Andy Fanton is a British comic strip creator, artist and writer who is best known for his work in The Dandy and The Beano.

Fanton's work first appeared in the first issue of the 2010 relaunched Dandy with his strip 'George Vs Dragon'. After the initial 12-week run finished, Fanton moved on to ghostly goings on in 'Boo!' from February 2011 to April 2011 plus a revamp of the 80's Dandy comic Harry And His Hippo which ran from March 2011 to April 2011, as part of "Strictly Come Laughing". Harry and His Hippo won the vote, ahead of Daredevil Dad, Tag Team Tastic and Phil's Finger. Andy Fanton later introduced more series such as Bad Grandad and Secret Agent Sir. Fanton's characters continue to appear in The Dandy Summer Specials and yearly Dandy Annual.

For the final print edition of The Dandy on its 75th anniversary, Andy Fanton drew Bad Grandad, Hungry Horace, Plum MacDuff and Harry and his Hippo. Andy Fanton is currently writing Minnie The Minx and The Bash Street Kids in The Beano.

Andy also publishes his own website fiction series; the Astonishing Adventures of Lord Likely, which has been running since 2007, along with his popular webcomic, The Carrotty Kid, which was commissioned into an animated pilot for ITV in 2004 by Cosgrove Hall Films.

However, the pilot of The Carrotty Kid was not transmitted due to ITV cutting back on new children's programming.

In 2018 Andy was asked to adapt and serialise Disney's pug-based live-action rom-com 'Patrick: Pug, Actually', which was later collected and released as a book.

Andrew lives in Portsmouth UK with his son.

List of published comics
 George VS. Dragon ~ The Dandy
 Boo! ~ The Dandy
 Harry and his Hippo ~ The Dandy
 Grampire ~ The Dandy
 Springwatch ~ The Dandy
 Mad March Hare ~ The Dandy
 Thor ~ The Dandy
 Dave the Squirrel ~ The Dandy
 Punslinger ~ The Dandy (writing)
 Elf and Safety ~ The Dandy
 Rude-olph ~ The Dandy
 Stupid Barrio Bros ~ The Dandy
 Iykan Si-Yu ~ The Dandy
 Bad Grandad ~ The Dandy
 Al Kazam ~ The Dandy
 Cavemen in Black ~ The Dandy
 The Chav Olympics ~ The Dandy
 The Dirty Radish ~ The Dandy
 Rocky Roller, Pest Controller ~ The Dandy
 Teacher Training ~ The Dandy
 Constable Clod ~ The Dandy
 Secret Agent Sir ~ The Dandy
 Plum MacDuff ~ The Dandy
 Something Funny ~ The Dandy
 Hungry Horace ~ The Dandy
 Little Plum ~ The Beano (writing)
 Constable Caveman ~ The Beano
 Emlyn the Gremlin ~ The Beano
 Robopop ~ The Beano
 Bertrum Muffet and the Violent Egg ~ Self Published
 Dan Morrison: Party Liaison - Self Published
 Eat, Pray, Fart - Self Published

References

External links
 Andy Fanton Dot Com
 The Astonishing Adventures of Lord Likely
 The Carrotty Kid
 Robot Wars trivia
 Review of new Dandy by Forbidden Planet
 Digital Spy News Report
 The Dandy News by Forbidden Planet

British comics artists
British comics writers
Living people
The Dandy people
The Beano people
Year of birth missing (living people)

Andy Fanton


Summertown Road is the second studio album by Canadian country music singer Brad Johner. It was released on October 18, 2005, by 306 Records. "She Moved", "I've Got It Good", "I'd Rather Be Lucky", "Your Love Is My Luck", "You Can't Beat an Original" and "What a Girl Wants" were released as singles.

The album was nominated for album of the year by the Canadian Country Music Association in 2006.

Track listing
"I'd Rather Be Lucky" (Giles Goddard, Tim Nichols) - 3:40
"I've Got It Good" (Ashley Gorley, Wade Kirby, Bryan Simpson) - 3:14
"Summertown Road" (John Barner, Tom Damphier, Bill Luther) - 3:36
"Your Love Is My Luck" (Kirby, Willie Mack) - 3:21
"She Moved" (Steve Fox, Cody Scaife) - 3:40
"Livin' Big" (Gregory Becker, Brad Johner) - 2:35
"What a Girl Wants" (Chris Farren, B. Johner) - 3:53
"Beautiful World" (Blair Daly, Gorley) - 3:47
"Every Other Saturday" (B. Johner, Rhea Johner, Marlee Scott) - 4:16
"You Can't Beat an Original" (Barner, Adam Dorsey) - 3:13

References

External links
[ Allmusic Summertown Road overview]

2005 albums
Brad Johner albums
Albums produced by Chris Farren (country musician)

Summertown Road


Daniel F. O'Brien Sr. (March 26, 1929 – January 16, 2017) was an American professional baseball executive who served as the general manager of the Texas Rangers, Seattle Mariners and California Angels of Major League Baseball (MLB).

Biography
Born in Elizabeth, New Jersey, O'Brien was a graduate of Thomas Jefferson High School. He attended Seton Hall University and graduated from Florida Southern College, where he played varsity baseball and basketball. He served in the United States Army during the Korean War and was discharged in 1954.

O'Brien was a general manager in Minor League Baseball during 1955–1963 in the Pittsburgh Pirates and Milwaukee Braves organizations, then spent another nine years (1964–1972) as the chief assistant to Phil Piton and Hank Peters, presidents at the time of the National Association of Professional Baseball Leagues (NAPBL), the governing body of the minor leagues.

O'Brien came to the major leagues when he joined the Texas Rangers as a vice president during the 1973 season, and was promoted to general manager of the Rangers later that year; he would continue in that post through 1978, although he shared power with co-general manager Eddie Robinson in both 1977 and 1978. In 1979, O'Brien became president of the Seattle Mariners, then in their third year as an American League expansion team, and he added the general manager title to his duties during 1981–1983, replacing Lou Gorman. He left Seattle in 1984 and joined the front office of the Cleveland Indians in 1986, working with Peters again as his top assistant during 1987–1989. O'Brien then moved to the California Angels as top aide to general manager Mike Port, and then succeeded Port as the team's GM from the close of the 1991 season through 1993. He was replaced by Whitey Herzog at the end of the 1993 campaign.

Of O'Brien's three major league teams, only the Rangers of the late 1970s experienced sustained success, contending for, but never winning, the American League West division title. The Mariners climbed to the middle of the pack in the AL West in 1982, then fell into the basement with 102 losses in O'Brien's last year. In Anaheim, O'Brien inherited a .500 team, but the Angels lost 90 games in 1992 and 91 games during the 1993 season.

His son and namesake, Dan O'Brien Jr., served as general manager of the Cincinnati Reds during 2003–2006.

O'Brien died on January 16, 2017, in Dallas, Texas, at the age of 87.

References

1929 births
2017 deaths
California Angels executives
Florida Southern Moccasins baseball players
Florida Southern Moccasins men's basketball players
Major League Baseball general managers
Major League Baseball team presidents
Minor league baseball executives
Seattle Mariners executives
Seton Hall University alumni
Sportspeople from Elizabeth, New Jersey
Texas Rangers executives
Thomas Jefferson High School (New Jersey) alumni
United States Army personnel of the Korean War

Dan O'Brien Sr.


"Smoke and Mirrors", known as "Pit of Secrets" in the United States, is the tenth and final episode of the second series, and the 16th episode overall of the British television series Spooks. It first aired on BBC One on 11 August 2003. The episode was written by Howard Brenton, and directed by Sam Miller. In the episode, Tom Quinn (Matthew Macfadyen) is being framed by thought-to-be-dead CIA agent Herman Joyce (Tomas Arana), as revenge for what happened to his daughter. After its original broadcast, the finale was seen by seven million people, a third of the television audience during its time slot. The episode, particularly due to its cliffhanger, received critical acclaim.

Plot
The episode begins in Miami, Florida, where three masked men break into the apartment of hitman Michael Karharias (Bruce Payne), who is under house arrest. The head of the group employs Karharias to kill an Englishman, but on the condition that he "do it dead". The leader then shoots Karharias to death.

Later, in London, Tom Quinn (Matthew Macfadyen) and CIA liaison Christine Dale (Megan Dodds) meet at a hotel, where Christine hands Tom a telex from the CIA office where they receive intelligence of Karharias (not knowing he is dead) travelling to London to assassinate a member of the British Cabinet. Because Christine has no clearance reading the file, and that the CIA does not intend to inform MI5 of the threat, Tom appoints a reluctant Danny Hunter (David Oyelowo) and Zoe Reynolds (Keeley Hawes) to run a secret operation to intercept the assassin without the knowledge of their superior Harry Pearce (Peter Firth). The trio try, and fail, to apprehend "Karharias" before the CIA does. Danny later decides to follow Tom as the latter is chasing a lead. There, Danny comes across a fake passport with Tom's picture on it, indicating that he is creating a legend without MI5's knowledge. Harry soon becomes aware of the trio's activities.

Tom, meanwhile, follows CIA agent Herb Zeigler (Tomas Arana) to a dead drop, leading to a countryside farm house. The trio are captured. After Danny is beaten, the group take Zoe. In that time, Danny confronts Tom about the legend he is creating, but Tom insists he is not making one. Danny's suspicion is solidified when the masked men act as if Tom was on their side, by letting him go. They sedate Danny and Zoe and leave them to escape when they regain consciousness. They report back to Harry, where they all reluctantly agree that Tom is setting up the legend to escape the country after the assassination; Karharias was found dead in Miami, and there is no record to suggest the CIA even had intelligence of an assassination plot.

