text:
Nice staff and room confort
It was not information about how to contact the reception by phone
It is the best hotel in Biel, but that doesn't mean much as in general hotel standards in Biel are not that high...
Small room and smaller bathroom
Friendly people, clean, nicely arranged, good breakfast
It was too hot in the room.
Customer service, cleanliness
Bar underneath that played music late at night
old interior and very noisy
Close to train station and lake, excellent breakfast, key also worked for front door, helpful staff, my window and curtain opened fine, quiet.
fast internet
the hotel needs renovation: my room window did not close, very noisy.my shutters did not close
Best value for money
There is no parking at the hotel.You must pay the city parking which is 2 swiss francs/hour and you should go every 2 hours to put the coin in the parking machine.
The breakfasts were good. They had a goo variety of food, and they were swiftly and pleasantly served.
It was a little difficult to communicate. Not everyone spoke English.
The bed was not too comfortable.
Room size
Information misleading - there is no park opposite and this was a reason for booking, thinking this would result in a nice outlook. Instead we felt very uncomfortable in hotel vicinity as hotel and vicinity covered in grafitti. Park is nothing more than some grass and a couple of seats which is around the corner and not opposite the hotel. The balcony has asbestos sheeting. Decor - 70's & poor.
good pizzeria near bye
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Maine Revised Statutes
§1555 MS-Word
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Ch. 85 Contents
Title 13 Contents
List of Titles
Maine Law
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Title 13: CORPORATIONS
Part 2: CORPORATIONS WITHOUT CAPITAL
Chapter 85: COOPERATIVES
Subchapter 1: CONSUMER COOPERATIVES
Article 2: ORGANIZATION AND BYLAWS
§1555. Bylaws
Bylaws shall be adopted, amended or repealed by at least a majority vote of the members voting.
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Office of the Revisor of Statutes
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I finally watched the webcast of the BIO CEO conference from Feb 12 (http://www.resverlogix.com/media/events.html). Great presentation IMO, and the one thing that really stood out to me was the second to last slide showing the timeline of current and future trials. In particular, the slide indicated "publications and abstracts" in Q2 of 2013, which we all know is also the same timeline for the completion and announcement of ASSURE trial data.
What struck me the most was that the slide text indicated "publications" not "publication" and "abstracts" not "abstract". RVX might be gearing up to release an onslaught of scientific data starting in Q2 2013 related not just to RVX-208 and CVD, but also to their other compounds improving other disease models.
Does anyone know if RVX has ever presented at scientific conferences (not investor conferences) on the cancer, autoimmune, diabetes, alzheimer's, or other programs? So we might not just be talking about SUSTAIN publication and ASSURE results announcement, but many simultaneous abstracts/publications related to RVX's pipeline, IMO.
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Pegna, Andrea Lopes MD*; Picozzi, Giulia MD†; Falaschi, Fabio MD‡; Carrozzi, Laura MD§; Falchini, Massimo MD‖; Carozzi, Francesca Maria MD¶; Pistelli, Francesco MD§; Comin, Camilla MD#; Deliperi, Annalisa MD‡; Grazzini, Michela MD**; Innocenti, Florio MD**; Maddau, Cristina MD¶; Vella, Alessandra MD, PhD††; Vaggelli, Luca MD‖‖; Paci, Eugenio MD, PhD¶¶; Mascalchi, Mario MD, PhD‖; for the ITALUNG Study Research Group
*Pneumonology Department, Careggi Hospital, Florence, Italy; †Radiodiagnostic Unit, Institute for Oncological Study and Prevention, Florence, Italy; ‡2nd Radiology Department, University Hospital of Pisa, Italy; §Cardiopulmonary Department, University Hospital, Pisa, Italy; ‖Radiodiagnostic Section, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Italy; ¶Analytical Cytology and Bio-Molecular Unit, Institute for Oncological Study and Prevention, Florence, Italy; #Pathology Department, Careggi Hospital, University of Florence, Italy; **Pneumonology, Hospital of Pistoia, Italy; ††Nuclear Medicine Unit, Le Scotte University Hospital, Siena, Italy; ‖‖Nuclear Medicine Unit, Careggi Hospital, Florence, Italy; and ¶¶Department of Epidemiology, Institute for Oncological Study and Prevention, Florence, Italy.
Disclosure: The authors declare no conflict of interest.
Members of the ITALUNG Study Research Group: Andrea Lopes Pegna, MD, Roberto Bianchi, MD, and Cristina Ronchi, MD: Pneumonology Department, Careggi Hospital, Florence Italy. Laura Carrozzi, MD, Ferruccio Aquilini, BSc, Stella Cini, MD, Mariella De Santis, MD, Francesco Pistelli, MD, Filomena Baliva, MD, Antonio Chella, MD, and Laura Tavanti, MD: Cardiopulmonary Department, University Hospital of Pisa, Italy. Michela Grazzini, MD, Florio Innocenti, MD, and Ilaria Natali, BSc: Pneumonology Department, Hospital of Pistoia, Italy. Mario Mascalchi, MD, PhD, Maurizio Bartolucci, MD, Elena Crisci, MD, Agostino De Francisci, MD, Massimo Falchini, MD, Silvia Gabbrielli, MD, Giulia Picozzi, MD, Giuliana Roselli, MD, and Andrea Masi, MD: Radiology Department, Careggi Hospital, University of Florence, Italy. Fabio Falaschi, MD, Luigi Battola, MD, Anna Lisa De Liperi, MD, and Cheti Spinelli, MD: Radiology Department, University Hospital of Pisa, Italy. Letizia Vannucchi, MD, Alessia Petruzzelli, MD, Davide Gadda, MD, Anna Talina Neri, MD, and Franco Niccolai, MD: Radiology Department, Hospital of Pistoia, Italy. Luca Vaggelli, MD: Nuclear Medicine Department, Careggi Hospital, Florence, Italy. Alessandra Vella, MD, PhD: Nuclear Medicine Department, Le Scotte University Hospital, Siena, Italy. Francesca Maria Carozzi, BSc and Cristina Maddau, BSc: Laboratory Unit, Institute for Oncological Study and Prevention, Florence, Italy. Alberto Janni, MD: Thoracic Surgery Department, Careggi Hospital, Florence, Italy. Alfredo Mussi, MD and Marco Lucchi, MD: Thoracic Surgery Department, University Hospital of Pisa, Italy. Camilla Comin, MD: Pathology Department, Careggi Hospital, University of Florence, Italy. Gabriella Fontanini, MD, Adele Renza Tognetti, MD, Pathology Department, University Hospital of Pisa, Italy. Eugenio Paci, MD, PhD, Giovanna Cordopatri, BSc, Francesco Giusti, BSc, PhD, and Ida Esposito, BSc: Department of Epidemiology Institute for Oncological Study and Prevention, Florence, Italy.
Address for correspondence: Mario Mascalchi, MD, PhD, Radiodiagnostic Section, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. E-mail: firstname.lastname@example.com
Introduction: Recruitment and nodule management are critical issues of lung cancer screening with low-dose computed tomography (LDCT). We report subjects' compliance and results of LDCT screening and management protocol in the active arm of the ITALUNG trial.
Methods: Three thousand two hundred six smokers or former smokers invited by mail were randomized to receive four annual LDCT (n = 1613) or usual care (n = 1593). Management protocol included follow-up LDCT, 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB).
Results: One thousand four hundred six subjects (87%) underwent baseline LDCT, and 1263 (79%) completed four screening rounds. LDCT was positive in 30.3% of the subjects at baseline and 15.8% subsequently. Twenty-one lung tumors in 20 subjects (1.5% detection) were found at baseline, and 20 lung tumors in 18 subjects (0.5% detection) in subsequent screening rounds. Ten of 18 prevalent (55%) and 13 of 17 incident (76%) non–small-cell cancers were in stage I. Interval growth enabled diagnosis of lung cancer in 16 subjects (42%), but at least one follow-up LDCT was obtained in 741 subjects (52.7%) over the screening period. FDG-PET obtained in 6.5% of subjects had 84% sensitivity and 90% specificity for malignant lesions. FNAB obtained in 2.4% of subjects showed 90% sensitivity and 88% specificity. Positivity of both FDG-PET and FNAB invariably predicted malignancy. Surgery for benign lesions was performed on four subjects (10% of procedures) but followed protocol violations on three subjects.
Conclusions: High-risk subjects recruited by mail who entered LDCT screening showed a high and stable compliance. Efficacy of screening is, however, weakened by low detection rate and specificity. Adhesion to management protocol might lessen surgery for benign lesions.
