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Esta 5ª edição do estudo analisa os esforços realizados em mais de 60 países para promover a diversidade de género nos conselhos de administração.


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News Feed
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Transparency is essential for public confidence in government. Good government is dependent upon good administration. I believe and stand for policies that ensure that the same values our city council operates by are the same values held by Lakewood residents. Transparency should allow our residents to fully understand and be included in the decision-making process, know how tax dollars are being spent and have the opportunity to hold council accountable. I support, and will work to pass ethics, campaign finance and public records legislation that have already been introduced.
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The health and safety of our residents, children and our first responders are a priority for me. Our police, fire, EMS and dispatch face unimaginable challenges serving and protecting our citizens every day. They deserve all of our respect and our support. They also deserve support from our representatives on council. We need to make sure we allocate resources to provide full, affordable health care coverage that is inclusive of mental health support to treat PTSD during the line of duty, as well as expand our emergency dispatch department. I will never vote to regionalize our emergency dispatch. In an emergency, one minute lost to transferring calls is too long. We must commit to keeping our families safe.


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Prostate Cancer
Volume 2015, Article ID 624736, 11 pages
Systematic Review of the Relationship between Acute and Late Gastrointestinal Toxicity after Radiotherapy for Prostate Cancer
1Department of Radiation Oncology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA
2Department of Radiation Oncology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY 10467, USA
Received 1 October 2015; Accepted 15 November 2015
Academic Editor: Robert Gardiner
Copyright © 2015 Matthew Sean Peach et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A small but meaningful percentage of men who are treated with external beam radiation therapy for prostate cancer will develop late gastrointestinal toxicity. While numerous strategies to prevent gastrointestinal injury have been studied, clinical trials concentrating on late toxicity have been difficult to carry out. Identification of subjects at high risk for late gastrointestinal injury could allow toxicity prevention trials to be performed using reasonable sample sizes. Acute radiation therapy toxicity has been shown to predict late toxicity in several organ systems. Late toxicities may occur as a consequential effect of acute injury. In this systematic review of published reports, we found that late gastrointestinal toxicity following prostate radiotherapy seems to be statistically and potentially causally related to acute gastrointestinal morbidity as a consequential effect. We submit that acute gastrointestinal toxicity may be used to identify at-risk patients who may benefit from additional attention for medical interventions and close follow-up to prevent late toxicity. Acute gastrointestinal toxicity could also be explored as a surrogate endpoint for late effects in prospective trials.
1. Introduction
Prostate cancer is the most commonly diagnosed noncutaneous malignancy in men in developed countries. Definitive external beam radiotherapy (RT) is a treatment option for the majority of patients who present with localized disease. Additionally, RT may be offered after radical prostatectomy for patients whose pathology demonstrates adverse pathologic features or as salvage therapy for recurrent disease after surgery.
Regardless of the treatment technique used, RT for prostate cancer exposes a portion of the lower gastrointestinal (GI) tract to ionizing radiation and consequently carries a risk of GI toxicity. GI toxicity is categorized as occurring within two possible phases: acute (typically within 3 months of treatment) and late (more than 3 months after treatment) [1, 2]. Symptoms can range from a mild increase in bowel movement frequency to more severe complications such as rectal bleeding, pain, or fistula. The acute phase of RT injury is characterized by inflammation in response to therapy, while the late phase is characterized by fibrosis and sclerosis within the GI tract [3]. While mild to moderate acute GI toxicity is more common than late toxicity, the potential permanent impact of late GI toxicity is thought to bear more clinical significance.
In an analysis of 35 studies including nearly 12,000 patients, rates of moderate (generally grade ≥ 2) and severe (grade ≥ 3) late GI toxicity following definitive external beam RT for prostate cancer were 15% and 2%, respectively [4]. Dose-escalated RT, which has been shown to improve disease control rates [5] and is now standard of care, increases the risk of late GI toxicity [4–7]. Reported rates of late GI toxicity appear to be decreased when dose-escalated RT is delivered using advanced treatment techniques such as intensity-modulated radiotherapy (IMRT) [4]. Other measures to limit GI toxicity, such as the administration of radioprotective medications [8] or the use of spacers to separate the prostate and rectum [9], are being explored. Randomized clinical trials, with large numbers of patients and lengthy follow-up, will be required to establish the efficacy of these toxicity prevention strategies.
There may be a consequential relationship between temporary acute GI toxicity and permanent late GI toxicity in prostate cancer patients treated with RT [10]. In this paper, we perform a systematic review to characterize the relationship between acute and late GI complications from prostate RT. We detail mechanisms by which acute toxicity may lead to consequential late effects. Finally, we explore the possibility of exploiting this connection for the identification of patients at risk of late GI toxicity and for the development of novel clinical trials for toxicity prevention.
2. Methods
2.1. Study Selection
We searched PubMed (http://www.ncbi.nlm.nih.gov/pubmed/) on May 1, 2013, for the terms "radiation therapy", "late", "early", and "side effects", with no limits placed on publication date. Duplicates and non-English language articles were excluded, and abstracts of all remaining manuscripts were read. Articles focusing on acute and late toxicity from external beam RT for prostate cancer were selected and examined in detail. Studies that examined the potential relationship between acute and late GI sequelae prostate RT were included in the final analysis. When two reports seemed to describe overlapping patient populations, the most recent publication was utilized for this analysis.
2.2. Data Extraction and Clinical Endpoints
Data abstraction was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement [11]. For each study, the following information was extracted: name of the first author, year of publication, name of the clinical trial (if applicable), sample size, and RT protocol. The primary measure of interest for this analysis was the association between late GI toxicity and acute GI toxicity. Hazard ratios, risk ratios, correlation coefficients, and other statistical measures describing the relationship between acute and late GI toxicity were extracted. Our preliminary analysis indicated that available data were not appropriate for meta-analysis, so we proceeded to perform a PRISMA-style systematic review.
3. Results
3.1. Study Selection
Search results are summarized in Figure 1. Our initial search yielded 266 results. Removal of duplicates and non-English language manuscripts reduced this number to 246. 109 papers met initial eligibility criteria and were read at full length to determine if statistical tests for a link between acute and late GI toxicity were reported. Most of the papers were eliminated for merely reporting rates of acute and/or late GI toxicity in the study population. Others were excluded because they combined GI and genitourinary effects in their analyses. Three papers described patient populations that were likely included in subsequent reports from the same institutions. In total, 19 manuscripts met all eligibility requirements and were included in this report.
