Talk:Prostate-specific antigen/Archive 1

Archive 1

Obesity

JAMA this week: obesity may reduce actual PSA level and could account for false-negatives. JFW | T@lk 08:35, 21 November 2007 (UTC)

I added this information & reference to the article Ryanjo (talk) 19:28, 27 April 2008 (UTC)

Discoverer of PSA laments proven lack of life saving value and costs and disabilities from its use as a screening test.

http://www.nytimes.com/2010/03/10/opinion/10Ablin.html?em

After testing 1,400+ men, 48 would be recommended further testing based on PSA. The author discusses the large studies debunking routine screening with PSA.

"...48 men would need to be treated to save one life. That’s 47 men who, in all likelihood, can no longer function sexually or stay out of the bathroom for long."

Citing: Mortality Results from a Randomized Prostate-Cancer Screening Trial (large U.S. trial) and Screening and Prostate-Cancer Mortality in a Randomized European Study,

Add to his comments the tangible and intangible transaction costs of overtreatment -- the time and money costs, inconvenience, and pain of the invasive and painful surgical diagnostic or treatment procedures themselves. —Preceding unsigned comment added by 68.165.11.214 (talk) 16:42, 11 March 2010 (UTC)

Bioanalysis and detection

Maybe we should expand the Prostate-specific antigen entries, and discuss in a short paragraph the technicalities of the bioanalytical protocols used. How well correlate these immuno-assay with other analytical methods such as LC-MS/MS? How would it be possible to focus more accurately on the specific diseases stages or on the differentiation between malignant and benign pathologies etc. Would you mind that I add some pertinent papers in that regard? I would absolutely not infringe on already existent text, and I welcome professionals in this field to edit and correct my contributions? 92.106.153.17 (talk) 14:42, 15 April 2011 (UTC)

Please try your edits and we will see what others think (I am not a professional in the field). When adding a new topic to a talk page, please click "new section" at the top, and sign your comment by adding a space and four tildes at the end of the last line (see WP:TP). Happy editing! Johnuniq (talk) 01:53, 16 April 2011 (UTC)

Minor edit to 'PSA is a misnomer' section.

The widely debated PSA test is a form of immunoassay. Since this requires that antibodies interact with the molecule being measured, it is an antigen by definition. I placed a link to the wiki page for Antigen, and changed the wording of the sentence that says the name Prostate Specific Antigen is a misnomer. Formerly it stated that PSA is not an antigen, now it says that PSA is an antigen, but is not prostate-specific, which I believe is more accurate. InsertNameHere (talk) 18:51, 6 June 2011 (UTC)

Popular Press? now using USPSTF 2012 statement for lead

The Economist is widely considered accurate and serves to provide guick to confirm info. If you want to help, please text the same facts and provide your reference (say the reference the Economist used). I'll replace Economist reference with the underlying source tomorrow, but in the meantime, users have the info.32cllou (talk) 04:56, 25 June 2012 (UTC)

I can not find the rules for what is to be treated as "popular press". I see newspaper and periodical article info all over this encyc., and don't find any restrictions. Where is your objection to be found?32cllou (talk) 15:29, 25 June 2012 (UTC)

Hi have a look at this: WP:IRS, leave a message here if it isn't what you are after and I'll try and help some more. Callanecc (talk) 15:42, 25 June 2012 (UTC)

Thank you, and I put that page in my bookmarks for future ref. I see why medical is treated somewhat different so the economist could be quoted in other non med, as it is, articles. It might have been OK if that econ article had referenced a source more directly?32cllou (talk) 22:17, 25 June 2012 (UTC)

Per referencing see WP:MEDRS. We already conver the info you added with the real source "A review commissioned by the U.S. Preventive Services Task Force concluded that "Prostate-specific antigen-based screening results in small or no reduction in prostate cancer-specific mortality and is associated with harms related to subsequent evaluation and treatments, some of which may be unnecessary." Doc James (talk · contribs · email) (please reply on my talk page) 00:10, 26 June 2012 (UTC)

I will only add info not currently there. Specific found harms.32cllou (talk) 01:10, 26 June 2012 (UTC)

