's disease: a marker of disease onset?

PubMed

Vogel, Adam P; Shirbin, Christopher; Churchyard, Andrew J; Stout, Julie C

2012-12-01

Speech disturbances (e.g., altered prosody) have been described in symptomatic Huntington's Disease (HD) individuals, however, the extent to which speech changes in gene positive pre-manifest (PreHD) individuals is largely unknown. The speech of individuals carrying the mutant HTT gene is a behavioural/motor/cognitive marker demonstrating some potential as an objective indicator of early HD onset and disease progression. Speech samples were acquired from 30 individuals carrying the mutant HTT gene (13 PreHD, 17 early stage HD) and 15 matched controls. Participants read a passage, produced a monologue and said the days of the week. Data were analysed acoustically for measures of timing, frequency and intensity. There was a clear effect of group across most acoustic measures, so that speech performance differed in-line with disease progression. Comparisons across groups revealed significant differences between the control and the early stage HD group on measures of timing (e.g., speech rate). Participants carrying the mutant HTT gene presented with slower rates of speech, took longer to say words and produced greater silences between and within words compared to healthy controls. Importantly, speech rate showed a significant correlation to burden of disease scores. The speech of early stage HD differed significantly from controls. The speech of PreHD, although not reaching significance, tended to lie between the performance of controls and early stage HD. This suggests that changes in speech production appear to be developing prior to diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

PubMed Central

Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.

2013-01-01

Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI.

PubMed

Wang, Xue; Zhao, Yu; Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen; Wang, Jinhong; Yan, Zhihan

2017-07-11

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10-3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers.

Evaluation and validation of the diagnostic value of the apparent diffusion coefficient for differentiating early-stage endometrial carcinomas from benign mimickers at 3T MRI

PubMed Central

Hu, Yumin; Zhou, Yongjin; Ye, Xinjian; Liu, Kun; Bai, Guanghui; Guo, Anna; Du, Meimei; Jiang, Lezhen

2017-01-01

Previous researchers obtained various apparent diffusion coefficient (ADC) cutoff values to differentiate endometrial carcinoma from benign mimickers with 1.5T magnetic resonance imaging (MRI). Few studies have used 3T MRI or validated the effectiveness of these cutoff ADC values prospectively. This study was designed in two stages to obtain a cutoff ADC value at 3T MRI and to validate prospectively the role of the ADC value. First, we conducted a retrospective study of 60 patients to evaluate the diagnostic value of ADC by obtain a theoretical cutoff ADC value for differentiating between benign and malignant endometrial lesions. Student's t test revealed that ADC values for stage I endometrial carcinomas were significantly lower than those for benign lesions. The area under the curve value of the receiver operating characteristic curve was 0.993, and the cutoff ADC value was 0.98 × 10−3 mm2/s. The sensitivity, specificity, and overall accuracy of diagnosing stage I endometrial carcinoma were 100%, 97.1%, and 98.3%, respectively. Second, we conducted a prospective study of 26 patients to validate the use of the cutoff ADC value obtained in the study's first stage. The sensitivity, specificity, and overall accuracy for differentiating malignant from benign endometrial lesions based on the cutoff ADC value obtained earlier were as follows: radiologist 1 attained 86.67%, 100.0%, and 92.31%, respectively; radiologist 2 attained 86.67%, 91.0%, and 88.5%, respectively. Our results suggest that ADC values could be a potential biomarker for use as a quantitative and qualitative tool for differentiating between early-stage endometrial carcinomas and benign mimickers. PMID:28634318

Adjuvant chemotherapy for resected early-stage non-small cell lung cancer.

PubMed

Burdett, Sarah; Pignon, Jean Pierre; Tierney, Jayne; Tribodet, Helene; Stewart, Lesley; Le Pechoux, Cecile; Aupérin, Anne; Le Chevalier, Thierry; Stephens, Richard J; Arriagada, Rodrigo; Higgins, Julian P T; Johnson, David H; Van Meerbeeck, Jan; Parmar, Mahesh K B; Souhami, Robert L; Bergman, Bengt; Douillard, Jean-Yves; Dunant, Ariane; Endo, Chiaki; Girling, David; Kato, Harubumi; Keller, Steven M; Kimura, Hideki; Knuuttila, Aija; Kodama, Ken; Komaki, Ritsuko; Kris, Mark G; Lad, Thomas; Mineo, Tommaso; Piantadosi, Steven; Rosell, Rafael; Scagliotti, Giorgio; Seymour, Lesley K; Shepherd, Frances A; Sylvester, Richard; Tada, Hirohito; Tanaka, Fumihiro; Torri, Valter; Waller, David; Liang, Ying

2015-03-02

To evaluate the effects of administering chemotherapy following surgery, or following surgery plus radiotherapy (known as adjuvant chemotherapy) in patients with early stage non-small cell lung cancer (NSCLC),we performed two systematic reviews and meta-analyses of all randomised controlled trials using individual participant data. Results were first published in The Lancet in 2010. To compare, in terms of overall survival, time to locoregional recurrence, time to distant recurrence and recurrence-free survival:A. Surgery versus surgery plus adjuvant chemotherapyB. Surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapyin patients with histologically diagnosed early stage NSCLC.(2)To investigate whether or not predefined patient subgroups benefit more or less from cisplatin-based chemotherapy in terms of survival. We supplemented MEDLINE and CANCERLIT searches (1995 to December 2013) with information from trial registers, handsearching relevant meeting proceedings and by discussion with trialists and organisations. We included trials of a) surgery versus surgery plus adjuvant chemotherapy; and b) surgery plus radiotherapy versus surgery plus radiotherapy plus adjuvant chemotherapy, provided that they randomised NSCLC patients using a method which precluded prior knowledge of treatment assignment. We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. Data from all patients were sought from those responsible for the trial. We obtained updated individual participant data (IPD) on survival, and date of last follow-up, as well as details of treatment allocated, date of randomisation, age, sex, histological cell type, stage, and performance status. To avoid potential bias, we requested information for all randomised patients, including those excluded from the investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival

Effects of chronic crude oil exposure on early developmental stages of the Northern krill (Meganyctiphanes norvegica).

PubMed

Arnberg, Maj; Moodley, Leon; Dunaevskaya, Evgenia; Ramanand, Sreerekha; Ingvarsdóttir, Anna; Nilsen, Marianne; Ravagnan, Elisa; Westerlund, Stig; Sanni, Steinar; Tarling, Geraint A; Bechmann, Renée K

2017-01-01

Rising oil and gas activities in northern high latitudes have led to an increased risk of petroleum pollution in these ecosystems. Further, seasonal high UV radiation at high latitudes may elevate photo-enhanced toxicity of petroleum pollution to marine organisms. Zooplanktons are a key ecological component of northern ecosystems; therefore, it is important to assess their sensitivity to potential pollutants of oil and gas activity. As ontogenetic development may be particularly sensitive, the aim of this study was to examine the impact of chronic exposure to oil water dispersion (OWD) on development and feeding of early life stages of the Northern krill, Meganyctiphanes norvegica. In a range of experiments, embryonic, nonfeeding, and feeding larval stages were exposed to concentrations of between 0.01 and 0.1 mg/L of oil or photo-modified oil for 19 and 21 d. No significant effects on egg respiration, hatching success, development, length and larval survival were observed from these treatments. Similarly, evolution of fatty acid composition patterns during ontogenetic development was unaffected. The results indicates a high degree of resilience of these early developmental stages to such types and concentrations of pollutants. However, feeding and motility in later calyptopis-stage larvae were significantly impaired at exposure of 0.1 mg/L oil. Data indicate that feeding larval stage of krill was more sensitive to OWD than early nonfeeding life stages. This might be attributed to the narcotic effects of oil pollutants, their direct ingestion, or accumulated adverse effects over early development.

Dissection and Downstream Analysis of Zebra Finch Embryos at Early Stages of Development

PubMed Central

Murray, Jessica R.; Stanciauskas, Monika E.; Aralere, Tejas S.; Saha, Margaret S.

2014-01-01

The zebra finch (Taeniopygiaguttata) has become an increasingly important model organism in many areas of research including toxicology1,2, behavior3, and memory and learning4,5,6. As the only songbird with a sequenced genome, the zebra finch has great potential for use in developmental studies; however, the early stages of zebra finch development have not been well studied. Lack of research in zebra finch development can be attributed to the difficulty of dissecting the small egg and embryo. The following dissection method minimizes embryonic tissue damage, which allows for investigation of morphology and gene expression at all stages of embryonic development. This permits both bright field and fluorescence quality imaging of embryos, use in molecular procedures such as in situ hybridization (ISH), cell proliferation assays, and RNA extraction for quantitative assays such as quantitative real-time PCR (qtRT-PCR). This technique allows investigators to study early stages of development that were previously difficult to access. PMID:24999108

Identification of early B cell precursors (stage 1 and 2 hematogones) in the peripheral blood.

PubMed

Kurzer, Jason H; Weinberg, Olga K

2018-05-25

Differentiating malignant B-lymphoblasts from early benign B cell precursors (hematogones) is a vital component of the diagnosis of B-lymphoblastic leukaemia. It has been previously reported that only late-stage B cell precursors circulate in the peripheral blood. Consequently, flow cytometric detection of cells with immunophenotypic findings similar to earlier stage precursors in the peripheral blood justifiably raises concern for involvement by B-lymphoblastic leukaemia. We report here, however, that benign early B cell precursors can indeed be detected in the peripheral blood, thus complicating the interpretation of flow cytometric findings derived from these sample types. A retrospective search of our collective databases identified 13 cases containing circulating early stage B cell precursors. The patients ranged in age from 15 days to 85 years old. All positive cases demonstrated that the earlier B cell precursors were associated with later stage precursors, a finding that could help differentiate these cells from B-lymphoblastic leukaemia. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Bridging the gap: facilities and technologies for development of early stage therapeutic mAb candidates.

PubMed

Munro, Trent P; Mahler, Stephen M; Huang, Edwin P; Chin, David Y; Gray, Peter P

2011-01-01

Therapeutic monoclonal antibodies (mAbs) currently dominate the biologics marketplace. Development of a new therapeutic mAb candidate is a complex, multistep process and early stages of development typically begin in an academic research environment. Recently, a number of facilities and initiatives have been launched to aid researchers along this difficult path and facilitate progression of the next mAb blockbuster. Complementing this, there has been a renewed interest from the pharmaceutical industry to reconnect with academia in order to boost dwindling pipelines and encourage innovation. In this review, we examine the steps required to take a therapeutic mAb from discovery through early stage preclinical development and toward becoming a feasible clinical candidate. Discussion of the technologies used for mAb discovery, production in mammalian cells and innovations in single-use bioprocessing is included. We also examine regulatory requirements for product quality and characterization that should be considered at the earliest stages of mAb development. We provide details on the facilities available to help researchers and small-biotech build value into early stage product development, and include examples from within our own facility of how technologies are utilized and an analysis of our client base.

Motor-cognitive dual-task deficits in individuals with early-mid stage Huntington disease.

PubMed

Fritz, Nora E; Hamana, Katy; Kelson, Mark; Rosser, Anne; Busse, Monica; Quinn, Lori

2016-09-01

Huntington disease (HD) results in a range of cognitive and motor impairments that progress throughout the disease stages; however, little research has evaluated specific dual-task abilities in this population, and the degree to which they may be related to functional ability. The purpose of this study was to a) examine simple and complex motor-cognitive dual-task performance in individuals with HD, b) determine relationships between dual-task walking ability and disease-specific measures of motor, cognitive and functional ability, and c) examine the relationship of dual-task measures to falls in individuals with HD. Thirty-two individuals with HD were evaluated for simple and complex dual-task ability using the Walking While Talking Test. Demographics and disease-specific measures of motor, cognitive and functional ability were also obtained. Individuals with HD had impairments in simple and complex dual-task ability. Simple dual-task walking was correlated to disease-specific motor scores as well as cognitive performance, but complex dual-task walking was correlated with total functional capacity, as well as a range of cognitive measures. Number of prospective falls was moderately-strongly correlated to dual-task measures. Our results suggest that individuals with HD have impairments in cognitive-motor dual-task ability that are related to disease progression and specifically functional ability. Dual-task measures appear to evaluate a unique construct in individuals with early to mid-stage HD, and may have value in improving the prediction of falls risk in this population. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiological and morphological changes during early and later stages of fruit growth in Capsicum annuum.

PubMed

Tiwari, Aparna; Vivian-Smith, Adam; Ljung, Karin; Offringa, Remko; Heuvelink, Ep

2013-03-01

Fruit-set involves a series of physiological and morphological changes that are well described for tomato and Arabidopsis, but largely unknown for sweet pepper (Capsicum annuum). The aim of this paper is to investigate whether mechanisms of fruit-set observed in Arabidopsis and tomato are also applicable to C. annuum. To do this, we accurately timed the physiological and morphological changes in a post-pollinated and un-pollinated ovary. A vascular connection between ovule and replum was observed in fertilized ovaries that undergo fruit development, and this connection was absent in unfertilized ovaries that abort. This indicates that vascular connection between ovule and replum is an early indicator for successful fruit development after pollination and fertilization. Evaluation of histological changes in the carpel of a fertilized and unfertilized ovary indicated that increase in cell number and cell diameter both contribute to early fruit growth. Cell division contributes more during early fruit growth while cell expansion contributes more at later stages of fruit growth in C. annuum. The simultaneous occurrence of a peak in auxin concentration and a strong increase in cell diameter in the carpel of seeded fruits suggest that indole-3-acetic acid stimulates a major increase in cell diameter at later stages of fruit growth. The series of physiological and morphological events observed during fruit-set in C. annuum are similar to what has been reported for tomato and Arabidopsis. This indicates that tomato and Arabidopsis are suitable model plants to understand details of fruit-set mechanisms in C. annuum. Copyright © Physiologia Plantarum 2012.

The associations of TERT-CLPTM1L variants and TERT mRNA expression with the prognosis of early stage non-small cell lung cancer.

PubMed

Chen, Z; Wang, J; Bai, Y; Wang, S; Yin, X; Xiang, J; Li, X; He, M; Zhang, X; Wu, T; Xu, P; Guo, H

2017-01-01

Lung cancer is the leading cause of cancer-related death in the world. Several genome-wide association studies (GWAS) have identified TERT-CLPTM1L as plausible causative locus for lung cancer development. This study aimed to investigate the associations of genetic variations in TERT-CLPTM1L and the expression level of TERT with the survival of early stage non-small cell lung cancer (NSCLC) patients. We selected three single-nucleotide polymorphisms of TERT-CLPTM1L (rs2853669, rs2736108 and rs31490) and genotyped in 140 early stage NSCLC patients by TaqMan assay. Associations between these variations and survival outcome of early stage NSCLC patients were further investigated. We also used TCGA data to evaluate the associations of TERT messenger RNA (mRNA) expression and survival outcome of early stage NSCLC patients. Survival analysis showed that, compared with early NSCLC patients carrying TERT rs2853669 TT+TC genotypes, patients with rs2853669 CC genotype had significantly longer median survival time (MST=102.2 vs 52.4 months; log-rank P=0.028) and lower death risk [hazard ratio (HR) with 95% confidence interval (CI))=0.38(0.17-0.82), P=0.014]. Early NSCLC patients carrying TERT rs2736108 AA genotype had significantly shorter MST (MST=29.0 vs 63.3 months; log-rank P=0.020) and increased death risk [HR (95% CI)=2.22(1.01-5.80), P=0.046], when compared with patients carrying rs2736108 GG genotypes. TCGA data revealed that early NSCLC patients with higher expression level of TERT mRNA in lung tumor tissues had a longer MST and decreased death risk than those with low expression level of TERT mRNA [MST=54.4 vs 49.0 months; log-rank P=0.041; adjusted HR (95% CI)=0.68(0.50-0.94)]. These findings may add potential evidence to understand the prognostic value of TERT and provide a new prospect of individualized prevention and treatment for early stage NSCLC.

The decline of venture capital investment in early-stage life sciences poses a challenge to continued innovation.

PubMed

Fleming, Jonathan J

2015-02-01

A key element required for translating new knowledge into effective therapies is early-stage venture capital that finances the work needed to identify a lead molecule or medical device prototype and to develop it to the proof-of-concept stage. This early investment is distinguished by great uncertainty over whether the molecule or prototype is safe and effective, the stability of the regulatory standards to which clinical trials are designed, and the likelihood that large follow-on investments for commercial development can be secured. Regulatory and reimbursement policies have a profound impact on the amount of capital and the types of life science projects that investors pursue. In this article I analyze several recent trends in early-stage venture capital funding, describe how these trends are influenced by regulatory and reimbursement policies, and discuss the role of policy makers in bringing new treatments to market. Policy makers can foster renewed private investment into critically needed early-stage products by increasing Small Business Innovation Research (SBIR) funding and public support for clinical trials in targeted areas of interest; creating regulatory pathways to enable early testing of experimental compounds in limited populations; and offering economic incentives for investors and developers in designated therapeutic areas. Project HOPE—The People-to-People Health Foundation, Inc.

A Prospective Longitudinal Clinical Trial Evaluating Quality of Life After Breast-Conserving Surgery and High-Dose-Rate Interstitial Brachytherapy for Early-Stage Breast Cancer

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

Garsa, Adam A.; Ferraro, Daniel J.; DeWees, Todd A.

2013-12-01

Purpose: To prospectively examine quality of life (QOL) of patients with early stage breast cancer treated with accelerated partial breast irradiation (APBI) using high-dose-rate (HDR) interstitial brachytherapy. Methods and Materials: Between March 2004 and December 2008, 151 patients with early stage breast cancer were enrolled in a phase 2 prospective clinical trial. Eligible patients included those with Tis-T2 tumors measuring ≤3 cm excised with negative surgical margins and with no nodal involvement. Patients received 3.4 Gy twice daily to a total dose of 34 Gy. QOL was measured using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, versionmore » 3.0, and QLQ-BR23 questionnaires. The QLQ-C30 and QLQ-BR23 questionnaires were evaluated during pretreatment and then at 6 to 8 weeks, 3 to 4 months, 6 to 8 months, and 1 and 2 years after treatment. Results: The median follow-up was 55 months. Breast symptom scores remained stable in the months after treatment, and they significantly improved 6 to 8 months after treatment. Scores for emotional functioning, social functioning, and future perspective showed significant improvement 2 years after treatment. Symptomatic fat necrosis was associated with several changes in QOL, including increased pain, breast symptoms, systemic treatment side effects, dyspnea, and fatigue, as well as decreased role functioning, emotional functioning, and social functioning. Conclusions: HDR multicatheter interstitial brachytherapy was well tolerated, with no significant detrimental effect on measured QOL scales/items through 2 years of follow-up. Compared to pretreatment scores, there was improvement in breast symptoms, emotional functioning, social functioning, and future perspective 2 years after treatment.« less

Dyslipidogenic microangiopathy in guinea pigs at early stages of atherogenesis.

PubMed

Bersenev, A V; Klimenko, E D; Kobozeva, L P; Michunskaya, A B; Onishchenko, N A; Pozdnyakov, O M

2003-08-01

We studied the effect of dyslipidemia on lipid metabolism, state of microcirculatory system, and morphological alterations in the aorta and liver of guinea pigs at the early stages of experimental atherogenesis. The important role of microcirculatory disorders in the development of regional pathology and atherosclerosis is confirmed. The proposed alimentary model can be used in the development of novel methods for prevention and treatment of atherosclerosis.

Analysis of Charges Associated with Definitive Nonsurgical Therapy for Early-Stage Lateralized Tonsil Cancer.