As this transpires, Tom is tricked into handling a Gepard M1 sniper rifle in order to get his fingerprints on the weapon. Zeigler reveals himself to be Herman Joyce, a legendary CIA agent who has a grudge against Tom. It is revealed that Tom recruited Joyce's daughter Lisa to infiltrate an anarchist group. The mission went wrong and as a result, Lisa is in a mental hospital in Maine. Joyce has been planning to elaborately frame Tom for an assassination. Joyce and his team leave Tom, who runs to a nearby house to report to his team. By this time, he learns that Sir John Stone, the Chief of the Defence Staff, was killed, with a sniper rifle left with his fingerprints on it. Danny, Zoe and Harry arrive at the house to tell Tom that Joyce was killed in a car accident five years ago. No longer believing his innocence, Harry is going to call for back-up, forcing Tom to shoot Harry with a shotgun. Tom later disappears into the North Sea.

Production

Writer Howard Brenton found writing the end difficult because the producers knew Matthew Macfadyen would leave the series, but not whether he'd return in the beginning of the third series. He stated that the producers "didn't know whether Matthew was going to return to the series or not. We knew there'd be a third series, but we didn't know whether he'd be in it. So I said 'well, is he going to be in it, or isn't he'. And for some times it was, 'oh he's not going to be', so I kill him. And then he said he is gonna be in it, so I unkill him." Because of this, Brenton wrote twelve drafts of the episode. In the end, he wrote a "big cliffhanger, in which he could be dead, could be gone forever, or what." The character Herman Joyce was created by Brenton to become a worthy opponent to Tom. Joyce's creation was inspired from the "great criminal minds" such as Karla from John le Carré and Moriarty from Sherlock Holmes. Brenton thought the addition of Joyce would be a fitting end, so that if Tom was defeated, it would be by a master who would later be undone in some way with or without him.

Brenton chose the name of an assassin, Mickey Karharias, because "Karharias" is Greek for Shark; the producers thought that Karharias was a "real villain name." Having him killed in the beginning to set up the episode was influenced by The Man Who Never Was. The episode also included Zoe being untrusting towards Tom, because Brenton wanted her to be resentful towards his affair with Dale, and placing allegiance with her rather than his team. In an interview on Top Gear in June 2008, Rupert Penry-Jones and Peter Firth commented on the near-death experiences on the characters. Regarding Harry's shooting, Penry-Jones joked to Jeremy Clarkson, "Every time [Peter Firth] asks for more money or five day weeks, they start giving him scenes where he might die."

The love scene between Christine Dale and Tom Quinn were one of actress Megan Dodds' favourite to film because she was relaxed. There was a discussion beforehand on how much clothing each of the actors are comfortable with removing. The scenes set in Miami took place in Peckham. Also, one scene where a shop owner props up water from the shelter and almost missing Macfadyen was not in the script, and was shot by accident. However, it was decided the incident would be useful.

Broadcast and reception
"Smoke and Mirrors" was initially broadcast on Monday, 11 August 2003 on BBC One. The finale was seen by a third of the television audience during its time slot, receiving overnight viewership of seven million. The episode beat Diamonds Are Forever on ITV1, which received 4.6 million viewers in the same time slot. According to the Broadcasters' Audience Research Board, the finale received final ratings of 7.32 million viewers, making Spooks the sixth most seen broadcast on BBC One, and is the 16th most seen broadcast in total the week it aired.

In the "Best of Drama" viewer polls at BBC Online, the cliffhanger was voted the second in the most "Favourite Moment" category. The scene was beaten only by the return of "Dirty Den" Watts in EastEnders. Whilst reviewing the seventh series, Leigh Holmwood of The Guardian's Organ Grinder blog named "Smoke and Mirrors" his "favourite Spooks episode." In review of the DVD boxset of the second series boxset, Dennis Landmann of MovieFreak reacted very positively to the finale, noting that the drama and intensity of the second series builds until the last episode. Landmann stated, "the last thirty or so minutes had me on the edge of my bed, [...] and the last five minutes were so powerful they affected how I felt for the next couple of days; I kept thinking about [Tom Quinn] and the tragic events that happened to him." Michael Mackenzie of Home Cinema called the finale "chaotic", and that the chain of events leading to the ending was "extremely well set up."

References

External links
 Series 2, Episode 10 at bbc.co.uk

2.10
2003 British television episodes

Smoke and Mirrors (Spooks)


In mathematical optimization and computer science, heuristic (from Greek εὑρίσκω "I find, discover") is a technique designed for problem solving more quickly when classic methods are too slow for finding an exact or approximate solution, or when classic methods fail to find any exact solution in a search space.  This is achieved by trading optimality, completeness, accuracy, or precision for speed.  In a way, it can be considered a shortcut.

A heuristic function, also simply called a heuristic, is a function that ranks alternatives in search algorithms at each branching step based on available information to decide which branch to follow. For example, it may approximate the exact solution.

Definition and motivation

The objective of a heuristic is to produce a solution in a reasonable time frame that is good enough for solving the problem at hand.  This solution may not be the best of all the solutions to this problem, or it may simply approximate the exact solution. But it is still valuable because finding it does not require a prohibitively long time.

Heuristics may produce results by themselves, or they may be used in conjunction with optimization algorithms to improve their efficiency (e.g., they may be used to generate good seed values).

Results about NP-hardness in theoretical computer science make heuristics the only viable option for a variety of complex optimization problems that need to be routinely solved in real-world applications.

Heuristics underlie the whole field of Artificial Intelligence and the computer simulation of thinking, as they may be used in situations where there are no known algorithms.

Trade-off

The trade-off criteria for deciding whether to use a heuristic for solving a given problem include the following:

 Optimality: When several solutions exist for a given problem, does the heuristic guarantee that the best solution will be found? Is it actually necessary to find the best solution?
 Completeness: When several solutions exist for a given problem, can the heuristic find them all? Do we actually need all solutions? Many heuristics are only meant to find one solution.
 Accuracy and precision: Can the heuristic provide a confidence interval for the purported solution? Is the error bar on the solution unreasonably large?
 Execution time: Is this the best-known heuristic for solving this type of problem? Some heuristics converge faster than others. Some heuristics are only marginally quicker than classic methods, in which case the 'overhead' on calculating the heuristic might have a negative impact.

In some cases, it may be difficult to decide whether the solution found by the heuristic is good enough because the theory underlying heuristics is not very elaborate.

Examples

Simpler problem

One way of achieving the computational performance gain expected of a heuristic consists of solving a simpler problem whose solution is also a solution to the initial problem.

Travelling salesman problem

An example of approximation is described by Jon Bentley for solving the travelling salesman problem (TSP):
 "Given a list of cities and the distances between each pair of cities, what is the shortest possible route that visits each city exactly once and returns to the origin city?"
so as to select the order to draw using a pen plotter. TSP is known to be NP-hard so an optimal solution for even a moderate size problem is difficult to solve. Instead, the greedy algorithm can be used to give a good but not optimal solution (it is an approximation to the optimal answer) in a reasonably short amount of time. The greedy algorithm heuristic says to pick whatever is currently the best next step regardless of whether that prevents (or even makes impossible) good steps later. It is a heuristic in the sense that practice indicates it is a good enough solution, while theory indicates that there are better solutions (and even indicates how much better, in some cases).

Search

Another example of heuristic making an algorithm faster occurs in certain search problems. Initially, the heuristic tries every possibility at each step, like the full-space search algorithm. But it can stop the search at any time if the current possibility is already worse than the best solution already found. In such search problems, a heuristic can be used to try good choices first so that bad paths can be eliminated early (see alpha–beta pruning). In the case of best-first search algorithms, such as A* search, the heuristic improves the algorithm's convergence while maintaining its correctness as long as the heuristic is admissible.

Newell and Simon: heuristic search hypothesis

In their Turing Award acceptance speech, Allen Newell and Herbert A. Simon discuss the heuristic search hypothesis: a physical symbol system will repeatedly generate and modify known symbol structures until the created structure matches the solution structure. Each following step depends upon the step before it, thus the heuristic search learns what avenues to pursue and which ones to disregard by measuring how close the current step is to the solution. Therefore, some possibilities will never be generated as they are measured to be less likely to complete the solution.

A heuristic method can accomplish its task by using search trees. However, instead of generating all possible solution branches, a heuristic selects branches more likely to produce outcomes than other branches. It is selective at each decision point, picking branches that are more likely to produce solutions.

Antivirus software

Antivirus software often uses heuristic rules for detecting viruses and other forms of malware. Heuristic scanning looks for code and/or behavioral patterns common to a class or family of viruses, with different sets of rules for different viruses. If a file or executing process is found to contain matching code patterns and/or to be performing that set of activities, then the scanner infers that the file is infected. The most advanced part of behavior-based heuristic scanning is that it can work against highly randomized self-modifying/mutating (polymorphic) viruses that cannot be easily detected by simpler string scanning methods. Heuristic scanning has the potential to detect future viruses without requiring the virus to be first detected somewhere else, submitted to the virus scanner developer, analyzed, and a detection update for the scanner provided to the scanner's users.