Here's paraphrased updated screening recommendation lead: United States Preventive Services Task Force USPSTF (May 2012) recommends against patients being screened for prostate cancer using the prostate-specific antigen PSA test because the “potential benefit does not outweigh the expected harms.” PSA testing may help 1 in 1000 avoid death, but 4 to 5 would still die from prostate cancer after 10 years. Expected harms include anxiety for 100 – 120 receiving false positives, biopsy pain, potential (1/3 of biopsies) complications, and frequent overdiagnosis because most prostate cancer is asymptomatic for life. Men found to have prostate cancer usually (90%) elect to receive treatment; therefore for every 1000 men screened, 29 will experience erectile dysfunction, 18 will suffer urinary incontinence, 2 will have serious cardiovascular events, 1 will suffer pulmonary embolus or deep venous thrombosis, and 1 perioperative death.

Taken from this direct quote:

Results of several large trials have shown that, at best, PSA screening may help 1 man in 1,000 avoid death from prostate cancer after at least 10 years. Most likely, the number helped is even smaller. This means that with PSA screening, 4-5 out of every 1,000 men will die from prostate cancer after 10 years.

Expected harms of screening

• False-positive results. About 100-120 of every 1,000 men screened receive a false-positive test. Most positive tests result in biopsy, and can cause worry and anxiety. Up to one-third of men undergoing biopsy will experience fever, infection, bleeding, urinary problems, and pain that they consider a moderate or major problem. One percent will be hospitalized for these complications.• Overdiagnosis. In most cases, prostate cancer does not grow or cause symptoms. If it does grow, it usually grows so slowly that it is not likely to cause health problems during a man’s lifetime. Currently, it is not possible to reliably distinguish indolent from aggressive cancers. Many cancers diagnosed would have remained asymptomatic for life and do not require treatment. • Overtreatment. Because of the uncertainty about which cancers need to be treated, 90 percent of men with prostate cancer found by PSA choose to receive treatment. Many of these men cannot benefit from treatment because their cancer will not grow or cause health problems. Harms of treatment include: Erectile dysfunction from surgery, radiation therapy, or hormone therapy (29 men affected per 1,000 men screened). Urinary incontinence from radiation therapy or surgery (18 men affected per 1,000 men screened). A small risk of death and serious complications from surgery:• 2 serious cardiovascular events per 1,000 men screened.• 1 case of pulmonary embolus or deep venous thrombosis per 1,000 men screened.• 1 perioperative death per every 3,000 men screened.32cllou (talk) 01:02, 3 July 2012 (UTC)

I have moved that paragraph to the screening section. The WP:LEAD of the article should not contain that level of detail, but summarize briefly what is in the body of the article. Yobol (talk) 01:14, 3 July 2012 (UTC)

Good but the bottom line the “potential benefit does not outweigh the expected harms.” and PDF link should be in lead too.32cllou (talk) 01:29, 3 July 2012 (UTC)

This topic is very reminiscent of the perpetual mammography controversy. On one side line up all the screening practitioners, the "high risk" worriers and the people who have been successfully treated, on the other line up the people who want the funds used for screening applied instead to other purposes. Somehow I've never seen (in either debate) an explanation of how a positive test result forces the choice of the aggressive treatment which is the proximate cause of the supposedly "expected" harms. Surely the sensible response to such a disconnect is watchful waiting, not willful blindness? LeadSongDog come howl! 17:03, 3 July 2012 (UTC)

Hopefully lay users READ the reference esp pdf leaflets for patients. I had to reedit back this reference best quality source meta review independent panel easy to read. It's a shame editors can't work together.32cllou (talk) 17:36, 3 July 2012 (UTC)

"Reedit back"? I don't follow. Could you clarify please? LeadSongDog come howl! 18:58, 3 July 2012 (UTC)

The last phrase and its' supporting reference in the last sentence second paragraph of the lead was removed. "[t]he potential benefit does not outweigh the expected harms."[7] I put that back in when that text was removed, including the key 2012 reference. I think users need to read that info pamphlet, as it's much better than wiki. I've better things to do than rewrite the whole outdated thing. I still don't like the lead with too many "and"s, plus run on, plus wasted text of the old info 2011 statement. I still think specific harms (the expected ones) should be listed in the lead.32cllou (talk) 23:55, 5 July 2012 (UTC)