PubMed

Lewis, Carol M; Chronowski, Gregory M; Dong, Wenli; Gunn, G Brandon; Rosenthal, David I; Weber, Randal S

2015-08-01

The cost of treatment as it affects comparative effectiveness is becoming increasingly more important. Because cost data are not readily available, we evaluated the charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancers. Patients treated with unilateral radiation therapy (RT) for T1 or T2 tonsil cancer between 1995 and 2007 were retrospectively reviewed. Total and radiation-specific charges, from 3 months before to 4 months after radiation, were adjusted for inflation. All facets of treatment were evaluated for significant associations with total billing. Eighty-four patients were identified. Three-year overall survival, disease-specific survival, and recurrence-free survival were 97 % [95 % confidence interval (CI) 0.88-0.99], 98 % (95 % CI 0.89-1), and 96 % (95 % CI 0.88-0.99), respectively. The median for radiation-specific charges was $60,412 (range $16,811-$84,792). The median for total charges associated with treatment was $109,917 (range $36,680-$231,895). Total billing for treatment was significantly associated with the year of diagnosis (p = 0.008), intensity-modulated radiation therapy versus wedge pair RT (p = 0.005), preradiation direct laryngoscopy (p < 0.0001), chemotherapy (p < 0.0001), gastrostomy tube placement (p = 0.004), and postradiation neck dissection (p = 0.005). Although cost data for treatment are not readily available, historically, the recovery rate is approximately 30 %. The charges associated with definitive nonsurgical therapy for early-stage lateralized tonsil cancer have a wide range likely due to treatment-related procedures, the use of chemotherapy, and evolving RT technologies. These benchmark data are important given renewed interested in primary surgery for tonsil cancer. Cost of care, disease control, and functional outcomes will be critical for comparisons of effectiveness when selecting treatment modalities.

Validation of a Molecular and Pathological Model for Five-Year Mortality Risk in Patients with Early Stage Lung Adenocarcinoma

PubMed Central

Bueno, Raphael; Hughes, Elisha; Wagner, Susanne; Gutin, Alexander S.; Lanchbury, Jerry S.; Zheng, Yifan; Archer, Michael A.; Gustafson, Corinne; Jones, Joshua T.; Rushton, Kristen; Saam, Jennifer; Kim, Edward; Barberis, Massimo; Wistuba, Ignacio; Wenstrup, Richard J.; Wallace, William A.; Harrison, David J.

2015-01-01

Introduction: The aim of this study was to validate a molecular expression signature [cell cycle progression (CCP) score] that identifies patients with a higher risk of cancer-related death after surgical resection of early stage (I-II) lung adenocarcinoma in a large patient cohort and evaluate the effectiveness of combining CCP score and pathological stage for predicting lung cancer mortality. Methods: Formalin-fixed paraffin-embedded surgical tumor samples from 650 patients diagnosed with stage I and II adenocarcinoma who underwent definitive surgical treatment without adjuvant chemotherapy were analyzed for 31 proliferation genes by quantitative real-time polymerase chain reaction. The prognostic discrimination of the expression score was assessed by Cox proportional hazards analysis using 5-year lung cancer-specific death as primary outcome. Results: The CCP score was a significant predictor of lung cancer-specific mortality above clinical covariates [hazard ratio (HR) = 1.46 per interquartile range (95% confidence interval = 1.12–1.90; p = 0.0050)]. The prognostic score, a combination of CCP score and pathological stage, was a more significant indicator of lung cancer mortality risk than pathological stage in the full cohort (HR = 2.01; p = 2.8 × 10−11) and in stage I patients (HR = 1.67; p = 0.00027). Using the 85th percentile of the prognostic score as a threshold, there was a significant difference in lung cancer survival between low-risk and high-risk patient groups (p = 3.8 × 10−7). Conclusions: This study validates the CCP score and the prognostic score as independent predictors of lung cancer death in patients with early stage lung adenocarcinoma treated with surgery alone. Patients with resected stage I lung adenocarcinoma and a high prognostic score may be candidates for adjuvant therapy to reduce cancer-related mortality. PMID:25396679

Fish early life stage: Developing AOPs to support targeted reduction and replacement

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

Functional and morphological assessment of ocular structures and follow-up of patients with early-stage Parkinson's disease.

PubMed

Hasanov, Samir; Demirkilinc Biler, Elif; Acarer, Ahmet; Akkın, Cezmi; Colakoglu, Zafer; Uretmen, Onder

2018-05-09

To evaluate and follow-up of functional and morphological changes of the optic nerve and ocular structures prospectively in patients with early-stage Parkinson's disease. Nineteen patients with a diagnosis of early-stage Parkinson's disease and 19 age-matched healthy controls were included in the study. All participants were examined minimum three times at the intervals of at least 6 month following initial examination. Pattern visually evoked potentials (VEP), contrast sensitivity assessments at photopic conditions, color vision tests with Ishihara cards and full-field visual field tests were performed in addition to measurement of retinal nerve fiber layer (RNFL) thickness of four quadrants (top, bottom, nasal, temporal), central and mean macular thickness and macular volumes. Best corrected visual acuity was observed significantly lower in study group within all three examinations. Contrast sensitivity values of the patient group were significantly lower in all spatial frequencies. P100 wave latency of VEP was significantly longer, and amplitude was lower in patient group; however, significant deterioration was not observed during the follow-up. Although average peripapillary RNFL thickness was not significant between groups, RNFL thickness in the upper quadrant was thinner in the patient group. While there was no difference in terms of mean macular thickness and total macular volume values between the groups initially, a significant decrease occurred in the patient group during the follow-up. During the initial and follow-up process, a significant deterioration in visual field was observed in the patient group. Structural and functional disorders shown as electro-physiologically and morphologically exist in different parts of visual pathways in early-stage Parkinson's disease.

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

Survival benefit of patients with early-stage ovarian carcinoma treated with paclitaxel chemotherapeutic regimens

PubMed Central

2018-01-01

Objective Adjuvant chemotherapy was introduced in patients with early-stage ovarian cancer (OC). The benefit of standard chemotherapeutic regimens including taxane has not been established. Methods Patients with early-stage OC from the National Health Insurance Research database of Taiwan who received platinum plus cyclophosphamide (CP) or platinum plus paclitaxel (PT) for 3–6 cycles were recruited, and the disease-free survival (DFS) and overall survival (OS) were determined. Results A total of 1,510 early-stage OC patients, including 841 who received CP regimen and 699 who received PT regimen, were included. The 2 groups had a similar estimated probability of 5-year DFS (PT vs. CP, 79.0% vs. 77.6%; p=0.410) and OS (84.6% vs. 84.3%; p=0.691). Patients >50 years of age who received the CP regimen had a lower 5-year DFS than the patients ≤50 years of age who received the CP (p<0.001) or PT regimens (p=0.001). Additionally, patients >50 years of age who received the CP regimen had a worse 5-year OS compared with the other 3 groups (p=0.019) (p=0.179 for patients >50 years of age in the PT group; p=0.002 for patients ≤50 years of age in the CP group; and p=0.061 for patients ≤50 years of age in the PT group). Patients with the CP or PT regimen for 3–5 cycles had a similar 5-year DFS and OS compared to 6 cycles (p>0.050). Conclusion Chemotherapeutic regimens with taxane could be recommended for early-stage OC patients >50 years of age. PMID:29185274

Stage-dependent remodeling of the nuclear envelope and lamina during rabbit early embryonic development.

PubMed

Popken, Jens; Schmid, Volker J; Strauss, Axel; Guengoer, Tuna; Wolf, Eckhard; Zakhartchenko, Valeri

2016-04-22

Utilizing 3D structured illumination microscopy, we investigated the quality and quantity of nuclear invaginations and the distribution of nuclear pores during rabbit early embryonic development and identified the exact time point of nucleoporin 153 (NUP153) association with chromatin during mitosis. Contrary to bovine early embryonic nuclei, featuring almost exclusively nuclear invaginations containing a small volume of cytoplasm, nuclei in rabbit early embryonic stages show additionally numerous invaginations containing a large volume of cytoplasm. Small-volume invaginations frequently emanated from large-volume nuclear invaginations but not vice versa, indicating a different underlying mechanism. Large- and small-volume nuclear envelope invaginations required the presence of chromatin, as they were restricted to chromatin-positive areas. The chromatin-free contact areas between nucleolar precursor bodies (NPBs) and large-volume invaginations were free of nuclear pores. Small-volume invaginations were not in contact with NPBs. The number of invaginations and isolated intranuclear vesicles per nucleus peaked at the 4-cell stage. At this stage, the nuclear surface showed highly concentrated clusters of nuclear pores surrounded by areas free of nuclear pores. Isolated intranuclear lamina vesicles were usually NUP153 negative. Cytoplasmic, randomly distributed NUP153-positive clusters were highly abundant at the zygote stage and decreased in number until they were almost absent at the 8-cell stage and later. These large NUP153 clusters may represent a maternally provided NUP153 deposit, but they were not visible as clusters during mitosis. Major genome activation at the 8- to 16-cell stage may mark the switch from a necessity for a deposit to on-demand production. NUP153 association with chromatin is initiated during metaphase before the initiation of the regeneration of the lamina. To our knowledge, the present study demonstrates for the first time major remodeling

Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

PubMed Central

Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

2014-01-01

Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

Early labour services: changes, triggers, monitoring and evaluation.

PubMed

Spiby, Helen; Green, Josephine M; Richardson-Foster, Helen; Hucknall, Clare

2013-04-01

to identify the changes to early labour services, their triggers and monitoring. a mixed methods approach in two stages, firstly a postal questionnaire survey of Heads of Midwifery (HoM) services in NHS Trusts in England (cover sheet to each HoM and questionnaire for each unit in their jurisdiction) and, secondly, semi-structured telephone interviews with a purposive sample of senior midwives. The interviews sought further information about reasons for change; the impact of changes and explored the unit's particular innovations. PARTICIPANTS AND RESPONSE RATE: 145 (89%) NHS Trusts provided data (cover sheet and/or questionnaire); responses were received from all areas and types of unit. Seventeen HoMs or designated senior midwives were interviewed. 83 of 170 units (49%) had made changes to early labour service provision during the past 5 years, including home assessment; the introduction of triage units and telephone assessment tools. Changes were more likely in high volume units and in consultant units with midwifery-led care areas. Further changes were planned by 93/178 (25%) units. Triggers for changes to early labour services comprised local or unit-based factors, including Category X (non-labour) admissions, response to service users and research evidence. The impact of Category X admissions on workload contributed to the triggers for change. Fifty-six (31%) could provide a confirmed figure or estimate for category X admissions. Experiences of introducing change included issues related to engagement of the workforce and the contribution of clinical leadership. Thirty-eight (48%) units did not routinely monitor use of early labour services. Overall monitoring of services was not significantly more likely in units that had made changes. Audit activity was reported more frequently in units that had made changes to their early labour services. early labour services had undergone significant changes following a range of triggers but the extent of change was not

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

Is Breast Conserving Therapy a Safe Modality for Early-Stage Male Breast Cancer?

PubMed

Zaenger, David; Rabatic, Bryan M; Dasher, Byron; Mourad, Waleed F

2016-04-01

Male breast cancer (MBC) is a rare disease and lacks data-based treatment guidelines. Most men are currently treated with modified radical mastectomy (MRM) or simple mastectomy (SM). We compared the oncologic treatment outcomes of early-stage MBC to determine whether breast conservation therapy (BCT) is appropriate. We searched the Surveillance, Epidemiology, and End Results database for MBC cases. That cohort was narrowed to cases of stage I-II, T1-T2N0 MBC with surgical and radiation therapy (RT) data available. The patients had undergone MRM, SM, or breast conservation surgery (BCS) with or without postoperative RT. We calculated the actuarial 5-year cause-specific survival (CSS). We identified 6263 MBC cases and included 1777 men with stage I or II, T1-T2, node-negative disease, who had the required treatment information available. MRM without RT was the most common treatment (43%). Only 17% underwent BCS. Of the BCS patients, 46% received adjuvant RT to complete the traditional BCT. No deaths were recorded in the BCT group, regardless of stage, or in the 3 stage I surgical groups if the men had received RT. The actuarial 5-year CSS was 100% in each BCT group. MRM alone resulted in an actuarial 5-year CSS of 97.3% for stage 1% and 91.2% for stage 2. The results from our study suggest that BCT for early-stage MBC yields comparable survival compared with more invasive treatment modalities (ie, MRM or SM alone). This could shift the treatment paradigm to less-invasive interventions and might have the added benefit of increased functional and psychological outcomes. Further prospective studies are needed to confirm our conclusions. Copyright © 2016 Elsevier Inc. All rights reserved.

Two consecutive pregnancies in early and late stage of amyotrophic lateral sclerosis.

PubMed

Sarafov, Stayko; Doitchinova, Maryana; Karagiozova, Zhvka; Slancheva, Boriana; Dengler, Reinhard; Petri, Susanne; Kollewe, Katja

2009-01-01

There are few reports on pregnancies in sporadic and familial amyotrophic lateral sclerosis (ALS). We report on a young woman with sporadic ALS who gave birth twice during the course of her disease. The first pregnancy occurred 13 months after the onset of symptoms, and one month after diagnosis. The pregnancy was uncomplicated and resulted in vaginal delivery of a healthy boy. Fifteen months later, when she was already bed-ridden, she became pregnant again. She received a percutaneous endoscopic gastrostomy in the 21st gestational week and underwent early Caesarean section in the 34th week of gestation. The child was ventilated for 72 h in a neonatological unit. The patient was tracheotomized and ventilated two months later, i.e. 47 months after symptom onset, and died nine months later from gastrointestinal haemorrhage. Her two children have developed without abnormalities to date. This case confirms that pregnancies in early-stage ALS can develop normally and may result in uncomplicated vaginal delivery. Pregnancies in late stages may be critical for mother and child, and early delivery by Caesarean section may become necessary although neonatal outcome can be good.

Endothelial binding of beta toxin to small intestinal mucosal endothelial cells in early stages of experimentally induced Clostridium perfringens type C enteritis in pigs.

PubMed

Schumacher, V L; Martel, A; Pasmans, F; Van Immerseel, F; Posthaus, H

2013-07-01

Beta toxin (CPB) is known to be an essential virulence factor in the development of lesions of Clostridium perfringens type C enteritis in different animal species. Its target cells and exact mechanism of toxicity have not yet been clearly defined. Here, we evaluate the suitability of a neonatal piglet jejunal loop model to investigate early lesions of C. perfringens type C enteritis. Immunohistochemically, CPB was detected at microvascular endothelial cells in intestinal villi during early and advanced stages of lesions induced by C. perfringens type C. This was first associated with capillary dilatation and subsequently with widespread hemorrhage in affected intestinal segments. CPB was, however, not demonstrated on intestinal epithelial cells. This indicates a tropism of CPB toward endothelial cells and suggests that CPB-induced endothelial damage plays an important role in the early stages of C. perfringens type C enteritis in pigs.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

Early, asymptomatic stage of degenerative joint disease in canine hip joints.

PubMed

Lust, G; Summers, B A

1981-11-01

The early stages of degenerative joint disease were investigated in coxofemoral joints from dogs with a hereditary predisposition to hip dysplasia. Alterations observed included mild nonsuppurative synovitis, increased volume of both synovial fluid and the ligamentum teres, and focal degenerative articular cartilage lesions. On radiologic examination, subluxation of the femoral head was seen, but only in the most severely affected joints. Synovial inflammation with increased synovial fluid and ligament volumes were indicators of early degenerative joint disease in dogs. These changes seemed to coincide with, or perhaps to precede, microscopic evidence for articular cartilage degeneration and occurred before radiologic abnormalities were detected.

Factors influencing recruitment of walleye and white bass to three distinct early ontogenetic stages

USGS Publications Warehouse

DeBoer, Jason A.; Pope, Kevin L.

2015-01-01

Determining the factors that influence recruitment to sequential ontogenetic stages is critical for understanding recruitment dynamics of fish and for effective management of sportfish, particularly in dynamic and unpredictable environments. We sampled walleye (Sander vitreus) and white bass (Morone chrysops) at 3 ontogenetic stages (age 0 during spring: ‘age-0 larval’; age 0 during autumn: ‘age-0 juvenile’; and age 1 during autumn: ‘age-1 juvenile’) from 3 reservoirs. We developed multiple linear regression models to describe factors influencing age-0 larval, age-0 juvenile and age-1 juvenile walleye and white bass abundance indices. Our models explained 40–80% (68 ± 9%; mean ± SE) and 71%–97% (81 ± 6%) of the variability in catch for walleye and white bass respectively. For walleye, gizzard shad were present in the candidate model sets for all three ontogenetic stages we assessed. For white bass, there was no unifying variable in all three stage-specific candidate model sets, although walleye abundance was present in two of the three white bass candidate model sets. We were able to determine several factors affecting walleye and white bass year-class strength at multiple ontogenetic stages; comprehensive analyses of factors influencing recruitment to multiple early ontogenetic stages are seemingly rare in the literature. Our models demonstrate the interdependency among early ontogenetic stages and the complexities involved with sportfish recruitment.

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

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

None, None

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

DOE PAGES

None, None

2016-03-22

Synthetic oligopeptides containing π-conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterize an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of ΔF ≈ -25kBT. Aggregation at high-pH produces disordered aggregates destabilized by Coulombic repulsion between negatively charged Asp termini (ΔF ≈ -5kBT). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuous-time Markovmore » process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates.« less

Evaluation of Vascular Endothelial Growth Factor as a Prognostic Marker for Local Relapse in Early-Stage Breast Cancer Patients Treated With Breast-Conserving Therapy

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

Moran, Meena S., E-mail: meena.moran@yale.edu; Yang Qifeng; Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, People's Republic of China

2011-12-01

Purpose: Vascular endothelial growth factor (VEGF) is an important protein involved in the process of angiogenesis that has been found to correlate with relapse-free and overall survival in breast cancer, predominantly in locally advanced and metastatic disease. A paucity of data is available on the prognostic implications of VEGF in early-stage breast cancer; specifically, its prognostic value for local relapse after breast-conserving therapy (BCT) is largely unknown. The purpose of our study was to assess VEGF expression in a cohort of early-stage breast cancer patients treated with BCT and to correlate the clinical and pathologic features and outcomes with overexpressionmore » of VEGF. Methods and Materials: After obtaining institutional review board approval, the paraffin specimens of 368 patients with early-stage breast cancer treated with BCT between 1975 and 2005 were constructed into tissue microarrays with twofold redundancy. The tissue microarrays were stained for VEGF and read by a trained pathologist, who was unaware of the clinical details, as positive or negative according the standard guidelines. The clinical and pathologic data, long-term outcomes, and results of VEGF staining were analyzed. Results: The median follow-up for the entire cohort was 6.5 years. VEGF expression was positive in 56 (15%) of the 368 patients. Although VEGF expression did not correlate with age at diagnosis, tumor size, nodal status, histologic type, family history, estrogen receptor/progesterone receptor status, or HER-2 status, a trend was seen toward increased VEGF expression in the black cohort (26% black vs. 13% white, p = .068). Within the margin-negative cohort, VEGF did not predict for local relapse-free survival (RFS) (96% vs. 95%), nodal RFS (100% vs. 100%), distant metastasis-free survival (91% vs. 92%), overall survival (92% vs. 97%), respectively (all p >.05). Subset analysis revealed that VEGF was highly predictive of local RFS in node-positive, margin

Prognostic factors for patients with early-stage uterine serous carcinoma without adjuvant therapy.

PubMed

Tate, Keisei; Yoshida, Hiroshi; Ishikawa, Mitsuya; Uehara, Takashi; Ikeda, Shun Ichi; Hiraoka, Nobuyoshi; Kato, Tomoyasu

2018-05-01

Uterine serous carcinoma (USC) is an aggressive type 2 endometrial cancer. Data on prognostic factors for patients with early-stage USC without adjuvant therapy are limited. This study aims to assess the baseline recurrence risk of early-stage USC patients without adjuvant treatment and to identify prognostic factors and patients who need adjuvant therapy. Sixty-eight patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-II USC between 1997 and 2016 were included. All the cases did not undergo adjuvant treatment as institutional practice. Clinicopathological features, recurrence patterns, and survival outcomes were analyzed to determine prognostic factors. FIGO stages IA, IB, and II were observed in 42, 7, and 19 cases, respectively. Median follow-up time was 60 months. Five-year disease-free survival (DFS) and overall survival (OS) rates for all cases were 73.9% and 78.0%, respectively. On multivariate analysis, cervical stromal involvement and positive pelvic cytology were significant predictors of DFS and OS, and ≥1/2 myometrial invasion was also a significant predictor of OS. Of 68 patients, 38 patients had no cervical stromal invasion or positive pelvic cytology and showed 88.8% 5-year DFS and 93.6% 5-year OS. Cervical stromal invasion and positive pelvic cytology are prognostic factors for stage I-II USC. Patients with stage IA or IB USC showing negative pelvic cytology may have an extremely favorable prognosis and need not receive any adjuvant therapies. Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.