Pitfalls

Some heuristics have a strong underlying theory; they are either derived in a top-down manner from the theory or are arrived at based on either experimental or real world data. Others are just rules of thumb based on real-world observation or experience without even a glimpse of theory. The latter are exposed to a larger number of pitfalls.

When a heuristic is reused in various contexts because it has been seen to "work" in one context, without having been mathematically proven to meet a given set of requirements, it is possible that the current data set does not necessarily represent future data sets (see: overfitting) and that purported "solutions" turn out to be akin to noise.

Statistical analysis can be conducted when employing heuristics to estimate the probability of incorrect outcomes. To use a heuristic for solving a search problem or a knapsack problem, it is necessary to check that the heuristic is admissible. Given a heuristic function  meant to approximate the true optimal distance  to the goal node  in a directed graph  containing  total nodes or vertices labeled , "admissible" means roughly that the heuristic underestimates the cost to the goal or formally that  for all  where .

If a heuristic is not admissible, it may never find the goal, either by ending up in a dead end of graph  or by skipping back and forth between two nodes  and  where .

Etymology

The word "heuristic" came into usage in the early 19th century. It is formed irregularly from the Greek word heuriskein, meaning "to find".

See also
Constructive heuristic
Metaheuristic: Methods for controlling and tuning basic heuristic algorithms, usually with usage of memory and learning.
Matheuristics: Optimization algorithms made by the interoperation of metaheuristics and mathematical programming (MP) techniques.
Reactive search optimization: Methods using online machine learning principles for self-tuning of heuristics.

References

de:Heuristik#Informatik

Heuristic (computer science)


Prostate cancer is the uncontrolled growth of cells in the prostate, a gland in the male reproductive system just below the bladder. Early prostate cancer usually causes no symptoms. As the cancer develops, one or more tumors can damage nearby organs causing erectile dysfunction, blood in the urine or semen, and trouble urinating. For some patients, the cancer eventually spread to other areas of the body, particularly the bones and lymph nodes. There, tumors cause severe bone pain, leg weakness or paralysis, and eventually death.

Most cases of prostate cancer are detected after screening tests – typically blood tests for levels of prostate-specific antigen (PSA) – indicate unusual growth of prostate tissue. A definitive diagnosis requires a biopsy of the prostate, which is examined by a pathologist under a microscope. If cancer is present, the pathologist assigns a Gleason score of 6 to 10, with higher scores representing a more dangerous cancer disease. Medical imaging is performed to look for cancer spread outside the prostate. Based on the Gleason score, PSA levels, and imaging results, a cancer case is assigned a stage 1 to 4. Higher stage signifies a more advanced, more dangerous disease. Prostate cancer is different from all other common cancers in that as many as three out of four patients have more than one primary cancer focus. The different tumor foci have different properties, including sets of somatic mutations, which complicates the diagnostics and prognostication of the disease.

Most prostate tumors remain small and cause no health problems. These are managed with active surveillance, monitoring the tumor with regular tests to ensure it has not grown. Tumors more likely to be dangerous can be destroyed with radiation therapy or surgically removed by radical prostatectomy. Those whose cancer returns or has already spread beyond the prostate, are treated with hormone therapy that reduces levels of the androgens (male sex hormones) that prostate cells need in order to survive. This halts tumor growth for a while, but eventually cancer cells grow resistant to this treatment. This most-advanced stage of the disease, called castration-resistant prostate cancer, is treated with continued hormone therapy alongside the chemotherapy drug docetaxel. Prostate cancer prognosis depends on how far the cancer has spread at diagnosis and on particular biological properties of the cancer cells. Most men are diagnosed with tumors confined to the prostate; 99% of them survive more than 10 years from their diagnoses. Tumors that have metastasized to distant body sites are most dangerous, with five-year survival rates of 30–40%.

The risk of developing prostate cancer increases with age; the average age of diagnosis is 67. Those with a family history of prostate cancer are more likely to have prostate cancer themselves. Each year 1.2 million cases of prostate cancer are diagnosed, and 350,000 die of the disease, making it the second-leading cause of cancer and cancer death in men. One in eight men is diagnosed with prostate cancer in his lifetime, while one in forty dies of the disease. Prostate tumors were initially thought to be rare, with an 1893 report describing just 50 cases in the medical literature. As surgery became more common, prostate tumors were found in surgical specimens from enlarged prostates. Surgery and radiation therapy methods to treat the disease were developed over the course of the 20th century. Major work describing prostate tumors' need for male sex hormones, and the subsequent development of hormone therapies for prostate cancer, earned Charles B. Huggins the 1966 Nobel Prize in Physiology or Medicine, and Andrzej W. Schally the 1977 Nobel Prize in Physiology or Medicine.

Signs and symptoms

Most cases of prostate cancer are diagnosed through screening tests, when tumors are too small to cause any symptoms. As a tumor grows beyond the prostate, it can damage nearby organs causing erectile dysfunction, blood in the urine or semen, or trouble urinating – often frequent urination and slow or weak urine stream. More than half of men over age 50 experience some form of urination problem, typically due to issues other than prostate cancer such as benign prostatic hyperplasia (non-cancerous enlargement of the prostate).

Advanced prostate tumors often metastasize to nearby bones of the pelvis and back; there they can cause fatigue, unexplained weight loss, and back or bone pain that does not improve with rest. Metastases can damage the bones around them, and around a quarter of those with metastatic prostate cancer develop a bone fracture. Growing metastases can also compress the spinal cord causing weakness in the legs and feet, or limb paralysis.

Screening

Prostate cancer screening searches for tumors in those without symptoms. Screening aims to separate men with high-risk cancers who would benefit from treatment, from those whose tumors are slow-growing and unlikely to impact health. This is typically done through blood tests for levels of the protein prostate-specific antigen (PSA), which are elevated in those with enlarged prostates, whether due to prostate cancer or benign prostatic hyperplasia. The average person's blood has around 1 nanogram (ng) of PSA per milliliter (mL) of blood tested. Those with PSA levels below average are very unlikely to develop dangerous prostate cancer over the next 8 to 10 years. Men with PSA above 3 ng/mL are at increased risk; 30% will have prostate cancer, and 10% a high-grade cancer that requires treatment. Those with PSA levels above 4 ng/mL are often referred for a prostate biopsy; however, even for this high risk group the majority of biopsies are negative for prostate cancer. Men with higher than average PSA levels are often recommended to repeat the blood test four to six weeks later, as PSA levels can fluctuate unrelated to prostate cancer. Those with elevated PSA may undergo secondary screening blood tests that measure subtypes of PSA and other blood proteins to better predict the likelihood that a person will develop aggressive prostate cancer; 4Kscore, Prostate Health Index, ExoDx Prostate Test, and SelectMDx are all available for this purpose.

Several large studies have found that men screened for prostate cancer have a reduced risk of dying from the disease; however, detection of cancer cases that would not have otherwise impacted health can cause anxiety, and lead to unneeded biopsies and treatments. Major national health organizations offer differing recommendations, attempting to balance the benefits of early diagnosis with the potential harms of treating people whose tumors are unlikely to impact health. Most medical guidelines recommend that men in good health and at high risk of prostate cancer (due to age, family history, ethnicity, or prior evidence of high blood PSA levels) be counseled on the risks and benefits of PSA testing, and be offered access to screening tests. Uptake of screening varies by geography – more than 80% of men are screened in the US and Western Europe, 20% of men in Japan, and screening is rare in regions with low human development index.

Diagnosis

Men suspected of having prostate cancer may undergo several tests to help assess the prostate. One common procedure is the digital rectal examination, in which a doctor inserts a lubricated finger into the rectum to feel the nearby prostate. Tumors feel like stiff, irregularly shaped lumps against the rest of the prostate. Hardening of the prostate can also be due to benign prostatic hyperplasia; around 20–25% of those with abnormal findings on their rectal exams have prostate cancer.

A diagnosis of prostate cancer requires a biopsy of the prostate. Prostate biopsies are typically taken by a needle passing through the rectum or perineum, guided by transrectal ultrasound imaging, magnetic resonance imaging (MRI), or a combination of the two. Ten to twelve samples are taken from several regions of the prostate to improve the chances of finding any tumors. Biopsies are examined under a microscope by a pathologist, who determines the type and extent of cancerous cells present. Cancers are first classified based on their appearance under a microscope. Over 95% of prostate cancers are classified as adenocarcinomas (resembling gland tissue), with the rest largely squamous-cell carcinoma (resembling squamous cells, a type of epithelial cell) and transitional cell carcinoma (resembling transitional cells).

Next tumor samples are graded based on how much the tumor tissue differs from normal prostate tissue; the more different the tumor appears, the faster the tumor is likely to grow. The Gleason grading system is commonly used, where the pathologist assigns a number from 1 (similar to prostate tissue) to 5 (least similar) for the most common pattern observed under the microscope, then does the same for the second-most common pattern. The sum of these two numbers is the Gleason score. The total scores of 2 through 5 are no longer commonly used in practice, making the lowest score 6, and the highest score 10. Scores are commonly grouped into Gleason grade groups: a score of 6 or lower is Gleason grade group 1; a score of 7 with the first number (from the most common pattern) 3 and the second number 4 is grade group 2; the reverse – first number 4, second number 3 – is grade group 3; a score of 8 is grade group 4; a score of 9 or 10 is grade group 5. Higher Gleason scores and higher grade groups represent cancer cases likely to be more aggressive with worse prognosis.