Ten manuscripts reported results from prospective trials [12–21] (Table 1), and nine were retrospective reviews of institutional experiences or databases [22–30] (Table 2). The trials that examined acute and late side effects involved a variety of techniques including conventional prostate RT [19], 3D conformal RT (3DCRT) [14, 15, 17, 24, 25, 30], high dose intensity modulated RT (IMRT) [27], hypofractionated IMRT [20, 23], combination brachytherapy + IMRT [29], and a mixed population treated with IMRT and 3DCRT [28]. Comparisons were also made in the manuscripts between different techniques including 3DCRT versus conventional RT [18]; 3DCRT dose escalation versus standard dose RT [12, 21]; 3DCRT versus hypofractionated 3DCRT [13]; a varied experience of 3DCRT and conventional RT ± ADT [22]; high dose IMRT versus high dose 3DCRT [26]; and high dose IMRT ± whole pelvis RT [16] (Table 1). The primary objective of most papers was to examine clinical factors leading to the development of acute GI and late GI toxicity [12–14, 16–18, 22, 28, 30], while some specifically focused on the relationship between acute and late side effects [14, 19, 21, 30]. The goal of other manuscripts was to simply report acute and late effects of a particular treatment [15, 20, 21, 23–27, 29]. Some of these studies tested medications to decrease toxicity, including rectal prostaglandin administration [15] and rectal sucralfate [19].
3.2. Evidence of Association between Acute and Late GI Toxicity
The manuscripts specifically looking for associations between acute and late effects demonstrated mild to strong correlations in various aspects of GI toxicity. Pinkawa et al. reported that acute bowel bothersome scores were associated with poor long-term bowel bothersome scores on univariate analysis, although with a HR of only 1.05; this relationship was not statistically significant in a multivariate analysis that accounted for RT dose and volume parameters [14]. Moderate to strong associations were found between multiple aspects of acute and late GI toxicity by Heemsbergen et al., where multivariable analysis suggested minimal contribution of RT dose and volume effects [21]. Acute proctitis was strongly (HR 2.9) associated with long-term diarrhea, defined as ≥6 stools a day. Acute mucosal discharge was predictive of later use of incontinence pads (HR 2.1). Interestingly, the authors note that more objective factors of GI toxicity such as bleeding not included in RTOG had a stronger correlation. This suggests that a different scoring scheme may better demonstrate consequential GI toxicity relationships [21]. Perhaps the strongest evidence of this relationship came from O'Brien et al., who found that grade ≥2 acute rectal pain was associated with grade ≥2 late rectal toxicity with a HR of 3.4 [19]. However this manuscript did not examine dosimetric parameters, so observations were not adjusted for potential RT dose-volume interactions.
The strongest findings attesting to the relationship of acute and late GI toxicity came from manuscripts not primarily interested in determining this effect. Zelefsky et al., while specifically looking at late toxicity response to 3DCRT dose escalation in 1571 participants, found that acute grade ≥2 GI toxicity was a strong predictor of late grade ≥2 GI toxicity (HR 6.95, ). There was little contribution from dosimetric factors on multivariate analysis [28]. A similarly strong relationship was found between acute grade ≥2 proctitis and late grade ≥1 GI toxicity (OR 6.05, ) in a trial looking at the effect of misoprostol suppository on late rectal toxicity following 3DCRT [15]. Further, multivariate examination of late GI toxicity in over 100 patients subjected to high dose 3DCRT demonstrated that grade ≥2 acute fecal incontinence was associated with chronic/late grade ≥2 fecal incontinence (OR 4.43, ) and a stronger relationship for acute grade 3 fecal incontinence (OR 6.9, ) [17]. Of the remaining papers, most of the correlations were mild to moderate or were not significant once placed in multivariate analysis with dosimetric considerations (Tables 1 and 2).
3.3. Mechanism for Associations
With some exceptions [13, 18, 19, 21, 30], most of the manuscripts that demonstrated an association between acute and late toxicities did not delve into the mechanism behind their findings. Koper et al. briefly discussed that their findings were most likely the result of consequential effects [18], namely, that acute toxicity leads to inflammation, leading to leakage of intestinal contents and eventual fibrosis manifesting as late toxicity. Alternatively, Arcangeli et al. concluded that the association between acute and late toxicity was evidence for a consequential mechanism but instead was a result of shared dosimetric risk factors. Interestingly, the association between acute and late effects observed in their conventionally fractionated RT arm was not observed in their hypofractionated RT arm [13].
Complementing their thorough data analysis, Heemsbergen et al. provided a more comprehensive explanation of the observed relationship between acute and late toxicity [21]. The authors put forth two possible mechanisms: the first a simple dose-volume relationship, and the second a continuum of consequential damage as has been observed in animal models [31]. In the former mechanism, severity of acute and late GI toxicity may correlate due to independent dose-volume effects on the RT at each time frame. Having the benefit of a large patient population, adequate follow-up, and uniform characterization of acute and late toxicity, the authors found on multivariate analysis that acute toxicity remained independently associated with late effects after adjusting for dosimetric variables and concluded that the relationship was most likely a combination of consequential effects and some dose volume effects. Of note, the group indicated that the acute RTOG score was not the most correlative factor; rather, tracking of individual GI symptoms was more revealing of the consequential pattern [21].
Heemsbergen indicated that other studies looking at acute-late correlation suffered from a lack of dose-volume considerations in their analysis [21]. This included the work of O'Brien et al. whose authors concede to not including dosimetric data but attest to dose-volume effects not contributing to acute toxicity in another study of a similar population and technique [19]. Koper et al. [18] offer alternative explanations to the observed correlation including inherent properties in individuals, such as yet described genetics or comorbidities that lead to greater tissue sensitivity to radiation both acutely and chronically. A different explanation offered by Heemsbergen et al. is that some patients are more likely to communicate their symptoms and thus will verbalize both acute and late side effects alike [21]. However, the authors felt this theory was unlikely, as more objective findings such as acute and late rectal bleeding demonstrated strong associations [21]. The article by Jereczek-Fossa et al. was the most recent manuscript to thoroughly expand upon a proposed mechanism behind their demonstrated acute-late GI toxicity association [30]. The group believed, given the lack of prostate dose influence on late toxicity in a cohort of nearly 100 patients, that the association stemmed from consequential effects initiated by damage to the GI mucosa in the acute phase, citing works looking at consequential rectal toxicity in cervical cancer. Additionally, the authors asserted that age factored into the development of consequential damage when applied to multivariable analysis, in particular affecting acute toxicity as a result of comorbidities or an indirect effect of treatment decision-making [30].