Epigenetic modifications in KDM lysine demethylases associate with survival of early-stage NSCLC.

PubMed

Wei, Yongyue; Liang, Junya; Zhang, Ruyang; Guo, Yichen; Shen, Sipeng; Su, Li; Lin, Xihong; Moran, Sebastian; Helland, Åslaug; Bjaanæs, Maria M; Karlsson, Anna; Planck, Maria; Esteller, Manel; Fleischer, Thomas; Staaf, Johan; Zhao, Yang; Chen, Feng; Christiani, David C

2018-01-01

KDM lysine demethylase family members are related to lung cancer clinical outcomes and are potential biomarkers for chemotherapeutics. However, little is known about epigenetic alterations in KDM genes and their roles in lung cancer survival. Tumor tissue samples of 1230 early-stage non-small cell lung cancer (NSCLC) patients were collected from the five independent cohorts. The 393 methylation sites in KDM genes were extracted from epigenome-wide datasets and analyzed by weighted random forest (Ranger) in discovery phase and validation dataset, respectively. The variable importance scores (VIS) for the sites in top 5% of both discovery and validation sets were carried forward for Cox regression to further evaluate the association with patient's overall survival. TCGA transcriptomic data were used to evaluate the correlation with the corresponding DNA methylation. DNA methylation at sites cg11637544 in KDM2A and cg26662347 in KDM1A were in the top 5% of VIS in both discovery phase and validation for squamous cell carcinomas (SCC), which were also significantly associated with SCC survival ( HR cg11637544  = 1.32, 95%CI, 1.16-1.50, P  = 1.1 × 10 -4 ; HR cg26662347  = 1.88, 95%CI, 1.37-2.60, P  = 3.7 × 10 -3 ), and correlated with corresponding gene expression (cg11637544 for KDM2A , P  = 1.3 × 10 -10 ; cg26662347 for KDM1A P  = 1.5 × 10 -5 ). In addition, by using flexible criteria for Ranger analysis followed by survival classification tree analysis, we identified four clusters for adenocarcinomas and five clusters for squamous cell carcinomas which showed a considerable difference of clinical outcomes with statistical significance. These findings highlight the association between somatic DNA methylation in KDM genes and early-stage NSCLC patient survival, which may reveal potential epigenetic therapeutic targets.

Dynamics of laser ablation at the early stage during and after ultrashort pulse

NASA Astrophysics Data System (ADS)

Ilnitsky, D. K.; Khokhlov, V. A.; Zhakhovsky, V. V.; Petrov, Yu V.; Migdal, K. P.; Inogamov, N. A.

2016-11-01

Study of material flow in two-temperature states is needed for a fundamental understanding the physics of femtosecond laser ablation. To explore phenomena at a very early stage of laser action on a metallic target our in-house two-temperature hydrodynamics code is used here. The early stage covers duration of laser pulse with next first few picoseconds. We draw attention to the difference in behavior at this stage between the cases: (i) of an ultrathin film (thickness of order of skin depth d skin or less), (ii) thin films (thickness of a film is 4-7 of d skin for gold), and (iii) bulk targets (more than 10d skin for gold). We demonstrate that these differences follow from a competition among conductive cooling of laser excited electrons in a skin layer, electron-ion coupling, and hydrodynamics of unloading caused by excess of pressure of excited free electrons. Conductive cooling of the skin needs a heat sink, which is performed by the cold material outside the skin. Such sink is unavailable in the ultrathin films.

Repair of Craniomaxillofacial Traumatic Soft Tissue Defects With Tissue Expansion in the Early Stage.

PubMed

Han, Yan; Zhao, Jianhui; Tao, Ran; Guo, Lingli; Yang, Hongyan; Zeng, Wei; Song, Baoqiang; Xia, Wensen

2017-09-01

Craniomaxillofacial traumatic soft tissue defects severely affect the function and appearance of the patients. The traditional skin grafting or free flap transplantation can only close the defects in the early stage of operation but cannot ensure similar color, texture, and relative aesthetic contour. In the present study, the authors have explored a novel strategy to repair craniomaxillofacial traumatic soft tissue defects by tissue expansion in the early stage and have obtained satisfactory results. Eighteen patients suffering large craniomaxillofacial traumatic soft tissue defects were treated by thorough debridement leaving the wounds unclosed or simply closed with thin split-thickness scalp grafts, adjacent expander implantation in the first stage, and expanded flap transposition in the second stage. There were 11 male patients and 7 female patients ranging in age from 3.5 to 40 years (mean, 19.4 ± 12.2 years), with average 15 months follow-up (range, 3-67 months). The average expansion time was 74.3 days (range, 53-96 days). The 18 patients with a total of 22 expanders were treated with satisfactory results. All the flaps survived and the skin color, texture, and contour well matched those of the peripheral tissue. Only 1 complication of infection happened in the 18 cases (5.56%) and the 22 expanders (4.55%), which was similar to the rate reported in the literature. No other complications related to the expanders occurred. Debridement and tissue expansion in the early stage has been proved to be a more effective strategy to repair craniomaxillofacial traumatic soft tissue defects. This strategy can not only achieve satisfactory color, unbulky and well-matched texture similar to normal, but also avoid unnecessary donor site injuries.

The reorganization of functional architecture in the early-stages of Parkinson's disease.

PubMed

Tuovinen, Noora; Seppi, Klaus; de Pasquale, Francesco; Müller, Christoph; Nocker, Michael; Schocke, Michael; Gizewski, Elke R; Kremser, Christian; Wenning, Gregor K; Poewe, Werner; Djamshidian, Atbin; Scherfler, Christoph; Seki, Morinobu

2018-05-01

The study aim was to identify longitudinal abnormalities of functional connectivity and its relation with motor disability in early to moderately advanced stages of Parkinson's disease patients. 3.0T structural and resting-state functional MRI was performed in healthy subjects (n = 16) and Parkinson's disease patients (n = 16) with mean disease duration of 2.2 ± 1.2 years at baseline with a clinical follow-up of 1.5 ± 0.3 years. Resting-state fMRI analysis included region-to-region connectivity in correlation with UPDRS-III scores and computation of Global Efficiency and Degree Centrality. At baseline, patients' connectivity increased between the cerebellum and somatomotor network, and decreased between motor regions (Rolandic operculum, precentral gyrus, supplementary motor area, postcentral gyrus) and cingulate connectivity. At 1.5 years follow-up, connectivity remained altered in the same regions identified at baseline. The cerebellum showed additional hyperconnectivity within itself and to the caudate nucleus, thalamus and amygdala compared to controls. These differences correlated with UPDRS-III scores. Seed-based connectivity revealed increased involvement of the default mode network with precentral gyrus in patients at follow-up investigation. Resting-state fMRI identified marked disturbances of the overall architecture of connectivity in Parkinson's disease. The noted alterations in cortical motor areas were associated with cerebellar hyperconnectivity in early to moderately advanced stages of Parkinson's disease suggesting ongoing attempts of recovery and compensatory mechanism for affected functions. The potential to identify connectivity alterations in regions related to both motor and attentional functions requires further evaluation as an objective marker to monitor disease progression, and medical, as well as surgical interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Identification of a Genomic Signature Predicting for Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2015-12-01

early stage ovarian cancer to help researchers worldwide identify biomarkers that can aid early detection and inform novel targets for therapy. This...to detect differentially expressed genes after transformation using Voom. When using the top 5 genes to build the classifier, it predicted...to analyze expression of micro-RNA in these samples. Thus, at the end of the third year of funding we started a parallel analysis of RNAseq, DNA- CNV

Hallux abductus interphalangeus in normal feet, early-stage hallux limitus, and hallux valgus.

PubMed

Castillo-Lopez, Jose M; Ramos-Ortega, Javier; Reina-Bueno, Maria; Domínguez-Maldonado, Gabriel; Palomo-Toucedo, Inmaculada C; Munuera, Pedro V

2014-03-01

Excessive deviation of the distal phalanx in abduction frequently occurs in advanced stages of hallux rigidus but not in hallux valgus. Therefore, theoretically there should be no significant differences in the hallux interphalangeal angle (HIPA) between individuals with normal feet, those with hallux valgus, and those with mild hallux limitus. The objective of the present study was thus to determine if significant differences in HIPA exist in the early stages of hallux valgus or hallux limitus deformities. The hallux interphalangeal angle was measured in three groups of participants: a control group with normal feet (45 participants), a hallux valgus group (49 participants), and a hallux limitus group (48 participants). Both of the pathologies were at an early stage. A dorsoplantar radiograph under weightbearing conditions was taken for each individual, and measurements (HIPA and hallux abductus angle [HAA]) were taken using AutoCAD (Autodesk Inc, San Rafael, California) software. Intergroup comparisons of HIPA, and correlations between HIPA, HAA, and hallux dorsiflexion were calculated. The comparisons revealed no significant differences in the values of HIPA between any of the groups (15.2 ± 5.9 degrees in the control group, 15.5 ± 3.9 degrees in the hallux valgus group, and 16.15 ± 4.3 in the hallux limitus group; P  =  0.634). The Pearson correlation coefficients in particular showed no correlation between hallux dorsiflexion, HAA, and HIPA. For the study participants, there were similar deviations of the distal phalanx of the hallux with respect to the proximal phalanx in normal feet and in feet with the early stages of the hallux limitus and hallux valgus deformities.

Cost implications of unwarranted imaging for distant metastasis in women with early-stage breast cancer in Ontario.

PubMed

Thavorn, K; Wang, Z; Fergusson, D; van Katwyk, S; Arnaout, A; Clemons, M

2016-02-01

Despite the publication of multiple evidence-based guidelines recommending against routine imaging for distant metastasis in patients with early-stage (i/ii) breast cancer, such imaging is frequently performed. The present retrospective cohort study was conducted to estimate the cost of unnecessary imaging tests in women with stage i and ii breast cancer diagnosed between 1 January 2007 and 31 December 2012 in Ontario. We obtained patient-level demographic and tumour data from a large provincial dataset. The total cost of unwarranted imaging tests (in 2015 Canadian dollars) was considered to be equal to the sum of imaging costs incurred between 2007 and 2012 and was stratified by disease stage, imaging modality, and body site. Of the 26,547 identified patients with early-stage breast cancer, 22,811 (85.9%) underwent at least 1 imaging test, with an average of 3.7 tests per patient (3.2 for stage i patients and 4.0 for stage ii patients) over 5 years. At least 1 imaging test was performed in 79.6% of stage i and 92.7% of stage ii patients. During a 5-year period, the cost of unwarranted imaging in patients with early-stage breast cancer ranged from CA$4,418,139 to CA$6,865,856, depending on guideline recommendations. Our study highlights the substantial cost of excess imaging that could be saved and re-allocated to patient care if evidence-based guidelines are followed. Future studies should assess strategies to ensure that evidence-based guidelines are followed and to increase awareness of the cost implications of nonadherence to guidelines.

[Feedback of ultrasound and RMI in the staging of endometrial carcinoma in early stage].

PubMed

Buhler, J; Routiot, T; Polet-Lefebvre, K; Morel, O

2015-04-01

Endometrial cancer is the most common gynecological cancer in France. The therapeutic management is based on preoperative staging. The recommended imaging examination remains the MRI. This is to evaluate ultrasound and MRI in the staging for localized cancers. This is a retrospective observational study, conducted from July 2012 to July 2014, at the University Hospital of Nancy, on all patients care for endometrial cancer stage I, who underwent a pelvic ultrasound and MRI for the assessment of myometrial infiltration. Twenty-nine patients were included with a mean age of 69 years and a BMI of 30 kg/m(2). Using ultrasound, we have a sensitivity of 58%, a specificity of 100%, a positive predictive value (PPV) of 100%, a negative predictive value (NPV) of 70% and an accuracy of 75%. Using MRI, we have a sensitivity of 83%, a specificity of 100%, a PPV of 83%, a VPN of 88%, and an accuracy of 86%. Transvaginal sonography should be performed before post-menopausal bleeding. It remains possible in the staging of localized cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Evaluation of an Internet, Stage-Based Physical Activity Intervention.

ERIC Educational Resources Information Center

Hager, Ronald L.; Hardy, Aaron; Aldana, Steven G.; George, James D.

2002-01-01

Evaluated the impact of online, stage-based materials on exercise behavior and stage of readiness to change. College faculty participated in stage-based, action-message, or control groups. Occupational and leisure activity, 7-day physical activity, exercise self-efficacy, and stage of readiness to change were assessed at baseline and 6 weeks.…

Late stages of accumulation and early evolution of the planets

NASA Technical Reports Server (NTRS)

Vityazev, Andrey V.; Perchernikova, G. V.

1991-01-01

Recently developed solutions of problems are discussed that were traditionally considered fundamental in classical solar system cosmogony: determination of planetary orbit distribution patterns, values for mean eccentricity and orbital inclinations of the planets, and rotation periods and rotation axis inclinations of the planets. Two important cosmochemical aspects of accumulation are examined: the time scale for gas loss from the terrestrial planet zone, and the composition of the planets in terms of isotope data. It was concluded that the early beginning of planet differentiation is a function of the heating of protoplanets during collisions with large (thousands of kilometers) bodies. Energetics, heat mass transfer processes, and characteristic time scales of these processes at the early stages of planet evolution are considered.

Identification of early-stage usual interstitial pneumonia from low-dose chest CT scans using fractional high-density lung distribution

NASA Astrophysics Data System (ADS)

Xie, Yiting; Salvatore, Mary; Liu, Shuang; Jirapatnakul, Artit; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2017-03-01

A fully-automated computer algorithm has been developed to identify early-stage Usual Interstitial Pneumonia (UIP) using features computed from low-dose CT scans. In each scan, the pre-segmented lung region is divided into N subsections (N = 1, 8, 27, 64) by separating the lung from anterior/posterior, left/right and superior/inferior in 3D space. Each subsection has approximately the same volume. In each subsection, a classic density measurement (fractional high-density volume h) is evaluated to characterize the disease severity in that subsection, resulting in a feature vector of length N for each lung. Features are then combined in two different ways: concatenation (2*N features) and taking the maximum in each of the two corresponding subsections in the two lungs (N features). The algorithm was evaluated on a dataset consisting of 51 UIP and 56 normal cases, a combined feature vector was computed for each case and an SVM classifier (RBF kernel) was used to classify them into UIP or normal using ten-fold cross validation. A receiver operating characteristic (ROC) area under the curve (AUC) was used for evaluation. The highest AUC of 0.95 was achieved by using concatenated features and an N of 27. Using lung partition (N = 27, 64) with concatenated features had significantly better result over not using partitions (N = 1) (p-value < 0.05). Therefore this equal-volume partition fractional high-density volume method is useful in distinguishing early-stage UIP from normal cases.

Serum cystatin C level is associated with carotid arterial wall elasticity in subjects with type 2 diabetes mellitus: A potential marker of early-stage atherosclerosis.

PubMed

Kaneko, Rei; Sawada, Shojiro; Tokita, Ai; Honkura, Rieko; Tamura, Noriko; Kodama, Shinjiro; Izumi, Tomohito; Takahashi, Kei; Uno, Kenji; Imai, Junta; Yamada, Tetsuya; Miyachi, Yukiya; Hasegawa, Hideyuki; Kanai, Hiroshi; Ishigaki, Yasushi; Katagiri, Hideki

2018-05-01

Detection of early-stage atherosclerosis in type 2 diabetes mellitus (T2DM) patients is important for preventing cardiovascular disease. A phased tracking method for evaluating arterial wall elasticity sensitively detects early-stage atherosclerosis. However, biochemical markers for early-stage atherosclerosis have yet to be established. This cross-sectional study enrolled 180 T2DM patients, who were classified as not having atherosclerosis according to the carotid intima-media thickness (IMT) criteria. We measured serum cystatin C, the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), and analyzed the associations between these markers and arterial wall elasticity (Eθ), IMT and the cardio-ankle velocity index. Multiple linear regression analyses revealed that cystatin C was significantly associated with Eθ, while neither eGFR nor ACR showed an association. Furthermore, among the examined atherosclerotic markers, Eθ was most reliably associated with cystatin C. Additionally, the association between cystatin C and Eθ disappeared in the low elasticity subgroup, which included subjects in whom no atherosclerotic changes had yet been initiated. In T2DM patients without apparent arterial wall thickening, cystatin C is strongly and independently associated with arterial wall elasticity, which reflects the degree of subclinical atherosclerosis. Thus, cystatin C is a potentially useful marker of early-stage atherosclerosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Reproductive and early life stages pathology - Histopathology workshop report

USGS Publications Warehouse

Bruno, D.W.; Nowak, B.; Elliott, Diane G.

2006-01-01

Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

Risk of Fatal Cerebrovascular Accidents after External Beam Radiation Therapy for Early Stage Glottic Larynx Cancer

PubMed Central

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O’Malley, Bert; Weinstein, Gregory S.; Bekelman, Justin E.

2013-01-01

Background This study compared the risk of fatal cerebrovascular accidents (CVA) in patients with early stage glottic larynx cancer receiving surgery or external beam radiation therapy (EBRT). Methods and Materials Using a competing risks survival analysis, we compared the risk of death due to CVA among patients with early stage glottic larynx cancer receiving surgery or EBRT in the SEER database. Results The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8 %; 95% CI 2.3%–3.4%) compared to surgery (1.5 %; 95% CI 0.8 %–2.3%, p= 0.024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted HR 1.75; 95% CI 1.04–2.96, p= 0.037). Conclusion Treatment of early stage glottic larynx cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. PMID:23595858

Arm swing magnitude and asymmetry during gait in the early stages of Parkinson's disease.

PubMed

Lewek, Michael D; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

2010-02-01

The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in "off" state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p = 0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p = 0.907) or less (p = 0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9 + or - 7.9%) compared to the control group (asymmetry angle: 5.1 + or - 4.0%; p = 0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. Copyright 2009 Elsevier B.V. All rights reserved.

Arm Swing Magnitude and Asymmetry During Gait in the Early Stages of Parkinson's Disease

PubMed Central

Lewek, Michael D.; Poole, Roxanne; Johnson, Julia; Halawa, Omar; Huang, Xuemei

2009-01-01

The later stages of Parkinson's disease (PD) are characterized by altered gait patterns. Although decreased arm swing during gait is the most frequently reported motor dysfunction in individuals with PD, quantitative descriptions of gait in early PD have largely ignored upper extremity movements. This study was designed to perform a quantitative analysis of arm swing magnitude and asymmetry that might be useful in the assessment of early PD. Twelve individuals with early PD (in “off” state) and eight controls underwent gait analysis using an optically-based motion capture system. Participants were instructed to walk at normal and fast velocities, and then on heels (to minimize push-off). Arm swing was measured as the excursion of the wrist with respect to the pelvis. Arm swing magnitude for each arm, and inter-arm asymmetry, were compared between groups. Both groups had comparable gait velocities (p=0.61), and there was no significant difference between the groups in the magnitude of arm swing in all walking conditions for the arm that swung more (p=0.907) or less (p=0.080). Strikingly, the PD group showed significantly greater arm swing asymmetry (asymmetry angle: 13.9±7.9%) compared to the control group (asymmetry angle: 5.1±4.0%; p=0.003). Unlike arm swing magnitude, arm swing asymmetry unequivocally differs between people with early PD and controls. Such quantitative evaluation of arm swing, especially its asymmetry, may have utility for early and differential diagnosis, and for tracking disease progression in patients with later PD. PMID:19945285

Efficient and Rapid Isolation of Early-stage Embryos from Arabidopsis thaliana Seeds

PubMed Central

Raissig, Michael T.; Gagliardini, Valeria; Jaenisch, Johan; Grossniklaus, Ueli; Baroux, Célia

2013-01-01

In flowering plants, the embryo develops within a nourishing tissue - the endosperm - surrounded by the maternal seed integuments (or seed coat). As a consequence, the isolation of plant embryos at early stages (1 cell to globular stage) is technically challenging due to their relative inaccessibility. Efficient manual dissection at early stages is strongly impaired by the small size of young Arabidopsis seeds and the adhesiveness of the embryo to the surrounding tissues. Here, we describe a method that allows the efficient isolation of young Arabidopsis embryos, yielding up to 40 embryos in 1 hr to 4 hr, depending on the downstream application. Embryos are released into isolation buffer by slightly crushing 250-750 seeds with a plastic pestle in an Eppendorf tube. A glass microcapillary attached to either a standard laboratory pipette (via a rubber tube) or a hydraulically controlled microinjector is used to collect embryos from droplets placed on a multi-well slide on an inverted light microscope. The technical skills required are simple and easily transferable, and the basic setup does not require costly equipment. Collected embryos are suitable for a variety of downstream applications such as RT-PCR, RNA sequencing, DNA methylation analyses, fluorescence in situ hybridization (FISH), immunostaining, and reporter gene assays. PMID:23770918

Effectiveness of a community-based program for suicide prevention among elders with early-stage dementia: A controlled observational study.