Extent of cancer spread is assessed by MRI or PSMA scan – a positron emission tomography (PET) imaging technique where a radioactive label that binds the prostate protein prostate-specific membrane antigen is used to detect metastases distant from the prostate. CT scans may also be used, but are less able to detect spread outside the prostate than MRI. Bone scintigraphy is used to test for spread of cancer to bones.

Staging

After diagnosis, the tumor is staged to determine the extent of its growth and spread. Prostate cancer is typically staged using the American Joint Committee on Cancer's (AJCC) three-component TNM system, with scores assigned for the extent of the tumor (T), spread to any lymph nodes (N), and the presence of metastases (M). Scores of T1 and T2 represent tumors that remain within the prostate: T1 is for tumors not detectable by imaging or digital rectal exam; T2 is for tumors detectable by imaging or rectal exam, but still confined within the prostate. T3 is for tumors that grow beyond the prostate – T3a for tumors with any extension outside the prostate; T3b for tumors that invade the adjacent seminal vesicles. T4 is for tumors that have grown into organs beyond the seminal vesicles. The N and M scores are binary (yes or no). N1 represents any spread to the nearby lymph nodes. M1 represents any metastases to other body sites.

The AJCC then combines the TNM scores, Gleason grade group, and results of the PSA blood test to categorize cancer cases into one of four stages, and their subdivisions. Cancer cases with localized tumors (T1 or T2), no spread (N0 and M0), Gleason grade group 1, and PSA less than 10 ng/mL are designated stage I. Those with localized tumors and PSA between 10 and 20 ng/mL are desigated stage II – subdivided into IIA for Gleason grade group 1, IIB for grade group 2, and IIC for grade group 3 or 4. Stage III is the designation for any of three higher risk factors: IIIA is for a PSA level about 20 ng/mL; IIIB is for T3 or T4 tumors; IIIC is for a Gleason grade group of 5. Stage IV is for cancers that have spread to lymph nodes (N1, stage IVA) or other organs (M1, stage IVB).

The United Kingdom National Institute for Health and Care Excellence recommends a five-stage system based on disease prognosis called the Cambridge Prognostic Group, with prognostic groups CPG 1 to CPG 5. CPG 1 is the same as AJCC stage I. Cases with localized tumors (T1 or T2) and either Gleason grade group 2 or higher PSA levels (10 to 20 ng/mL) are designated CPG 2. CPG 3 represents either Gleason grade group 3, or the combination of the CPG 2 criteria. CPG 4 is similar to AJCC stage 3 – any of Gleason grade group 4, PSA levels above 20 ng/mL, or a tumor that has grown beyond the prostate (T3). CPG 5 is for the highest risk cases: either a T4 tumor, Gleason grade group 5, or any two of the CPG 4 criteria.

Prevention

No drug or vaccine is approved by regulatory agencies for the prevention of prostate cancer. Several studies have shown 5α-reductase inhibitors to reduce the incidence of prostate cancer; however, whether they reduce disease is not clear.

Management

Treatment of prostate cancer varies based on how advanced the cancer is, the risk it may spread, and the affected person's health and personal preferences. Those with localized disease at low risk for spread are often at greater threat from treatment side effects than disease effects, and so are monitored regularly by active surveillance – repeat testing for a worsening of their disease. Those at higher risk may receive treatment to eliminate the tumor – typically prostatectomy (surgery to remove the prostate) or radiation therapy, sometimes alongside hormone therapy. Those with metastatic disease are additionally treated with chemotherapy, as well as additional radiation or other agents to alleviate the symptoms of metastatic tumors. Throughout the treatment course, blood PSA levels are monitored to assess the effectiveness of treatments, and whether the disease is advancing.

Localized disease
Men diagnosed with low-risk cases of prostate cancer often defer treatment and are instead monitored regularly for cancer progression by active surveillance. Active surveillance involves monitoring the tumor for growth at fixed intervals by PSA tests (around every six months), digital rectal exam (annually), and MRI or repeat biopsies (every one to three years). The goal of active surveillance is to postpone treatment, and avoid overtreatment and its side effects, given a slow-growing or self-limited tumor that in most people is unlikely to cause problems. Various risk-calculating algorithms have been designed that attempt to predict a person with prostate cancer's risk of disease progression based on their clinical characteristics and test results. These include the Partin table and D'Amico risk grouping – which take into account a person's PSA levels, Gleason score, and TNM score – as well as the CAPRA score, which also considers an affected person's age and the percent of their prostate biopsies in which cancerous cells were found. The NICE-endorsed Predict Prostate algorithm and webtool looks at individualized prognosis and benefit from treatment versus conservative management in non-metastatic disease.

Those who elect to have therapy typically receive radiation therapy or a prostatectomy. Radiation can be delivered by intensity-modulated radiation therapy, which allows for high doses (greater than 80 Gy) to be delivered to the prostate with relatively little radiation to other organs, or by brachytherapy, where a radioactive source is surgically placed next to the prostate. Radiotherapy is typically given in several treatments over the course of eight to nine weeks. Radiation damage to nearby organs can increase the risk of subsequent bladder cancer and cause erectile dysfunction, infertility, and gastronintestinal problems: diarrhea, bloody stools, fecal incontinence, and pain. For those with relatively high-risk localized disease, combining radiation with androgen deprivation therapy improves overall survival.

Radical prostatectomy aims to surgically remove the cancerous part of the prostate, along with the seminal vesicles, and parts of the vas deferens. This is typically done by robot-assisted surgery, where robotic tools inserted through small holes in the abdomen allow a surgeon to make small and exact movements during surgery. This method results in shorter hospital stays, less blood loss, and fewer complications than traditional open surgery. In places where robot-assisted surgery is unavailable, prostatectomy can be performed laparoscopically (using a camera and hand tools through small holes in the abdomen), or through traditional open surgery with an incision above the penis (retropubic approach) or below the scrotum (perineal approach). The four approaches result in similar rates of cancer control. Damage to nearby tissue during surgery can result in erectile dysfunction and urinary incontinence. Erectile dysfunction is more likely in those who are older or had previous erectile issues. Incontinence is more common in those who are older and have shorter urethras. Both for cancer progression outcomes and surgical side effects, the skill and experience of the individual surgeon doing the procedure are among the greatest determinants of success.

Radiotherapy and surgery result in similar outcomes with respect to bowel, erectile and urinary function after five years. Successful radiotherapy causes a drop in PSA levels due to destruction of the tumor, while prostatectomy causes PSA to drop to undetectable levels. After treatment for localized prostate cancer, PSA levels are  monitored regularly. Up to half of those treated will eventually have a rise in PSA levels, suggesting the tumor or small metastases are growing again. People with high or rising PSA levels are often offered another round of radiation therapy directed at the former tumor site. This reduces risk for further progression by 75%. Those suspected of metastases can undergo PET scanning with sensitive radiotracers C-11 choline, F-18 fluciclovine, and F-18 or Ga-68 attached to a PSMA-targeting drug, each of which is able to detect small metastases more sensitively than alternative imaging methods.

Metastatic disease

For those with metastatic disease, the standard of care is androgen deprivation therapy, drugs that reduce levels of androgens (male sex hormones) that prostate cells require in order to grow. Various drugs are used to lower androgen levels by blocking the synthesis or action of testosterone, the primary androgen. The first line of treatment is typically GnRH agonists like leuprolide, goserelin, triptorelin, or leuprolide mesylate by injection monthly or less frequently if needed. GnRH agonists cause a brief rise in testosterone levels at treatment initiation, which can worsen disease in people with significant symptoms of metastases. In these people, GnRH antagonists like degarelix or relugolix are given instead, and can also rapidly reduce testosterone levels. Hormone therapy halts tumor growth in more than 95% of those treated, with PSA levels returning to normal in up to 70%.

Despite reduced testosterone levels, eventually nearly all prostate cancers continue to grow – typically manifested by rising blood PSA levels, and metastases to nearby bones. This is the most advanced stage of the disease, called castration-resistant prostate cancer (CRPC). CRPC is typically treated with systemic chemotherapy alongside continued hormone therapy. The standard of care is docetaxel given every three weeks. Most CRPC cases still rely on androgen signaling, and so antiandrogen drugs are often used, namely the androgen receptor antagonists enzalutamide, apalutamide, and darolutamide, as well as the testosterone production inhibitor abiraterone acetate. Those whose cancer becomes resistant to docetaxel may receive the second-generation taxane drug cabazitaxel. An alternative is the cell therapy procedure Sipuleucel-T, where the affected person's immune cells are removed, treated to more effectively target prostate cancer cells, and re-injected into the same person.

Supportive care

Bone metastases – present in around 85% of those with metastatic prostate cancer – are the primary cause of symptoms and death from metastatic prostate cancer. Metastases can cause severe pain and bone weakening, with around 25% of those affected developing a bone fracture. Those with constant pain are often prescribed nonsteroidal anti-inflammatory drugs. However, people with bone metastases often experience "breakthrough pain", sudden bursts of severe pain that resolve within around 15 minutes, before pain medications can take effect. Single sites of pain can be treated with external beam radiation therapy to shrink nearby tumors. More dispersed bone pain can be treated with radioactive compounds that disproportionately accumulate in bone, like radium-223 and samarium-153-EDTMP, which help reduce the size of bone tumors. Similarly, the systemic chemotherapeutics used for metastatic prostate cancer can reduce pain as they shrink tumors. Other bone modifying agents like zoledronic acid and denosumab can reduce prostate cancer bone pain, even though they have little effect on tumor size. Metastases compress the spinal cord in up to 12% of those with metastatic prostate cancer causing pain, weakness, numbness, and paralysis. Inflammation in the spine can be treated with high-dose steroids, as well as surgery and radiotherapy to shrink spinal tumors and relieve pressure on the spinal cord.