In Western countries, lung cancer is the most common malignant neoplasm in men, and its frequency is constantly increasing in women.1 Non–small-cell lung cancer (NSCLC) accounts for approximately 85% of these neoplasms.2,3 Although the age-adjusted trends of mortality are decreasing, survival rates for lung cancer are still 10% to 16%.4,5 In particular, only 15% to 20% of symptomatic patients have lesions amenable to radical surgical resection.6
Randomized clinical trials (RCTs) with chest radiograph as screening test for lung cancer failed to show any benefit in smokers and former smokers because of an excess of deaths in the screened arm. This was presumably because of the high number of surgically resected cancers with associated side effects and unnecessary surgical procedures for indolent cancers in the active arm.7–10
After publication of the Early Lung Cancer Action Project (ELCAP) study results in 1999,11 several observational (one-arm) studies assessed the performance of low-dose computed tomography (LDCT) as a screening tool for lung cancer in at-risk individuals.12 The largest observational study, the International-ELCAP study,13 confirmed the high sensitivity of LDCT as a screening test and reported a 88% 10-year survival rate after surgical resection in screen-detected stage I lung cancers. However, observational studies are insufficient to establish the efficacy of a screening test in reducing tumor-specific mortality because they suffer from lead time, length, and overdiagnosis bias.14–16
Accordingly, several RCTs for lung cancer screening with LDCT have been implemented in United States and Europe.17–25 In 2011, the largest RCT in United States, namely the National Lung Screening Trial (NLST),26 was halted because an interim analysis after 8 years of follow-up showed a 20% mortality reduction in the screened arm receiving annual LDCT for three rounds as compared with control arm receiving annual chest radiograph for three rounds.27 The result of the NLST is the first one supporting the efficacy of LDCT as a screening test in reducing mortality from lung cancer in high-risk individuals, and has considerably renewed interest and enthusiasm, as also criticisms28–30 about the possibility of offering LDCT on a large scale to smokers and former smokers. The latter has been recently recommended31,32 despite the negative short-term results concerning decrease of mortality of three small RCTs in Europe.18,33,34
Variable approaches concerning subjects recruitment, timing and reading of the LDCT screening test, and the protocol for management of screen-detected suspicious nodules were proposed.18,21,25,27,35–37 Comparative analyses of the different studies are fundamental for a thorough evaluation of efficacy of the screening procedure. To date, the complete, namely during the entire screening period, performance of both LDCT as a screening test and the management strategy for suspicious nodules was reported in five RCTs, namely the Lung Screening Study,38 the NLST,27 the DANTE and MILD trials in Italy,18,33 and the Danish Lung Cancer Screening trial.34,37
The Italian Lung (ITALUNG) study is an RCT part of an international cooperation, aimed at the pooled evaluation of the results of the RCTs of lung cancer screening with LDCT in Europe and possibly United States.39 The ITALUNG study design, enrolment procedure, and the results of the baseline screening round were previously reported.20 Herein, we present the final data concerning the compliance of the subjects recruited in the active arm of the trial, who were invited to undergo four annual LDCT, the results of the LDCT screening test in the four screening rounds, and the results of management protocol for screen-detected suspicious nodules.
ITALUNG is an RCT aimed to evaluate the efficacy of chest LDCT as a screening test in reducing lung cancer mortality, which is carried out in the Tuscany region of Italy.
The study was conducted in accordance with the amended Declaration of Helsinki (http://www.wma.net/en/30publications/10policies/b3/) and approved by the Local Ethic Committees of the participating institution (approval number 29–30 of September 30, 2003; number 23 of October 27, 2003; and number 00028543 of May 13, 2004).
Strategy and results of the exclusive mail recruitment of trail participants were previously reported.20 Those eligible for the trial were asymptomatic smokers and formers smokers aged 55 to 69 years, with a smoking history of at least 20 pack-years, and no history of cancer, other than nonmelanoma skin cancer, or general conditions precluding thoracic surgery.
Subjects randomized to the control arm received a letter communicating their allocation in the usual care arm of the study, in which no LDCT or chest radiograph is scheduled. Subjects randomized into the active arm were contacted by phone to fix an appointment for counseling, during which a pneumonologist, after providing further information about the screening LDCT examination and management of positive screening tests, collected the consent for LDCT examination, and scheduled the LDCT screening test. An additional written consent for enrolment in a biomarkers-collateral study was requested during the interview.40 A free-access invitation for a smoking cessation program was provided to smokers enrolled both in the active and in the control arms.
All randomized subjects are planned for follow-up by cancer registry of the Tuscany region (http://www.ispo.toscana.it) for 7 years from randomization, to assess incidence of lung cancer and mortality from lung cancer or other causes. Although no specific instruction about the workup of cases of lung cancer in the control arm was provided to general practitioner or the enrolled subject, the low rate of migration of patients, who receive a diagnosis of primary lung cancer in the Tuscany region (< 3%, personal unpublished observation, 2011 ), makes it probable that they will be referred in the same structures participating in the ITALUNG trial. Because the management of the suspicious nodules in the ITALUNG trial is derived by the clinical practice (see below), it is expected that no major discrepancies will be active in the workup, diagnosis, and staging of such cases, and that the related information will be available and gathered from hospital chart recordings at the end of the study. The first mortality data concerning the subjects enrolled in the ITALUNG are expected for 2014.
The present report is based on the data of the subjects randomized to the active arm of the trial, who underwent baseline LDCT and were invited again for the next three annual repeat LDCT examinations. Individuals in whom lung cancer was diagnosed were not offered subsequent screening rounds.
The LDCT examinations were obtained in the three screening centers on eight different spiral scanners, which included one with a single row of detectors, and seven with multiple rows of detectors (3 with 4, 2 with 16, and 2 with 64 rows). The following technical parameter ranges were selected to contain the radiation dose: 120 to 140 kV, 20 to 43 mAs, pitch 1 to 2. The section collimations ranged between 3 mm in the single-detector scanner, and 0.75 mm in the 64-row detector scanner.
Because double reading increases the sensitivity of LDCT screening,41 each LDCT examination was assessed on a workstation independently by two of 17 certified radiologists having at least 5 years of experience in chest computed tomography (CT). A consensus between the two radiologists was reached in case of disagreement. All previous LDCT examinations of the subject obtained in the context of the trial were available for comparison. Management of positive screening tests was carried out at each screening center according to a shared protocol,20 which is fundamentally derived from that of the International-ELCAP Study.35 This includes follow-up LDCT with or without 1 month of antibiotic therapy, chest 2-[18F]fluoro-2-deoxy-D glucose positron emission tomography (FDG-PET), and CT-guided fine-needle aspiration biopsy (FNAB). Optical fibrobronchoscopy (FBS) was also performed on selected cases.
The FDG-PET examinations were performed in three centers using four scanners, two of which were dedicated positron emission tomographs (one GE Advance positron emission tomography [PET] scanner; General Electric, Milwaukee, WI; one ECAT Exact HR+ scanner; Siemens, Erlangen, Germany), and two dual-modality PET-CT scanners (1 Discovery LS; General Electric, Milwaukee, WI; 1 Gemini; Philips, Eindhoven, The Netherlands). Three trained nuclear medicine physicians visually evaluated the tracer uptake of the suspicious lesion and classified the result of the FDG-PET as positive, indeterminate (mild or faint FDG uptake, typically similar to that of mediastinum), or negative. Because most of the nodules to be investigated were of small size, we did not use the standardized uptake value because it can be unreliable in characterizing nodule uptake.37.42 Moreover, taking into consideration that tumors identified at lung cancer screening with LDCT can show low FDG uptake,42,43 for the purpose of computation of performance of FDG-PET, we assimilated indeterminate to positive FDG-PET results.
The majority (35 of 38) of the CT-guided FNAB was performed by two experienced interventional radiologists on a single-detector spiral CT scanner (Somatom plus 4; Siemens, Erlangen, Germany) used for the LDCT examination in one screening center, where aspiration material was evaluated by one trained cytopathologist, with rapid onsite examination (ROSE) technique.44,45 Three CT-guided FNAB without ROSE were performed by a chest radiologist on a four-detector spiral CT scanner (Somatom Volume Zoom; Siemens, Erlangen, Germany) used for LDCT examination in another screening center. For the purpose of computation of performance of CT-guided FNAB, we assimilated inconclusive results because of inadequate or insufficient material to negative FNAB.
Positivity of the LDCT screening test was fundamentally based on the nodule size or growth measured in terms of mean diameter, which was manually computed by the radiologist with electronic callipers on workstations.20 In particular, significant growth was defined as an increase of at least 1 mm in mean diameter of a solid or nonsolid nodule, taking into account the intra- and interoperator variability in measuring mean diameter of solid nodules,46 or the appearance or increase of a solid component in a nonsolid or part-solid nodule in two successive LDCT examinations.35 The criteria for positive tests and further diagnostic investigations concerning baseline screening round were previously detailed.20 At annual repeat screening rounds, the LDCT examination was considered positive if either a new solid, part-solid or nonsolid nodule was identified, or at least one solid, part-solid or nonsolid nodule already present in the last LDCT showed interim growth. If the new nodule had a mean diameter 3 mm or less, the subject received a 6-month follow-up LDCT, whereas a 3-month follow-up LDCT was obtained in case of a new nodule with mean diameter between 3mm and 5mm. In case of a nodule that was 5 mm or more in size, or if the screening test revealed multiple focal solid or nonsolid abnormalities consistent with inflammatory disease, a follow-up LDCT after 1 month of antibiotic therapy was recommended. In case of complete resolution of the abnormalities, the subject was sent for annual repeat screening, whereas, a further follow-up LDCT after 2 months was performed in case of partial or lack of resolution after antibiotic therapy.