PubMed

Kim, Jong-Pill; Yang, Jinhyang

The purpose of this study was to develop a small-group-focused suicide prevention program for elders with early-stage dementia and to assess its effects. This was a quasi-experimental study with a control group pretest-posttest design. A total of 62 elders diagnosed with early-stage dementia who were receiving care services at nine daycare centers in J City Korea participated in this study. The experimental group participated in the suicide prevention program twice a week for 5 weeks with a pretest and two posttests The developed suicide prevention program had a significant effect on the perceived health status, social support, depression, and suicidal ideation of elders with early-stage dementia. Nurses should integrate risk factors such as depression and protective factors such as health status and social support into a suicide prevention program. This community-based program in geriatric nursing practice can be effective in preventing suicide among elders with early-stage dementia. Copyright © 2016 Elsevier Inc. All rights reserved.

The power of personality in discriminating between healthy aging and early-stage Alzheimer's disease.

PubMed

Duchek, Janet M; Balota, David A; Storandt, Martha; Larsen, Randy

2007-11-01

This study examined differences in personality in the earliest stages of dementia of the Alzheimer type (DAT) relative to healthy aging, and the power of personality in discriminating healthy aging from early-stage DAT. Four groups of participants (middle-aged controls, older controls, persons with very mild DAT, and persons with mild DAT) and their families were administered Costa and McCrae's NEO Five-Factor Inventory. On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. Moreover, informant reports of neuroticism and conscientiousness capture substantial unique variance in discriminating healthy aging and very mild DAT, above and beyond standard neuropsychological tests. Discussion focuses on the importance of personality traits as a noncognitive indicator of early-stage DAT.

iROLL: does 3-D radioguided occult lesion localization improve surgical management in early-stage breast cancer?

PubMed

Bluemel, Christina; Cramer, Andreas; Grossmann, Christoph; Kajdi, Georg W; Malzahn, Uwe; Lamp, Nora; Langen, Heinz-Jakob; Schmid, Jan; Buck, Andreas K; Grimminger, Hanns-Jörg; Herrmann, Ken

2015-10-01

To prospectively evaluate the feasibility of 3-D radioguided occult lesion localization (iROLL) and to compare iROLL with wire-guided localization (WGL) in patients with early-stage breast cancer undergoing breast-conserving surgery and sentinel lymph node biopsy (SLNB). WGL (standard procedure) and iROLL in combination with SLNB were performed in 31 women (mean age 65.1 ± 11.2 years) with early-stage breast cancer and clinically negative axillae. Patient comfort in respect of both methods was assessed using a ten point scale. SLNB and iROLL were guided by freehand SPECT (fhSPECT). The results of the novel 3-D image-based method were compared with those of WGL, ultrasound-based lesion localization, and histopathology. iROLL successfully detected the malignant primary and at least one sentinel lymph node in 97% of patients. In a single patient (3%), only iROLL, and not WGL, enabled lesion localization. The variability between fhSPECT and ultrasound-based depth localization of breast lesions was low (1.2 ± 1.4 mm). Clear margins were achieved in 81% of the patients; however, precise prediction of clear histopathological surgical margins was not feasible using iROLL. Patients rated iROLL as less painful than WGL with a pain score 0.8 ± 1.2 points (p < 0.01) lower than the score for iROLL. iROLL is a well-tolerated and feasible technique for localizing early-stage breast cancer in the course of breast-conserving surgery, and is a suitable replacement for WGL. As a single image-based procedure for localization of breast lesions and sentinel nodes, iROLL may improve the entire surgical procedure. However, no advantages of the image-guided procedure were found with regard to prediction of complete tumour resection.

Purine-related metabolites and their converting enzymes are altered in frontal, parietal and temporal cortex at early stages of Alzheimer's disease pathology.

PubMed

Alonso-Andrés, Patricia; Albasanz, José Luis; Ferrer, Isidro; Martín, Mairena

2018-01-24

Adenosine, hypoxanthine, xanthine, guanosine and inosine levels were assessed by HPLC, and the activity of related enzymes 5'-nucleotidase (5'-NT), adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) measured in frontal (FC), parietal (PC) and temporal (TC) cortices at different stages of disease progression in Alzheimer's disease (AD) and in age-matched controls. Significantly decreased levels of adenosine, guanosine, hypoxanthine and xanthine, and apparently less inosine, are found in FC from the early stages of AD; PC and TC show an opposing pattern, as adenosine, guanosine and inosine are significantly increased at least at determinate stages of AD whereas hypoxanthine and xanthine levels remain unaltered. 5'-NT is reduced in membranes and cytosol in FC mainly at early stages but not in PC, and only at advanced stages in cytosol in TC. ADA activity is decreased in AD when considered as a whole but increased at early stages in TC. Finally, PNP activity is increased only in TC at early stages. Purine metabolism alterations occur at early stages of AD independently of neurofibrillary tangles and β-amyloid plaques. Alterations are stage dependent and region dependent, the latter showing opposite patterns in FC compared with PC and TC. Adenosine is the most affected of the assessed purines. © 2018 International Society of Neuropathology.

Early stages in the biogenesis of eukaryotic β-barrel proteins.

PubMed

Jores, Tobias; Rapaport, Doron

2017-09-01

The endosymbiotic organelles mitochondria and chloroplasts harbour, similarly to their prokaryotic progenitors, β-barrel proteins in their outer membrane. These proteins are encoded on nuclear DNA, translated on cytosolic ribosomes and imported into their target organelles by a dedicated machinery. Recent studies have provided insights into the import into the organelles and the membrane insertion of these proteins. Although the cytosolic stages of their biogenesis are less well defined, it is speculated that upon their synthesis, chaperones prevent β-barrel proteins from aggregation and keep them in an import-competent conformation. In this Review, we summarize the current knowledge about the biogenesis of β-barrel proteins, focusing on the early stages from the translation on cytosolic ribosomes to the recognition on the surface of the organelle. © 2017 Federation of European Biochemical Societies.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar

USGS Publications Warehouse

Duffy, Tara A.; Iwanowicz, Luke R.; McCormick, Stephen D.

2014-01-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (four day) exposures using three doses each of 17α-ethinylestradiol (EE2), 17β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and one year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embyos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting this is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2 and plasma T3 decreased at the highest dose of EE2. Our results indicate that all life stages after hatching are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild.

Comparative responses to endocrine disrupting compounds in early life stages of Atlantic salmon, Salmo salar.

PubMed

Duffy, T A; Iwanowicz, L R; McCormick, S D

2014-07-01

Atlantic salmon (Salmo salar) are endangered anadromous fish that may be exposed to feminizing endocrine disrupting compounds (EDCs) during early development, potentially altering physiological capacities, survival and fitness. To assess differential life stage sensitivity to common EDCs, we carried out short-term (4 day) exposures using three doses each of 17 α-ethinylestradiol (EE2), 17 β-estradiol (E2), and nonylphenol (NP) on four early life stages; embryos, yolk-sac larvae, feeding fry and 1 year old smolts. Differential response was compared using vitellogenin (Vtg, a precursor egg protein) gene transcription. Smolts were also examined for impacts on plasma Vtg, cortisol, thyroid hormones (T4/T3) and hepatosomatic index (HSI). Compound-related mortality was not observed in any life stage, but Vtg mRNA was elevated in a dose-dependent manner in yolk-sac larvae, fry and smolts but not in embryos. The estrogens EE2 and E2 were consistently stronger inducers of Vtg than NP. Embryos responded significantly to the highest concentration of EE2 only, while older life stages responded to the highest doses of all three compounds, as well as intermediate doses of EE2 and E2. Maximal transcription was greater for fry among the three earliest life stages, suggesting fry may be the most responsive life stage in early development. Smolt plasma Vtg was also significantly increased, and this response was observed at lower doses of each compound than was detected by gene transcription suggesting plasma Vtg is a more sensitive indicator at this life stage. HSI was increased at the highest doses of EE2 and E2, and plasma T3 was decreased at the highest dose of EE2. Our results indicate that all life stages are potentially sensitive to endocrine disruption by estrogenic compounds and that physiological responses were altered over a short window of exposure, indicating the potential for these compounds to impact fish in the wild. Copyright © 2014 Elsevier B.V. All rights

Audit of the autoantibody test, EarlyCDT®-lung, in 1600 patients: an evaluation of its performance in routine clinical practice.

PubMed

Jett, James R; Peek, Laura J; Fredericks, Lynn; Jewell, William; Pingleton, William W; Robertson, John F R

2014-01-01

EarlyCDT(®)-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. EarlyCDT-Lung has been extensively tested and validated in case-control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation

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

Gunther, Jillian R.; Fanale, Michelle A.; Reddy, Jay P.

Purpose: The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). Methods and Materials: We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicitiesmore » were evaluated. Results: The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Conclusions: Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky

Treatment of Early-Stage Unfavorable Hodgkin Lymphoma: Efficacy and Toxicity of 4 Versus 6 Cycles of ABVD Chemotherapy With Radiation.

PubMed

Gunther, Jillian R; Fanale, Michelle A; Reddy, Jay P; Akhtari, Mani; Smith, Grace L; Pinnix, Chelsea C; Milgrom, Sarah A; Yehia, Zeinab Abou; Allen, Pamela K; Osborne, Eleanor M; Mawlawi, Osama; Dabaja, Bouthaina S

2016-09-01

The German Hodgkin Study Group HD11 trial validated 4 cycles of doxorubicin, bleomycin, vinblastine, dacarbazine (ABVD) chemotherapy followed by involved field radiation therapy (IFRT) for early unfavorable Hodgkin lymphoma (HL) patients. However, practitioners often recommend 6 cycles followed by RT, especially for bulky disease. We compared patient outcomes after treatment with 4 or 6 cycles of ABVD followed by RT (IFRT and involved site RT [ISRT]). We identified 128 patients treated for early unfavorable HL (GHSG criteria) between 2000 and 2013. Clinical outcomes (overall survival [OS] and freedom from relapse [FFR]) were estimated using Kaplan-Meier analysis. Toxicities were evaluated. The median follow-up time was 5.0 years. Patients received 4 (70 patients, 55%) or 6 (58 patients, 45%) cycles of chemotherapy. Bulky disease was present in 22 patients (31%; 0 stage IA, 3 stage IB, 19 stage IIA) of the 4-cycle group and 42 patients (72%; 5 stage IA, 3 stage IB, 34 stage IIA) of the 6-cycle group. For patients receiving 4 and 6 cycles, the 6-year OS was 100% and 97% (P=.35), respectively, and the 6 year FFR was 100% and 98% (P=.28), respectively. More patients received 6 cycles if they were treated before 2010 (HD11 report) (P=.01) and if they had bulky disease (P<.01). Sixty-eight percent of patients received ISRT. The 6-year FFR was 99% and 100% for patients receiving ISRT and IFRT, respectively (P=.58). More patients experienced bleomycin pulmonary toxicity in the 6-cycle group (20% vs 31%, P=.16). For patients with bulky disease, the 4-year FFR was similar with receipt of 4 (100%) or 6 (98%) cycles (P=.48) and IFRT (100%) or ISRT (98%) (P=.52). There were no deaths among patients with bulky disease. Patients with early unfavorable HL have excellent outcomes with 4 cycles of ABVD chemotherapy followed by ISRT. Six cycles of chemotherapy does not appear superior for disease control, even for bulky disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

PubMed

Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

2014-12-01

In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator

PubMed Central

Zheng, Louise D.; Linarelli, Leah E.; Brooke, Joseph; Smith, Cayleen; Wall, Sarah S.; Greenawald, Mark H.; Seidel, Richard W.; Estabrooks, Paul A.; Almeida, Fabio A.; Cheng, Zhiyong

2016-01-01

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention. PMID:27298712

Mapping thalamocortical functional connectivity in chronic and early stages of psychotic disorders

PubMed Central

Woodward, Neil D.; Heckers, Stephan

2015-01-01

Objective There is considerable evidence that the thalamus is abnormal in psychotic disorders. Resting-state fMRI (RS-fMRI) has revealed an intriguing pattern of thalamic dysconnectivity in psychosis characterized by reduced prefrontal cortex (PFC) connectivity and increased somatomotor-thalamic connectivity. However, critical knowledge gaps remain with respect to the onset, anatomical specificity, and clinical correlates of thalamic dysconnectivity in psychosis. Method RS-fMRI was collected on 105 healthy subjects and 148 individuals with psychosis, including 53 early stage psychosis patients. Using all 253 subjects, the thalamus was parceled into functional regions-of-interest (ROIs) on the basis of connectivity with six a-priori defined cortical ROIs covering most of the cortical mantle. Functional connectivity between each cortical ROI and its corresponding thalamic ROI was quantified and compared across groups. Significant differences in the ROI-to-ROI analysis were followed up with voxel-wise seed-based analyses to further localize thalamic dysconnectivity. Results ROI analysis revealed reduced PFC-thalamic connectivity and increased somatomotor-thalamic connectivity in both chronic and early stages psychosis patients. PFC hypo-connectivity and motor cortex hyper-connectivity correlated in patients suggesting they result from a common pathophysiological mechanism. Seed-based analyses revealed thalamic hypo-connectivity in psychosis localized to dorsolateral PFC, medial PFC, and cerebellar areas of the well-described ‘executive control’ network. Across all subjects, thalamic connectivity with areas of the fronto-parietal network correlated with cognitive functioning, including verbal learning and memory. Conclusions Thalamocortical dysconnectivity is present in both chronic and early stages of psychosis, includes reduced thalamic connectivity with the executive control network, and is related to cognitive impairment. PMID:26248537

Hydrodynamic instability of elastic-plastic solid plates at the early stage of acceleration.

PubMed

Piriz, A R; Sun, Y B; Tahir, N A

2015-03-01

A model is presented for the linear Rayleigh-Taylor instability taking place at the early stage of acceleration of an elastic-plastic solid, when the shock wave is still running into the solid and is driven by a time varying pressure on the interface. When the the shock is formed sufficiently close to the interface, this stage is considered to follow a previous initial phase controlled by the Ritchmyer-Meshkov instability that settles new initial conditions. The model reproduces the behavior of the instability observed in former numerical simulation results and provides a relatively simpler physical picture than the currently existing one for this stage of the instability evolution.

Early stages of zeolite growth

NASA Astrophysics Data System (ADS)

Kumar, Sandeep

Zeolites are crystalline nonporous aluminosilicates with important applications in separation, purification, and adsorption of liquid and gaseous molecules. However, an ability to tailor the zeolite microstructure, such as particle size/shape and pore-size, to make it benign for specific application requires control over nucleation and particle growth processes. But, the nucleation and crystallization mechanisms of zeolites are not fully understood. In this context, the synthesis of an all-silica zeolite with MFI-type framework has been studied extensively as a model system. Throughout chapters 2, 4 and 5, MFI growth process has been investigated by small-angle x-ray scattering (SAXS) and transmission electron microscopy (TEM). Of fundamental importance is the role of nanoparticles (~5 nm), which are present in the precursor sol, in MFI nucleation and crystallization. Formation of amorphous aggregates and their internal restructuring are concluded as essential steps in MFI nucleation. Early stage zeolite particles have disordered and less crystalline regions within, which indicates the role of structurally distributed population of nanoparticles in growth. Faceting occurs after the depletion of nanoparticles. The chapter 6 presents growth studies in silica sols prepared by using a dimer of tertaprpylammonium (TPA) and reports that MFI nucleation and crystallization are delayed with a more pronounced delay in crystal growth.

The temporal characteristics of the early and late stages of the L- and M-cone pathways that signal color

PubMed Central

Petrova, Daniela; Henning, G. Bruce; Stockman, Andrew

2013-01-01

Flickering long-wavelength light appears more yellow than steady light of the same average intensity. The hue change is consistent with distortion of the visual signal at some nonlinear site (or sites) that produces temporal components not present in the original stimulus (known as distortion products). We extracted the temporal attenuation characteristics of the early (prenonlinearity) and late (post-nonlinearity) filter stages in the L- and M-cone chromatic pathway by varying the input stimulus to manipulate the distortion products and the measuring of the observers' sensitivity to them. The early, linear, filter stage acts like a band-pass filter peaking at 10–15 Hz with substantial sensitivity losses at both lower and higher frequencies. Its characteristics are consistent with nonlinearity being early in the visual pathway but following surround inhibition. The late stage, in contrast, acts like a low-pass filter with a cutoff frequency around 3 Hz. The response of the early stage speeds up with radiance, but the late stage does not. A plausible site for the nonlinearity, which modelling suggests may be smoothly compressive but with a hard limit at high input levels, is after surround inhibition from the horizontal cells. PMID:23457358

Socioeconomic Factors Are Associated With Readmission After Lobectomy for Early Stage Lung Cancer.

PubMed

Medbery, Rachel L; Gillespie, Theresa W; Liu, Yuan; Nickleach, Dana C; Lipscomb, Joseph; Sancheti, Manu S; Pickens, Allan; Force, Seth D; Fernandez, Felix G

2016-11-01

Data regarding risk factors for readmissions after surgical resection for lung cancer are limited and largely focus on postoperative outcomes, including complications and hospital length of stay. The current study aims to identify preoperative risk factors for postoperative readmission in early stage lung cancer patients. The National Cancer Data Base was queried for all early stage lung cancer patients with clinical stage T2N0M0 or less who underwent lobectomy in 2010 and 2011. Patients with unplanned readmission within 30 days of hospital discharge were identified. Univariate analysis was utilized to identify preoperative differences between readmitted and not readmitted cohorts; multivariable logistic regression was used to identify risk factors resulting in readmission. In all, 840 of 19,711 patients (4.3%) were readmitted postoperatively. Male patients were more likely to be readmitted than female patients (4.9% versus 3.8%, p < 0.001), as were patients who received surgery at a nonacademic rather than an academic facility (4.6% versus 3.6%; p = 0.001) and had underlying medical comorbidities (Charlson/Deyo score 1+ versus 0; 4.8% versus 3.7%; p < 0.001). Readmitted patients had a longer median hospital length of stay (6 days versus 5; p < 0.001) and were more likely to have undergone a minimally invasive approach (5.1% video-assisted thoracic surgery versus 3.9% open; p < 0.001). In addition to those variables, multivariable logistic regression analysis identified that median household income level, insurance status (government versus private), and geographic residence (metropolitan versus urban versus rural) had significant influence on readmission. The socioeconomic factors identified significantly influence hospital readmission and should be considered during preoperative and postoperative discharge planning for patients with early stage lung cancer. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Trastuzumab in early stage breast cancer: a cost-effectiveness analysis for Belgium.