Although not identified in the literature review, we are aware of the work by Campostrini et al. that showed more robust evidence of pathological consequential toxicity in humans [32]. Their group followed the progress of 130 patients from immediately after prostate RT and throughout the late period endoscopically (median follow-up of 84 months). It was noted that acute damage affected both the rectum and the anal canal macroscopically, with the most notable finding of hemorrhoid congestion, which was a major contributor to acute rectal bleeding. Interestingly, two patients had acute proctoscopic findings that were not manifested clinically. The finding of clinical and/or proctoscopic acute proctitis was strongly predictive of late toxicity (HR 5.6. 95% CI 2.1–15.2, ) on multivariate analysis that incorporated dosimetric parameters [32].
3.4. Difficulties in Reporting the Correlation between Acute and Late Toxicities
Some of the authors of the manuscripts that did not observe a correlation between acute and late toxicities commented on the lack of findings, when viewed from the perspective of contradictory findings. Ballar et al. attributed the observed lack of correlation to a lower than normal acute toxicity found in their particular study compared to others [25]. Similarly, Zelefesky and colleagues manuscript did not identify a relationship between acute and late toxicities after combination brachytherapy and external beam RT, and they stated that this was likely due to fewer acute and late side effects than found in most similar studies [29]. Likewise, some manuscripts that did observe a relationship between acute and late toxicities also indicated potential study shortcomings that would underestimate the true consequential effect, such as short follow-up and newer RT techniques including IMRT that may cause less severe toxicity in both the acute and late setting [30]. Jereczek-Fossa et al. also noted that retrospective studies may suffer from underreported acute and late GI toxicity rates, complicated by the complexity of reporting late term side effects in prostate RT [30]. It has also been suggested that physician-based toxicity scoring, rather than patient-directed assessments, may introduce significant reporting bias [23].
4. Discussion
4.1. Acute Toxicity Is Predictive of Late Toxicity
The heterogeneity of the available data precludes quantitative synthesis in a formal meta-analysis, but we believe that the findings from this review shed significant light on the relationship between acute and late GI complications from prostate RT. Thirteen of the 19 studies that met inclusion criteria demonstrated an association between acute and late complications. Reports where no such associations were found tended to have a significantly smaller sample size than "positive" studies. Restricting our analysis to series with at least 200 subjects, for example, would leave nine remaining studies, all of which report a statistically significant link between acute and late complications. We therefore conclude that the overwhelming majority of the published evidence supports the presence of an association between acute and late GI toxicity following RT for prostate cancer.
Campostrini et al. provided strong evidence of pathologically confirmed acute toxicity as a significant predictor of late GI toxicity, even when dosimetric parameters as well as RT technique are taken into account. These findings are further bolstered by animal studies showing a stepwise pathologic progression from acute to late effects [33, 34]. Therefore, the trends found in this systematic review of clinical studies, combined with observations from animal models, support a second important conclusion: acute toxicity may serve as an appropriate surrogate for late GI toxicity as a way to identify patients at high risk of developing permanent late GI toxicity, potentially for clinical trials of novel therapies intended to prevent development of consequential late GI toxicity, and as a surrogate endpoint for clinical trials.
4.2. Significance of Consequential Effect for Research
Since clinically significant late GI toxicity occurs in a minority of patients, clinical trials of medical interventions designed to prevent GI toxicity after prostate RT may require an excessively large sample size, if the trial designs are such that any prostate RT patient is eligible. However, establishing a consequential relationship between acute and late GI toxicity presents the opportunity to develop more efficient trial designs by focusing on a high-risk population. If acute GI toxicity is used as an eligibility criterion, which would restrict the study population to those at highest risk of late GI toxicity, a candidate medical intervention could be studied in clinical trial with a higher likelihood of identifying an effective strategy to reduce late GI toxicity. For example, if the study population has a 40% risk of late GI toxicity after IMRT (based on including only patients with significant acute toxicity), then a randomized, controlled trial of intervention versus placebo with a sample size of just 100 subjects would have 71% power to detect a 50% reduction in late toxicity events (personal communication, Nolan Wages, Ph.D.). If the baseline toxicity risk was 10% and all other parameters were unchanged, the study would only have a power of 25%. Notably, this hypothetical example is potentially realistic, based on the available evidence identified in this report: assuming a 15% average risk of grade 2 or higher late GI toxicity [4] and a three- to sixfold increase in rates of late GI toxicity among patients with grade 2 or higher acute GI toxicity [19, 21, 28], the risk of late toxicity among those patients with acute toxicity would be at least 40% and likely much higher.
The consequential nature of GI toxicity could be therefore exploited in research trials looking at interventions to avoid late toxicity in a number of ways:(1)In future studies, acute toxicity may be used as a surrogate endpoint for late toxicity. This could decrease the duration and sample size required for prospective trials.(2)Patients who demonstrate acute toxicity can be selected for long-term studies of late toxicity.(3)Previously treated cohorts for which acute toxicity data are recorded can be assessed selectively for late toxicity, sampling only those patients who demonstrated acute GI toxicity.
4.3. Future Potential Studies: Pharmacological
With the above study framework, there are a number of pharmacological and nonpharmacological interventions than can be explored, some of which have already demonstrated the ability to prevent GI toxicity in pelvic radiation. This topic has been detailed in several recent reviews [35–37]. In regard to pharmacological interventions, the Cochrane review by Ali and Habib best summarizes the available options including such interventions as aminosalicylic acid (ASA) derivatives, sucralfate, arginine, vitamin E, probiotics, misoprostol, short chain fatty acid enemas, corticosteroids, cholestyramine, vitamin A, estrogen/progesterone, and octreotide [38]. Highlights from that review included manuscripts demonstrating the prevention of acute GI toxicity with oral sulphasalazine in prostate RT [39], as well as a decrease in acute and late GI toxicity when oral sucralfate is applied during and after RT for prostate and bladder cancer [40]. However, the previously cited work [19] and an earlier manuscript [41] by O'Brien et al. counter these findings when sucralfate is applied as a suppository during prostate RT in studies of similar size. Lastly, Ali and Habib referenced a small study showing that misoprostol suppositories applied before prostate external beam RT had protective properties [38]. Again, works encountered in this systematic review with larger numbers of participants did not find any benefit of misoprostol suppositories in the acute and late term [15].