When a solid nodule observed at baseline or repeat screening round attained a mean diameter 8 mm or more, and persisted after antibiotic therapy, chest FDG-PET examination was recommended. However, in some cases of large lesions, strongly suggestive for malignancy, CT-guided FNAB or FBS were directly performed. For FDG-PET–positive nodules, a CT-guided FNAB with ROSE was recommended, whereas, a further 3-month follow-up LDCT was obtained in FDG-PET–indeterminate or –negative nodules. A 3-month follow-up LDCT was also scheduled for nodules with positive or indeterminate FDG-PET and negative or inconclusive CT-guided FNAB. All subjects showing no nodule growth at this latter follow-up LDCT were invited to the subsequent annual repeat LDCT scan. For pure nonsolid noncalcified nodules of at least 10 mm diameter at baseline, and for new or growing nonsolid or part-solid nodule of at least 8 mm diameter at annual repeat screening, which persisted after antibiotic therapy, CT-guided FNAB was scheduled because FDG-PET is not indicated.47
All subjects with FNAB evidence of malignancy underwent a staging full-dose chest CT examination, with intravenous iodinated contrast administration extended to upper abdomen and head. Surgery was recommended for nodules with findings consistent with malignancy at FNAB and also in subjects with an FDG-PET–positive solid nodule, which was inconclusively evaluated at FNAB. All the surgically removed lesions were evaluated according to the World Health Organization criteria.48 Staging of screen-detected lung cancer was based on the pathology report when available, or on clinical and contrast-enhanced CT findings in the cases not amenable to surgical resection.
Sputum and blood samples were obtained from each participant at baseline LDCT screening test and again in case of positive LDCT examination; all the samples were stored for subsequent biomarker evaluation.40 The global and individual radiation dose to subjects recruited in the active arm of the ITALUNG trial has been previously reported.49
One thousand six hundred thirteen subjects (1035 men and 578 women; mean age = 60.7 years; mean pack-years = 42.9; 553 former smokers) were randomized to the active arm, and 1593 (1039 men and 554 women; mean age = 61.0 years; mean pack-years = 41.6; 575 former smokers) to the control arm. The first baseline LDCT was obtained in March 2004 and the last annual LDCT examination in February 2010. Table 1 summarizes the compliance of the subjects randomized to the active arm, the results of the screening LDCT, the nodule management, and the screen-detected NSCLC in the four screening rounds of the ITALUNG trial.
One thousand four hundred six (910 men with a mean age of 61.1 years and 496 women with a mean age of 60.6 years) of the subjects (87.1%) randomized to the active arm underwent the baseline LDCT. After exclusion from the next round of invitation of subjects in whom the screening procedure revealed lung cancer, 1356 (85.1%) executed the second, 1308 (82.3%) the third, and 1263 (79.8%) the fourth annual screening round with LDCT.
LDCT was positive in 30.3% at baseline and 15.7% (range, 13.7–17.3%) at the three annual repeat screening rounds (Table 1). Twenty-one cancers (18 NSCLC, 1 carcinoid, 2 small-cell lung cancers [SCLCs]) were found in 20 subjects at baseline screening round (prevalent cancers detection rate 1.5%), and 20 (17 NSCLC, 2 carcinoid, 1 SCLC) cancers in 18 subjects at the third annual repeat screening rounds (mean incident cancers detection rate 0.5%). Adenocarcinoma (AC) accounted for nine of 18 (50%) of the NSCLCs at baseline and for 15 of 17 (88%) at subsequent annual repeat screening rounds. Three subjects of 38 (7.8%) in whom lung cancers were screen detected had two malignant lung tumors. One had AC in right lung and SCLC (limited disease) in the left lung, one had AC in the right lung and a carcinoid in the left lung, and one had AC in the right lung and AC with bronchiole-alveolar features in the left lung. Isolated lung metastases (from gastrointestinal and renal cancer, 2 each) were detected by LDCT in four subjects during the entire screening cycle. Two interval cancers, namely lesions that were diagnosed outside the screening frame, were observed in the active arm during the screening period: one SCLC with extensive disease diagnosed between the second and third screening rounds, and one stage IV NSCLC diagnosed between the third and fourth screening rounds.
The characteristics of the screen-detected primary lung cancers found at baseline and annual repeat LDCT screening rounds are reported in Supplemental Table 1 (Supplemental Digital Content 1, http://links.lww.com/JTO/A409). Excluding two SCLCs and one large hilar mass, the average mean diameter of the screen-detected tumors was 24.2 mm at baseline, and 17.3 mm at subsequent annual screening rounds (p = not significant). Ten (56%) of the 18 prevalent NSCLCs were in stage I (8 in stage IA and 2 in stage IB) as compared with 13 of the 17 incident NSCLCs (76%) (11 in stage IA and 2 stage IB) (p = not significant) (Table 1).
As part of management of positive screening tests, 966 (120 after 1 month of antibiotic therapy, 745 after 3 months, and 101 after 6 months) follow-up LDCT examinations were obtained. They accounted for 15% (966 of 6299) of the total number of LDCT examinations performed in the active arm of the ITALUNG trial. Seven hundred forty-one of the 1406 subjects (52.7%) who underwent the baseline LDCT had at least one positive LDCT examination for noncalcified nodule over the entire screening cycle. Lung cancer was diagnosed in 16 of 38 subjects (42%) after evidence of lesion growth at follow-up LDCT examinations. Nodule disappearance or size reduction at LDCT after 1 month of antibiotic therapy was observed in 80 of 120 subjects (67%) (in 11 of 31 subjects [35%] at baseline and 69 of 89 subjects [77%] at annual repeat screening rounds).
Ninety-seven chest FDG-PET examinations were obtained in 92 subjects, namely 6.5% of the subjects randomized to the active arm who underwent baseline LDCT. Five subjects had two FDG-PET each. Fifty-seven PET-FDG examinations were performed at baseline, and 40 at subsequent annual screening rounds. Thirty-eight primary (n = 35) or secondary (n = 3) lung cancers were ultimately diagnosed in 35 subjects (3 subjects had 2 lesions, 1 a mixed cancer and SCLC, 1 a carcinoid and AC, and 1 subject had an AC and a controlateral early AC). On a total of 102 target lesions in 92 subjects (84 subjects had a single lesion and were examined once, 5 subjects had a single lesion and were examined twice, 2 subjects had 2 lesions and were examined once, and 1 subject had 2 lesions and was examined twice) and assimilating to positive the seven indeterminate FDG-PET results, which corresponded to lung cancer in six, the overall sensitivity of FDG-PET was 84% and specificity 89% (Table 2). Overall sensitivity and specificity assimilating indeterminate FDG-PET to negative results were 68% and 90%, respectively.
Thirty-eight CT-guided FNAB (with ROSE in 34) were obtained in 38 lesions in 34 subjects, that is, 2.4% of subjects randomized to the active arm who underwent baseline LDCT. In four subjects, two CT-guided FNAB were performed on two distinct lesions. Eighteen FNAB were performed on lesions detected at baseline screening round and 20 on lesions detected at subsequent annual screening rounds. The mean diameter of the nodules referred to FNAB was 18.2 mm (range, 5–48). Overall, 34 of 38 (89%) procedures yielded adequate material for the cytological examination (Table 2). CT-guided FNAB was positive and histological examination of the surgical specimen revealed lung cancer (n = 25) or metastasis(n = 2) in 27 of 38 (71%) lesions and atypical adenomatous hyperplasia (AAH) in one lesion. CT-guided FNAB was negative in six subjects (with lung cancer in 1 subject) and inconclusive in four subjects (with lung cancer and renal metastasis in 1 subject each). By assimilating the inconclusive to the negative FNAB results, the overall sensitivity of FNAB was 90% and specificity 88%. Sensitivity was 96% and specificity 83% after exclusion of the inconclusive FNAB for insufficient material. Pneumothorax occurred in 11 of 38 (29%) of the procedures, but only two subjects (5%) needed thoracic drainage.
FBS was obtained in 30 subjects, that is, 2.1% of the subjects who underwent baseline LDCT screening. Twenty were performed at baseline and 10 at the subsequent screening rounds. FBS was positive in eight subjects (all with lung cancer) and negative in 22 subjects. In six subjects with negative FBS, a diagnosis of lung cancer was finally reached. Overall sensitivity of FBS was 57% and specificity 100%.
Twenty-eight subjects received both FDG-PET and CT-guided FNAB as part of management of suspicious nodules. Positivity of both FDG-PET and CT-guided FNAB enabled prediction of lung malignancy in all 18 subjects with such a combination of results. In particular, primary lung cancer was found in 16 cases and solitary metastases (from gastrointestinal cancers) in two cases. FDG-PET and CT-guided FNAB were both negative in four subjects without lung cancer. Discrepancies between the results of FDG-PET and CT-guided FNAB were observed in six cases. In three subjects with final diagnosis of lung cancer, FDG-PET was positive and CT-guided FNAB was negative. However in one of the three subjects, because of the deep location of the nodule, the negative FNAB was performed under transoesophegeal ultrasound guidance rather than under CT guidance. In one additional subject with a final diagnosis of lung cancer FDG-PET was negative and CT-guided FNAB was positive. In the two final subjects in whom no lung cancer was ultimately diagnosed during the screening period, the FDG-PET was positive and the CT-guided FNAB was negative in one case, and the FDG-PET was negative and the CT-guided FNAB was inconclusive in the other.