Unsure why you are removing high quality references such as you did here [1] Also concerned with you replacing high quality sources by popular press peices [2].Doc James (talk · contribs · email) (please reply on my talk page) 01:48, 6 July 2012 (UTC)

References

Use of paraphrase or quotes

I used the same quote method shown to me by editor Anthonyhcole. It's OK in scientific writing and encyc's. I see long quotes in my old encyclopedia britannica. Seems common in other articles here. I just read WP:MOS again (I had before) and didn't see where is says you can't quote a few short paragraphs as long as you use that box. Can you direct me to the section where what I did is prohibited? I think when info is different from what lay people believe it's important to be precise as with exact pertinent quotes! I could shorten that quote box by half if you insist. Please advise.

I will try to paraphrase the quotes in breast cancer and mammography tomorrow if you insist, but in the meantime it's more important to be precise and make sure women know to NOT seek mammography screening so I undid your edits. Even saving one woman from mammogram screening is important based on those findings. Please help paraphrase if you insist, but please use the article(s) talk so others can see. I will go into Economist and find the source to quote directly in PSA if you require. Please advise.

The 2012 leaflet information is more up to date and complete than the 2011 Cochrane you mention. I'll use the 2011 you cite also, or instead of the 2008, if you want. Or how about only using the 2012 cochrane? 2012 covers it all and the US cochrane refers to the Nordic so it's not like we're referencing a bunch of vikings attacking medical dogma. Please advise.32cllou (talk) 05:44, 25 June 2012 (UTC)32cllou (talk) 01:13, 26 June 2012 (UTC)

Not ignoring you, just busy with other stuff. This page discusses quotes. One of the issues with the text you added was the quote length per [3]. For medical articles we also rarely use quotes at all. The other issue is one of WP:DUE weight and the fact that we already covered the content you added (thus duplication of content).

Regarding using the Economist. This is specifically not recommended per [4]

Now you restored your edit and it was removed a second time by another editor. I am happy to discuss improvements and by the way I agree with the Cochrane's conclusions and agree it is an excellent source. With respect to the leaflet, was it peer reviewed similar to other Cochrane publications? Doc James (talk · contribs · email) (please reply on my talk page) 01:34, 26 June 2012 (UTC)

Thank you for your help, and those writing pages are now to the issues you raised and I understand your points. To paraphrase tomorrow. I'll only use the 2012 Cochrane so you see the need, and not overlap with the 2011 wording. The article is wrongly vague and not specific as it stands.32cllou (talk) 01:52, 26 June 2012 (UTC)

Sure happy to work on improving it together. The conclusions of Cochrane are not accepted by everyone however (including some very large medical organizations). Thus we do need to present their conclusions with appropriate weight. Doc James (talk · contribs · email) (please reply on my talk page) 01:57, 26 June 2012 (UTC)

I won't end up adding much and paraphrased. I'll only use the 2012 Cochrane, so not overlap with the 2011 info. The article is wrongly not specific as it stands. Appropriate weight is simply to relay the new pertinent info. I see your point about the box.

I understand from the writing style page you recommended that Cochrane is always preferred and peer reviewed but how can I confirm the peer review as you request? Note that the US Cochrane refers us the Nordic Cochrane and they update the US with newer info.

The 2012 includes updated info that other screening and treatments now better so mammogram is even less worthy, and specific info on "charity sites" missinfo on mastectomy incidence. If you have peer reviewed info from "large medical" guys it should be included at least by light "weight" 2012, otherwise its wrong to understate importance of Cochrane info. Those large guys are under tremendous political pressure to downplay new info like the 2012 Cochrane.32cllou (talk) 02:18, 26 June 2012 (UTC)

Agree. I am happy if you paraphrase the 2012 Cochrane and add what is not already covered by the 2011 paper on which I assume much of it is based. Doc James (talk · contribs · email) (please reply on my talk page) 02:28, 26 June 2012 (UTC)

So far, the first sentence in the second paragraph is not supported by the reference. As for the second sentence in that paragraph, 15% might be used, but women really want to know the "absolute risk reduction of 0.05%", and then all the harms not mentioned. Missing is the primary sentence saying "It is thus not clear whether screening does more good than harm." Please direct me to the source or reference the source otherwise those sentences must be removed.32cllou (talk) 23:30, 26 June 2012 (UTC)