There are other promising potential pharmacological compounds for preventing GI toxicity during pelvic RT. In regard to ASA derivatives, patients randomized to oral balsalazide during prostate RT achieved a CTC v2.0 prostate index of 35.3 versus 74.1 in placebo at two weeks after therapy () [42]. However, a trial arm examining the rectal application of the ASA derivative mesalazine was prematurely terminated because of increased acute toxicity during prostrate 3DCRT in comparison to sucralfate enema control (HR 2.5, 95% CI 1.1–5.7, and ) [43]. In the same study, no difference was found between sucralfate enema and hydrocortisone enema in preventing acute rectal toxicity [43]. Intrarectal application of the steroid beclomethasone in a more recent placebo controlled study did demonstrate an improved irritable bowel disease quality of life index, less rectal bleeding, and superior Vienna Rectoscopy Score up to 12 months following prostate RT [44]. Hyaluronic acid suppositories have also demonstrated the ability to decrease and delay acute radiation proctitis, according to RTOG scoring, when compared to historical prostate RT controls [45].
The free radical scavenger amifostine, when administered regularly during RT, has shown great potential in preventing acute rectal toxicity. In a randomized trial of 36 patients undergoing a mix of pelvic RT, intrarectal amifostine resulted in a significant decrease in RTOG score (), a decrease in LENT-SOMA score (), and improved proctoscopic tissue examination compared to controls [46]. More recent work has shown that increasing the dose of amifostine results in greater reduction of GI toxicity as determined by the EPIC bowel bothersome score during treatment and at 12 months after external prostate RT [47]. Lastly, the feasibility of rectal injections of Botox as a preventative measure against acute rectal toxicity has recently been studied based on Botox's effect on muscle spasticity, with future efficacy trials planned [48]. In total, there are a great deal more pharmaceutical compounds that have shown success in treating acute GI toxicity than treating late GI toxicity or preventing acute or late GI toxicity. Reassessment of some of these compounds as outlined above may be able to tease out greater usefulness in the above and other compounds.
4.4. Future Studies: Nonpharmacological
In regard to nonpharmacological strategies to prevent GI toxicity from pelvic RT, rectal balloons have been studied for a number of years and are used routinely in some practices, particularly in proton beam RT. However, there appears to be only one small work to show decreased late GI toxicity, compared to treatment without a rectal balloon, as determined by proctoscopic assessment at two-year follow-up [49]. Rectal balloons have shown good patient compliance and tolerance [50]. The use of injectable spacers is an alternative approach that creates space between the prostate target volume and the rectum. For example, prospective evaluation with a polyethylene glycol hydrogel spacer in small study of 10 patients demonstrated very low acute GI toxicity. [51]. Collagen injections have also been used to increase prostate-rectal distance, resulting in a 50% decrease in the RT dose to the rectum [52]. Recently, a hybrid idea that in simulation appears to function well is the biodegradable interstitial balloon [53]. In comparison to some of the pharmacologically based preventative measures, studies of spacer interventions are for the most part lacking assessment on late term effects and would greatly benefit from study designs where acute toxicity was applied as a surrogate for late toxicity or used for patient selection in long-term trials.
5. Conclusions
Published data strongly support the presence of an association between acute and late GI toxicity following RT for prostate cancer. We suggest that acute GI toxicity may be used by physicians to identify patients who may benefit from personalized counseling and supportive care to address a high risk of permanent late GI toxicity. Furthermore, trials of strategies to prevent late morbidity might be enhanced by the preferential enrollment of subjects who develop acute toxicity in order to evaluate potential preventive strategies in a cohort of patients at high risk of late toxicity.
Conflict of Interests
The authors have no conflict of interests to report.
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Do you need to purchase quality safety equipment or hire any security services? Get to know the best safety services in India
As we do at home by installing security systems, we need to procure safety everywhere else since nobody knows when something may go wrong. There are different occasions and events when safety procedures take a vital importance, like when we organise an event full of people, if dangerous materials are handled and we need to provide safety in the workplace or when young children are involved, for example.
Every situation is different and, as a result, a specific safety plan is needed. Whatever your company is about, a health and safety policy must be followed at every time in order to prevent all kind of danger and damages, including material and personal loses. This task needs to be carefully carried, and it is better when the company counts on a professional safety manager who is able to perfectly study and understand risks, design a safety plan and set down safety rules for everybody to follow. As important is to set them down as letting everybody know them.
Fire safety, and other emergency plans involving health aids are just few of the many concerns that a good safety officer must be able to manage.
Luckily, there are plenty of companies offering the best safety services in India and counting with professionals that will provide you with everything you need, from safety tips to equipment like safety glasses or helmets.
Discover the best ones thanks to the Infoisinfo directory.
How to find the best safety services in India
At Infoisinfo we always work hard to be able to offer you the most useful information so that you can easily find the best products and services for you and your company in India. We want you to feel secure everywhere and make you able to guarantee safety at every event your company organise. For this reason, we have prepared a list of the best safety services in India among which you could spot from safety clothing to security guard services, for example.
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The 10 Best Safety Services in India
1 - ASHEI- NEBOSH IOSH, Safety Training Institute - Kochi
1st Floor, Suprans Arcade, Aiswarya Road, Palarivattom, Kochi-25, Kochi. Kochi. Ernakulam.
IDIP OSH| NEBOSH IGC| HSW| IOSH| ISO 45001| IADC| MEDIC FIRST AID| H2S| EMS @ ASHEI KOCHI Contact:9745126655,9447609617 Safety Training InstituteAnil Menon's Safety Health and…
2 - Indusuno.com - Gurgaon
Plot No. 122, Near Artemis Hospital, Sector 51. Gurgaon. Gurgaon.