Six subjects with final diagnosis of lung cancer did not undergo FDG-PET. Three of them had large cancers (diameter range, 35–48 mm) detected at baseline screening round, for which the protocol enabled direct CT-guided FNAB. Two subjects had cancers appearing as a part-solid nodule with a very small solid component at annual repeat screening rounds, which directly underwent CT-guided FNAB. One final subject had a small peripheral solid nodule at baseline screening, which exhibited significant growth at follow-up, and also directly underwent CT-guided FNAB.
Eight subjects with final diagnosis of lung cancer did not undergo CT-guided FNAB. Five subjects with histological lung malignancy (4 NSCLC and 1 metastasis from renal cancer) had a positive FDG-PET and were directly sent to surgery as well as two subjects with carcinoid who had an indeterminate or negative FDG-PET, and one final subject with metastasis from renal cancer and negative FDG-PET.
Therapy of screen-detected primary lung cancers included surgery (lobectomy n = 29; sublobar resection n = 6; pneumonectomy n = 1) in 34 subjects with lung cancer (30 with NSCLC, 3 with carcinoids, and 1 with both NSCLC and SCLC) alone (n = 29), or in combination with both chemo and radiation therapy (n = 3) or just chemotherapy (n = 2). Six subjects with primary lung cancers did not receive surgery. Two subjects were treated with combined chemo and radiation therapy and four with chemotherapy alone.
Surgical resection for benign lung pathology was carried out in four subjects, corresponding to 10% (4 of 38) of the subjects undergoing surgical resections of lung lesions detected by LDCT screening. Three of them followed violations of the management protocol. In particular, the first subject was referred to surgery without undergoing FDG-PET or CT-guided FNAB because a comparison between the baseline LDCT and a prior chest CT performed for other reasons 2 years before enrolment in the trial showed increase of the mean diameter of a solid nodule from 5 mm to 8 mm. Histological examination revealed hamartocondroma. The second subject showed a new part-solid nodule of 10-mm mean diameter at the last annual repeat screening round, which doubled its diameter at 3-month follow-up LDCT. The lesion was positive to FDG-PET and was surgically removed without preliminary CT-guided FNAB. Surgical pathology failed to identify malignant cells. The third subject underwent surgery for a solid lesion positive to FDG-PET and CT-guided FNAB in the right upper lung, which increased in mean diameter from 6 mm to 9 mm in the last annual repeat screening round, and which on pathological examination was found to be an AC. However, during the same surgical session the thoracic surgeon also decided to resect a purely nonsolid nodule of 10 mm in diameter in the right inferior lobe, which was not previously evaluated with FNAB, and whose pathology showed it to be AAH. The fourth subject underwent surgical removal of a nonsolid nodule that showed an increased diameter from 8 mm to 12 mm mean diameter from baseline to second annual repeat screening round with indeterminate FDG-PET and positive CT-guided FNAB, but the histological diagnosis also in this case was AAH.
Five extrapulmonary malignancies (2 cases of malignant mesothelioma, 1 of primary breast cancer, 1 of primary kidney cancer, and 1 thymoma) were detected in the subjects of the arm undergoing LDCT screening.
Comparative analyses of the recruitment strategies, subjects' compliance, performance of LDCT as screening test, and management protocols for suspicious nodules are fundamental for a thorough evaluation of efficacy and cost effectiveness of the screening procedure of lung cancer with LDCT in at-risk populations and for its standardization. Moreover, they are mandatory before data pooling of RCTs.
Different from all other observational studies12 and several RCTs17,18,21,27 that recruited volunteers in response to advertisements in the media implying a selection bias, we recruited participants to the ITALUNG trial by direct mailing to subjects potentially at high risk of lung cancer because of age and smoking history.20 A similar recruitment procedure was adopted in the Dutch-Belgian Lung Cancer Screening Trial (NELSON) and German trials.19,24 In general, this procedure follows the one used in the Tuscany region of Italy for population screening of breast cancer with mammography, and of colorectal cancer with fecal occult blood test; both involved direct mailing to registered residents. Admittedly, the overall 23.9% adhesion in terms of replies to mail invitation in the ITALUNG trial is lower than the 32% to 33% reported in the NELSON and German trial,19,24 and much lower than that of breast (60–70%)50 and colorectal screening (56%) in Tuscany.51 In our opinion, besides general reasons for nonattendance to cancer screening procedures, including distrust in medicine and screening and a sense of fatality about diseases, two additional reasons for the lower adhesion to the mail invitation in the ITALUNG trial are the unproven efficacy of the LDCT screening at the time of enrollment (2004–2006), and the possibility of being randomized in the control arm receiving usual care. Further information about the experience of the participants to the ITALUNG trial is being collected with follow-up questionnaires.
We observed a high and sustained compliance of the subjects randomized to the active arm, with a 79% proportion of the subjects that completed four annual LDCT rounds. Notably, the greatest drop out (12.8%) in the active arm of our study occurred between the consensus to be randomized and execution of the baseline LDCT, which is similar to what was observed in the Depiscan (12.7%)52 and in the Detection and Screening of Early Lung Cancer by Novel Imaging Technology and Molecular Essays (DANTE) (19%)33 RCTs, but remarkably higher than in the NLST (2.6%)27 and Danish (0.2%)34 RCTs. In our opinion, this phenomenon is presumably because of our study design, in which we first obtained the participant's consent to the randomization and then invited the eligible subjects allocated to the active arm to LDCT testing. In the period between compilation of the questionnaire for eligibility and the date of the LDCT, these subjects might have elaborated their fear and anxiety about the screening procedure, especially after explanation during the preliminary counseling of the screening procedure with LDCT and of the probability of obtaining a false-positive test, which would require further possibly invasive investigations in absence of a lung cancer.12 This detailed information could have the effect of discouraging subjects passively recruited by mail,23 and ultimately determine decline in the test appointment. This mechanism is unlikely to occur in studies recruiting volunteers, and indicates that further investigation is worthwhile to improve the communication with high-risk subjects.
In our study, 90% of the subjects who executed baseline LDCT completed the four screening rounds. The final 79% compliance was higher than those in several observational studies and RCTs,12 but lower than those in the Lung Screening Study (LSS) (84% at the second year),38 NLST (90% at the third year),27 Multicentric Italian Lung Detection (MILD) (95% and 96%),18 and Danish trial (90% at the fifth year),34 which, however, recruited volunteers. The adhesion and compliance rates in the ITALUNG trial might constitute valuable reference terms for future screening programs of lung cancer with LDCT involving population-based invitation (by mail or counseling) of subjects at high risk of lung cancer. In the active arm of the ITALUNG trial we observed a low rate of screen-detected lung cancers, which were mostly represented by ACs in early stages and were surgically resectable. The 1.5% prevalence of screen-detected lung cancers in ITALUNG is substantially in line with those reported in observational studies (range, 0.2%–2.7%)12 and RCTs (range, 0.8%–2.4%)17,18,21,22,24,27,52,53 that recruited elderly heavy smokers and former smokers. Also, the 0.5 mean annual incidence rate of screen-detected lung cancers in ITALUNG is comprised within the range of previous observational studies and RCTs, in which it was consistently lower than 1%.12,13,18,27,33,34,38,53
In ITALUNG AC accounted for 56% of NSCLC at baseline and for 88% of NSCLC at subsequent annual repeat screening rounds. This predominance of AC in screen-detected lung cancers is well established13,18,24,27,34 and presumably reflects the capability of LDCT to show small ACs appearing as peripheral nodules, whereas, detection with LDCT of central tumors developing in the large and medium-size airways, which more frequently correspond to squamous carcinomas, is suboptimal.54
The majority of the screen-detected NSCLC (23 of 35, 66%) in the ITALUNG was in stages IA or IB and with a small and not statistically significant increase of such low-stage cancers from baseline (56%) to subsequent annual repeat (76%) screening rounds. Increase of low-stage cancers in LDCT screening rounds after baseline (stage shift) is considered an indirect element militating in favor of the capability of LDCT screening to efficiently impact on lung cancer mortality, but available data on stage shift in lung cancer screening with LDCT are inconsistent.55,56 The predominance of low-stage NSLCL was observed in all prior observational studies12 and RCTs.18,21,24,38,53 As expected, screen-detected lung cancers in low stages are amenable to surgical resection, and this occurred in 35 of 41 of cancers (85%) in the ITALUNG trial, which again is in line with other observational studies and RCTs.