Those with advanced prostate cancer often suffer fatigue, lethargy, and a generalized weakness. This is caused in part by gastrointestinal problems, with loss of appetite, weight loss, nausea, and constipation all common. These are typically treated with appetite-increasing drugs – megestrol acetate or corticosteroids – antiemetics, or treatments that focus on underlying gastrointestinal issues. General weakness can also be caused by anemia, itself caused by a combination of the disease itself, poor nutrition, and damage to the bone marrow from cancer treatments or bone metastases. Anemia can be improved various ways depending on the cause, or can be addressed directly with blood transfusions. Organ damage and metastases in the lymph nodes can lead to uncomfortable accumulation of fluid (called lymphedema) in the genitals or lower limbs. These swellings can be extremely painful, curtailing an affected person's ability to urinate, have sex, or walk normally. Lymphedema can be treated by applying pressure to aid drainage, surgically draining pooled fluid, and cleaning and treating nearby damaged skin.

People with prostate cancer are around twice as likely to experience anxiety or depression compared to those without cancer. When added to normal prostate cancer treatments, psychological interventions such as psychoeducation and cognitive behavioural therapy can help reduce anxiety, depression, and general distress.

As those severely ill with metastatic prostate cancer near the end of their lives, most experience confusion and may hallucinate or have trouble recognizing loved ones. Confusion is caused by various conditions, including kidney failure, sepsis, dehydration, and as a side effect of various drugs, especially opioids. Most people sleep for long periods, and some feel drowsy when awake. Restlessness is also common, sometimes caused by physical discomfort from constipation or urinary retention, sometimes caused by anxiety. In their last few days, affected men's breathing may become shallow and slow, with long pauses between breaths. Breathing may be accompanied by a rattling noise as fluid lingers in the throat, but this is not uncomfortable for the affected person. Their hands and feet may cool to the touch, and skin become blotchy or blue due to weaker blood circulation. Many stop eating and drinking, resulting in dry-feeling mouth, which can be aided by moistening the mouth and lips. The person becomes less and less responsive, and eventually the heart and breathing stop.

Prognosis
The prognosis of diagnosed prostate cancer varies widely based on the cancer's grade and stage at the time of diagnosis; those with lower stage disease have vastly improved prognoses. Around 80% of prostate cancer diagnoses are in men whose cancer is still confined to the prostate. These men often survive long after diagnosis, with as many as 99% still alive 10 years from diagnosis. Men whose cancer has metastasized to a nearby part of the body (around 15% of diagnoses) have poorer prognoses, with five-year survival rates of 60–80%. Those with metastases in distant body sites (around 5% of diagnoses) have relatively poor prognoses, with five-year survival rates of 30–40%.

Those who have low blood PSA levels at diagnosis, and whose tumors have a low Gleason grade and less-advanced clinical stage tend to have better prognoses. After prostatectomy or radiotherapy, those who have a short time between treatment and a subsequent rise in PSA levels, or a rapid rate of PSA level increases are more likely to die from their cancers. However, the prognostic models are not very accurate, and there is extensive research with aim to develop improved risk classification models.

Castration-resistant metastatic prostate cancer is incurable, and kills a majority of those whose disease reaches this stage.

Cause

Prostate cancer is caused by the accumulation of genetic mutations to the DNA of cells in the prostate. These mutations affect genes involved in cell growth, replication, cell death, and DNA damage repair. Changes to these genes can cause cells in the prostate to grow uncontrollably, resulting in a tumor. Over time, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or bladder. Eventually, tumor cells develop the ability to travel through the lymphatic system to nearby lymph nodes, or through the bloodstream to the bone marrow and (more rarely) other body sites. At these new sites, the cancer cells disrupt normal body function and continue to grow. Metastases cause most of the discomfort associated with prostate cancer, and eventually can kill the affected person.

Pathophysiology

Most prostate tumors begin in the peripheral zone – the outermost part of the prostate. As cells begin to grow out of control, they form a small clump of disregulated cells called a prostatic intraepithelial neoplasia (PIN). Some PINs continue to grow, forming layers of tissue that stop expressing genes common to their original tissue location – p63, cytokeratin 5, and cytokeratin 14 – and begin expressing genes common to cells that makeup the innermost lining of the pancreatic duct – cytokeratin 8 and cytokeratin 18. These multilayered PINs also often overexpress the gene AMACR, which is associated with prostate cancer progression.

Particularly large PINs can eventually grow into tumors. This is commonly accompanied by large-scale changes to the genome, with chromosome sequences being rearranged or copied repeatedly. Some genomic alterations are partiuclarly common in early prostate cancer, namely gene fusion between TMPRSS2 and the oncogene ERG (up to 60% of prostate tumors), mutations that disable SPOP (up to 15% of tumors), and mutations that hyperactivate FOXA1 (up to 5% of tumors).

Metastatic prostate cancer tends to have more genetic mutations than localized disease. Many of these mutations are in genes that protect from DNA damage, such as p53 (mutated in 8% of localized tumors, more than 27% of metastatic ones) and RB1 (1% of localized tumors, more than 5% of metastatic ones). Similarly mutations in the DNA repair-related genes BRCA2 and ATM are rare in localized disease but found in at least 7% and 5% of metastatic disease cases respectively.

The transition from castrate-sensitive to castrate-resistant prostate cancer is also accompanied by the acquisition of various gene mutations. In castrate-resistant disease, more than 70% of tumors have mutations in the androgen receptor signaling pathway – amplifications and gain-of-function mutations in the receptor gene itself, amplification of its activators (e.g. FOXA1), or inactivating mutations in its negative regulators (e.g. ZBTB16 and NCOR1). These androgen receptor disruptions are only found in up to 6% of biopsies of castrate-sensitive metastatic disease. Similarly, deletions of the tumor suppressor PTEN are harbored by 12–17% of castrate-sensitive tumors, but over 40% of castrate-resistant tumors. Less commonly, tumors have aberrant activation of the Wnt signaling pathway via disruption of members APC (9% of tumors) or CTNNB1 (4% of tumors); dysregulation of the PI3K pathway via PI3KCA/PI3KCB mutations (6% of tumors) or AKT1 (2% of tumors).

Epidemiology

Prostate cancer is the second-most frequently diagnosed cancer in men, and the second-most frequent cause of cancer death in men (after lung cancer). Around 1.2 million new cases of prostate cancer are diagnosed each year, and 350,000 men die of the disease. One in eight men are diagnosed with prostate cancer in their lifetime, and around one in forty die of the disease. Rates of prostate cancer rise with age. Due to this, prostate cancer rates are generally higher in parts of the world with higher life expectancy, which also tend to be areas with higher gross domestic product and higher human development index. Australia, Europe, North America, New Zealand, and parts of South America have the highest incidence. South Asia, Central Asia, and sub-Saharan Africa have the lowest incidence of prostate cancer; though incidence is increasing in these regions at among the fastest rates in the world. Prostate cancer is the most diagnosed cancer in men in over half of the world's countries, and the leading cause of cancer death in men in around a quarter of countries.

Prostate cancer is rare in those under 40 years old. The overwhelming majority of cases are diagnosed in those over 60 years, with the average person diagnosed at 67. The average person who dies from prostate cancer is 77. Only a minority of prostate cancer cases are ever diagnosed. Autopsies of men who died at various ages have shown cancer in the prostates of over 40% of men over age 50. Incidence rises with age, and nearly 70% of men autopsied at age 80–89 had cancer in their prostates.

Genetics
Prostate cancer is more common in some families. Men with an affected first-degree relative (father or brother) have more than twice the risk of developing prostate cancer, and those with two first-degree relatives have a five-fold greater risk compared with men with no family history. Increased risk also runs in some ethnic groups, with men of African and African-Caribbean ancestry at particularly high risk – having prostate cancer at higher rates, and having more-aggressive prostate cancers that develop at earlier ages. Large genome-wide association studies have identified over 100 gene variants associated with increased prostate cancer risk. The greatest risk increase is associated with variations in BRCA2 (up to an eight-fold increased risk) and HOXB13 (three-fold increased risk), both of which are involved in repairing DNA damage. Variants in other genes involved in DNA damage repair have also been associated with an increased risk of developing prostate cancer – particularly early-onset prostate cancer – including BRCA1, ATM, NBS1, MSH2, MSH6, PMS2, CHEK2, RAD51D, and PALB2. Additionally, variants in the genome near the oncogene MYC are associated with increased risk. As are single-nucleotide polymorphisms in the vitamin D receptor common in African-Americans, and in the androgen receptor, CYP3A4, and CYP17 involved in testosterone synthesis and signaling. Together known gene variants are estimated to cause around 25% of prostate cancer cases, including 40% of early-onset prostate cancers. It is noteworthy that the somatic mutations found in one cancer focus are completely divergent from those detected in another focus of the same patient.