Indusuno.com is an online marketplace for buying and selling industrial equipment, and business goods and supplies. We have the largest product catalog in B2B e-commerce space in India.…
3 - Macro Industrial Tools - Bellary
Door no 43 2nd Ward Khaderiya Masjid Street, Nalagadda, Bangalore Road Beside Balaji Sports Bellary.., Bellary. Bellary. Bellary.
Lathe Machines,Welding Machines,S S Bench Wises,Bench Grinder,Grinding Machines, Wood Turning Lathe, Broach Cutter Magnetic Drill Machines,Broach TCT Cutters,HSS Cutters,Band…
4 - CREATIVE CORPORATION - Arang
FIRST FLOOR GT COMPLEX KHAMTARAI RAIPUR, Khamtarai. Arang. Raipur.
Established in the year 2005, we, Creative Corporation is one of the leading organizations in supplying a comprehensive range of End to End Equipment Solution like Material…
5 - Ennovacion Instruments - Howrah
14/5, Kailash Bose 3rd Bye Lane.. Howrah. Howrah.
Ennovacion Instruments are global leaders in manufacturing of Dewpoint & Moisture Analyzer, Process & Trace Gas Analyzers, Fugitive Gas detectors, Combustion & Emission Gas Analyzers…
6 - SURAKCHHA - Agra
57, North Vijay Nagar Colony. Agra. Agra.
We are glad to introduce ourselves as one of the leading contractor, supplier, planner and annual maintenance contractor (AMC) in different types of Fire & Safety Equipments and…
7 - Traditional School of Martial Arts,India - Howrah
Adarshanagar,Kanagarh,Naldanga,Hooghly station, Howrah. Howrah. Howrah.
Affiliated to: Taekwondo Board of India : National Taekwondo Head Quarter Amateur Ashitedo Akhada Association,India (govt. registered) International Combat Taekwondo Union District…
8 - RAVIRAJ Technologies - Pune
Pune, Pune. Pune. Pune.
RAVIRAJ Technologies provide biometrics security products integrate fingerprint, face, iris, voice, and signature recognition. Our biometric devices and biometrics software products…
9 - Industrial Safety Bazaar - New Delhi
NEW DELHI, Delhi. New Delhi. New Delhi.
INDUSTRIAL SAFETY SHOES This blog is for all those people who want to learn about the safety shoes on internet world, if we start a topic on safety shoes so these are the biggest area…
10 - DM STARK INDUSTRIES - Bhubaneswar
Plot:1586/2066, DPS Road, Nakhara, Po:Phulnakhara, Bhubaneswar-754001, Dist:Khurda (Odisha) INDIA., Bhubaneswar. Bhubaneswar. Khordha.
WELCOME : We, at DM STARK INDUSTRIES, began our operations in the year 2012, under the leadership of . Further, we matured into one of the leading Indian Manufacturer, Trader…
Manpower Solution In Haryana - Jalalpur
Shop No. 111 , Near Ahir College , Naiwali Chowk , Rewari , Haryana, Rewari. Jalalpur. Saran.
Labour Contractor,Security Service,Housekeeping Services, Manpower Solution Kirti Manpower Solution Expert In House Keeping, Casual Labour & Security Services A Complete Solution…
Keshav Engg PVT.LTD - Baglan
Mumbai-Goa Road, Mahad. Baglan. Nashik.
Company Profile Well-equipped with modern machinery and a highly skilled work force, the Keshav Engg Pvt llc Fabrication Unit caters to all types of structural fabrication work…
Xsort Technologies LLP - Noida
B8, Block B, Sector 60, Sector 60. Noida. Gautam Buddha Nagar.
We are the exclusive distributor in India for URFOG Fogging Security systems, an Italian product with unique features make the organization safe and secure, with proprietary technology…
Vijay Hygiene Product - New Delhi
Building No.25, Street No.7-B, Ashok Vihar,, Gurgaon. New Delhi. New Delhi.
We "Vijay Hygiene Products" are delivering a versified range of Housekeeping Products, Housekeeping Material in Gurgaon from a single window. We have multi Brands of Housekeeping…
Energy Vision - Bokaro
Near KK Singh Colony Main Gate, Chira Chas, Bokaro, Bokaro Steel City, Jharkhand. Bokaro. Bokaro.
Maintance Free Chemical Earthing System is a complex safety system, which needs careful consideration to ensure complete safety to those working on electrical circuits and equipment,…
Perfect Safety House - South West Delhi
Dwarka, New Delhi, Palam. South West Delhi. South West Delhi.
Perfect Safety House is proud to introduce ourselves as one of the leading firms engaged in Supply safety equipment's. We are a leading dealer and exporter of a wide range of…
Safety Equipment Evergreen sales - Dhariwal
14, vandana cloth market, 1st floor, NR. Panchkuva Gate, Ahmedabad, Ahmedabad. Dhariwal. Gurdaspur.
we deals in all kinds of safety equipments. we are an Ahmedabad Gujarat based one of the leading whole seller in this segment. Industrial safety equipment, Road safety equipment,…
safe box - Indore
My Space Complex, Near Rani Bagh Gate. Indore. Indore.
we are eminent manufacturer and supplier of safe deposit lockers. our lockers are 100% secured from theft. No one can hack, cut, break or lift our lockers.
Prakritii Cultivating Green - New Delhi
5891 Basti Har Phool Singh, Sadar Bazar, Delhi, Delhi. New Delhi. New Delhi.
We deals in Eco-friendly Disposable Kitchenware and Dinnerware items. They are made from the fallen leaves of Arecanut (Soprai). They are 100% natural, chemical free, safe and…
vidur security system - Indore
Flat # 3, Ashutosh Apartments 76, Shri Nagar Main, Indore. Indore. Indore.
VIDUR Security System as a company into providing Electronic Security solutions to its customers in India. The company was set up with an aim to provide quality products,…
Green Fire safety Services - Vellore
16,Old Bye Pass Road. Vellore. Vellore.
Green Fire safety Services Supply all type of fire extinguishers like A B C Type Dry Powder Fire Extinguisher, CO 2 Fire Extinguisher, Dry Powder Fire Extinguisher, Mechanical Foam…
Almas Industrial Safety Shoes Supplier in Mumbai - Thane
Princess Street, MUMBAI- 400 002.. Thane. Thane.