No, the 2012 is based on more complete data they say, making mammograms even more harmful.32cllou (talk) 23:32, 26 June 2012 (UTC)

I gotta say whats going on here because the USPSTF really says not sure if it does more harm than good, but if you want to get screened its best to wait until 50 ect.32cllou (talk) 23:40, 26 June 2012 (UTC)

So sorry net benefit moderate binnial 50 - 74.32cllou (talk) 23:44, 26 June 2012 (UTC)

Let move this discussion to the talk page for mammography. This page is about PSA. Doc James (talk · contribs · email) (please reply on my talk page) 00:03, 27 June 2012 (UTC)

Proposed para in lead

I realize the main dispute is Yobol's removal of "overtreatment" but leaving in overdiagnosis and controversy. Below is more true to the reference, removes the Economist stuff (I didn't put that back in who did?), removes the old findings, removes the NYT:

PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders. The United States Preventive Services Task Force (USPSTF, 2012) does not recommend PSA screening, noting that the test may result in “overdiagnosis” and “overtreatment” because "most prostate cancer is asymptomatic for life," and treatments involve risks of complications. The USPSTF concludes "the potential benefit does not outweigh the expected harms."32cllou (talk) 15:20, 6 July 2012 (UTC)

Adding in over treatment which I do not think anyone here has an issue with. Doc James (talk · contribs · email) (please reply on my talk page) 21:01, 6 July 2012 (UTC)

Actually overtreatment was already there? And I do not see Yobol's removal.

" The USPSTF found that PSA-based prostate cancer screening conveys small or non-existent reductions in prostate-cancer–specific mortality, and is associated with overdiagnosis and over-treatment,"

Doc James (talk · contribs · email) (please reply on my talk page) 21:04, 6 July 2012 (UTC)

Agree. But that sentence was supported by the 2011 statement, which is now updated and info consolidated.32cllou (talk) 22:56, 6 July 2012 (UTC)

References

Post-treatment monitoring: no references. Incorrect units?

The unreferenced values of 0.2 ng/dL seem implausible regardless of the no citation issue. Note that 0.2 ng/dL = 0.002 microgram/L (equivalently ng/mL). If the author was following a verifiable source, perhaps he or she accidentally wrote 0.2 ng/dL instead of 0.2 ng/mL? — Preceding unsigned comment added by 68.99.204.219 (talk) 06:24, 4 February 2014 (UTC)

Varaibility of PSA

My edit was reverted three times. I couldnt understand that how the information given is false just becuase it is publish in a non-reputed journal. I can definately show you n number of article published in so called reputed journals indexed with medline and scopus giving false information. Article published in a non - reputed journal doesnt mean that it is false infomation. The information is based on experience and not allwing this information to reach people will be a social crime what i think.

Very low PSA vaue as reliable indicator of the absence of prostata cancer?

Is a permanently (very low) PSA of say, 0.8 (person's age 60) a reliable indicator of the absence of prostate cancer? ++--84.73.123.149 (talk) 08:48, 16 March 2015 (UTC)--++

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New USPSTF recommendations on PSA screening

Hello Wikipedians. I have never edited an article, and I am very hesitant to muck it up, but this article needs to be revised ASAP. Would someone with experience want to take that on?

I am one of the unlucky people that would have had great benefit from PSA screening, but my primary physician recommended against it based on the outdated information contained in this article.

Here's the basic new information:

USPSTF is about to release a new recommendation for PSA tests that no longer recommends against it's use as a screening tool. To quote their new recommendation:

"The USPSTF recommends that clinicians inform men ages 55 to 69 years about the potential benefits and harms of prostate-specific antigen (PSA)–based screening for prostate cancer.