Body and lifestyle
Men who are taller are at a slightly increased risk for developing prostate cancer, as are men who are obese. High levels of blood cholesterol are also associated with increased prostate cancer risk; consequently, those who take the cholesterol-lowering drugs, statins, have a reduced risk of advanced prostate cancer. Chronic inflammation can cause various cancers. Potential links between infection (or other sources of inflammation) and prostate cancer have been studied but none definitively found, with one large study finding no link between prostate cancer and a history of gonorrhea, syphilis, chlamydia, or infection with various human papillomaviruses.

Regular vigorous exercise may reduce one's chance of developing advanced prostate cancer, as can several dietary interventions. Those with a diet rich in cruciferous vegetables, fish, genistein, or lycopene (found in tomatoes) are at a reduced risk of symptomatic prostate cancer. Conversely, those who consume high levels of dietary fats, polycyclic aromatic hydrocarbons (from cooking red meats), or calcium may be at an increased risk of developing advanced prostate cancer. Several dietary supplements have been studied and found not to impact prostate cancer risk, including selenium, vitamin C, vitamin D, and vitamin E.

History
A tumor in the prostate was first described in 1817 by the English surgeon George Langstaff, following the autopsy of a man who had died at age 68 with lower-body pain and urinary issues. In 1853, London Hospital surgeon John Adams described another prostate tumor from a man who had died with urinary issues; Adams had a pathologist examine the tumor, providing the first histologically confirmed case of a cancerous tumor in the prostate. The disease was initially thought to be uncommon as it was rarely distinguished from other causes of urinary obstruction. An 1893 report found only 50 cases described in the medical literature. Around the turn of the 19th century, prostate surgery to relieve urinary obstruction became more common, allowing surgeons and pathologists to examine the removed prostate tissue. Two studies around the time found cancer in as many as 10% of surgical specimens, suggesting prostate cancer was a fairly common cause of prostate enlargement.

For much of the 20th century, the primary therapy for prostate cancer was surgery to remove the prostate. Perineal prostatectomy was first performed in 1904 by Hugh H. Young at Johns Hopkins Hospital. Young's method became the widespread standard, initially done primarily to relieve symptoms of urinary blockage. In 1931 a new surgical method, transurethral resection of the prostate, became available, replacing perineal prostatectomy for symptomatic relief of obstruction. In 1945, Terence Millin described a retropubic prostatectomy approach, which provided easier access to pelvic lymph nodes to assist in staging the extent of disease, and was easier for surgeons to learn. This was improved upon by Patrick C. Walsh's 1983 description of a retropubic prostatectomy approach that avoided damage to the nerves near the prostate, preserving erectile function.

Radiation therapy for prostate cancer was used occasionally in the early 20th century, with radium implanted into the urethra or rectum to reduce the tumor size and associated symptoms. In the 1950s the advent of more powerful radiation machines allowed for external beam radiotherapy to reach the prostate. By the 1960s, this was often combined with hormone therapy to improve the potency of therapy. In the 1970s, Willet Whitmore pioneered an open surgery technique where needles of Iodine-125 were placed directly into the prostate. This was improved upon by Henrik H. Holm in 1983 by using transcrectal ultrasound to guide the implantation of radioactive material.

The observation that the testicles (and the hormones they secrete) influence prostate size was made as early as the late 18th century via castration experiments in animals. However, occasional experimentation over the next century bore mixed results, likely due to the inability to separate prostate tumors from prostates enlarged due to benign prostatic hyperplasia. In 1941, Charles B. Huggins and Clarence V. Hodges published two studies using surgical castration or oral estrogen to reduce androgen levels and improve prostate cancer symptoms. Huggins was awarded the 1966 Nobel Prize in Physiology or Medicine for this discovery, the first systemic therapy for prostate cancer. In the 1960s, large studies showed estrogen therapy to be as effective as surgical castration at treating prostate cancer, but that those on estrogen therapy were at increased risk of suffering blood clots. Through the 1980s, Andrzej W. Schally's studies of GnRH led to the development of GnRH agonists, which were found to be as effective as estrogen without the increased risk of clotting. Schally was awarded the 1977 Nobel Prize in Physiology or Medicine for his work on GnRH and prostate cancer.

Systemic chemotherapy for prostate cancer has been studied since the 1950s, with clinical trials failing to show benefits in most people who receive the drug. In 1996, the US Food and Drug Administration approved the systemic chemotherapy mitoxantrone for those with castration-resistant prostate cancer based on trials showing that it improved symptoms even though it failed to enhance survival. In 2004, docetaxel was approved as the first chemotherapy to increase survival in those with castration-resistant prostate cancer. After additional trials in 2015, docetaxel use was extended to those with castration-sensitive prostate cancer.

Society and culture
Prostate cancer screening and awareness have been widely promoted since the early 2000s by Prostate Cancer Awareness Month in September and Movember in November. Analyses of internet searches and social media posts suggest neither event changes the level of prostate cancer interest or discussion, in contrast to the more established Breast Cancer Awareness Month. A light blue ribbon is used to promote prostate cancer awareness.

Research

Prostate cancer is a major topic of ongoing research, with the U.S. National Cancer Institute (NCI, the world's largest funder of cancer research) spending $209 million on prostate cancer research in 2020 – the sixth highest among cancer types. Despite high gross spending, prostate cancer research funding is relatively low for the number of deaths it causes. The NCI spends around $5,700 per prostate cancer death, considerably lower than for brain cancer ($21,000 per death), breast cancer ($13,000 per death) or cancer as a whole ($11,000 per death). A similar trend holds for private nonprofit organizations. Annual revenues of prostate cancer-focused nonprofits rank sixth among cancer types, but prostate cancer nonprofits have lower revenue than would be expected for the number of cases, deaths, and potential years of life lost.

Research into prostate cancer relies on a number of laboratory models to test aspects of the disease. Several prostate immortalized cell lines are widely used, namely the classic lines DU145, PC-3, and LNCaP, as well as more recent cell lines 22Rv1, LAPC-4, VCaP, and MDA-PCa-2a and −2b. Research requiring more complex models of the prostate uses organoids – clusters of prostate cells that can be grown from human prostate tumors or stem cells. Modeling tumor growth and metastasis requires a model organism, typically a mouse. Researchers can either surgically implant human prostate tumors into immunocompromised mice (a technique called a patient derived xenograft), or can induce prostate tumors in mice either with chemical exposure or genetic engineering. These genetically engineered mouse models typically use a Cre recombinase system to disrupt tumor suppressors or activate oncogenes specifically in prostate cells.

References

Works cited

External links

Male genital neoplasia
Neoplastic and hyperplastic prostate disorders
Types of cancer

Prostate cancer


The Eurovision Song Contest (sometimes shortened to ESC or simply Eurovision) is a song contest run by the European Broadcasting Union. It started in 1956. Each year, different singers representing countries in Europe perform a song and the winner is decided through voting.

Around 160 million people watch every year. This makes it the largest music competition in the world.

Past famous winners include ABBA (1974), Céline Dion (1988), Sandie Shaw (1967), Lordi (2006), Alexander Rybak (2009), Loreen (2012 and 2023), Conchita Wurst (2014), Netta Barzilai (2018), Duncan Laurence (2019) and Måneskin (2021). Famous contestants who did not win include Olivia Newton-John, Bonnie Tyler, Blue, Jedward and Engelbert Humperdinck.

Creation
The Eurovision Song Contest was created by the European Broadcasting Union to experiment live television and broadcasting across multiple countries. The first contest was held in 1956 with the aim of uniting the countries of Europe following World War II. Seven countries took part in the first contest, which was hosted in Lugano. It was won by Lys Assia, who was representing Switzerland.

Expansion of the contest
More countries began to join very quickly. In the 1970s, countries from outside Europe began to participate (such as Israel). Morocco also participated once (and is the only African country to do so). The early 1990s saw the fall of both the Soviet Union and Yugoslavia, with both split into multiple countries (all in Eastern Europe). All of these new countries wanted to join so the 1993 contest had a miniature contest held beforehand between seven new Eastern European countries. The three winners of the contest would participate in the actual Eurovision Contest.

Relegation system (1994—2003)
The 1994 contest introduced a relegation system. This meant that each year, the countries that ranked lowest would not be allowed to participate the following year in order to allow other countries to enter. Eurovision 1999 introduced a new rule where the United Kingdom, Spain, France and Germany (this group was called the "Big Four") were given the right to participate in every contest, even if they ranked at the bottom.

Semi-finals (2004—present)
The relegation system was used until the Eurovision Song Contest 2004, which introduced a semi-final. The Big 4 and the ten highest-scoring acts of the previous contest would automatically qualify to the final while the rest would have to participate in a semi-final (the ten winners of the semi-final would join the others in the final).

In 2008, a second semi-final was introduced. Now, the ten highest-ranking countries from each semi-final join the host country and the Big Four in the Grand Final. The Big Four expanded to the "Big Five" when Italy re-joined the contest.

Recent history
The Eurovision Song Contest 2020 was cancelled due to the COVID-19 pandemic. This is the first time the contest was cancelled. It was replaced by a replacement show called Eurovision: Europe Shine a Light. It showed the selected entries in place of the Grand Final on 16 May 2020. The BBC also organised an all-stars contest, where ABBA's "Waterloo" was voted best Eurovision song. That same year, a film named Eurovision Song Contest: The Story of Fire Saga was released starring Will Ferrell and Rachel McAdams.

Current competition format

Each year, every country taking part will send in one song which is performed by up to six singers. Each song is performed in a large arena in front of an audience of fans. The winner is decided through a complicated system of voting.