Almas shoes provides solution to human safety by taking extracare inrespect of quality & production. We are in collabration with mash group. Our mutual cooperation has explored our…
Fire Resistant Safes Lockers n' Cabinets - New Delhi
2nd Floor, Nr District Centre, Laxminagar, Delhi. New Delhi. New Delhi.
C & B class Fire & Burglary Resistant Filing & Media Cabinets n' Vault Safes in India with max. internal temp. 136 C(For papers) & 40 C (For Computer Media). Also have CBRI/BIS…
Amazing Enterprises - Jabalpur
Above john deere tractor agency, in front of rajpoot gun service, NH-7, dekha, Rewa. Jabalpur. Jabalpur.
we are wholesale supplier of cctv camera, ro system, dvr, audio/vedio door phones, epabx, biometric attendance system, alarm lock etc
Serene Eye - Anand
59, Arogya Jyoti Pharmacy Comp., G.I.D.C., V.U.Nagar.. Anand. Anand.
Deals in CCTV, Door Phone, Access Control System, Attendance System, Burglar Alarm System, Fire Alarm System and Home Automation. Provide Service, Installation, AMC and maintainance on call.


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ECOVACS Deebot 710 Robot Vacuum
ECOVACS Deebot 710 is a state-of-the-art robot vacuum cleaner featuring Alexa and Google Home compatibility. It is also equipped with Navi2.0 in order to map your home and clean specific patterns - cleaning every inch possible in your house. D710 is one of the quietest robot out there and offers several cleaning modes , so you can clean your whole home, spot clean specific areas of concern, or clean around the edges of your space.
Main features


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When I heard that Sam Lipsyte had a new novel out called Hark, which is a synonym for "listen," that's exactly what I did.
I mostly prefer to experience literary fiction in book form, especially those read for language rather than story or plot; but Lipsyte is a wildly comic writer who translates well to audio format. Plus, the novel is read by Lipsyte himself, which sealed the deal for me.
Lipsyte has written four novels and a pair of short story collections, and enjoys something like a cult following among irreverent readers. I first encountered his work in a strange literary journal called J&L Illustrated, which included Lipsyte's "Ode to Oldcorn," a sad, strange and deeply funny story about a shot-put coach.
That story was eventually published in his second short story collection, The Fun Parts, but it set the stage for much of his current work, which is often centered on male misfits who are more nebbish than menace. After all, they're just struggling to find their way in what Lipsyte calls "this hard turd of a world."
Hark is like this as well, but in a more circumspect way. The figure at the heart of the story is Hark Morner, a handsome, charismatic man who has developed a technique called "mental archery" that he believes will help people focus. It's kind of like The Force in the Star Wars universe, but mental archery is more of an extended metaphor. Those drawn to Hark can't help but see a grander design behind his message. Hark, however, lacks the evangelical zeal of a for-profit prophet and keeps insisting there is no message.
At one event, Hark proclaims, "One aims at the future, but not a static future. One shoots where the stag, the target, one's chance for fulfillment, are about to appear. You lead your prey. You don't dress for the job you want. You dress for the job your child will someday be denied."
These are the empty calories of guru claptrap, and the loose collection of enablers in Hark's orbit know it. But what if there really is a message behind the BS, perhaps one that Hark himself isn't aware of?
Lipsyte has been crafting deadpan dystopias for the better part of two decades (the publication of his first novel, The Subject Steve, on September 11, 2001, reads like a cosmic joke). Hark not only hits the mark, but it just might be Lipsyte's most accessible and fulfilling work to date.


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[ kron-uh-graf, -grahf ]
/ ˈkrɒn əˌgræf, -ˌgrɑf /
a timepiece fitted with a recording device, as a stylus and rotating drum, used to mark the exact instant of an occurrence, especially in astronomy.
a timepiece capable of measuring extremely brief intervals of time accurately, as a stopwatch able to record fractions of a second as well as elapsed time.
verb (used with object)
to time by means of a chronograph.
Nearby words
chronicles, chrono, chrono-, chronobiology, chronogram, chronograph, chronol., chronological, chronological age, chronological order, chronologist
Related formschro·nog·ra·pher [kruh-nog-ruh-fer] /krəˈnɒg rə fər/, nounchron·o·graph·ic [kron-uh-graf-ik] /ˌkrɒn əˈgræf ɪk/, adjectivechron·o·graph·i·cal·ly, adverbchro·nog·ra·phy, noun
Dictionary.com Unabridged Based on the Random House Unabridged Dictionary, © Random House, Inc. 2019
Examples from the Web for chronographic
The influence of Hippolytus was felt chiefly through his works on chronographic and ecclesiastical law.
A reproduction of the chronographic record of one of these experiments is seen in figure 9.Descriptive Zoopraxography|Eadweard Muybridge
British Dictionary definitions for chronographic
/ (ˈkrɒnəˌɡrɑːf, -ˌɡræf, ˈkrəʊnə-) /
an accurate instrument for recording small intervals of time
any timepiece, esp a wristwatch designed for maximum accuracy
Derived Formschronographer (krəˈnɒɡrəfə), nounchronographic (ˌkrɒnəˈɡræfɪk), adjectivechronographically, adverb
Collins English Dictionary - Complete & Unabridged 2012 Digital Edition © William Collins Sons & Co. Ltd. 1979, 1986 © HarperCollins Publishers 1998, 2000, 2003, 2005, 2006, 2007, 2009, 2012


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Fun and educational sights in and around the village of Aubeterre, Charante, southern France
On this page you can find various places of interest in and around Aubeterre sur Dronne. We have listed all the fun activities to make your vacation easier.
Places of interest
The Charente is not the most mentioned French region, but there is much to see and do. Some examples:
Museum and gallerys/ateliers in Aubeterre
The history of the village can be seen in the small museum Ludovic Trarieux.
In the Tourist Office, at the very top of the village, there is not only a huge amount of information but also an art gallery that is open to the public.
There are four open workshops in the village, two (Xavier and Manon) of totally different ceramists and a shared workshop with different artists/craftsmen.
An art gallery that has been open to the public since 2018: www.facebook.com/galerie.chezMarguerite
Saint-Emilion (Gironde) is in the heart of the Bordeaux-wine region. A historical village to visit and offcourse the place to go if you want to take some great wines back home.