It is noteworthy that despite the different recruitment strategies mentioned above, the variable schedule of the screening LDCT rounds with a couple of studies offering biennial rather than annual LDCT screening rounds,18,53 and some additional minor differences in the target population (sex, age, or pack-years distribution), in the LDCT acquisition technique (slice collimation ranging between 5 mm17,21 and 0.75 mm18, implying a possible lower sensitivity to small solid and nonsolid nodules in LDCT examinations adopting thicker collimation) and in the criteria of positivity of the screening test (mean diameter of > 4 or > 5 mm and volume > 50 or > 60 mm3 for prevalent solid nodules)17,18,22,36 and nodule management (see below), the yield of the LDCT in terms of rates and types of screen-detected lung cancers is remarkably similar in observational and randomized studies involving elderly heavy smokers and former smokers. The low detection rate for prevalent and especially incident lung cancers are key elements in explaining the high cost/effectiveness ratio of lung cancer screening with LDCT alone.12,18 This clearly indicates that alternative or supplemental strategies for increasing the rates of screen-detected lung cancers with LDCT by improving the selection of the target population are needed. Inclusion of subjects with additional risk factors besides smoking history and age, such as occupational asbestos exposure,57 chronic obstructive pulmonary disease,58 and especially, inclusion of sputum or blood biomarkers40,59,60 in a multidimensional integrated screening strategy should be explored in this context.
In the active arm of the ITALUNG, we observed two interval lung cancers, both in advanced stage, over a screening period of 4 years in 1406 subjects, confirming that the most virulent forms of lung cancer can rarely elude LDCT screening.18,61 Ascertainment, using cancer registry, of interval lung cancer cases in the active arm of ITALUNG trial is still underway. However, the above mentioned low rate of interval cancers apparently seems to support efficacy of the screening procedure in identifying lung cancers.
In ITALUNG, we observed a 30.3% recall rate at baseline LDCT screening test, which almost halved (15.7%) and stabilized at subsequent annual screening rounds. The baseline figures seem higher than the average 20% reported in observational studies and RCTs12 with the exception of three.62–64 This high recall rate might be because of the radiologist learning curve or reflect characteristics of screened population. As a matter of fact, at the end of four annual screening rounds, 52.7% of subjects in the active arm of the ITALUNG were recalled at least once for follow-up LDCT. This high cumulative false-positivity rate is in line with the data in the Mayo Clinic study in which 69% of the participants had at least one false-positive finding over the 5-year program,56 and both substantially match the 21% cumulative probability of one or more false-positive LDCT examinations after one screening and 33% after two, calculated using the Kaplan–Meier analysis.23
Reduction of the numbers of follow-up or recall LDCT would be valuable, and in our opinion, two basic strategies can be hypothesized. The first concerns recent developments in the efforts to radiologically characterize solitary lung lesions, possibly using CT texture analysis.65,66 The second solution entails combination of LDCT with blood or sputum biomarker status, which could independently contribute in identifying subjects with lethal lung cancers appearing as small nodules.40,59
At variance with NLST, in which management of screen-detected suspicious nodules was left to the subject's personal health provider, the members of the ITALUNG trial adopted a shared protocol for management of positive LDCT screening test, which is simple, cheap, and clinically based. In fact, it basically relies on double reading for nodule detection on LDCT and on operator's measurement of mean diameter to assess lesion growth, on visual assessment of FDG-PET uptake of the suspicious nodule, and on CT-guided FNAB with ROSE. Other protocols are more technologically oriented because they are based on adoption of software for nodule volumetry18,36 and computation of the standardized uptake value of FDG-PET,18,36,67–69 and do not include CT-guided FNAB.18,22,67–69 One additional distinguishing feature of the ITALUNG protocol as compared with other observational studies and RCTs is the adoption of antibiotic therapy before 1-month follow-up LDCT, which is expected to decrease the rate of subsequent investigations by revealing the active inflammatory nature, especially of incident nodules.47,70
The main instrument used for management of suspicious nodules in the ITALUNG trial was follow-up LDCT, which accounted for the majority of further investigations, and although associated with additional exposure to low-dose radiation,49 often completed the management. In particular, the 36% rate of total or partial regression after 1 month of antibiotic therapy of prevalent nodules as compared with the 77% rate of total or partial regression of incident nodules in the ITALUNG trial is in line with the 29% disappearance or reduction after 1 month of antibiotic therapy of nodules detected at baseline screening and with the 74% disappearance or reduction of nodules detected at annual repeat by the ELCAP group.70 This is in line with the view that prevalent nodules are frequently scars of benign processes, whereas, incident nodules frequently correspond to active infective or inflammatory processes.
The second most frequently used investigation for nodule management in our study was FDG-PET, which overall was carried out in 6.5% of the subjects randomized to the active arm who underwent baseline LDCT. This frequency of FDG-PET is higher than in other observational studies and RCTs (range, 2%–4.5%).18,27,33,42,68,71 The excess of FDG-PET in our study was related to the high number of FDG-PET examinations performed at baseline (59%), whereas, the mean number of FDG-PET at the subsequent annual repeat LDCT screening round was 13.6%. By assimilating the indeterminate to the positive FDG-PET results, we observed overall 84% sensitivity and 90% specificity, which are substantially in line with those previously reported.37,42,68,69,71
In ITALUNG, 2.4% of subjects randomized to the active arm ultimately had FNAB during the screening cycle (CT-guided in 37 lesions and ultrasound-guided in 1 lesion) as part of their diagnostic workup (38 lesions in 34 subjects). This rate is similar to another LDCT screening studies adopting FNAB as part of the protocol,72 but higher than in the NELSON (< 1 %)53 and German (1.5 %)24 trials. In the majority (89%) of lesions, FNAB was carried out with ROSE, which is associated with lower rate of nondiagnostic results, in our series it was 11%, as compared with FNAB alone.73 The large majority of the subjects (32 of 38) in whom a primary lung cancer was ultimately diagnosed at histological examination underwent preliminary FNAB. If we assimilate the inconclusive to negative FNAB results, we obtained a 90% sensitivity and 88% specificity. These figures are better than those reported both in an LDCT screening program, in which 21% FNAB yielded unsatisfactory results and 12% FNAB were false-positives leading to surgery on benign pathology,72 and in the clinical practice in which the average sensitivity is also 90% but 21% of FNABs produce nondiagnostic results.74 The unique false-positive result of FNAB in our study, which led to surgery for benign pathology was a case of AAH. This is considered a preneoplastic lesion and is indistinguishable on cytological examination from the former category of bronchioloalveolar carcinoma,44,46 which corresponds to the new category of early AC, comprising AC in situ, minimally invasive AC, and lepidic predominant AC.75
In a study the combination of volumetry at follow-up LDCT with FDG-PET improved the sensitivity for diagnosis of lung cancer from 71% (volumetry or FDG-PET alone) to 90% with a decrease of specificity from 91% to 82%.37 In our study the combination of positive FDG-PET and CT-guided FNAB invariably predicted primary or secondary lung malignancy, that is, a 100% sensitivity was reached, and no double false-positive (at FDG-PET and FNAB) was observed. These data, although obtained in a relatively small sample, justify the view that CT-guided FNAB with ROSE is very useful for management of suspicious nodules detected in LDCT lung cancer screening.
The rate of surgical curative therapy in the subjects with screen-detected lung cancer in the ITALUNG trial is in line with previous data,12,18,34 and reflects the early stages of the large majority of the screen-detected lesions.
The 10% rate of surgery for benign lesions in the ITALUNG trial is lower than those reported in the majority of other screening studies, which can be as high as 33%.76 This low rate supports the validity of our management protocol and seems noteworthy, especially if one considers that two of the four cases referred to surgery for benign lesions corresponded to AAH and that in three cases referral to surgery followed protocol violations. Strict adherence to a protocol derived by the clinical routine and including follow-up LDCT with or without 1 month of antibiotic therapy, FDG-PET, and CT-guided FNAB with ROSE is expected to further lessen the rate of surgery for benign lesions in LDCT screening of lung cancer.29
The results of the ITALUNG trial indicate that high-risk subjects recruited by mail to participate in an RCT offering LDCT or usual care for screening of lung cancer show a lower adhesion than subjects invited to undergo other consolidated population-based screening programs such as those for breast or colorectal cancer. However, the adherents randomized to receive four annual LDCTs show a high and sustained compliance throughout the screening cycle.
The low rate of screen-detected lung cancers and the high recall rate in the ITALUNG trial are in line with those of other observational and randomized studies, and confirm that improved definition of target population and maybe integration of the risk stratification with biomarkers are required to increase the cost effectiveness of lung cancer screening programs.
Adoption of a shared protocol for nodule management derived by the clinical routine, including follow-up LDCT (with 1 month after antibiotic therapy) and measurement of nodule mean diameter, visual assessment of FDG-PET, and CT-guided FNAB with ROSE yields high accuracy for preoperative detection of lung malignancies, the few surgical interventions for benign lesions being associated with protocol violations.
The ITALUNG trial was entirely funded by the Health Department of the Tuscany Region, Italy (Decision n. 1014; February 25, 2004).
Cancer; Computed tomography; Nuclear medicine; Pulmonary biopsy
Copyright © 2013 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.