Participation
In the first few years of the contest, a small group of countries competed against each other in one show. As more countries wanted to join, it was eventually decided that there would be two semi-finals, where the ten highest-ranked countries from each semi-final would go into the final. The United Kingdom, France, Spain, Germany and Italy automatically qualify for the final because they give a lot of money to the contest. In addition to this, the host country also automatically makes it to the final. This makes an average of 26 finalists (25 if the host country is a member of the Big Five).

Voting and winner selection

Until the late 1990s, the winner was decided by experts from each country, called a jury. There were multiple jurors per country and each one would award points to their favourite song. The way that the points were awarded changed over the years.

In the late 1990s, televoting was introduced for some countries while others used juries. From 1998 to 2008, the winner was entirely decided by a public televote.

It was decided that the juries would come back because countries kept voting for their allies. Since 2009, the winner has been decided by a combination of a jury vote and public vote. The top 10 countries from each country's jury vote and public vote are awarded points. The country with the most points wins.

In 2023, the "Rest of the World" vote was introduced for the public vote, which allowed viewers from other countries to vote. This gave the public 50.6% say in the voting while the juries now have 49.4%.

Hosting

According to the Eurovision rules, the winner of each contest will host the next year's contest. This rule has been applied most of the time, with a notable exception being the 2023 contest, which was hosted in the United Kingdom because the previous year's winner, Ukraine, was unable to host.

Each year, the contest is hosted by a number of presenters. Usually, these are celebrities from the hosting country or can also be past winners and contestants.

The presenters will usually speak in English or the language of the host country. In addition to the presenters, each participating country has a "commentator" who narrates the event for the viewers in their language.

Contestant selections

In order for a country to participate, it must be a part of the European Broadcasting Union. This includes all of Europe, some Asian and African countries as well as Australia. Each country has a television channel (called broadcasters) which broadcasts the Contest in that country. The only European countries which have never participated are Liechtenstein and the Vatican. The only African country to have ever participated was Morocco.

Entry selections
There are three main types of selections which choose who will represent what country:

 An internal selection is when the channel showing the Contest in a country chooses the contestant and song. For example, the BBC (which airs the Contest in the UK) has chosen the song and contestant without involving the public for several years.
 A national selection is where a country holds its own competition to decide who will represent them in Eurovision. For example, Sweden's national selection is Melodifestivalen, which is the most watched national selection.
 A combination of both selections is a rare method. It is often when the broadcaster chooses the contestant and lets the public vote on the song.

List of contests
The first Contest was won by Swiss singer Lys Assia with the song "Refrain". The first man to win (André Claveau) won the third Contest. ABBA was the first group to win. The first person to win the Contest twice was Johnny Logan. The first woman to win twice was Loreen, whose second win is the most recent victory.

International versions
There are some other versions of Eurovision including:

 Junior Eurovision Song Contest
 Eurovision Dance Contest
 Turkvision Song Contest
 American Song Contest
 Eurovision Young Musicians
 Eurovision Young Dancers
 OTI Festival
 AfriMusic Song Contest
 Bundevision Song Contest
 Asia Song Contest

Notes
  In 1969 four countries were joint winners as there was no rule for a tie.
  Cancelled in 2020 due to the COVID-19 pandemic, Replaced by a programme called Eurovision: Europe Shine a Light.

Other websites
 Eurovision.tv - the official website of the Eurovision Song Contest
 ebu.ch - the official website of the European Broadcasting Union
 The Official Eurovision Shop - Selection of Eurovision items
 The Eurovision History - National Finals & Eurovision Entries

1956 establishments in Europe

Eurovision Song Contest


Cruimthear Mac Carthaigh (the presbyter Mac Carrthaigh), fl. c. 550.

In the genealogies, Mac Carthaigh - his forename, not his surname - is stated as being a native of Conmaícne Cúl Toland in what is now along the County Galway - County Mayo. Thus he was from the same tribal group of Jarlath of Tuam. This branch of the Conmaicne were said to converge, or descend, from Cumhscraidh mac Céacht, who in turn was a descendant of Lugaid mac Con. It is unclear which church he was attached to.

References

 Irish Kings and High Kings, Francis John Byrne, 2001 (second edition).
 The Great Book of Irish Genealogies, 731.3, 731.5, pp. 718–19, volume two, Dubhaltach MacFhirbhisigh; edited, with translation and indices by Nollaig Ó Muraíle, 2003-2004. .

Christian clergy from County Galway
Monarchs from County Mayo
6th-century Irish priests
People of Conmaicne Cuile Toladh

Cruimthear Mac Carthaigh


Charlotte Emma Moore Sitterly (September 24, 1898 – March 3, 1990) was an American astronomer. She is known for her extensive spectroscopic studies of the Sun and chemical elements. Her tables of data are known for their reliability and are still used regularly.

Early life and education

Charlotte Moore was born to George W. and Elizabeth Walton Moore in Ercildoun, Pennsylvania, a small village near Coatesville. Her father was the Superintendent of Schools for Chester County and her mother was a schoolteacher. Her parents were Quakers and Charlotte was a lifelong member of Fallowfield Friends Meeting.

She attended Swarthmore College, where she participated in many extracurricular activities such as ice hockey, student government, glee club, and tutoring.  In order to pay her tuition, Moore was a substitute teacher, one of the few ways she thought she could work her way through college. She wanted to pursue a career outside teaching because "I did not enjoy the teaching that I did from first grade through high school. I succeeded at it, but I didn't like it; it was too wearing."

Moore graduated from Swarthmore in 1920 with a Bachelor of Arts degree in mathematics and went on to Princeton to work as a human computer.

Career

On the recommendation of her mathematics professor at Swarthmore, John. Miller, Moore obtained a job at the Princeton University Observatory working for Professor Henry Norris Russell as a human computer carrying out calculations needed to use photographic plates in determining the position of the Moon. While working for Russel, Moore initially felt nervous about her inexperience, but over time her interest in astrophysics began to blossom.  Russell and Moore researched binary stars and stellar mass, and published extensively on the subject over the years of their collaboration. Her research included an effort to classify 2500 stars based on their spectra.

Although she spent five years at Princeton working under Russell, he refused to consider her a PhD, an unexceptional fact since there were no women in any of Princeton's graduate programs until 1961. Moore said "I was used to prejudice against women because Princeton was a man's stronghold, and a woman was really out of step there." Though in 1926, Russell left his own name off a paper they worked on together and used hers alone.

After five years at Princeton, Moore took a leave of absence due to ill health and she moved to the Mount Wilson Observatory as part of an ongoing collaboration between Russell and research groups there. While at Mount Wilson she worked extensively on solar spectroscopy, analyzing the spectral lines of the Sun and thereby identifying the chemical elements in the Sun. With her collaborators, she analyzed the spectra of sunspots. Moore was able to deduce the temperature of sunspots to be about 4,700 kelvins. Her pictures from the Mount Wilson Observatory helped redetermine the new International Angstrom scale.

She earned a Ph.D. in astronomy in 1931 from the University of California, Berkeley, which had more relaxed rules on women graduates than Princeton, on a Lick Fellowship. Princeton still did not accept women – and would not for the next 30 years. While working on her Ph.D, she continued researching spectroscopy and collected and analyzed data about the spectra of chemical elements and molecules. After obtaining her Ph.D, she returned to Princeton to continue work with Russell as a research assistant.

One of her most significant contributions to physics was her identification of technetium in sunlight, the first example of technetium naturally existing. She joined the then National Bureau of Standards (NBS) in 1945. Her tables of atomic spectra and energy levels, published by NBS, have remained essential references in spectroscopy for decades. While there, she began to research the infrared solar spectrum and atomic energy levels. Beginning in 1946, Moore was able to extend her work on ultraviolet spectral lines thanks to the work of Richard Tousey and measurements taken on V-2 rockets; prior to this Moore's studies were limited to telescopic observations partially blocked by the earth's atmosphere. Moore collaborated with Tousey for decades and led to her 1950 publication "Ultraviolet Multiplet Table."

In 1949 she became the first woman elected as an associate of the Royal Astronomical Society of Great Britain, in honor of her work on multiplet tablets and in identifying solar spot electra. Throughout her career she authored and co-authored over 100 papers and attended the tenth general assembly of the International Astronomical Union on the Joint Commission on Spectroscopy in Moscow in 1958. Sitterly retired from her position at the NBS when she turned 70, in 1968, but continued her research at the Naval Research Laboratory. Sitterly was honored by the Journal of the Optical Society of America by a commemorative issue in 1988.

Personal life

While working at Princeton in the 1920s, she met physicist Bancroft W. Sitterly, whom she eventually married on May 30, 1937. She continued to publish journals under her maiden name because most of her recognition was under that name. She believed that traveling is one of the most important aspects of a scientist's life, as it promotes collaboration between scientists. She enjoyed gardening, traveling, and music with her husband until his death in 1977. She continued her research until her death from heart failure at the age of 91.