The village has the vastest monolithic church of Europe. You can visit the church every day in a self-guided tour (headphone). In former times the pilgrims, on their way to Santiago the Compostella, visited the village. Even today, pilgrims follow the route Saint Jacques the Compostella through Aubeterre.
The village, with its narrow winding picturesque streets, is build in the form of an amphitheatre, following the slope of the cretaceous bedrock underneath the surface of the village. Lots of Cretaceous fossils have, and can still be found, in this area. Aubeterre originates from 'Alba-Terra' which means as much as White Ground, and reflects the white Chalk-stone that most of the houses are build of. The village is listed as one of the 100 most beautiful villages of France. Out of a total of about 32.000 villages, this is not a bad score!
Saintes, as well as Bordeaux are beautiful ancient cities with remnants of the Roman age. Both cities worthwhile visiting.
The famous village of Cognac is not far away. By the way; a famous product of this region is the Pineau, a product that is linked to the production of cognac and a famous apperitive here.
Angoulême, three quarters of an hour's drive from Aubeterre, is situated on a plateau and on the Charente river. The city of cartoon characters. They are present on the walls everywhere. Five museums and the art academy for illustration, video games and interactive media. A beautiful old town centre.
Bordeaux (Gironde), one and a half hour drive from Aubeterre. Part of the city (Port de la Lune) is on the UNESCO World Heritage List. Bordeaux is famous for its wines and has so much more to offer (wine regions of Médoc, Graves, Sauternes, Entre-Deux-Mers and Saint Emilion): theatres, major events and music festivals.
A bit further away is Dune Pilat, on the Atlantic coast. Here you'll find the highest dunes of Europe. Great place to go on a warm summers day sunbathing and swimming.
If you want to stay closer to Aubeterre, The river Dronne is the place where the locals swim. At different places there are small beaches, often with a little bar where you can buy something to eat and drink.
You can walk anywhere. There are plenty of hiking maps. Walking maps are available at the tourist office.


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I can't download anything on my computer without a pop up telling me it has a virus. Doesn't matter what it is! Even a simple picture from my phone will not download and the bar pops up and says it has a virus. Tried to download hitmanpro and it won't do it. Same bar comes up every time!! Been like this for a month.
message edited by shetaz711
Download and burn an antivirus live cd and burn it on cd.
Here you'll find a list of live CDs:
Reboot the computer from this cd and do a full scan.
When finished, download and install Malwarebytes and let it scan your computer for additional viruses and malware.
Post the exact message and explain when you see it. What browser are you using?
Naturally, you have to use a good internet connection to do your download.
try tapping f8 on bootup and then select safe mode with networking....you should be able to download then....
HELP in posting on Computing.net plus free progs and instructions *7 Golds*
I'd love to download any anti-virus but I already have Stopzilla and it didn't get rid of that ONE problem of being able to download ANYTHING. I've already tried to download in 'safemode' and can't do it there either. The same pop up shows in the bottom after u hit the run key and it goes directly to "this action was deleted a virus was found'.
When trying to download a picture to my computer to save it, the is the message: downsize(24).jpg contained a virus and was deleted. When downloading any website (such as trying to get chrome back) it will say that site contained a virus and was deleted. And it does the same thing is safe mode.
"I'd love to download any anti-virus"
You cannot do it on your comp, you are infected.
paulsep post #1 gave you ways to do it, here is another.
Print or write this down.
Run ESET Online Scanner, Copy and Paste the contents of the log please. This scan may take a very long while, so please be patient. Maybe start it before going to work or bed.
You may have to download ESET from a good computer, put it on a flash/thumb/pen drive & run it from there, if your comp is unbootable, or won't let you download.
Create a ESET SysRescue CD or USB drive
How do I use my ESET SysRescue CD or USB flash drive to scan and clean my system?
Configure ESET this way & disable your AV.
How to Temporarily Disable your Anti-virus
Which web browsers are compatible with ESET Online Scanner?
Online Scanner not working
Why Would I Ever Need an Online Virus Scanner?
I already have an antivirus program installed, isn't that enough?
Once onto a machine, malware can disable antivirus programs, prevent antimalware programs from downloading updates, or prevent a user from running antivirus scans or installing new antivirus software or malware removal tools. At this point even though you are aware the computer is infected, removal is very difficult.
5: Why does the ESET Online Scanner run slowly on my computer?
If you have other antivirus, antispyware or anti-malware programs running on your computer, they may intercept the scan being performed by the ESET Online Scanner and hinder performance. You may wish to disable the real-time protection components of your other security software before running the ESET Online Scanner. Remember to turn them back on after you are finished.
17: How can I view the log file from ESET Online Scanner?
The ESET Online Scanner saves a log file after running, which can be examined or sent in to ESET for further analysis. The path to the log file is "C:\Program Files\EsetOnlineScanner\log.txt". You can view this file by navigating to the directory and double-clicking on it in Windows Explorer, or by copying and pasting the path specification above (including the quotation marks) into the Start ? Run dialog box from the Start Menu on the desktop.
If no threats are found, you will simply see an information window that no threats were found.
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From stunning lights and nightly projections, to Christmas themed dishes and cocktails, there is so much to experience in the city at Christmas. As we approach the final stretch, we've put together a handy list of things to see and do before Christmas is done for another year.
Visit the Christmas tree at Federation Square
Head to the Christmas Festival Hub at Federation Square to see a stunning light show from the giant Christmas tree. It's on every night from 9pm as part of the 2018 Christmas Festival.
Watch the Christmas Projections
While in the city, don't miss the magical, colourful Christmas Projections at Federation Square, Melbourne Town Hall (non-animated) and along New Quay Promenade, Docklands. While in Docklands, watch the colourful state-of-the-art Christmas lighting installation at the Light House at 888 Collins Street.
Get snowed on in the city
Nothing beats a well earned bevvy at Chuckle Park after a long December day. This little laneway bar is getting the full white Christmas treatment, and if you order a 'Sherbert Peaks' to sip on it might just start snowing (literally!). Grab a round of drinks, tuck into a s'mores dessert pizzas and be transported to the North Pole.
Soak up the sun at La Boca
Mega musical Evita will get everyone crying for Argentina at Arts Centre Melbourne this summer. But out in the forecourt there's a hot Buenos Aires party vibe at the Stomping Ground La Boca pop-up beer garden. Live la vida loca, from tango lessons to a Collingwood craft brewery's event-exclusive Argentine-inspired lager. On until Sunday 24 February 2019.