The decision about whether to be screened for prostate cancer should be an individual one. Screening offers a small potential benefit of reducing the chance of dying of prostate cancer..."

https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementDraft/prostate-cancer-screening1

Tbrucebowers (talk) 01:42, 16 August 2017 (UTC)

I completely agree. That recommendation, which was a 180 degree change from the previous recommendation, should never have been added in so prominent a way. Also the specification of doubling time is not a sentennce. I am leaving the text in, as is, not because it is correct, but as an embarassment to wikipedia, or the wikipedian who entered it, as well as to medical practice in America. Not my problem. There already is a main article about the controversy. This is not a "news" article about PSA. Plus the advice, made by a panel that includes no urologists or onconogists is dangerous and insane. The death rate decline in prostate cancer is due primarily to early detection. The claim that the PSA test leads to overtreatment is to fix a problem and kill patients. The whole situation is wrong on so many levels. If I had a time machine, I maybe would go back and try to change things, but no not now. ( Martin | talk • contribs 15:03, 29 August 2017 (UTC))

oh ok i just deleted the text. Here is what I took out

)))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))) The United States Preventive Services Task Force (USPSTF, 2012) does not recommend PSA screening for prostate cancer, noting that the test may result in "overdiagnosis" and "overtreatment" because "most prostate cancer is asymptomatic for life" and treatments involve risks of complications including impotence (erectile dysfunction) and incontinence. The USPSTF concludes "the potential benefit does not outweigh the expected harms". PSA is not a unique indicator of prostate cancer, but may also detect prostatitis or benign prostatic hyperplasia. 30 percent of patients with high PSA have prostate cancer diagnosed after biopsy. Rate of PSA velocity=>0.75ng/ml/year.It is more specific in relation with Carcinoma Prostate. ))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))

References

( Martin | talk • contribs 15:10, 29 August 2017 (UTC))

Nope, per MEDRS this kind of guidance is some of the strongest sourcing we have. You will need to better sources to downgrade this, and all I don't see a single one above. Jytdog (talk) 03:19, 30 August 2017 (UTC)

yup.( Martin | talk • contribs 10:49, 7 September 2017 (UTC)) 1) did you read the new recommendation, posted right above?? 2) this caution about the psa is a news item, so out of place in the lead. 3) this bad medical advice, now changed, has killed peoplw. have a heart you cold blooded murder ( Martin | talk • contribs 10:49, 7 September 2017 (UTC)) not completely serious of course, but you are ignoring the possible consequences of your actions ( Martin | talk • contribs 10:49, 7 September 2017 (UTC))

There is a draft proposal to change the recommendation, yes. The actual recommendation hasn't changed yet. Jytdog (talk) 05:45, 8 September 2017 (UTC)

Proposals

Proposal to include Canadian Urological Association recommendations in the lead

Proposed wording for lead: "The Canadian Urological Association in 2017 suggests screening be offered to those who are expected to live more than 10 years with the final decision based on shared decision making. They recommend a starting age for most people at age 50 and age 45 among those at high risk." QuackGuru (talk) 16:34, 6 March 2018 (UTC)

References

Support

• Support, as proposer. Quality information for those under 50 as well as over 50 for the lead. QuackGuru (talk) 16:34, 6 March 2018 (UTC)

• Support, I don't much mind what goes into the lede in this matter, but see my entry under support in the body. JonRichfield (talk) 11:05, 7 March 2018 (UTC)

Proposal to include Canadian Urological Association recommendations in Prostate-specific antigen#Screening section

Proposed wording for body: "The Canadian Urological Association in 2017 suggests screening be offered to those who are expected to live more than 10 years with the final decision based on shared decision making. They recommend a starting age for most people at age 50 and age 45 among those at high risk." QuackGuru (talk) 16:32, 6 March 2018 (UTC)

References

Support

• Support, as proposer. Good information for those under 50 as well as over 50 for the body. QuackGuru (talk) 16:32, 6 March 2018 (UTC)

• Support, I see little point the the objections, and less point to the idea of delay, partly since the grounds for objections do not promise to eventuate in any sort of undebatable resolution. Nor is any party's impatience with patients bearing printouts and delusions of comprehension or authority, any justification for censorship of their permissible and technically correct reading matter. Such half-informed patients are no more pernicious than patients who turn up only after they no longer are treatable, having lived uncomprehendingly, and now dying uncomprehendingly and unhelped, though perhaps less troublesomely than their more inquiring fellow-sufferers. But ignore me; I am not a medical man. JonRichfield (talk) 11:02, 7 March 2018 (UTC)

Discussion on Canadian Urological Association recommendations

The lead and body does not provide any useful information regarding prostate cancer screening for those under 50 years of age. The proposals will fix the issues. QuackGuru (talk) 16:32, 6 March 2018 (UTC)

• Oppose RFC. As a general rule, I never advise working on the lead without first clearing up the body of the article. I consider that approach to editing to be a mistake that should be reserved for novice editors. (Although it is exactly what we see in this entire suite of prostate articles, indeed, throughout medical editing ... editors who clean up leads only, and ignore the bodies of articles.)