PubMed

Neyt, Mattias; Huybrechts, Michel; Hulstaert, Frank; Vrijens, France; Ramaekers, Dirk

2008-08-01

Although trastuzumab is traditionally used in metastatic breast cancer treatment, studies reported on the efficacy and safety of trastuzumab in adjuvant setting for the treatment of early stage breast cancer in HER2+ tumors. We estimated the cost-effectiveness and budget impact of reimbursing trastuzumab in this indication from a payer's perspective. We constructed a health economic model. Long-term consequences of preventing patients to progress to metastatic breast cancer and side effects such as congestive heart failure were taken into account. Uncertainty was handled applying probabilistic modeling and through probabilistic sensitivity analyses. In the HERA scenario, applying an arbitrary threshold of euro30000 per life-year gained, early stage breast cancer treatment with trastuzumab is cost-effective for 9 out of 15 analyzed subgroups (according to age and stage). In contrast, treatment according to the FinHer scenario is cost-effective in 14 subgroups. Furthermore, the FinHer regimen is most of the times cost saving with an average incremental cost of euro668, euro-1045, and euro-6869 for respectively stages I, II and III breast cancer patients whereas the HERA regimen is never cost saving due to the higher initial treatment costs. The model shows better cost-effectiveness for the 9-week initial treatment (FinHer) compared to no trastuzumab treatment than for the 1-year post-chemotherapy treatment (HERA). Both from a medical and an economic point of view, the 9-week initial treatment regimen with trastuzumab shows promising results and justifies the initiation of a large comparative trial with a 1-year regimen.

The effects of parasites on the early life stages of a damselfish

NASA Astrophysics Data System (ADS)

Sun, D.; Blomberg, S. P.; Cribb, T. H.; McCormick, M. I.; Grutter, A. S.

2012-12-01

Early life history traits, such as larval growth, influence the success of coral reef fish in the transition from the larval to the juvenile life phase. Few studies, however, have examined the relationship between parasites and growth in the early life history stages of such fishes. This study examined how parasite prevalence (% infected) and load, and the relationship between parasite presence and fish growth, differed among life stages of the damselfish Pomacentrus amboinensis. Parasite prevalence decreased significantly between the larval stage, which was sampled immediately before settlement on the reef (97 %) and recently settled juveniles (60 %); prevalence was also high for 4-month-old juveniles (90 %), 7-month-old juveniles (100 %) and adult fish (100 %). Total numbers of parasites per fish decreased dramatically (fourfold) between larval and recently settled fish, and then increased in the older stages to levels similar to those observed in larvae, but they did so more gradually than did prevalence. One explanation for these patterns is that heavily infected larvae were preferentially removed from the population during or soon after settlement. Daily fish growth, determined from otolith increments, revealed that growth did not differ between parasitised and non-parasitised larval fish, whereas recently settled fish that were parasitised had faster growth; these parasitised recently settled fish also displayed faster growth prior to settlement. These data provide evidence that parasites may explain some of the variation in growth and survival observed among coral reef fishes after settlement and thereby have a greater impact on population dynamics than previously understood.

Multiscale Investigations of the Early Stage Oxidation on Cu Surfaces

NASA Astrophysics Data System (ADS)

Zhu, Qing; Xiao, Penghao; Lian, Xin; Yang, Shen-Che; Henkelman, Grame; Saidi, Wissam; Yang, Judith; University of Pittsburgh Team; University of Texas at Austin Team

Previous in situ TEM experiments have shown that the oxidation of the three low index Cu surfaces (100), (110) and (111) exhibit different oxide nucleation rates, and the resulting oxides have 3-dimensional (3D) island shapes or 2D rafts under different conditions. In order to better understand these results, we have investigated the early stages of Cu oxidation using a multiscale computational approach that employs density functional theory (DFT), reactive force field (ReaxFF), and kinetic Mote Carlo (KMC). With DFT calculation, we have compared O2 dissociation barriers on Cu (100), (110) and (111) surfaces at high oxygen coverage to evaluate the kinetic barrier of sublayer oxidization. We found that O2 dissociation barriers on Cu(111) surface are all lower than those on (110) and (100) surfaces. This trend agrees with experimental observations that (111) surface is easier to oxidize. These DFT calculated energy barriers are then incorporated into KMC simulations. The large scale ReaxFF molecular dynamics and KMC simulations detail the oxidation dynamics of the different Cu surfaces, and show the formation of various oxide morphologies that are consistent with experimental observations.

SU-F-R-24: Identifying Prognostic Imaging Biomarkers in Early Stage Lung Cancer Using Radiomics

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

Zeng, X; Wu, J; Cui, Y

2016-06-15

Purpose: Patients diagnosed with early stage lung cancer have favorable outcomes when treated with surgery or stereotactic radiotherapy. However, a significant proportion (∼20%) of patients will develop metastatic disease and eventually die of the disease. The purpose of this work is to identify quantitative imaging biomarkers from CT for predicting overall survival in early stage lung cancer. Methods: In this institutional review board-approved HIPPA-compliant retrospective study, we retrospectively analyzed the diagnostic CT scans of 110 patients with early stage lung cancer. Data from 70 patients were used for training/discovery purposes, while those of remaining 40 patients were used for independentmore » validation. We extracted 191 radiomic features, including statistical, histogram, morphological, and texture features. Cox proportional hazard regression model, coupled with the least absolute shrinkage and selection operator (LASSO), was used to predict overall survival based on the radiomic features. Results: The optimal prognostic model included three image features from the Law’s feature and wavelet texture. In the discovery cohort, this model achieved a concordance index or CI=0.67, and it separated the low-risk from high-risk groups in predicting overall survival (hazard ratio=2.72, log-rank p=0.007). In the independent validation cohort, this radiomic signature achieved a CI=0.62, and significantly stratified the low-risk and high-risk groups in terms of overall survival (hazard ratio=2.20, log-rank p=0.042). Conclusion: We identified CT imaging characteristics associated with overall survival in early stage lung cancer. If prospectively validated, this could potentially help identify high-risk patients who might benefit from adjuvant systemic therapy.« less

Prognostic value of periostin in early-stage breast cancer treated with conserving surgery and radiotherapy.

PubMed

Li, Changyou; Xu, Jing; Wang, Qi; Geng, Shaoqing; Yan, Zheng; You, Jin; Li, Zhenfeng; Zou, Xiao

2018-05-01

The present study was performed to explore the prognostic significance of periostin expression in a cohort of patients with early-stage breast cancer treated with breast conserving surgery following radiotherapy. A tissue microarray of tumor samples from 259 patients with early-stage breast cancer was assayed for periostin, estrogen receptor (ER), progesterone receptor (PR), ErbB2 receptor tyrosine kinase 2 and Ki-67 expression by immunohistochemistry. The association of periostin with other clinicopathological parameters and clinical outcomes, including local recurrence free survival (RFS), distant metastasis free survival (DFS) and overall survival (OS), were assessed through log-rank tests and univariate and multivariate analysis. Periostin expression was identified in 91 of the 259 tissue samples (35%). The periostin status was significantly associated with histological grade (P=0.001), nodal status (P=0.023), molecular subtype (P<0.01), ER status (P<0.01), PR status (P<0.01) and Ki-67 expression (P=0.011). Furthermore, periostin expression was associated with an increased risk of five-year local recurrence (95.8% vs. 89.0%; P=0.017) and distant metastasis (92.3% vs. 79.1%; P=0.001) in patients with early stage breast cancer. Multivariate analysis using Cox's proportional hazards model demonstrated that periostin expression was an independent predictor of all clinical outcomes in breast cancer (RFS, P=0.018; DFS, P=0.025; OS, P=0.047). Therefore, it was concluded that periostin is associated with an increased risk of local relapse and distant metastasis in early-stage breast cancer treated with conserving surgery and radiotherapy. This association should be further investigated in larger cohorts to validate the clinical significance of periostin expression.

Reflectance spectroscopy for noninvasive evaluation of hair follicle stage

NASA Astrophysics Data System (ADS)

Liu, Caihua; Guan, Yue; Wang, Jianru; Zhong, Xiewei; Liu, Xiuli; Zhu, Dan

2015-05-01

Hair follicle offers an excellent model for systems biology and regenerative medicine. So far, the stages of hair follicle growth have been evaluated by histological examination. In this work, a noninvasive spectroscopy was proposed by measuring the diffuse reflectance of mouse skin and analyzing the melanin value. Results show that the skin diffuse reflectance was relatively high when hair follicles were at the telogen stage and at the beginning of the anagen stage, and decreased with the progression of the anagen stage. When the hair follicle entered into the catagen stage, the diffuse reflectance gradually increased. The changes in the melanin content of skin had contrary dynamics. Substages of the hair follicle cycle could be distinguished by comparing the changes in melanin value with the histological examination. This study provided a new method for noninvasive evaluation of the hair follicle stage, and should be valuable for basic and therapeutic investigations on hair regeneration.

On the role of extracellular polymeric substances during early stages of Xylella fastidiosa biofilm formation.

PubMed

Lorite, Gabriela S; de Souza, Alessandra A; Neubauer, Daniel; Mizaikoff, Boris; Kranz, Christine; Cotta, Mônica A

2013-02-01

The structural integrity and protection of bacterial biofilms are intrinsically associated with a matrix of extracellular polymeric substances (EPS) produced by the bacteria cells. However, the role of these substances during biofilm adhesion to a surface remains largely unclear. In this study, the influence of EPS on Xylella fastidiosa biofilm formation was investigated. This bacterium is associated with economically important plant diseases; it presents a slow growth rate and thus allows us to pinpoint more precisely the early stages of cell-surface adhesion. Scanning electron microscopy and atomic force microscopy show evidence of EPS production in such early stages and around individual bacteria cells attached to the substrate surface even a few hours after inoculation. In addition, EPS formation was investigated via attenuated total reflectance (ATR) Fourier transform infrared spectroscopy (FTIR). To this end, X. fastidiosa cells were inoculated within an ATR liquid cell assembly. IR-ATR spectra clearly reveal EPS formation already during the early stages of X. fastidiosa biofilm formation, thereby providing supporting evidence for the hypothesis of the relevance of the EPS contribution to the adhesion process. Copyright © 2012 Elsevier B.V. All rights reserved.

Finite element simulation of ultrasonic waves in corroded reinforced concrete for early-stage corrosion detection

NASA Astrophysics Data System (ADS)

Tang, Qixiang; Yu, Tzuyang

2017-04-01

In reinforced concrete (RC) structures, corrosion of steel rebar introduces internal stress at the interface between rebar and concrete, ultimately leading to debonding and separation between rebar and concrete. Effective early-stage detection of steel rebar corrosion can significantly reduce maintenance costs and enable early-stage repair. In this paper, ultrasonic detection of early-stage steel rebar corrosion inside concrete is numerically investigated using the finite element method (FEM). Commercial FEM software (ABAQUS) was used in all simulation cases. Steel rebar was simplified and modeled by a cylindrical structure. 1MHz ultrasonic elastic waves were generated at the interface between rebar and concrete. Two-dimensional plain strain element was adopted in all FE models. Formation of surface rust in rebar was modeled by changing material properties and expanding element size in order to simulate the rust interface between rebar and concrete and the presence of interfacial stress. Two types of surface rust (corroded regions) were considered. Time domain and frequency domain responses of displacement were studied. From our simulation result, two corrosion indicators, baseline (b) and center frequency (fc) were proposed for detecting and quantifying corrosion.

Evaluation of the dosimetric impact of applying flattening filter-free beams in intensity-modulated radiotherapy for early-stage upper thoracic carcinoma of oesophagus

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

Zhang, Wuzhe; Lin, Zhixiong; Yang, Zhining

2015-06-15

Flattening filter-free (FFF) radiation beams have recently become clinically available on modern linear accelerators in radiation therapy. This study aimed to evaluate the dosimetric impact of using FFF beams in intensity-modulated radiotherapy (IMRT) for early-stage upper thoracic oesophageal cancer. Eleven patients with primary stage upper thoracic oesophageal cancer were recruited. For each patient, two IMRT plans were computed using conventional beams (Con-P) and FFF beams (FFF-P), respectively. Both plans employed a five-beam arrangement and were prescribed with 64 Gy to (planning target volume) PTV1 and 54 Gy to PTV2 in 32 fractions using 6 MV photons. The dose parameters ofmore » the target volumes and organs at risks (OARs), and treatment parameters including the monitor units (MU) and treatment time (TT) for Con-P and FFF-P were recorded and compared. The mean D{sub 5} of PTV1 and PTV2 were higher in FFF-P than Con-P by 0.4 Gy and 0.3 Gy, respectively. For the OARs, all the dose parameters did not show significant difference between the two plans except the mean V{sub 5} and V{sub 10} of the lung in which the FFF-P was lower (46.7% vs. 47.3% and 39.1% vs. 39.6%, respectively). FFF-P required 54% more MU but 18.4% less irradiation time when compared to Con-P. The target volume and OARs dose distributions between the two plans were comparable. However, FFF-P was more effective in sparing the lung from low dose and reduced the mean TT compared with Con-P. Long-term clinical studies are suggested to evaluate the radiobiological effects of FFF beams.« less

Genomic Copy Number Imbalances Associated with Bone and Non-bone Metastasis of Early-Stage Breast Cancer

PubMed Central

Liu, Yanhong; Zhou, Renke; Baumbusch, Lars O.; Tsavachidis, Spyros; Brewster, Abenaa M.; Do, Kim-Anh; Sahin, Aysegul; Hortobagyi, Gabriel N.; Taube, Joseph H.; Mani, Sendurai A.; Aarøe, Jørgen; Wärnberg, Fredrik; Børresen-Dale, Anne-Lise; Mills, Gordon B.; Thompson, Patricia A.; Bondy, Melissa L.

2014-01-01

Purpose To identify and validate copy number aberrations in early-stage primary breast tumors associated with bone or non-bone metastasis. Patients and Methods Whole-genome molecular inversion probe arrays were used to evaluate copy number imbalances (CNIs) in breast tumors from 960 early-stage patients with information about site of metastasis. The CoxBoost algorithm was used to select metastasis site-related CNIs and to fit a Cox proportional hazards model. Results Gains at 1q41 and 1q42.12 and losses at 1p13.3, 8p22, and Xp11.3 were significantly associated with bone metastasis. Gains at 2p11.2, 3q21.3–22.2, 3q27.1, 10q23.1, and 14q13.2–3 and loss at 7q21.11 were associated with non-bone metastasis. To examine the joint effect of CNIs and clinical predictors, patients were stratified into three risk groups (low, intermediate, and high) based on the sum of predicted linear hazard ratios (HRs). For bone metastasis, the hazard (95% confidence interval) for the low-risk group was 0.32 (0.11–0.92) compared to the intermediate-risk group and 2.99 (1.74–5.11) for the high-risk group. For non-bone metastasis, the hazard for the low-risk group was 0.34 (0.17–0.66) and 2.33 (1.59–3.43) for the high-risk group. The prognostic value of loss at 8p22 for bone metastasis and gains at 10q23.1 for non-bone metastasis, and gain at 11q13.5 for both bone and non-bone metastases were externally validated in 335 breast tumors pooled from four independent cohorts. Conclusions Distinct CNIs are independently associated with bone and non-bone metastasis for early-stage breast cancer patients across cohorts. These data warrant consideration for tailoring surveillance and management of metastasis risk. PMID:24305980

Goal-oriented cognitive rehabilitation in early-stage dementia: study protocol for a multi-centre single-blind randomised controlled trial (GREAT)

PubMed Central

2013-01-01

Background Preliminary evidence suggests that goal-oriented cognitive rehabilitation (CR) may be a clinically effective intervention for people with early-stage Alzheimer’s disease, vascular or mixed dementia and their carers. This study aims to establish whether CR is a clinically effective and cost-effective intervention for people with early-stage dementia and their carers. Methods/design In this multi-centre, single-blind randomised controlled trial, 480 people with early-stage dementia, each with a carer, will be randomised to receive either treatment as usual or cognitive rehabilitation (10 therapy sessions over 3 months, followed by 4 maintenance sessions over 6 months). We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia; improving quality of life, self-efficacy, mood and cognition of people with early-stage dementia; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia. The incremental cost-effectiveness of goal-oriented cognitive rehabilitation compared to treatment as usual will also be examined. Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation, it will be important to examine how the goal-oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision. Our aim is to provide training and develop materials to support the implementation of this approach following trial completion. Trial registration Current Controlled Trials ISRCTN21027481 PMID:23710796

Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

PubMed

Bychkovsky, Brittany L; Lin, Nancy U

2017-02-01

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Histopathological diagnosis of acral lentiginous melanoma in early stages.

PubMed

Fernandez-Flores, Angel; Cassarino, David S

2017-02-01

Acral lentiginous melanoma is a rare variant of melanoma that is associated with a relatively low survival rate. The latter is partly due to the advanced stage in which the tumor is usually diagnosed. The diagnostic delay is mainly due to difficulties in identifying the very early histopathological signs of acral melanoma. The current article is a review of diagnostic clues, concepts, and definitions from the literature, as well as illustrating examples from our own archives. We have sought to provide an article that can be easily consulted in difficult cases of acral lentiginous melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales promelas.

PubMed

Stoddard, K I; Huggett, D B

2014-10-01

Sucralose, an intense artificial sweetener, has been detected in wastewater and surface waters at concentrations ranging from ng/L to low µg/L. Although over a hundred studies have been conducted to evaluate the safety of sucralose for human consumption, few studies have focused on the chronic ecotoxicological effects of this compound in fish. As a remedy to this data gap, an early-life stage toxicity test was conducted to assess the effects of sucralose on hatching, survival, and growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows determined by this study are >98 and 98 mg/L, respectively. The results from this study suggest that the concentrations of sucralose detected in the environment are well below those required to cause adverse effects to developing aquatic organisms.

Treatment of early-stage uterine papillary serous carcinoma at Roswell Park Cancer Institute, 1992-2006.

PubMed

Tchabo, Nana E; McCloskey, Susan; Mashtare, Terry L; Andrews, Christopher; Singh, Anurag K; Mhawech-Fauceglia, Paulette; Odunsi, Kunle; Lele, Shashikant; Jaggernauth, Wainwright

2009-11-01

Optimal management of early-stage uterine papillary serous carcinoma (UPSC) remains controversial. We reviewed our outcomes in this patient population. The Roswell Park Cancer Institute (RPCI) tumor registry identified all patients with Stages I and IIA UPSC treated between January 1992 and June 2006. The Fisher's exact test was used to compare recurrence rates by adjuvant therapy received. Overall survival (OS) estimates were made using the Kaplan-Meier method. Fifty-eight patients with Stage I or IIA UPSC underwent surgery. Thirty-four patients (59%) were surgically staged. Among 21 patients with Stage IA disease, 15 received adjuvant therapy. With a median follow-up of 44.7 months, only one recurrence was observed in a patient who received adjuvant brachytherapy. The 5-year OS was 66%. Among 37 patients with Stages IB-IIA, 30 patients received adjuvant therapy. With a median follow-up of 29 months, there were 7 recurrences. The 5-year OS was 60%. Although there were no significant differences in recurrence by adjuvant therapy received, a significant OS benefit was found in those who received radiation. There was no significant difference in OS distributions of those patients who received Carboplatin/Paclitaxel chemotherapy. Despite the limitations of our retrospective study, we have shown that even comprehensively staged early-stage UPSC patients are still at risk for recurrence despite adjuvant therapy received. Hence, all patients with this histologic diagnosis should be considered at high risk for recurrence and counseled appropriately regarding the risks and benefits of adjuvant therapy.

Portfolio management in early stage drug discovery - a traveler's guide through uncharted territory.