Visit the Gingerbread Village
Marvel at a miniature Melbourne made out of biscuits and help a good cause at the Gingerbread Village by Epicure. On until Christmas Eve, the village is a remarkable feat of baking that also raises money for charity. This year proceeds will be going to the Royal Children's Hospital Foundation, so give generously.
Ice skate at the Queen Vic
Cool down at Melbourne's only summer ice skating rink, located at the Queen Victoria Market. Not only can you dazzle with your best pirouettes (or just try and tackle staying up straight), but there's also maple syrup ice cream, delicious Canadian poutine, fairy floss, festive drinks and more. The rink is open during market hours until Christmas Eve.
Load up on cheese, croissants and fresh produce
After you've worked up an appetite on the ice, stock up on delicious foodie treats from the Queen Victoria Market's seemingly endless food stalls. There's local and international cheeses in the dairy hall, fresh and organic fruit and veg under the iconic sheds, fresh seafood and pastries galore. Buy up big and impress the family on Christmas day with all your foodie finds.
Finally finish your shopping
Left it to the last minute again? Never fear, a trip to the city is easier than ever with most shops extending their hours to help busy gift buyers in the lead up to Christmas. Between QV Melbourne's free Friday fun, Melbourne Central's Snow Room and Merry Litmas Neon Room pop ups and complimentary gift wrapping at St Collins Lane, it'll barely feel like you're stress shopping at all. Read up on all the after hours locations in our guide to late night Christmas shopping.
Bonus idea (we couldn't just leave it at eight!) – stock up on mince pies from Baker D. Chirico
Baker D Chirico knows every Christmas dessert needs the 'holy trinity' of flavours – vanilla bean, cinnamon and spicy rum. From traditional mince pies, shortcrust speculoos stars and Italian mini panettone, these warm baked goods are an instant Christmas crowd pleaser. Find them in Carlton and Domain Road, South Yarra, opposite the Royal Botanic Gardens.


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What's up PewdiePie? The troubling content of YouTube's biggest star
Childish, offensive and immensely popular, the YouTube star – whose real name is Felix Kjellberg – continues to command a huge audience. But what is he really saying?
PewdiePie has started a book club. Once a month, the YouTuber sits in his box room studio, bathed in soft pink light, and critiques a set of texts for his audience. The choices so far have tended towards sci-fi – I Am Legend,Brave New World – but also included The Picture of Dorian Gray and American Psycho. "For me to discover how much joy you can get through reading", the 28-year-old Swede said, "It's been so much fun." This month, he wants his viewers to join him in ploughing through Moby Dick.
A readalong of Herman Melville's opus is unlikely to generate the same interaction as more common YouTuber fare like playing a violent prank or dissing a rival. That said, the first PewdiePie "Book Review" has still been watched 3.5m times. Right-thinking individuals may have struggled to engage young people with classic literature for decades. Felix Kjellberg just turns up and does it from his closet.
Given the scale of his audience and his influence, not much is written about PewdiePie. Tech sites like The Verge and Polygon report on him and often critique him severely. But in the mainstream media, his name has broken through only either as a result of novelty or scandal. He was profiled several times by the British press when YouTubers entered the public consciousness in 2014 (no doubt helped by the fact Kjellberg lived in Brighton at the time). Last year he made news globally after paying two Indian men to hold a sign saying "Death to all Jews". Three months later he drew headlines again after using the "n" word while live-streaming a video game.
PewdiePie's content is written about even less often. In a way it reflects how we in the media still classify YouTube as a tech rather than a cultural phenomenon. It's also perhaps because adults have a fixed view of what YouTubers are; narcisssists with a webcam and a sponsorship deal. PewdiePie is not immune from such behaviour; he has his own brand of ergonomic chair, ideal for gaming, that he sells for $399. But Kjellberg's videos are more largely concerned with critiquing the internet.
Each week, alongside reactive content like his savaging of Logan Paul's suicide video, PewdiePie posts three different "shows". In the first, You Laugh You Lose (YLYL), Kjellberg watches a stream of supposedly humorous, or perhaps laughable clips. He mocks them and tries not to laugh. On Last Week I Asked You (LWIAY) he sets his audience challenges and reviews the output. Those challenges largely involve creating memes and in the third show, Kjellberg reviews the more popular memes on the internet. This show is called Meme Review.
The format has been updated however. The internet provides Kjellberg with a near infinite supply of material. He also swears an awful lot more than James ever did. More than many of his peers he plays around with form and visual effects (he has a team of editors who work on each piece). Sharp cuts, interpolations, green screen scenes and filters which warp the image or subvert the sound are standard. The combined effect is to turn one man and his desk into something both hyperactive and psychedelic.
Pewdiepie has come a long way since he posted his first YouTube video in 2010. His style has developed considerably. He gained his celebrity from "Let's Play" videos recording himself gaming with a commentary of yelps and curses on top. He rarely posts such content any more. His first non-gameplay video came in 2011, a short clip in which he apologised for taking time away from his channel to go on holiday. In that video he is shy, demurring and can barely look the camera in the eye. That clean shaven cutie pie is now a man with a hefty beard, a shock of peroxide hair, and great deal more confidence.
Why are YouTube stars so popular?
Why are YouTube stars so popular?
Because of the way that YouTube (a company owned by Google's parent company Alphabet) guards its data, it's unclear precisely who watches PewdiePie's content. Data provided to Kjellberg by the company, which he screenshotted and posted during a 2017 video, suggested his largest demographic was among the 18-24 age group, followed by 25-34. It seems unlikely that he is not also very popular among teenagers, however. It has been observed that you can pretend to be older than you are on the internet. Many of the fans who engage with PewdiePie by posting content either on YouTube or Reddit are under 18.
Felix "PewdiePie" Kjellberg is funny, intelligent, innovative and highly charismatic. He also has one of the world's biggest public platforms and a remit restricted only by YouTube's terms of service. To call him an alt-right agitator would perhaps be unfair as he has never publicly identified with the proto-fascist movement. But he shares much of their culture and amplifies it across the world. People should pay PewdiePie more attention.


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Thesis Editing and enhancing: How To Write down Text
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Thesis Editing and enhancing: How To Write down Text
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