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text: I'm 6'- 230 I ride a TREK here in Northwest ALABAMA, mostly by myself not alot of riders here in hickville. From what I read on here from some of you, hillclimbing is tough on you. Well it's a state of mind over muscle. During warm weather whatever the temp 60- 110, 30-40 miles a day(alot of long hills)at around 20mph average. Riding by myself you have to self motivate. I have certain riders around who I've asked to ride with but the answer is tooo many hills on my rides. The way I look at it, to go downhill you've first got to climb.


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Hill's® Science Diet®
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It's about one-on-one home tutoring techniques. The intention is to make it like a training manual or handbook or simply a reference for my home tutor. He or she can use or select teaching or tutoring tools available - depending on the students needs or learning styles to be more effective in their teaching / tutoring of the students. The scope may probably extend to include the interaction with parents and any other relevant factors.
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I was a professional cyclist. I did make videos on YouTube it's like a self made really show about my life! Now I am a rep for JL Velo awesome cycling gear!
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- Equipment World - http://www.equipmentworld.com -
LiuGong's 915D excavator features smart engineering
Posted By Kerry Clines On September 20, 2012 @ 8:56 am In eRoadPro Newsletter | No Comments
[1]LiuGong says its new 915D excavator boosts work efficiency by 10 percent while reducing fuel consumption by 10 percent when compared to its predecessor. The unit's smart engineering starts with its Computer Aided Power Control System (CAPC), which the company says automatically and continuously matches hydraulic output to the ever-changing workload, delivering the right amount of power needed for each load while metering out the precise amount of fuel. When extra breakout force is needed, the operator can activate the automatic power boost to provide a 10-second power boost of up to 10 percent additional force. The machine's straight-travel function automatically holds the machine in a true line while moving forward.
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text: Publications Search Results Your query returned 1 citations. Results 1 - 1 Per page: 25 50 100 Sort by: Pub Date (newest) Title Recent Additions Author 1 Clear All Pub. Year Citation 2002 Wang, Youfa, Monteiro, Carlos, Popkin, Barry M. Trends of obesity and underweight in older children and adolescents in the United States, Brazil, China, and Russia. American Journal of Clinical Nutrition. 75, (6), 971-977. Full Text Options: Worldcat Google Scholar Export Options: RIS EndNote XML Results 1 - 1 1


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Dog Health Questions? Ask a Dog Vet for Answers ASAP
Tartar in Dogs
What is tartar in dogs?
Tartar in dogs is often known as mineral accumulation that is gathered on the dog's teeth. Tartar may occur above or even below the dog's gums, as well as tartar may become hardened. These accumulations may be easy to see simply because tartar may stain a dog's teeth brown or even yellow. These stains may not actually be on the teeth, but instead on the tartar and this is known as calculus or even buildup. The tartar buildup is different of plaque whereas plaque may often cause bacteria to form on the teeth.
How to remove tartar in dogs?
In order to remove tartar on a dog's teeth there are some common steps that may need to be followed. In the first step, the pet owner will need to brush the dog's teeth with pet tartar control toothpaste whenever possible. When brushing the dog's teeth, the individual may mix a
or beef flavor on the toothpaste so that the dog is more willing to allow the toothpaste in its mouth. Step two would consist of giving the dog canine dental
in order to help clean the tartar off of their teeth. These types of dental treats may be found in biscuits and chews that are edible and help scrape the tartar off. Next, step three the individual may need to give the dog a rawhide chew for what is known as a long lasting treat that also helps clean the dog's teeth. Also, an individual may need to leave a hard chew toy for the dog in order for them to clean their teeth on. These hard dog toys may often help scrub the dog's teeth, however these toys may not be edible. When a dog is experiencing lots of tartar buildup, the individual may often need to change the dog's
to a dental
; and also lowering the amount of canned or even soft
dog food
that the dog consumes. When a dog is eating lots of canned or soft dog food, the soft dog food is not helping remove tartar like harder dog food.
When an individual has noticed that their dog has tartar buildup on their teeth, many questions may arise regarding the tartar treatment, home remedies for tartar removal or what causes tartar on teeth. Read below where Experts have answered many commonly asked questions regarding tartar in dogs.
What can be done to help prevent tartar in dogs?
In order to prevent tartar buildup in dogs there may be three different solutions that can be followed. One would be to change the dog's food to a dental diet, which may often consist of Science Diet T/D
. This type of food does not crack when the dog chews it, so in return the food goes down into the dog's teeth and then helps remove anything on the surface of the teeth. Another solution may be to brush the dog's teeth. There are many different dental kits that can be bought over the counter. Finally, an individual may often be able to use a type of CET oral hygiene rinse.
What is the cost for dental tartar removal in dogs?
In some situations, the cost for dental tartar removal may vary. The price may all depend on where the individual is located, if the individual goes to a vet, or a medical clinic and what type of services are needed to be done. There are some clinics that only charge a couple hundred dollars, whereas other places may charge almost a thousand dollars.
What is an effective way to remove tartar in dogs without having to use dog toothpaste because of the toxic?
However, some individuals may believe that there are
ingredients in a dog's toothpaste; however this may not be the case. In most toothpaste for dogs, this is organic enzymes that are safe for the use on bets and actually helps break down the tartar buildup. The enzymes in the toothpaste may not have to be scrubbed, instead just leaving it on the dog's teeth, may often help remove the tartar. However, in the case the individual is still not convinced, the individual may be able to just simply brush the dog's teeth with a soft toothbrush with warm water, as well as leaving the dog some dental bones to help clean the teeth.
Dental tartar in dogs may be very common. Even though tartar in dogs may be common, the solutions and home remedies may still be unknown to many individuals. For more information pertaining to tartar in dogs as well as the causes, home remedies and treatment, individuals may contact an Expert.
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text:
Imphal-kohima 1942,india and Burma Part Three
The Battle of Imphal-Kohima 1942,India and Burma part three.
Major-General O.WINGATE 1st expedition into burma on foot ,there came a dramatic change in the Japanese thinking due to the pressure excerted by the forceful Mutaguchi whose opinion carried weight in high places. He was impressed by the way in which Wingate had overcome the problems of operating in the wilderness of the mountains,jungle and rivers. He became convinced that given good weather and having adequate preparation an offensive operations on a loarge scale were both desireable and possible. The other factors had bearing the British preparations the airfields the building of roads forward etc. had not gone unnoticed . The Japanese realized that an offensive could not be long delayed. The Japanese know that the Chinese had reorganized and were pressing for an Allied offensive. Morale at home had been deteriorated as the result of the land and sea defeats suffered at the hands of General MacArthur.
The capture of Imphal therefor had much to recommend it in the eyes of the Japanese High Command in Tokyo. It would raise morale among the Japanese people and undoubtedly lead to panic in India. The consequent embarrassment to the Indian Government and also depriving the British of their base. It would rule out any possiblitity of a British offensive into Burma for a long time to come and thereby deal a serious blow to the Allied cause. A series of confrences and much coming and going between Tokyo ,Singapore and Rangoon .The decision to capture Imphal was taken in September 1943.
General KAWABE in command of Burma Area Army a new headquaters introduced to control all operations in Burma. Mutaguchi now promoted to the command of the 15th Army ,prepare plans for Operation U-Go in other words the invasion of MANIPUR. To carry out his task Mutaguchi was alloted the 15th,31st and the 33rd Divisions and the 1st Indian National Army Division. Which was of unknown quality being made up of prisoners of war taken in Singapore and other theatres in the Far East. Nevertheless members of Mutaguchi's own staff who doubted the wisdom of the undertaking on the grounds that the troops available were insufficent and the difficulties of supplying them once across the Chindwin too great.
I hope you all like this story and let me know what you think of it.
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No detail on a Jasmine product is over-looked. All components are
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- Filed Under
The last Second Saturday Art Stroll for 2012 will take place on Saturday, Nov. 10, with a variety of special events throughout the late afternoon and evening.
Participating shops and galleries will be open from 6-10 p.m., unless otherwise noted.
During the afternoon, stop by Threadgoodes on Main St. from 2-4 p.m. to meet White House trained calligrapher Anne Riley and see samples of her work.
Start the evening portion of the stroll at Island Arts on Maddox Boulevard, where Jasmine Seesfar Bogush exhibits her Native American beadwork.
Then head back toward Main St. to visit more shops and galleries.
Get into the holiday spirit by making your own light bulb ornament.
Three shops are participating in a progressive art project to help kids of all ages make their own unique piece of art.
Start at Egret Moon Artworks, next to the Island Theatre, to pick up your bulb and get the creative juices going.
The head to Island Butterfly for more goodies to decorate your bulb.
Finish your ornament at Threadgoodes, where a personalized tags and ribbon will be added to your work of art.
The Art Stroll is sponsored by the Chincoteague Cultural Alliance.
For more information, visit the CCA website at www.ChincoteagueCulturalAlliance.org.


text:
Movie review: "Synecdoche, New York"
Samantha Morton and Philip Seymour Hoffman in "Synecdoche, New York."