PubMed

Betz, Ulrich A K

2011-07-01

Portfolio management in drug development has become a best practice in the pharmaceutical industry. By contrast, early on in the value chain - the discovery phase - portfolio management is still in its infancy. Nevertheless, owing to the attrition of R&D projects from phase to phase and the cost of capital involved, these early phases of drug discovery play a significant part for the overall cost of bringing new, innovative drugs to the market. This paper describes various approaches to manage a portfolio of projects in early-stage drug discovery and provides crucial factors that determine the success of such an approach. Copyright © 2011 Elsevier Ltd. All rights reserved.

The utility of serum CA-125 in predicting extra-uterine disease in apparent early-stage endometrial cancer.

PubMed

Nicklin, James; Janda, Monika; Gebski, Val; Jobling, Thomas; Land, Russell; Manolitsas, Tom; McCartney, Anthony; Nascimento, Marcelo; Perrin, Lewis; Baker, Jannah F; Obermair, Andreas

2012-08-15

Surgical staging in early-stage uterine cancer is controversial. Preoperative serum CA-125 may be of clinical value in predicting the presence of extra-uterine disease in patients with apparent early-stage endometrial cancer. Between October 6, 2005, and June 17, 2010, 760 patients were enrolled in an international, multicentre, prospective randomized trial (LACE) comparing laparotomy with laparoscopy in the management of endometrial cancer apparently confined to the uterus. Of these, 657 patients with endometrial adenocarcinoma had a preoperative serum CA-125 value recorded. Multiple cross-validation analysis was undertaken to correlate preoperative serum CA-125 with stage of disease (Stage I vs. Stage II+) after surgery. Patients' median preoperative serum CA-125 was 14 U/ml. A cutoff point of 30 U/ml was associated with the smallest misclassification error, and using this cutoff, 98 patients (14.9%) had elevated CA-125 levels. Of those, 36 (36.7%) had evidence of extra-uterine disease. Of the 116 patients (17.7%) with evidence of extra-uterine disease, 31.0% had an elevated CA-125 level. On univariate and multivariable logistic regression analysis, only preoperative CA-125 level, but no other preoperative clinical characteristics were found to be associated with extra-uterine spread of disease. Utilizing a cutoff point of 30 U/ml achieved a sensitivity, specificity, positive predictive value and negative predictive value of 31.0, 88.5, 36.7 and 85.7%, respectively. Elevated CA-125 above 30 U/ml in patients with apparent early-stage disease is a risk factor for the presence of extra-uterine disease and may assist clinicians in the management of patients with clinical Stage I endometrial cancer. Copyright © 2011 UICC.

Risk of fatal cerebrovascular accidents after external beam radiation therapy for early-stage glottic laryngeal cancer.

PubMed

Swisher-McClure, Samuel; Mitra, Nandita; Lin, Alexander; Ahn, Peter; Wan, Fei; O'Malley, Bert; Weinstein, Gregory S; Bekelman, Justin E

2014-05-01

This study compared the risk of fatal cerebrovascular accidents (CVAs) in patients with early-stage glottic laryngeal cancer receiving surgery or external beam radiation therapy (EBRT). Using a competing risks survival analysis, we compared the risk of death because of CVA among patients with early-stage glottic laryngeal cancer receiving surgery or EBRT in the Surveillance, Epidemiology, and End Results (SEER) database. The cumulative incidence of fatal CVA at 15 years was higher in patients receiving EBRT (2.8%; 95% confidence interval [CI], 2.3% to 3.4%) compared to surgery (1.5%; 95% CI, 0.8% to 2.3%; p = .024). In multivariable competing risks regression models, EBRT remained associated with an increased risk of fatal CVA compared to surgery (adjusted hazard ratio [HR], 1.75; 95% CI, 1.04-2.96; p = .037). Treatment for early-stage glottic laryngeal cancer with EBRT was associated with a small increase in the risk of late fatal CVA events relative to surgery. Copyright © 2013 Wiley Periodicals, Inc.

Early life stages contribute strongly to local adaptation in Arabidopsis thaliana.

PubMed

Postma, Froukje M; Ågren, Jon

2016-07-05

The magnitude and genetic basis of local adaptation is of fundamental interest in evolutionary biology. However, field experiments usually do not consider early life stages, and therefore may underestimate local adaptation and miss genetically based tradeoffs. We examined the contribution of differences in seedling establishment to adaptive differentiation and the genetic architecture of local adaptation using recombinant inbred lines (RIL) derived from a cross between two locally adapted populations (Italy and Sweden) of the annual plant Arabidopsis thaliana We planted freshly matured, dormant seeds (>180 000) representing >200 RILs at the native field sites of the parental genotypes, estimated the strength of selection during different life stages, mapped quantitative trait loci (QTL) for fitness and its components, and quantified selection on seed dormancy. We found that selection during the seedling establishment phase contributed strongly to the fitness advantage of the local genotype at both sites. With one exception, local alleles of the eight distinct establishment QTL were favored. The major QTL for establishment and total fitness showed evidence of a fitness tradeoff and was located in the same region as the major seed dormancy QTL and the dormancy gene DELAY OF GERMINATION 1 (DOG1). RIL seed dormancy could explain variation in seedling establishment and fitness across the life cycle. Our results demonstrate that genetically based differences in traits affecting performance during early life stages can contribute strongly to adaptive differentiation and genetic tradeoffs, and should be considered for a full understanding of the ecology and genetics of local adaptation.

Cumulative Effects of Nutrient Enrichment and Elevated Temperature Compromise the Early Life History Stages of the Coral Acropora tenuis

PubMed Central

Noonan, Sam H. C.; Willis, Bette L.; Fabricius, Katharina E.; Negri, Andrew P.

2016-01-01

Inshore coral reefs are experiencing the combined pressures of excess nutrient availability associated with coastal activities and warming seawater temperatures. Both pressures are known to have detrimental effects on the early life history stages of hard corals, but studies of their combined effects on early demographic stages are lacking. We conducted a series of experiments to test the combined effects of nutrient enrichment (three levels) and elevated seawater temperature (up to five levels) on early life history stages of the inshore coral Acropora tenuis, a common species in the Indo-Pacific and Red Sea. Gamete fertilization, larval survivorship and larval settlement were all significantly reduced as temperature increased, but only fertilization was further affected by simultaneous nutrient enrichment. Combined high temperatures and nutrient enrichment affected fertilization in an additive manner, whereas embryo abnormalities increased synergistically. Higher than normal temperatures (32°C) increased coral juvenile growth rates 1.6-fold, but mortality also increased by 50%. The co-occurrence of nutrient enrichment with high temperatures reduced juvenile mortality to 36%, ameliorating temperature stress (antagonistic interaction). Overall, the types of effect (additive vs synergistic or antagonistic) and their magnitude varied among life stages. Gamete and embryo stages were more affected by temperature stress and, in some cases, also by nutrient enrichment than juveniles. The data suggest that coastal runoff events might exacerbate the impacts of warming temperatures on fertilization if these events co-occur during corals spawning. The cumulative impacts of simultaneous exposure to nutrient enrichment and elevated temperatures over all early life history stages increases the likelihood for failure of larval supply and recruitment for this coral species. Our results suggest that improving the water quality of river discharges into coastal areas might help to

Daily Physical Activity Patterns During the Early Stage of Alzheimer's Disease.

PubMed

Varma, Vijay R; Watts, Amber

2017-01-01

Alzheimer's disease (AD) is a neurodegenerative disease that results in severe disability. Very few studies have explored changes in daily physical activity patterns during early stages of AD when components of physical function and mobility may be preserved. Our study explored differences in daily physical activity profiles, independent of the effects of non-cognitive factors including physical function and age, among individuals with mild AD compared to controls. Patients with mild AD and controls (n = 92) recruited from the University of Kansas Alzheimer's Disease Center Registry, wore the Actigraph GT3X+ for seven days, and provided objective physical function (VO2 max) and mobility data. Using multivariate linear regression, we explored whether individuals with mild AD had different daily average and diurnal physical activity patterns compared to controls independent of non-cognitive factors that may affect physical activity, including physical function and mobility. We found that mild AD was associated with less moderate-intensity physical activity (p < 0.05), lower peak activity (p < 0.01), and lower physical activity complexity (p < 0.05) particularly during the morning. Mild AD was not associated with greater sedentary activity or less lower-intensity physical activity across the day after adjusting for non-cognitive covariates. These findings suggest that factors independent of physical capacity and mobility may drive declines in moderate-intensity physical activity, and not lower-intensity or sedentary activity, during the early stage of AD. This underscores the importance of a better mechanistic understanding of how cognitive decline and AD pathology impact physical activity. Findings emphasize the potential value of designing and testing time-of-day specific physical activity interventions targeting individuals in the early stages of AD, prior to significant declines in mobility and physical function.

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study.

PubMed

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-04-01

Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. To explore processes underpinning the implementation of CKD management in primary care. Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity.

Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging

PubMed Central

Harlow, Siobán D.; Gass, Margery; Hall, Janet E.; Lobo, Roger; Maki, Pauline; Rebar, Robert W.; Sherman, Sherry; Sluss, Patrick M.; de Villiers, Tobie J.

2012-01-01

Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage –3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage–1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. PMID:22343510

How has early testicular cancer affected your life? A study of sexual function in men attending active surveillance for stage one testicular cancer.

PubMed

Brand, Sue; Williams, Hilary; Braybrooke, Jeremy

2015-06-01

Testicular cancer is the most common cancer in young men, it is frequently diagnosed at key times in relationship formation. In early stage disease the vast majority of tumours will be cured by surgery alone with patients being offered active surveillance rather than adjuvant therapies. To date, research has not evaluated how surveillance alone impacts on sexual function. The aim of this quantitative longitudinal study was to ascertain the sexual function of men with stage one disease at 3 and 12 months post diagnosis and to compare with normative data. Additional data was collected on the information men sought regarding sexual function and media they used to access this. This study shows that men's sexual function is altered at diagnosis and improves by 3 months. At 12 months, whilst not statistically significant, sexual function improves but not to the same level as normative data comparison. Men appear to find verbal information useful at 3 months, however men appear to be seeking written and online information at 12 months. The intricacies of sexual function together with the low number of participants may have been best met with a qualitative approach. However, the information data indicates the importance of further research into the effects of early stage testicular cancer on sexual function. Therefore, further qualitative research is recommended to explore the effects of early stage testicular cancer in relation to sexual function. Copyright © 2014 Elsevier Ltd. All rights reserved.

40 CFR 63.78 - Early reduction demonstration evaluation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

40 CFR 63.78 - Early reduction demonstration evaluation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 9 2011-07-01 2011-07-01 false Early reduction demonstration... Regulations Governing Compliance Extensions for Early Reductions of Hazardous Air Pollutants § 63.78 Early reduction demonstration evaluation. (a) The permitting authority will evaluate an early reduction...

Endoscopic methods in the treatment of early-stage esophageal cancer

PubMed Central

2014-01-01

Most patients with early esophageal cancer restricted to the mucosa may be offered endoscopic therapy, which is similarly effective, less invasive and less expensive than esophagectomy. Selection of appropriate relevant treatment and therapy methods should be performed at a specialized center with adequate facilities. The selection of an endoscopic treatment method for high-grade dysplasia and early-stage esophageal adenocarcinoma requires that tumor infiltration is restricted to the mucosa and that there is no neighboring lymph node metastasis. In squamous cell carcinoma, this treatment method is accepted in cases of tumors invading only up to the lamina propria of mucosa (m2). Tumors treated with the endoscopic method should be well or moderately differentiated and should not invade lymphatic or blood vessels. When selecting endoscopic treatments for these lesions, a combination of endoscopic resection and endoscopic ablation methods should be considered. PMID:25097676

Efficacy of adjuvant chemotherapy in early stage uterine leiomyosarcoma: A systematic review and meta-analysis.

PubMed

Bogani, Giorgio; Fucà, Giovanni; Maltese, Giuseppa; Ditto, Antonino; Martinelli, Fabio; Signorelli, Mauro; Chiappa, Valentina; Scaffa, Cono; Sabatucci, Ilaria; Lecce, Francesca; Raspagliesi, Francesco; Lorusso, Domenica

2016-11-01

We sought to review the current evidence in order to test the efficacy of adjuvant chemotherapy in improving disease-free survival in patients affected by early stage uterine leiomyosarcoma. On July 2016, literature was searched in order to identify trials comparing different postoperative adjuvant strategies for patients diagnosed with early stage uterine leiomyosarcoma. Our analysis included 360 patients: 145 (40%), 53 (15%), and 155 (43%) had chemotherapy (with or without radiotherapy), radiotherapy, and observation, respectively. Seven (2%) patients who had radiotherapy with or without chemotherapy were excluded from further analysis in order to reduce risk of biases. Administration of chemotherapy (with or without radiotherapy) did not improve outcomes in comparison to observation (OR: 0.79 (95%CI: 0.48, 1.29)), or radiotherapy (OR: 0.90 (95%CI: 0.42, 1.94)). Loco-regional recurrence rate was similar comparing patients undergoing chemotherapy (with or without radiotherapy) with having observation alone (OR: 0.84 (95%CI: 0.44, 1.60)). Similarly, pooled results suggested that chemotherapy administration did not affect distant recurrence rate in comparison to no chemotherapy (OR: 0.80 (95%CI: 0.50, 1.28)), and observation alone (OR: 0.99 (95%CI: 0.60, 1.64)). However, patients undergoing chemotherapy (with or without radiotherapy) experienced a trend towards lower risk of developing distant recurrences (OR: 0.49 (95%CI: 0.24, 1.03)) and a higher risk of developing loco-regional recurrences (OR: 3.45 (95%CI: 1.02, 11.73)) than patients undergoing radiotherapy. In early stage uterine leiomyosarcoma, the role of adjuvant chemotherapy remains unclear. Owing to the high recurrence rate, even in the early stage of disease, further innovative therapeutic strategies have to be tested. Copyright © 2016 Elsevier Inc. All rights reserved.

Arthroscopic Synovectomy Combined with Autologous Fat Grafting in Early Stages of CMC Osteoarthritis of the Thumb.

PubMed

Kemper, Robert; Wirth, Johanna; Baur, Eva-Maria

2018-04-01

Background  Minimal invasive treatments such as arthroscopic techniques may be adequate to restore the anatomy and functional integrity of the thumb CMC (carpometacarpal) joint. In this paper, we reported the interposition of autologous fat tissue in combination with arthroscopic synovectomy/debridement for early stage of the thumb CMC joint osteoarthritis. Patients and Methods  Twelve patients with a mean age of 46 years with early radiological stages of thumb CMC joint osteoarthritis were included. Evaluation of outcome was measured prior and 3, 12, and 24 months after surgery including, Visual Analog Scale (VAS), QuickDASH, grip and pinch strength, range of motion (ROM), and patient satisfaction. Results  Pain at rest (or with load) was reduced from preoperative 4,7 (8,7) to 2 (5,9) at 3 to 6 months; 1,4 (4,3) at 12 months; and 0,75 (2,7) at 2 years after the surgery. Initial preoperative QuickDASH value of 52 points reduced to 33 (17-65) at 6 months, 23 (2-70) at 12 months, and 20 (11-29) at 24 months after the surgery. Grip strength and thumb pinch with respect to the contralateral untreated thumb was reduced in the first 12 months but recovered subsequently. ROM was equal to the contralateral thumb. Three patients suffered from tendinitis and required surgical treatment. One patient indicated prolonged pain symptoms. No infections were noted and no donor-site morbidity or side effects were detected. Conclusion  Arthroscopic synovectomy combined with autologous fat graft is a reliable surgical option for early thumb CMC joint osteoarthritis and that effect continues for more than 24 months.

Detection and differentiation of early acute and following age stages of myocardial infarction with quantitative post-mortem cardiac 1.5T MR.

PubMed

Schwendener, Nicole; Jackowski, Christian; Persson, Anders; Warntjes, Marcel J; Schuster, Frederick; Riva, Fabiano; Zech, Wolf-Dieter

2017-01-01

Recently, quantitative MR sequences have started being used in post-mortem imaging. The goal of the present study was to evaluate if early acute and following age stages of myocardial infarction can be detected and discerned by quantitative 1.5T post-mortem cardiac magnetic resonance (PMCMR) based on quantitative T1, T2 and PD values. In 80 deceased individuals (25 female, 55 male), a cardiac MR quantification sequence was performed prior to cardiac dissection at autopsy in a prospective study. Focal myocardial signal alterations detected in synthetically generated MR images were MR quantified for their T1, T2 and PD values. The locations of signal alteration measurements in PMCMR were targeted at autopsy heart dissection and cardiac tissue specimens were taken for histologic examinations. Quantified signal alterations in PMCMR were correlated to their according histologic age stage of myocardial infarction. In PMCMR seventy-three focal myocardial signal alterations were detected in 49 of 80 investigated hearts. These signal alterations were diagnosed histologically as early acute (n=39), acute (n=14), subacute (n=10) and chronic (n=10) age stages of myocardial infarction. Statistical analysis revealed that based on their quantitative T1, T2 and PD values, a significant difference between all defined age groups of myocardial infarction can be determined. It can be concluded that quantitative 1.5T PMCMR quantification based on quantitative T1, T2 and PD values is feasible for characterization and differentiation of early acute and following age stages of myocardial infarction. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A microengineered pathophysiological model of early-stage breast cancer.

PubMed

Choi, Yoonseok; Hyun, Eunjeh; Seo, Jeongyun; Blundell, Cassidy; Kim, Hee Chan; Lee, Eunhee; Lee, Su Hyun; Moon, Aree; Moon, Woo Kyung; Huh, Dongeun

2015-08-21

A mounting body of evidence in cancer research suggests that the local microenvironment of tumor cells has a profound influence on cancer progression and metastasis. In vitro studies on the tumor microenvironment and its pharmacological modulation, however, are often hampered by the technical challenges associated with creating physiological cell culture environments that integrate cancer cells with the key components of their native niche such as neighboring cells and extracellular matrix (ECM) to mimic complex microarchitecture of cancerous tissue. Using early-stage breast cancer as a model disease, here we describe a biomimetic microengineering strategy to reconstitute three-dimensional (3D) structural organization and microenvironment of breast tumors in human cell-based in vitro models. Specifically, we developed a microsystem that enabled co-culture of breast tumor spheroids with human mammary ductal epithelial cells and mammary fibroblasts in a compartmentalized 3D microfluidic device to replicate microarchitecture of breast ductal carcinoma in situ (DCIS). We also explored the potential of this breast cancer-on-a-chip system as a drug screening platform by evaluating the efficacy and toxicity of an anticancer drug (paclitaxel). Our microengineered disease model represents the first critical step towards recapitulating pathophysiological complexity of breast cancer, and may serve as an enabling tool to systematically examine the contribution of the breast cancer microenvironment to the progression of DCIS to an invasive form of the disease.

Test Design Optimization in CAT Early Stage with the Nominal Response Model

ERIC Educational Resources Information Center

Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

2007-01-01

The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

Effects of gamma radiation on the early developmental stages of Zebrafish (Danio rerio).

PubMed

Praveen Kumar, M K; Shyama, S K; Kashif, Shamim; Dubey, S K; Avelyno, D'costa; Sonaye, B H; Kadam Samit, B; Chaubey, R C

2017-08-01

The zebrafish is gaining importance as a popular vertebrate model organism and is widely employed in ecotoxicological studies, especially for the biomonitoring of pollution in water bodies. There is limited data on the genetic mechanisms governing the adverse health effects in regards to an early developmental exposure to gamma radiation. In the present study zebrafish (Danio rerio) embryos were exposed to 1, 2.5, 5, 7.5 and 10Gy of gamma radiation at 3h post fertilization (hpf). Different developmental toxicity endpoints were investigated. Further, expression of genes associated with the development and DNA damage i.e. (sox2 sox19a and p53) were evaluated using Quantitative PCR (qPCR). The significant changes in the expression of sox2 sox19a and p53 genes were observed. This data was supported the developmental defects observed in the zebrafish embryo exposed to gamma radiation such as i.e. increased DNA damage, decreased hatching rate, increase in median hatching time, decreased body length, increased mortality rate, increased morphological deformities. Further, study shows that the potential ecotoxicological threat of gamma radiation on the early developmental stages of zebrafish. Further, it revealed that the above parameters can be used as predictive biomarkers of gamma radiation exposure. Copyright © 2017. Published by Elsevier Inc.