  To jump straight to an RFC about the lead, with no previous discussion on this talk page of broader issues in the article, is untimely. Fix the article first, and the lead becomes a summary. SandyGeorgia (Talk) 16:38, 6 March 2018 (UTC)

  • I am not jumping to the lead first. There are two proposals. One for the body and the other for the lead. QuackGuru (talk) 17:28, 6 March 2018 (UTC)
    • Maybe. We still have people here who are simply not talking to each other, and not considering all sources. And personally, I will be at hospital, and cannot keep up with messy talk pages, littered with excess markup and RFCs that will bring in people who know nothing of prostates.

      While, at the same time, we have a specific example over at the talk page of the screening article, that shows that if you will all slow down and start talking to each other, we can fix text. (On the other hand, it is with great appreciation that I say that the screening article has greatly improved ... it is now at least to a point that it won't kill people, and that is pretty much all one can hope for with Wikipedia. No rational being actually living with cancer would consult any other article on Wikipedia -- once you are dealing with it, you know the good sources. Our main problem was that the screening article was deadly to men who might not have known they had cancer. At least now it is not. Thank you :) Please use the successful example over at Talk Prostate cancer screening to talk instead of arguing. SandyGeorgia (Talk) 17:34, 6 March 2018 (UTC)

      • The text I added to the body and lead was deleted without anyone trying to adjust the wording. QuackGuru (talk) 17:44, 6 March 2018 (UTC)
        • I have not looked, and will not look for that diff, so as not to bias my response. Which is. So, when editors behave that way, you save the diff for future reference, in dispute resolution. You are not going to fix deeply entrenched POV with an RFC. And you are not going to fix these articles by going at it line by line. An adjustment in attitude, recognition of poor POV editing, and a return to GOOD editing practices (talk page discussion, incorporation of all reliable sources) is what is needed, and an RFC will only drive further entrenchment, a "desire to win", when too much ego is involved. SandyGeorgia (Talk) 18:22, 6 March 2018 (UTC)
          • Both proposals are based on improving the article. If there are other suggestions or sources for improving content I can try to add them. At the Prostate cancer page I spotted sources that failed to verify each claim. Comments were made in the thread, but the specific issue I raised remains unresolved IMO. I started a RfC to address the issue. Talk page discussion does not always resolve issues. Others can read the comments and proposals and make suggestions. QuackGuru (talk) 18:47, 6 March 2018 (UTC)
            • Patience. The articles are no longer deadly; change can come at a more deliberative pace. At some point, the proponents of *one* source are going to come to the realization that I am not only living the example: I am also spending my life now with institutions, organizations, and physicians who are are practicing medicine at the heart of this controversy, and are the ones who write the secondary reviews (no, I am not referring to Catalona :) Change will come, because it is in the pipeline, and urologists are not going to watch men die from cancer that could have been detected at a curable stage. Whether Wikipedia will be a part of the controversy, or an impartial observer of it, is up to us. Time will reveal. I have not seen anyone in here who is not editing exactly as they always have. Now would be a good time to contemplate change; filling talk pages with RFCs will not result in the much needed changes. Wikipedia has a medical editor who knows Wikipedia policy and guideline, is living the consequences of the controversy, is immersed in the secondary sources, and pointed out that Wikipedia had a suite of prostate articles that were outdated, poorly written and deadly wrong. So let's fix it. SandyGeorgia (Talk) 19:15, 6 March 2018 (UTC)
              • For the record: Jytdog removed a response from QuackGuru. SandyGeorgia (Talk) 17:16, 8 March 2018 (UTC)

User:Jytdog, I forgot to pull this RfC. Please accept my apologies. QuackGuru (talk) 18:55, 10 March 2018 (UTC)

History section apparently plagiarized

The history section appears to be a lightly rewritten version taken from this abstract, [5] and should be rewritten. Daveicd (talk) 16:29, 6 February 2019 (UTC)