Rating: 77
To say that Charlie Kaufman's "Synecdoche, New York" is an encapsulation of human frailty, yearning, love, lust, life and death makes the film sound pretentious and overreaching. But Kaufman, the pop surrealist who wrote "Eternal Sunshine of the Spotless Mind" and "Being John Malkovich," has been building up to this his entire career.
Caden Cotard (Philip Seymour Hoffman) is a 40-ish theater director bound by his own neuroses and mired in an artistic rut, directing "Death of a Salesman" for his Schenectady, N.Y. community theater. His obsessions and psychosomatic illnesses drive his wife Adele (Catherine Keener) away, but not in a melodramatic way. She simply stops respecting him, and chooses to spirit their young daughter Olive away to Berlin, where Adele becomes a famous painter of miniscule portraits and they live with Adele's unstable best friend (Jennifer Jason Leigh).
But then Caden receives a MacArthur Foundation "genius grant," allowing him full reign to create something meaningful with his talents. What transpires is a tremendously ambitious theatrical production in a New York City warehouse in which all the people in his life — his lover Hazel (Samantha Morton), his second wife Claire (Michelle Williams) and everyone around them — are played by actors in an enormous stage resembling the teeming city outside the warehouse walls.
That is the central quirk, the Kaufmanesque essence of "Synecdoche," and at key points the film's "art imitating life imitating art" conceit resembles a snake eating its tail. But this film is not simply an absurdist look at theatrical ambition. Kaufman shows Caden's life in full, a 40-year series of missteps, miscommunications, sad attempts at reconciliation, parental failure, lost love and the end that awaits us all.
"Synecdoche, New York" not an easy film and is likely to be a great polarizer, frustrating some viewers to the point of hatred. And it could take at least two or three viewings for Kaufman's full intent to be felt, but few films dare examine humanity's truths with such bare emotion as this odd, difficult journey through Caden Cotard's "Death of a Salesman" life.


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"What about Bob?"
If that was your burning question entering the latest episode of "The Walking Dead," then you must have walked away satisfied. This week's hour, titled "Alone," was very heavy on Bob Stookey, the former medic and alcoholic newbie on the run with Maggie and Sasha. "Alone" began with Bob, and nearly ended with him — but there was plenty of Daryl and Beth to enjoy as well, if you didn't get enough of them in last week's hour.
As is the case with most "Walking Dead" episodes, "Alone" left us with several burning questions. Seventeen of them, to be precise — and here they are:
1. Where's Wallace? Sorry, I had to.
2. What's Bob's safe word? Clearly, it's not "ow."
3. How awesome does Beth look with a crossbow? Pretty awesome. The Daryl Dixon School of Marksmanship produces strong students!
4. How would you prefer to travel: On Daryl Dixon's motorcycle, or on Daryl Dixon? The choice is obvious here, people. Piggyback, every time.
5. How many people have held Daryl's hand before? Other than Beth, I'm betting not too many, based on what we now know about the bowman's past.
6. What good reason does Sasha have not to go in search of Terminus? I can't think of a one. It makes all the sense in the world to seek out sanctuary, when there are no other leads. I like Sasha, but lord, I just don't understand her thinking sometimes.
7. Did anyone else half-expect Nathaniel Fisher Sr. to pop up with some beyond-the-grave advice in that funeral parlor? Or am I the only "Six Feet Under" fan in the house?
8. Are you getting hungry yet? The "Walking Dead" food catalogue continues to grow! Peanut butter and jelly, diet soda and pig's feet in the funeral home, plus the can of corn Sasha was eating.
9. Would you have ditched Bob and Sasha? Maggie feels she has nothing left to live for, other than Glenn. And she's pretty badass — I think she can handle herself on her own. Still, in these post-apocalyptic times, I think it wiser to stick together, don't you?
10. What do you think of Maggie's penmanship? Pretty smart to leave those blood-painted signs behind for Glenn, don't you think?
11. Would you want a dog in the zombie apocalypse? Pets rule, but you can't control the barking, and barking attracts noise; plus, it's another mouth to feed. Then again, hard to turn down a dog in need…
12. Did I totally call Bob and Sasha hooking up or what? Yeah, I totally did .
13. By the way, I know what I said about Sasha, but what about Bob? Sasha was clearly into the kiss. Why go searching for Maggie instead of sticking with the girl who wants to make kissy face with you from now until the end of the world? (Well, technically, the world already ended; you know what I mean.)
14. Is Maggie's signpost axe the coolest weapon on "Walking Dead" now? It's certainly in the running with Daryl's crossbow and Michonne's katana. Perhaps not as iconic, but still very cool.
15. Do we trust Joe? No. We don't. And right about now, we should be very worried about the company Daryl's keeping.
16. Where did Beth go? She's off on her own in the car, now, without a Dixon to protect her. Can she handle herself? Will she find Maggie's Terminus signs? How will we run into Beth again?
17. When will Glenn and Maggie reunite? Because now that "Terminus" is on Glenn's radar, it's a matter of when, not if. I don't think we'll see them together until the finale, based on the pace of this half-season, but it's inevitable.
Answer our "Walking Dead" burning questions and answer your own in the comments below!


text:
AHS Ladycats vs. Springtown at Aledo;
Varsity, 6:30 p.m.
JV, 5 p.m.
9th, 5 p.m.
From Weatherford Independent School Disctrict
"Notice of Work Session Meeting
The Board of Trustees
Weatherford Independent School District
A Work Session meeting of the Board of Trustees of Weatherford Independent School District will be held August 7, 2012, beginning at 5:00 PM in the Board Room of the District Services Building, 1100 Longhorn Drive, Weatherford, Texas.
The subjects to be discussed or considered or upon which any formal action may be taken are as listed below. Items do not have to be taken in the order shown on this meeting notice.
1. Call to order
2. Work Session
A. Budget Workshop
3. Adjournment
If, during the course of the meeting, discussion of any item on the agenda should be held in a closed meeting, the Board will conduct a closed meeting in accordance with the Texas Open Meetings Act, Government Code, Chapter 551, Subchapters D and E. Before any closed meeting is convened, the presiding officer will publicly identify the section or sections of the Act authorizing the closed meeting. All final votes, actions, or decisions will be taken in open meeting.
The notice for this meeting was posted in compliance with the Texas Open Meeting Act on ____________, at ____________
For the Board of Trustees"
AHS Ladycats vs. Springtown at Aledo;
Varsity, 6:30 p.m.
JV, 5 p.m.
9th, 5 p.m.


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I use and re-use them with jars of fermented vegetables. The lids are good for refrigerator storage. No rust after repeated uses like traditional metal Ball jar lids and rings.
One caution is that these plastic lids are not water-tight. Liquid contents will leak out if jars are tipped over or shaken forcefully.
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"It was the highest doses, well beyond those examined in previous studies, that were most beneficial."
Related quotes
"Life's challenges are not supposed to paralyze you, they're supposed to help you discover who you are."
"If a man carefully examines his thoughts he will be surprised to find how much he lives in the future. His well-being is always ahead. Such a creature is probably immortal."
"Statesmen will invent cheap lies, putting blame upon the nation that is attacked, and every man will be glad of those conscience-soothing falsities, and will diligently study them, and refuse to examine any refutations of them; and thus he will by an"
"The Center for Medicare and Medicaid Services (CMS) should commission rapid studies to examine the impact of formulary restrictions and changes in cost sharing on the use of essential medication and health outcomes."
"Instead of being fired, perhaps he should be studied and examined, much as one might probe the victim of a once-rare psychiatric disorder that has become rampant. Ward Churchill might be more valuable to the opponents of the academic left employed than unemployed. Above all, he can serve as a living window into the intellectual, moral, and political bankruptcy of the left."


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Will this work with no rubbing... If not, 13-27?
Thinking about a 13-14-15-16-17-19-21-23-26-27 or 28 From a stock Centaur 13-26 (removing 18?)
Will this work with no rubbing... If not, 13-27?
Thinking about a 13-14-15-16-17-19-21-23-26-27 or 28 From a stock Centaur 13-26 (removing 18?)
Last edited by pjcampbell; 11-10-10 at 05:20 PM.
The 26 to 27 shift is less than a 4% increase, that hardly seems worth it. Above 25 teeth, 3 tooth jumps always work best for me.
If you go by what people on BF say, anything you have that is not Trek, Specialized, Cannondale or Giant will someday explode next to a school bus full of orphans driven by a nun.
Campy recommends a spread of 15 for the Max. I use a 13 -29 10 spd cassette with a 53/39 on the front without any problems. I have a 13 - 28 (a canadian company sold a 28 tooth for the old EXA cassette) on an older campy 8 speed short cage with no problem either.
You use a 13-29 with no problems on a short derailleur?
I am undecided about 27t or 28t. If 28t fits, I will go for it. I did a quick estimate and we are talking about 74RPM, 77RPM and 80RPM at around 12% for 26t, 27t and 28t at my race pace.
Sorry it's a 10 speed Record rear derailleur. It says:
Largest Cog26teethChain Wrap Capacity27teeth
Not sure what chain wrap capacity is vs largest cog.