Quantitative Tissue Proteomics Analysis Reveals Versican as Potential Biomarker for Early-Stage Hepatocellular Carcinoma.

PubMed

Naboulsi, Wael; Megger, Dominik A; Bracht, Thilo; Kohl, Michael; Turewicz, Michael; Eisenacher, Martin; Voss, Don Marvin; Schlaak, Jörg F; Hoffmann, Andreas-Claudius; Weber, Frank; Baba, Hideo A; Meyer, Helmut E; Sitek, Barbara

2016-01-04

Hepatocellular carcinoma (HCC) is one of the most aggressive tumors, and the treatment outcome of this disease is improved when the cancer is diagnosed at an early stage. This requires biomarkers allowing an accurate and early tumor diagnosis. To identify potential markers for such applications, we analyzed a patient cohort consisting of 50 patients (50 HCC and 50 adjacent nontumorous tissue samples as controls) using two independent proteomics approaches. We performed label-free discovery analysis on 19 HCC and corresponding tissue samples. The data were analyzed considering events known to take place in early events of HCC development, such as abnormal regulation of Wnt/b-catenin and activation of receptor tyrosine kinases (RTKs). 31 proteins were selected for verification experiments. For this analysis, the second set of the patient cohort (31 HCC and corresponding tissue samples) was analyzed using selected (multiple) reaction monitoring (SRM/MRM). We present the overexpression of ATP-dependent RNA helicase (DDX39), Fibulin-5 (FBLN5), myristoylated alanine-rich C-kinase substrate (MARCKS), and Serpin H1 (SERPINH1) in HCC for the first time. We demonstrate Versican core protein (VCAN) to be significantly associated with well differentiated and low-stage HCC. We revealed for the first time the evidence of VCAN as a potential biomarker for early-HCC diagnosis.

Descemet membrane endothelial keratoplasty (DMEK) early stage graft failure in eyes with preexisting glaucoma.

PubMed

Treder, Maximilian; Alnawaiseh, Maged; Eter, Nicole

2017-07-01

To evaluate the effect of a preexisting glaucoma on the early postoperative outcome of a descemet membrane endothelial keratoplasty (DMEK). All patients who underwent DMEK surgery at the Department of Ophthalmology of the University of Muenster with a follow-up of at least 3 months (90d) were included in this study. The best corrected distance visual acuity (BCDVA), the intraocular pressure (IOD), the rate of re-keratoplasty and the rebubbling rate were inter alia recorded. The results of patients with (group 1) and without a preexisting glaucoma (group 2) were compared. 74 eyes of 59 patients with a mean follow-up of 152 ± 70 days were included. 65 eyes were in group 1 and 9 eyes in group 2. The BCDVA significantly improved in both groups after surgery (p < 0.03). The Re-keratoplasty rate (p = 0.172), the number of rebubblings per patient (p = 0.571) and the rebubbling rate (p = 0.939) were not significantly different in patients without glaucoma compared to patients with a preexisting glaucoma. In the early stage outcome of DMEK no significant impact of a preexisting glaucoma was found.

Time-resolved metabolomics analysis of individual differences during the early stage of lipopolysaccharide-treated rats.

PubMed

Dai, Die; Gao, Yiqiao; Chen, Jiaqing; Huang, Yin; Zhang, Zunjian; Xu, Fengguo

2016-10-03

Lipopolysaccharide (LPS) can lead to uncontrollable cytokine production and eventually cause fatal sepsis syndrome. Individual toxicity difference of LPS has been widely reported. In our study we observed that two thirds of the rats (24/36) died at a given dose of LPS, while the rest (12/36) survived. Tracking the dynamic metabolic change in survival and non-survival rats in the early stage may reveal new system information to understand the inter-individual variation in response to LPS. As the time-resolved datasets are very complex and no single method can elucidate the problem clearly and comprehensively, the static and dynamic metabolomics methods were employed in combination as cross-validation. Intriguingly, some common results have been observed. Lipids were the main different metabolites between survival and non-survival rats in pre-dose serum and in the early stage of infection with LPS. The LPS treatment led to S-adenosly-methionine and total cysteine individual difference in early stage, and subsequent significant perturbations in energy metabolism and oxidative stress. Furthermore, cytokine profiles were analyzed to identify potential biological associations between cytokines and specific metabolites. Our collective findings may provide some heuristic guidance for elucidating the underlying mechanism of individual difference in LPS-mediated disease.

Evaluation of cardiovascular risk in stages of gout by a complex multimodal ultrasonography.

PubMed

Gancheva, Rada; Kundurdjiev, Atanas; Ivanova, Mariana; Kundurzhiev, Todor; Kolarov, Zlatimir

2017-01-01

The aim of our work was to assess ultrasound features of cardiovascular (CV) risk in stages of gout. Cross-sectional complex multimodal ultrasound study of 169 age-matched patients, with similar distribution of arterial hypertension, diabetes mellitus, obesity and chronic renal failure, was divided into four groups: 41 with asymptomatic hyperuricemia, 52 gout without tophi, 42 gouty tophi and 34 controls with osteoarthritis. Parameters independently associated with CV risk were measured: renal resistive index (RRI), left ventricular mass index (LVMi), mitral annulus early diastolic velocity (e'), intima-media thickness (IMT) and common carotid artery resistive index (CCARI). Multivariate analyses were performed to evaluate the impact of gout stages and CV risk factors on ultrasound alterations. Gouty tophi increased the risk of having IMT >0.90 mm with an OR 11.51 (95 % CI 2.32-57.21, p = 0.003), gout without tophi raised the risk with an OR 6.25 (95 % CI 1.37-28.44, p = 0.018), while asymptomatic hyperuricemia had no effect on IMT. The category of CCARI >0.70 was influenced by tophi with an OR 11.18 (95 % CI 2.61-47.83, p = 0.001) and by arterial hypertension with an OR 3.22 (95 % CI 1.11-9.36, p = 0.032). Neither asymptomatic hyperuricemia nor gout without tophi modified the development of abnormally high CCARI. Gout stages had no impact on LVMi, e' and RRI. Tophi are related to worsened ultrasonographic parameters evaluating target organs in gout, relative to earlier stages of the disease. They create a strong risk of carotid arteries' changes even beyond arterial hypertension.

Can early hepatic fibrosis stages be discriminated by combining ultrasonic parameters?

PubMed

Bouzitoune, Razika; Meziri, Mahmoud; Machado, Christiano Bittencourt; Padilla, Frédéric; Pereira, Wagner Coelho de Albuquerque

2016-05-01

In this study, we put forward a new approach to classify early stages of fibrosis based on a multiparametric characterization using backscatter ultrasonic signals. Ultrasonic parameters, such as backscatter coefficient (Bc), speed of sound (SoS), attenuation coefficient (Ac), mean scatterer spacing (MSS), and spectral slope (SS), have shown their potential to differentiate between healthy and pathologic samples in different organs (eye, breast, prostate, liver). Recently, our group looked into the characterization of stages of hepatic fibrosis using the parameters cited above. The results showed that none of them could individually distinguish between the different stages. Therefore, we explored a multiparametric approach by combining these parameters in two and three, to test their potential to discriminate between the stages of liver fibrosis: F0 (normal), F1, F3, and/without F4 (cirrhosis), according to METAVIR Score. Discriminant analysis showed that the most relevant individual parameter was Bc, followed by SoS, SS, MSS, and Ac. The combination of (Bc, SoS) along with the four stages was the best in differentiating between the stages of fibrosis and correctly classified 85% of the liver samples with a high level of significance (p<0.0001). Nevertheless, when taking into account only stages F0, F1, and F3, the discriminant analysis showed that the parameters (Bc, SoS) and (Bc, Ac) had a better classification (93%) with a high level of significance (p<0.0001). The combination of the three parameters (Bc, SoS, and Ac) led to a 100% correct classification. In conclusion, the current findings show that the multiparametric approach has great potential in differentiating between the stages of fibrosis, and thus could play an important role in the diagnosis and follow-up of hepatic fibrosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Measurement of the human esophageal cancer in an early stage with Raman spectroscopy

NASA Astrophysics Data System (ADS)

Maeda, Yasuhiro; Ishigaki, Mika; Taketani, Akinori; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

2014-02-01

The esophageal cancer has a tendency to transfer to another part of the body and the surgical operation itself sometimes gives high risk in vital function because many delicate organs exist near the esophagus. So the esophageal cancer is a disease with a high mortality. So, in order to lead a higher survival rate five years after the cancer's treatment, the investigation of the diagnosis methods or techniques of the cancer in an early stage and support the therapy are required. In this study, we performed the ex vivo experiments to obtain the Raman spectra from normal and early-stage tumor (stage-0) human esophageal sample by using Raman spectroscopy. The Raman spectra are collected by the homemade Raman spectrometer with the wavelength of 785 nm and Raman probe with 600-um-diameter. The principal component analysis (PCA) is performed after collection of spectra to recognize which materials changed in normal part and cancerous pert. After that, the linear discriminant analysis (LDA) is performed to predict the tissue type. The result of PCA indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by LDA which model is made by tryptophan bands.

Assessing the risk of pelvic and para-aortic nodal involvement in apparent early-stage ovarian cancer: A predictors- and nomogram-based analyses.

PubMed

Bogani, Giorgio; Tagliabue, Elena; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Casarin, Jvan; Chiappa, Valentina; Dondi, Giulia; Leone Roberti Maggiore, Umberto; Scaffa, Cono; Borghi, Chiara; Montanelli, Luca; Lorusso, Domenica; Raspagliesi, Francesco

2017-10-01

To estimate the prevalence of lymph node involvement in early-stage epithelial ovarian cancer in order to assess the prognostic value of lymph node dissection. Data of consecutive patients undergoing staging for early-stage epithelial ovarian cancer were retrospectively evaluated. Logistic regression and a nomogram-based analysis were used to assess the risk of lymph node involvement. Overall, 290 patients were included. All patients had lymph node dissection including pelvic and para-aortic lymphadenectomy. Forty-two (14.5%) patients were upstaged due to lymph node metastatic disease. Pelvic and para-aortic nodal metastases were observed in 22 (7.6%) and 42 (14.5%) patients. Lymph node involvement was observed in 18/95 (18.9%), 1/37 (2.7%), 4/29 (13.8%), 11/63 (17.4%), 3/41 (7.3%) and 5/24 (20.8%) patients with high-grade serous, low-grade-serous, endometrioid G1, endometrioid G2&3, clear cell and undifferentiated, histology, respectively (p=0.12, Chi-square test). We observed that high-grade serous histology was associated with an increased risk of pelvic node involvement; while, histology rather than low-grade serous and bilateral tumors were independently associated with para-aortic lymph node involvement (p<0.05). Nomograms displaying the risk of nodal involvement in the pelvic and para-aortic areas were built. High-grade serous histology and bilateral tumors are the main characteristics suggesting lymph node positivity. Our data suggested that high-grade serous and bilateral early-stage epithelial ovarian cancer are at high risk of having disease harboring in the lymphatic tissues of both pelvic and para-aortic area. After receiving external validation, our data will help to identify patients deserving comprehensive retroperitoneal staging. Copyright © 2017 Elsevier Inc. All rights reserved.

Cysts mark the early stage of metastatic tumor development in non-small cell lung cancer

PubMed Central

Thakur, Chitra; Rapp, Ulf R.; Rudel, Thomas

2018-01-01

Identifying metastatic tumor growth at an early stage has been one of the biggest challenges in the treatment of lung cancer. By genetic lineage tracing approach in a conditional model of Non-Small Cell Lung Cancer (NSCLC) in mice, we demonstrate that cystic lesions represent an early stage of metastatic invasion. We generated a mouse model for NSCLC which incorporated a heritable DsRed fluorescent tag driven by the ubiquitous CAG promoter in the alveolar type II cells of the lung. We found early cystic lesions in a secondary organ (liver) that lacked the expression of bona fide lung makers namely Scgb1a1 and surfactant protein C Sftpc and were DsRed positive hence identifying lung as their source of origin. This demonstrates the significant potential of alveolar type II cells in orchestrating the process of metastasis, rendering it as one of the target cell types of the lung of therapeutic importance in human NSCLC. PMID:29464089

Virtual exploration of early stage atherosclerosis.

PubMed

Olivares, Andy L; González Ballester, Miguel A; Noailly, Jérôme

2016-12-15

Biological mechanisms contributing to atherogenesis are multiple and complex. The early stage of atherosclerosis (AS) is characterized by the accumulation of low-density lipoprotein (LDL) droplets, leading to the creation of foam cells (FC). To address the difficulty to explore the dynamics of interactions that controls this process, this study aimed to develop a model of agents and infer on the most influential cell- and molecule-related parameters. FC started to accumulate after six to eight months of simulated hypercholesterolemia. A sensitivity analysis revealed the strong influence of LDL oxidation rate on the risk of FC creation, which was exploited to model the antioxidant effect of statins. Combined with an empirical simulation of the drug ability to decrease the level of LDL, the virtual statins treatment led to reductions of oxidized LDL levels similar to reductions measured in vivo. An Open source software was used to develop the agent-based model of early AS. Two different concentrations of LDL agents were imposed in the intima layer to simulate healthy and hypercholesterolemia groups of 'virtual patients'. The interactions programmed between molecules and cells were based on experiments and models reported in the literature. A factorial sensitivity analysis explored the respective effects of the less documented model parameters as (i) agent migration speed, (ii) LDL oxidation rate and (iii) concentration of autoantibody agents. Finally, the response of the model to known perturbations was assessed by introducing statins agents, able to reduce the oxidation rate of LDL agents and the LDL boundary concentrations. jerome.noailly@upf.eduSupplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Improving Dual-Task Control With a Posture-Second Strategy in Early-Stage Parkinson Disease.

PubMed

Huang, Cheng-Ya; Chen, Yu-An; Hwang, Ing-Shiou; Wu, Ruey-Meei

2018-03-31

To examine the task prioritization effects on postural-suprapostural dual-task performance in patients with early-stage Parkinson disease (PD) without clinically observed postural symptoms. Cross-sectional study. Participants performed a force-matching task while standing on a mobile platform, and were instructed to focus their attention on either the postural task (posture-first strategy) or the force-matching task (posture-second strategy). University research laboratory. Individuals (N=16) with early-stage PD who had no clinically observed postural symptoms. Not applicable. Dual-task change (DTC; percent change between single-task and dual-task performance) of posture error, posture approximate entropy (ApEn), force error, and reaction time (RT). Positive DTC values indicate higher postural error, posture ApEn, force error, and force RT during dual-task conditions compared with single-task conditions. Compared with the posture-first strategy, the posture-second strategy was associated with smaller DTC of posture error and force error, and greater DTC of posture ApEn. In contrast, greater DTC of force RT was observed under the posture-second strategy. Contrary to typical recommendations, our results suggest that the posture-second strategy may be an effective dual-task strategy in patients with early-stage PD who have no clinically observed postural symptoms in order to reduce the negative effect of dual tasking on performance and facilitate postural automaticity. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Quality of life of early stage colorectal cancer patients in Morocco.

PubMed

Mrabti, Hind; Amziren, Mounia; ElGhissassi, Ibrahim; Bensouda, Youssef; Berrada, Narjiss; Abahssain, Halima; Boutayeb, Saber; El Fakir, Samira; Nejjari, Chakib; Benider, Abdellatif; Mellas, Nawfel; El Mesbahi, Omar; Bennani, Maria; Bekkali, Rachid; Zidouh, Ahmed; Errihani, Hassan

2016-10-12

A multicentre cohort study was held in Morocco, designed to evaluate the quality of life of cancer patients. The aim of this paper is to report the assessment of the quality of life of early colorectal cancer patients, before and after cancer treatment, to identify other factors which are related to this quality of life. We used the third version of the QLQ-C30 questionnaire of the European organization for Research and treatment of Cancer (EORTC) after a transcultural validation. The Data collection was done at inclusion and then every twelve weeks to achieve one year of follow up. Overall 294 patients presented with early colorectal cancer, the median age was 56 years (range: 21-88). The male-female sex ratio was 1.17. At inclusion, the global health status was the most affected functional dimension. For symptoms: financial difficulties and fatigue scores were the highest ones. Emotional and social functions were significantly worse in rectal cancer. Most symptoms were more present in rectal cancer. At inclusion, global health status score was significantly worse in stage III. Anorexia was significantly more important among colorectal female patients. For Patients over 70 years-old, the difference was statistically significant for the physical function item which was lower. Overall, Functional dimensions scores were improved after chemotherapy. The symptoms scores did not differ significantly for patients treated by radiotherapy, between inclusion and at one year. Our EORTC QLQ C30 scores are overall comparable to the reference values. Neither chemotherapy, nor radiotherapy worsened the quality of life at one year.

MicroRNA-196a-5p is a potential prognostic marker of delayed lymph node metastasis in early-stage tongue squamous cell carcinoma

PubMed Central

Maruyama, Tessho; Nishihara, Kazuhide; Umikawa, Masato; Arasaki, Akira; Nakasone, Toshiyuki; Nimura, Fumikazu; Matayoshi, Akira; Takei, Kimiko; Nakachi, Saori; Kariya, Ken-Ichi; Yoshimi, Naoki

2018-01-01

MicroRNAs (miRs) are expected to serve as prognostic tools for cancer. However, many miRs have been reported as prognostic markers of recurrence or metastasis in oral squamous cell carcinoma patients. We aimed to determine the prognostic markers in early-stage tongue squamous cell carcinoma (TSCC). Based on previous studies, we hypothesized that miR-10a, 10b, 196a-5p, 196a-3p, and 196b were prognostic markers and we retrospectively performed miR expression analyses using formalin-fixed paraffin-embedded sections of surgical specimens. Total RNA was isolated from cancer tissues and adjacent normal tissue as control, and samples were collected by laser-capture microdissection. After cDNA synthesis, reverse transcription-quantitative polymerase chain reaction was performed. Statistical analyses for patient clinicopathological characteristics, recurrence/metastasis, and survival rates were performed to discern their relationships with miR expression levels, and the 2−ΔΔCq method was used. miR-196a-5p levels were significantly upregulated in early-stage TSCC, particularly in the lymph node metastasis (LNM) group. The LNM-free survival rate in the low miR-196a-5p ΔΔCq value regulation group was found to be lower than that in the high ΔΔCq value regulation group (P=0.0079). Receiver operating characteristic analysis of ΔΔCq values revealed that miR-196a-5p had a P-value=0.0025, area under the curve=0.740, and a cut-off value=−0.875 for distinguishing LNM. To our knowledge, this is the first study to examine LNM-related miRs in early-stage TSCC as well as miRs and ‘delayed LNM’ in head and neck cancer. miR-196a-5p upregulation may predict delayed LNM. Our data serve as a foundation for future studies to evaluate miR levels and facilitate the prediction of delayed LNM during early-stage TSCC, which prevent metastasis when combined with close follow-up and aggressive adjuvant therapy or elective neck dissection. Moreover, our data will serve as a foundation

Understanding the management of early-stage chronic kidney disease in primary care: a qualitative study

PubMed Central

Blakeman, Tom; Protheroe, Joanne; Chew-Graham, Carolyn; Rogers, Anne; Kennedy, Anne

2012-01-01

Background Primary care is recognised to have an important role in the delivery of care for people with chronic kidney disease (CKD). However, there is evidence that CKD management is currently suboptimal, with a range of practitioner concerns about its management. Aim To explore processes underpinning the implementation of CKD management in primary care. Design and setting Qualitative study in general practices participating in a chronic kidney disease collaborative undertaken as part of the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for Greater Manchester. Method Semi-structured interviews were conducted with GPs and practice nurses (n = 21). Normalisation Process Theory provided a framework for generation and analysis of the data. Results A predominant theme was anxiety about the disclosure of early-stage CKD with patients. The tensions experienced related to identifying and discussing CKD in older people and patients with stage 3A, embedding early-stage CKD within vascular care, and the distribution of work within the practice team. Participants provided accounts of work undertaken to resolve the difficulties encountered, with efforts having tended to focus on reassuring patients. Analysis also highlighted how anxiety surrounding disclosure influenced, and was shaped by, the organisation of care for people with CKD and associated long-term conditions. Conclusion Offering reassurance alone may be of limited benefit, and current management of early-stage CKD in primary care may miss opportunities to address susceptibility to kidney injury, improve self-management of vascular conditions, and improve the management of multimorbidity. PMID:22520910

Omission of axillary staging in elderly patients with early stage breast cancer impacts regional control but not survival: A systematic review and meta-analysis.