Honors
Awards
Annie J. Cannon Award (1937)
Fellow of the Optical Society (1959) – member of the first class of OSA Fellows, one of only five women in the class of 115.
Federal Woman's Award (1961)
William F. Meggers Award of the Optical Society (1972)
Bruce Medal (1990)
Service
 Vice President, American Astronomical Society
 Vice President, American Association for the Advancement of Science Section D
 President, Commission on Fundamental Spectroscopic Data, International Astronomical Union
Named after her
Asteroid 2110 Moore-Sitterly

Works
A Multiplet Table of Astrophysical Interest, 1933
The Solar Spectrum  (with Harold D. Babcock), 1947
The Masses of the Stars (with Henry Norris Russell), 1940
Ultraviolet Multiplet Table, 1950
Atomic Energy Levels as Derived from the Analyses of Optical Spectra, 1958

Further reading
Bibliography from the Astronomical Society of the Pacific

References

External links

American women astronomers
1898 births
1990 deaths
Recipients of the Annie J. Cannon Award in Astronomy
Swarthmore College alumni
People from Chester County, Pennsylvania
20th-century American astronomers
20th-century American women scientists
Fellows of Optica (society)
American women physicists

Charlotte Moore Sitterly


Heiner Stadler (April 9, 1942 – February 18, 2018) was a jazz composer, record producer, pianist and arranger whose work has traversed genres including jazz, blues and country, baroque, classical, romantic and contemporary classical music. He was also the founder and CEO of Labor Records, distributed by Naxos Records.

Early life
Stadler was born April 9, 1942, in West Prussia (now part of Poland) in the town of Lessen (Łasin) in the county of Graudenz (Grudziąd).  His great-grandmother was Josephine Amann-Weinlich,
 who founded and conducted Europe's first women's orchestra, the Wiener Damen-Orchester (later the Erste Europäische Damenorchester), which toured extensively, including an 1871 appearance at New York's Steinway Hall.  Stadler studied piano at the Hamburg Conservatory and composition privately with composer Walter Steffens.

Jazz Composer and Arranger
Stadler relocated to New York City in 1965 to begin a career as a jazz composer and pianist. His first commercially released work, an arrangement of  Duke Ellington's composition Main Stem featuring saxophonist James Moody, Ron Carter, Kenny Barron, Freddie Waits et al., was issued in 1969 on the Milestone label. Prior to that, at a recording session in December 1966 at Nola Penthouse Sound Studios, Stadler recorded his composition entitled ''The Fugue #2'' which would become part of the pioneering 1973 release Brains on Fire.  The 1966 session included Jimmy Owens on trumpet, Joe Farrell on tenor sax, trombonist Garnett Brown, pianist Don Friedman,  bassist Barre Phillips and drummer Joe Chambers. The 1973 release also included sessions from 1971 featuring bassist Reggie Workman, Tyrone Washington on tenor sax and drummer Lenny White, along with Stadler himself on piano.

''Brains on Fire'' was reissued in 2012 with additional tracks recorded through 1974.  One notable addition was a twenty-minute duet between vocalist Dee Dee Bridgewater and Workman on bass (recorded July 3, 1973, at Generation Sound Studios, New York City, under the composer's supervision). The re-release also included Stadler's arrangement of Russ Freeman's composition Bea's Flat, originally written for trumpeter Chet Baker. Commissioned by the NDR Big Band and conducted by Dieter Glawischnig, the arrangement featured musicians Manfred Schoof, Gerd Dudek, Albert Mangelsdorff, Wolfgang Dauner, Lucas Lindholm and Tony Inzalaco.

As producer and arranger, Stadler was responsible for the iconic 1978 album Tribute to Bird and Monk featuring Thad Jones, George Adams, George Lewis, Stanley Cowell, Reggie Workman and Lenny White.  The widely acclaimed release received excellent reviews from Neil Tesser in Jazz Magazine and from DownBeat Magazine which honored the album with a five-star rating and recognized Stadler in the magazine's Annual Critic's Poll as a Talent Deserving Wider Recognition.

Other releases of Stadler's own works include Jazz Alchemy (1976) featuring Charles McGhee, Richard Davis, Marilyn Crispell, Joshua Pierce (Recorded on August 13, 1975, at Minot Sound Studios, White Plains, New York)  and Retrospection (a 1989 reissue including several previously unreleased tracks). Stadler has been a four-time recipient of National Endowment for the Arts Grants for composition as well as a grant recipient from the Creative Artist Public Service Program of the New York State Council on the Arts.

In 1988, dancer/choreographer Sin Cha Hong's Laughing Stone company performed her original work Seraphim at the Joyce Theater incorporating environmental sounds arranged by Stadler with a score by Pierre Henry, Diamanda Galas and Kirk Nurock's Natural Sounds Ensemble. In addition to his own work, in the 1970s he produced (together with partner Kent Cooper) concerts at New York's Hunter College and the Brooklyn Academy of Music with artists such as Pete Seeger, Arlo Guthrie, Sonny Terry & Brownie McGhee, John Lee Hooker, Lightnin' Hopkins, Buddy Guy & Junior Wells, Koko Taylor), Albert King, Louisiana Red and Peg Leg Sam.

Record Producer
Stadler's record productions include releases by blues musicians John Lee Hooker, Sonny Terry and Brownie McGhee, Louisiana Red, Johnny Shines and Roosevelt Sykes; classical pianists such as the Brazilian João Carlos Martins (the complete clavier works of Bach) and Arthur Moreira Lima (music of Chopin), Grete Sultan, Bulgarian musicians such as Pavlina Dokovska, Angela Tosheva, Nadejda Vlaeva, Ivan Spassov, Ivo Papazov and Gheorghi Arnaoudov, Lithuanian pianist , the Chinese-American pianist Margaret Leng Tan (new music by John Cage and others); the Brazilian guitarist Carlos Barbosa-Lima, jazz musicians Dee Dee Bridgewater, Thad Jones, George Lewis, Tyrone Washington, Reggie Workman, Ken Peplowski, Randy Sandke, and Jay Clayton; the Harlem Spiritual Ensemble; a large group of important twentieth-century composers including the Americans Harry Partch and Petr Kotik, Japanese composer Somei Satoh, Korean composer Isang Yun and many others.

He is particularly known for his extensive recordings of the American avant-garde pioneer John Cage, begun in cooperation with the composer and continuing until his death. He also supervised the release of  Philip Glass's famous recording of Einstein on the Beach (originally for Tomato, currently available on Sony).  Stadler has produced for Labor Records, Arabesque Records, Zoho,  WERGO Records, Tomato Records, Arcadia Records and several labels within the Concord Music Group.

Labor Records
He founded Labor Records in 1973 as one of the first labels with what would subsequently be called a "cross-over" or "multi-cultural" point of view, and has served as owner, CEO, Producer and Executive Producer since inception. Labor's current catalogue focuses on unusual and often unknown repertoire coupled with landmark editions such as the complete keyboard works of J. S. Bach performed by legendary Brazilian pianist João Carlos Martins. Other projects include Music of Tribute, Labor's ambitious piano series as well as genre-crossing releases by Germany's Hanns Eisler/Bertolt Brecht, Walter Steffens (Music to Art), American Eric Salzman, Uruguay's Eduardo Fernández, and Brazil's Duo Caramuru/Baldanza.

In 2000, Stadler traveled to Albania to record the music of Aleksandër Peçi. This was the first time in history that a foreign company had gone directly to Albania to produce two albums of contemporary classical music, a landmark event in the history of this impoverished country on the Balkan Peninsula.

Tomato Records
Stadler served as Director of Artists and Repertoire at Tomato Records from 1978 to 1981 and as the company's Director of Operations/Executive Producer from 1987 until 1991.  In the latter position, he supervised the company's complete reissue program (a catalogue of over 65 releases).

Arcadia and Concord Records
Stadler was Vice president/Producer of Arcadia Records from 1991 to 1994, supervising all aspects of financial, production and manufacturing matters with respect to Arcadia's recording program. As producer he traveled twice to North Korea in the 1990s, to help develop an ambitious project in close cooperation with Korean composer Isang Yun. The idea was to create an event bringing North and South Korean musicians together in a joint concert, but the project never materialized and was not revisited.

Then, from 1995 until 2000 he served as Staff Producer/Label Manager for Concord Concerto (a division of  Concord Records, Inc.), overseeing all aspects of the Concerto division.  In addition, he produced for other labels of the Concord Group such as Concord Jazz, Concord Picante, Jazz Alliance and The Blues Alliance.

References

External links
Labor records website

1942 births
2018 deaths
German composers
German record producers
German pianists
Reichsgau Danzig-West Prussia
People from Grudziądz County

Heiner Stadler


The  was a method of making sake during the Edo period at the  in the Amagasaki Domain of the former Settsu Province of Japan (now Takarazuka, Hyōgo Prefecture). Today, the method is used by homebrew enthusiasts or by small boutique brewers.

History
The Kohama style is a direct descendant of techniques used by temple priests near the Mukogawa River in southeastern Hyōgo Prefecture, who learned their distillation techniques from the Nara style. This style spread quickly through the area by Sessen Jūnigō (摂泉十二郷) to places such as Itami, Ikeda, and Kōike. The sake was produced, then shipped down the Mukogawa River to Osaka, where it was then shipped to Edo. However, Sessen fell out of favor with the shogunate, which then began to regulate the brewing of the Kohama sake, and the style eventually disappeared by the middle of the Edo period.

Formula
The recipe for making Kohama style sake was discovered in old documents from the period, and it was found to similar to a more dry type of the Itami style of sake, while having its own bouquet. The mold used to make the sake helps to precipitate the proteins out of the sake brew, thereby helping it to clarify into the final product. The full details are found in the , a record from the Edo Period.

References

Science and technology during the Edo period
Hyōgo Prefecture
Japanese drinks

Kohama style