I have a compact in the front 34/50, also Campy Record, and I would like to throw in a Miche 28t back there if it is not going to cause problems. Obviously may have to make adjustments and/or increase chain length but I am more talking about the cog hitting the pulleys versus minor adjustments.
Last edited by pjcampbell; 11-11-10 at 07:02 AM.
Chain wrap capacity is a completely different issue. Keep in mind, a rear derailleur has two main functions: move the chain from cog to cog, and keep the chain tensioned properly. The chain tension function works because of the spring action of the cage, which allows the derailleur to keep steady tension on the chain even as the chain moves from cog to cog or from chainring to chainring up front. In other words, it "wraps" the excess chain, and a derailleur can only wrap so much; this is known as it's chain wrap capacity. The longer a derailleur's cage, the more chain it can "wrap." A drivetrain has a maximum chainwrap requirement, and to insure that the chain will remain tensioned properly in all possible gear combos, you need a derailleur that has enough chain wrap capacity to meet the maximum chainwrap requirement of the drivetrain.
A simple formula is used to determine a drivetrain's max. chain wrap requirement: Largest chainring minus smallest chainring plus largest cog minus smallest cog equals max. chainwrap requirement. Example: 53-39+28-11=31. So a drivetrain with a 53/39 crankset combined with a 11 x 28 cassette would need a derailleur with a chainwrap capacity of 31 teeth. This assumes the chain is sized so that it is only as long as necessary to safely cover the big ring/largest cog combo.
ALWAYS size your chain at least long enough to cover the big/big combo; the results can be catastrophic if it will not and you shift to this combo. On the other end, smallest chainring/ smallest cog, a little slack in the chain is not nearly as big a concern; of course you shouldn't be in this combo anyway, so if you're going to use a deraiilleur with not quite enough chainwrap capacity for your drivetrain, make sure the chain's long enough to cover big/big and try to avoid small chainring/smallest cog or two.
Last edited by well biked; 11-11-10 at 09:21 AM.
Campy under rates the short cage RD's actual wrap capacity. The 27T value is just the maximum difference between the cogs and chainrings, sold at that time. The same RD that was once said to have only a 27T wrap was able to wrap a 50/34 with a 12-25 (29T) after compact cranks came out.
Some people get by using a short cage with a 53/39 and 13-29, but it does not have the wrap capacity for a 50/34 with a 13-28 or 13-29 on all bikes. You really need a medium cage RD.
One thing that is rarely considered is that chainstay length affects the wrap capacity. The perfect chainstay length can add up to 3T of wrap compared to the worst case. Go to the Park tool website and plug the proper numbers in the rigorous chain length formula to find what chain length is required for your setup. If you get a length like 53.25 inches, you have to use 54 inches and that's a worst case. If the number is just under a whole inch value, like 53 or 54 inches, then you have a best case, using every bit of chain available.
FWIW, the current 11 speed short cage RD can handle a 50/34 with a 12-29, but that required a different B screw mechanism to swing the upper pulley further back to clear the 29T cog. Only 2010 and newer RDs have that.
Last edited by DaveSSS; 11-11-10 at 05:20 PM.
my chain stay length came up with like 53.89 or something
50-34+28-13 = 31.
I guess I can try the 28t and see what happens.
Last edited by pjcampbell; 11-12-10 at 05:10 AM.


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Don't ever say no to the Black Man. Ever.
looks like it feels good
great video - would lovev to get gang banged like that guy....
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very lucky bottom cheers
love that you don't stop despite his moaning. Wished he was handcuffed while doing that to him


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About This Activity
This class is an early childhood program that will teach the basic fundamentals of Tae-Kwon-Do and Karate. This class will focus on building self-respect, self-confidence, coordination of mind and body and self-discipline.(Must be 4 or 5) Students must sign up on or before the first class of each session.


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text:
Bernanke: Financial Crisis Era Execs Should've Been Fitted For Orange Jumpsuits
The former Federal Reserve chairman wouldn't have gotten involved in the handcuffing but he *would* have happily watched from a squad car as, for example, a guy whose name rhymes with Mick Tuld was escorted from his home.
Uber Better Rethink Posting Bail For Their Jailed French Executives
Uber better stop playing "Poulet" with French regulators if it's going to keep spending money like a Greek.
McKesson, Blue Cross top digital health's most trusted corporate VCs
Corporate venture capital has begun to rival "traditional" venture capital and angel investing in its importance as an investment source for healthcare industry innovation. However, unlike VCs and angels, there is a dearth of information on how the various players in the corporate venture sector operate.
Brian Dalton
Local Man Who Could Have Avoided Jail: Jail Is Best Avoided
Michael Kimelman learned this the hard way.
Dennis Kozlowski 'Bout Ready To Print Up New Business Cards
The ex-con has plans to run an M&A consulting shop, if you know anyone who's interested.
Emma Thompson's Husband, Emma Thompson Not Going To Pay More Taxes 'Til HSBC "Evil Bastards" Go To Prison
You hear that, Stu Gulliver?
25 Year Old Who Spent Six-Figures On Single Bottle Of Champagne Going Away For A While
Attention, UK nightclub owners: put your bottle of bubbly on ice. Alex Pope, the Brit […]
Hedge Fund Manager Who Loved Teddy Bears More Than Freedom Sentenced To Decade In Prison
Remember Paul Greenwood? Hedge fund manager convicted a while back of running a thirteen year […]
Unfortunately, this is a business, not pleasure trip: yesterday marked Day 1 of 3,285 of […]
Banker Who Faked His Own Death Fielding Hedge Fund Jobs Offers Left And Right, Says Banker Who Faked His Own Death
Remember Aubrey Lee Price? Georgian banker who screwed investors out of millions, faked his own […]
Investment banking continues to be a laborious, tedious practice. Banks are implementing ways to boost […]
It's Now An Extra Good Idea Not To Insider Trade
If the previous odds of a considerable stay in jail didn't deter you before…
SAC Capital Alum Will Do 9 Years For Trading On Material Non-Public Information
Mathew Martoma, he of the "most lucrative insider-trading scheme in history" Martomas, is going to […]
Mathew Martoma Is Still Going To Jail
Despite his lawyer's arguments that 1) The government's key witness can't be trusted and 2) […]
Raj Rajaratnam May Have Compensated A Few Prisoners To Keep Himself In The Lifestyle He'd Grown Accustomed To
Last August, a report came out claiming that Raj Rajaratnam was having the time of […]
Disguising Insider Trading With Phrases Like "Fat Man Has A Friend" And "The Fat Man Walks Alone" Not As Airtight A Plan As Once Thought
Remember the group of old high school buddies, who put Colonia High Class of '88 […]
Civil Penalty Watch '14: Rajat Gupta
Ex-Goldman Sachs board member Rajat Gupta reported to prison earlier today for, among other things, […]
Raj Rajaratnam's 23-Second Man Reporting To Prison Next Month
Rajat Gupta, the Goldman Sachs director who waited but 23 seconds after a Goldman board […]
Close Working Relationship With Bernie Madoff Apparently Not Such A Great Thing
Five former aides to Bernard Madoff who spent decades working for his firm were found […]
SAC's Steinberg Is Going To Prison
This probably does not come as any more of a surprise to him than it […]
Who Among Us Wouldn't Listen To A Guy Pitch An Investment Involving "Pay-Per-View Programming Starring Carmen Electra" And Proceed To Wire Him $195,000?
For one Maine couple, the allure of James Philbrook's pitch proved too irresistible. In fairness […]
Raj Rajaratnam's Prison Party Train Keeps On Rollin'
If various sources are to be believed, Raj Rajaratnam is having the time of his […]
Jordan "Wolf Of Wall Street" Belfort Had A Pretty Nice Little Set Up In Prison
He reported to a federal prison camp in Taft, Calif., in 2004. It was during […]
Raj Rajaratnam Not Leaving The Big House Anytime Soon
On the one hand, it'd be hard to argue that the former hedge fund manager […]
Justice Department Agrees To Let Jeff Skilling Out Early So They Never Have To Hear From Him Again
One of the country's most notorious financial scandals came to a protracted legal conclusion Friday […]
"One of the Great Ones" Is Getting Out Of Jail, Will Be Available For Financial Consulting Work Come June 16
That's, right, everyone: while you're celebrating Father's Day this Sunday, take some time to raise […]
For many people, prison is a terrible place that breaks their spirit and turns them […]
Life is terribly unfair. You help bring down Raj Rajaratnam and get yelled at by a defense lawyer during another insider-trading trial, but you tell a few white lies, destroy some evidence, warn some of your friends—including the only fugitive in the whole insider-trading crackdown—that the Feds are on to them and perjure yourself a little, and you don't get to get away with your second insider-trading conviction.
Turkey Offers Two Options For People With Nothing Nice To Say About Its Capital Markets
Option A: shut the hell up. Option B: spend time in prison.
CEO Sentenced To 50 Years In Prison For Defrauding Investors Wishes He'd Made His Intent To Screw Them A Bit More Clear, In Retrospect
Timothy S. Durham, the onetime chief executive officer of National Lampoon Inc., was sentenced to […]


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"Best Brazilian Jazz Guitarist in U.S."
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