PubMed

Liang, Shuyin; Hallet, Julie; Simpson, Jory S; Tricco, Andrea C; Scheer, Adena S

2017-03-01

Management of early breast cancer in the elderly population is challenging due to different breast cancer biology and limited tolerance to aggressive treatments. The aim of this study is to evaluate whether the omission of axillary staging impacts breast cancer outcomes in elderly patients. A systematic review and meta-analysis was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The electronic databases were searched in August 2014 using the following inclusion criteria: RESULTS: Two RCTs met the eligibility criteria and were included. A meta-analysis of the included RCTs of 692 patients found that axillary staging reduced the risk of axillary recurrence compared to no axillary staging (RR 0.24, 95% CI: 0.06 to 0.95, I 2 =0%, p=0.04). There were no differences observed in in-breast recurrence or distant recurrence (RR 1.20, 95% CI: 0.55 to 2.64, I 2 =62%, p=0.65, RR 1.17, 95% CI: 0.75 to 1.82, I 2 =0%, p=0.48, respectively). There were no differences observed in overall or breast-cancer specific mortality (RR 0.99, 95% CI: 0.79 to 1.24, I 2 =0%, p=0.92, RR 1.07, 95% CI: 0.72 to 1.57, I 2 =0%, p=0.75, respectively). Omission of axillary staging in elderly patients with clinically negative axillae results in increased regional recurrence but does not appear to impact survival. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tumor Marker Usage and Medical Care Costs Among Older Early-Stage Breast Cancer Survivors

PubMed Central

Ramsey, Scott D.; Henry, N. Lynn; Gralow, Julie R.; Mirick, Dana K.; Barlow, William; Etzioni, Ruth; Mummy, David; Thariani, Rahber; Veenstra, David L.

2015-01-01

Purpose Although American Society of Clinical Oncology guidelines discourage the use of tumor marker assessment for routine surveillance in nonmetastatic breast cancer, their use in practice is uncertain. Our objective was to determine use of tumor marker tests such as carcinoembryonic antigen and CA 15-3/CA 27.29 and associated Medicare costs in early-stage breast cancer survivors. Methods By using Surveillance, Epidemiology, and End Results-Medicare records for patients diagnosed with early-stage breast cancer between 2001 and 2007, tumor marker usage within 2 years after diagnosis was identified by billing codes. Logistic regression models were used to identify clinical and demographic factors associated with use of tumor markers. To determine impact on costs of care, we used multivariable regression, controlling for other factors known to influence total medical costs. Results We identified 39,650 eligible patients. Of these, 16,653 (42%) received at least one tumor marker assessment, averaging 5.7 tests over 2 years, with rates of use per person increasing over time. Factors significantly associated with use included age at diagnosis, diagnosis year, stage at diagnosis, race/ethnicity, geographic region, and urban/rural status. Rates of advanced imaging, but not biopsies, were significantly higher in the assessment group. Medical costs for patients who received at least one test were approximately 29% greater than costs for those who did not, adjusting for other factors. Conclusion Breast cancer tumor markers are frequently used among women with early-stage disease and are associated with an increase in both diagnostic procedures and total cost of care. A better understanding of factors driving the use of and the potential benefits and harms of surveillance-based tumor marker testing is needed. PMID:25332254

The Treatment Effect of Porous Titanium Alloy Rod on the Early Stage Talar Osteonecrosis of Sheep

PubMed Central

Zhang, Yong-Quan; Zhang, Zhi-Yong; Guo, Zheng

2013-01-01

Osteonecrosis of the talus (ONT) may severely affect the function of the ankle joint. Most orthopedists believe that ONT should be treated at an early stage, but a concise and effective surgical treatment is lacking. In this study, porous titanium alloy rods were prepared and implanted into the tali of sheep with early-stage ONT (IM group). The curative effect of the rods was compared to treatment by core decompression (DC group). No significant differences in bone reconstruction were observed between the two groups at 1 month after intervention. After 3 months, the macroscopic view of gross specimens of the IM group showed ordinary contours, but the specimens of the DC group showed obvious partial bone defects and cartilage degeneration. Quantitative analysis of the reconstructed trabeculae by micro-CT and histological study suggested that the curative effect of the IM group was superior to that of the DC group at 3 months after intervention. These favorable short-term results of the implantation of porous titanium alloy rods into the tali of sheep with early-stage ONT may provide insight into an innovative surgical treatment for ONT. PMID:23516485

Utility of the PET-CT in the evaluation of early response to treatment in the diffuse large B-cell lymphoma. Preliminary results.

PubMed

Cortés Romera, M; Gámez Cenzano, C; Caresia Aróztegui, A P; Martín-Comín, J; González-Barca, E; Ricart Brulles, Y; Palacios Abufón, A; Robles Barba, J; Rodríguez-Bel, L; Rossi Seoane, S; Fernández de Sevilla, A

2012-01-01

To assess the role of FDG-PET/CT performed after the first cycles of chemotherapy in the prediction of response to treatment in patients with diffuse large B-cell lymphoma. Twenty patients (mean age: 48 years) were included, 16 initial staging and 4 relapse. All patients underwent PET/CT at 3 times: 1) Baseline, 2) After 1-3 cycles of chemotherapy (early response assessment), and 3) End of treatment (evaluation of final response). Early PET/CT findings were correlated to the end-treatment PET/CT and follow-up. The evaluation of the response was established according to the decrease in uptake of the lesions (SUVmax). In the early assessment, a good response indicator (GRI) was obtained when the lesion disappeared or had more than 50% reduction in SUVmax. At the end of the treatment, a complete metabolic response (CMR) was determined in negative PET scans. Follow-up was superior to 19 months and final outcome was established as progression/relapse or no evidence of disease (NED). At the early treatment evaluation, 16/16 patients of initial staging (100%) and 2/4 of relapse (50%) achieved GRI. At the end of treatment evaluation, 14/16 patients of initial staging with GRI achieved CMR and 1/16 PMR: 14 were alive with NED in the follow-up while 1 relapsed. In the second group, 2/2 patients with GRI achieved CMR (100%): 1 continued with NED in the follow-up and another relapsed. FDG-PET/CT after the first cycles of chemotherapy is useful to monitor treatment due to its high negative predictive value (87.5%), using it to modify treatment early in the non-responders. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

Treatment of early-stage prostate cancer among rural and urban patients.

PubMed

Baldwin, Laura-Mae; Andrilla, C Holly A; Porter, Michael P; Rosenblatt, Roger A; Patel, Shilpen; Doescher, Mark P

2013-08-15

Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men

Development sites, feeding modes and early stages of seven European Palloptera species (Diptera, Pallopteridae).

PubMed

Rotheray, Graham E

2014-12-19

Two hundred and ninety-eight rearing records and 87 larvae and puparia were obtained of seven species of Palloptera Fallén (Diptera, Pallopteridae), mainly in Scotland during 2012-2013. The third stage larva and puparium of each species were assessed morphologically and development sites and feeding modes investigated by rearing, observation and feeding tests. Early stages appear to be distinguished by the swollen, apico-lateral margins of the prothorax which are coated in vestiture and a poorly developed anal lobe with few spicules. Individual pallopteran species are separated by features of the head skeleton, locomotory spicules and the posterior respiratory organs. Five species can be distinguished by unique character states. Observations and feeding tests suggest that the frequently cited attribute of zoophagy is accidental and that saprophagy is the primary larval feeding mode with autumn/winter as the main period of development. Food plants were confirmed for flowerhead and stem developing species and rain is important for maintaining biofilms on which larvae feed. Due to difficulties in capturing adults, especially males, the distribution and abundance of many pallopteran species is probably underestimated. Better informed estimates are possible if early stages are included in biodiversity assessments. To facilitate this for the species investigated, a key to the third stage larva and puparium along with details on finding them, is provided. 

Comparative Effectiveness of 5 Treatment Strategies for Early-Stage Non-Small Cell Lung Cancer in the Elderly

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

Shirvani, Shervin M.; Jiang, Jing; Chang, Joe Y.

2012-12-01

Purpose: The incidence of early-stage non-small cell lung cancer (NSCLC) among older adults is expected to increase because of demographic trends and computed tomography-based screening; yet, optimal treatment in the elderly remains controversial. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare cohort spanning 2001-2007, we compared survival outcomes associated with 5 strategies used in contemporary practice: lobectomy, sublobar resection, conventional radiation therapy, stereotactic ablative radiation therapy (SABR), and observation. Methods and Materials: Treatment strategy and covariates were determined in 10,923 patients aged {>=}66 years with stage IA-IB NSCLC. Cox regression, adjusted for patient and tumor factors, compared overall and disease-specificmore » survival for the 5 strategies. In a second exploratory analysis, propensity-score matching was used for comparison of SABR with other options. Results: The median age was 75 years, and 29% had moderate to severe comorbidities. Treatment distribution was lobectomy (59%), sublobar resection (11.7%), conventional radiation (14.8%), observation (12.6%), and SABR (1.1%). In Cox regression analysis with a median follow-up time of 3.2 years, SABR was associated with the lowest risk of death within 6 months of diagnosis (hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.38-0.63; referent is lobectomy). After 6 months, lobectomy was associated with the best overall and disease-specific survival. In the propensity-score matched analysis, survival after SABR was similar to that after lobectomy (HR 0.71; 95% CI 0.45-1.12; referent is SABR). Conventional radiation and observation were associated with poor outcomes in all analyses. Conclusions: In this population-based experience, lobectomy was associated with the best long-term outcomes in fit elderly patients with early-stage NSCLC. Exploratory analysis of SABR early adopters suggests efficacy comparable with that of surgery in select

Minimally Invasive Surgical Staging in Early-stage Ovarian Carcinoma: A Systematic Review and Meta-analysis.

PubMed

Bogani, Giorgio; Borghi, Chiara; Leone Roberti Maggiore, Umberto; Ditto, Antonino; Signorelli, Mauro; Martinelli, Fabio; Chiappa, Valentina; Lopez, Carlos; Sabatucci, Ilaria; Scaffa, Cono; Indini, Alice; Ferrero, Simone; Lorusso, Domenica; Raspagliesi, Francesco

Few studies investigated the efficacy and safety of minimally invasive surgery for the treatment of early-stage epithelial ovarian cancer (eEOC). In this context, we aimed to review the current evidence comparing laparoscopy and the laparotomic approach for staging procedures in eEOC. This systematic review was registered in the International Prospective Register of Systematic Reviews. Overall, 3065 patients were included: 1450 undergoing laparoscopy and 1615 undergoing laparotomic staging. Patients undergoing laparoscopy experienced a longer (but not statistically significant) operative time (weighted mean difference [WMD] = 28.3 minutes; 95% confidence interval [CI], -2.59 to 59.2), a lower estimated blood loss (WMD = -156.5 mL; 95% CI, -216.4 to -96.5), a shorter length of hospital stay (WMD = -3.7 days; 95% CI, -5.2 to -2.1), and a lower postoperative complication rate (odds ratio [OR] = 0.48; 95% CI, 0.29-0.81) than patients undergoing laparotomy. The upstaging (OR = 0.81; 95% CI, 0.55-1.20) and cyst rupture (OR = 1.32; 95% CI, 0.52-3.38) rates were similar between groups. Laparoscopic staging is associated with a shorter time to chemotherapy than laparotomic procedures (WMD = -5.16 days; 95% CI, -8.68 to -1.64). Survival outcomes were not influenced by the route of surgery. Pooled data suggested that the minimally invasive surgical approach is equivalent to laparotomy for the treatment of eEOC and may be superior in terms of perioperative outcomes. However, because of the low level of evidence of the included studies, further randomized trials are warranted. Copyright © 2017 AAGL. Published by Elsevier Inc. All rights reserved.

Maintenance phase in psoralen-ultraviolet A phototherapy of early-stage mycosis fungoides. A critically appraised topic.

PubMed

Grandi, V; Delfino, C; Pileri, A; Pimpinelli, N

2017-08-01

A 65-year-old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a 'period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy' by slowly tapering the number of psoralen-ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow-up. The aim of this critically appraised topic (CAT) was to determine if a maintenance phase gives a significant benefit in terms of relapse rate (RR) and RFI in patients affected by early-stage MF who had achieved CR under PUVA phototherapy. Embase, PubMed and TRIP databases were searched for 'mycosis fungoides' AND [('photochemotherapy' OR 'puva') OR 'psoralen'] in June 2016. Three articles matched our inclusion criteria and are discussed in this CAT. In this field of research the literature is poor and the reported level of evidence is low. Only one of the studies was conducted prospectively, and none were randomized. No significant difference in terms of reduction in relapse rate or increase in RFI in patients who underwent a PUVA maintenance phase emerged when compared with those who went for simple follow-up. Further randomized clinical trials (RCTs) are required in order to evaluate maintenance phase vs. no treatment before it can be favoured as the standard protocol of treatment in early-stage MF. At the time of writing this paper, we report an ongoing Austrian multicentre RCT (Clinical Trial.gov identifier: NCT01686594) that will hopefully give useful results in this topic. © 2017 British Association of Dermatologists.

Biopsy Findings After Breast Conservation Therapy for Early-Stage Invasive Breast Cancer

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

Vapiwala, Neha; Starzyk, Jill; Harris, Eleanor E.

2007-10-01

Purpose: To determine the patterns and factors predictive of positive ipsilateral breast biopsy after conservation therapy for early-stage breast cancer. Methods and Materials: We performed a retrospective review of Stage I-II breast cancer patients initially treated with lumpectomy and radiotherapy between 1977 and 1996, who later underwent post-treatment ipsilateral breast biopsies. Results: A total of 223 biopsies were performed in 193 treated breasts: 171 single and 22 multiple biopsies. Of the 223 biopsies, 56% were positive and 44% were negative for recurrence. The positive biopsy rate (PBR) was 59% for the first and 32% for subsequent biopsies. The median timemore » to the first post-treatment biopsy was 49 months. Of the patients with negative initial biopsy findings, 11% later developed local recurrence. The PBR was 40% among patients with physical examination findings only, 65% with mammographic abnormalities only, and 79% with both findings (p = 0.001). Analysis of the procedure type revealed a PBR of 86% for core and 58% for excisional biopsies compared with 28% for aspiration cytology alone (p = 0.025). The PBR varied inversely with age at the original diagnosis: 49% if {>=}51 years, 57% if 36-50 years, and 83% if {<=}35 years (p = 0.05). The PBR correlated directly with the interval after radiotherapy: 49% if {<=}60 months, 59% if 60.1-120 months, 77% if 120.1-180 months, and 100% if >180 months after completing postlumpectomy radiotherapy (p = 0.01). The PBR was not linked with recurrence location, initial pathologic T or N stage, estrogen receptor/progesterone receptor status, or final pathologic margins (all p {>=} 0.15). Conclusion: After definitive radiotherapy for early-stage breast cancer, a greater PBR was associated with the presence of both mammographic and clinical abnormalities, excisional or core biopsies, younger age at the initial diagnosis, and longer intervals after radiotherapy completion.« less

Optimization of a novel enzyme treatment process for early-stage processing of sheepskins.

PubMed

Lim, Y F; Bronlund, J E; Allsop, T F; Shilton, A N; Edmonds, R L

2010-01-01

An enzyme treatment process for early-stage processing of sheepskins has been previously reported by the Leather and Shoe Research Association of New Zealand (LASRA) as an alternative to current industry operations. The newly developed process had marked benefits over conventional processing in terms of a lowered energy usage (73%), processing time (47%) as well as water use (49%), but had been developed as a "proof of principle''. The objective of this work was to develop the process further to a stage ready for adoption by industry. Mass balancing was used to investigate potential modifications for the process based on the understanding developed from a detailed analysis of preliminary design trials. Results showed that a configuration utilising a 2 stage counter-current system for the washing stages and segregation and recycling of enzyme float prior to dilution in the neutralization stage was a significant improvement. Benefits over conventional processing include a reduction of residual TDS by 50% at the washing stages and 70% savings on water use overall. Benefits over the un-optimized LASRA process are reduction of solids in product after enzyme treatment and neutralization stages by 30%, additional water savings of 21%, as well as 10% savings of enzyme usage.

Early Life Stages

EPA Pesticide Factsheets

Childhood should be viewed as a sequence of lifestages, from birth through infancy and adolescence. When assessing early life risks, consideration is given to risks resulting from fetal exposure via the pregnant mother, as well as postnatal exposures.

Communication in the Early Stage of Language Development in Children with CHARGE Syndrome

ERIC Educational Resources Information Center

Peltokorpi, Sini; Huttunen, Kerttu

2008-01-01

CHARGE syndrome is characterized by multiple physical abnormalities, and impaired vision and hearing. In this pilot study, communication in the early stage of language development in three one- to eight-year-old children with CHARGE syndrome was explored using video recorded free-play interaction sessions and a parental questionnaire. The children…

Effects of temperature on survival and development of early life stage Pacific and western brook lampreys

USGS Publications Warehouse

Meeuwig, M.H.; Bayer, J.M.; Seelye, J.G.

2005-01-01

We examined the effects of temperature (10, 14, 18, and 22??C) on survival and development of Pacific lampreys Lampetra tridentata and western brook lampreys L. richardsoni during embryological and early larval stages. The temperature for zero development was estimated for each species, and the response to temperature was measured as the proportion of individuals surviving to hatch, surviving to the larval stage, and exhibiting abnormalities at the larval stage (i.e., malformations of the body). The estimated temperature for zero development was 4.850C for Pacific lampreys and 4.97??C for western brook lampreys. Survival was greatest at 18??C, followed by 14, 10, and 22??C, significant differences being observed between 22??C and the other temperatures. Overall survival was significantly greater for western brook lampreys than for Pacific lampreys; however, the overall difference in proportion of individuals surviving was only 0.02. Overall survival significantly decreased from the time of hatch (proportion surviving = 0.85) to the larval stage (0.82; i.e., during the free-embryo stage). The proportion of individuals exhibiting abnormalities at the larval stage was greatest at 22??C, followed by 18, 10, and 14??C, significant differences being observed between 22??C and the other temperatures. These data provide baseline information on the thermal requirements of early life stage Pacific and western brook lampreys and will aid in assessment and prediction of suitable spawning and rearing habitats for these species.

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma

PubMed Central

Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

2017-01-01

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC. PMID:27926516

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

PubMed

Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

2017-01-10

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy

PubMed Central

Jang, Won Hyuk; Shim, Sehwan; Wang, Taejun; Yoon, Yeoreum; Jang, Won-Suk; Myung, Jae Kyung; Park, Sunhoo; Kim, Ki Hean

2016-01-01

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis. PMID:26755422

MYC and Human Telomerase Gene (TERC) Copy Number Gain in Early-stage Non–small Cell Lung Cancer

PubMed Central

Flacco, Antonella; Ludovini, Vienna; Bianconi, Fortunato; Ragusa, Mark; Bellezza, Guido; Tofanetti, Francesca R.; Pistola, Lorenza; Siggillino, Annamaria; Vannucci, Jacopo; Cagini, Lucio; Sidoni, Angelo; Puma, Francesco; Varella-Garcia, Marileila; Crinò, Lucio

2015-01-01

Objectives We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non–small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P = 0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P = 0.032 [UCCC criteria] or P = 0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P = 0.02) and the ROC classification (P = 0.008). Conclusions Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. PMID:25806711

Forecasting the impact of stereotactic ablative radiotherapy for early-stage lung cancer on the thoracic surgery workforce.