New approach to cancer treatment carries success with caveat

first_imgIn people with chronic infections or cancer, disease-fighting T cells tend to behave like an overworked militia — wheezing, ill-prepared, tentative, in a state of “exhaustion” that allows disease to persist. In a paper posted online today by the journal Science, researchers at the Dana-Farber/Boston Children’s Cancer and Blood Disorders Center report that, in mice with chronic viral infection, exhausted T cells are controlled by a fundamentally different set of molecular circuits than T cells effectively battling infections or cancer. This finding suggests a way to increase the staying power of CAR T cells, a promising form of immunotherapy for cancer.An accompanying study, led by researchers at the University of Pennsylvania and co-authored by Dana-Farber scientists, reports that these differences in circuitry remain largely unchanged by a type of cancer immunotherapy known as checkpoint inhibition, potentially closing off one avenue of improving this technique.The studies bring renewed focus to the epigenetics of T cells — the multilayered system of molecular switches, accelerators, and throttles that controls the activity of genes. Scientists have known for years that the pattern of genes is different in exhausted T cells than in functional T cells that are fully engaged in fighting disease, but the actual extent of these differences has been uncertain.One difference that is clear is that exhausted T cells express the programmed cell death protein-1 (PD-1), which commands them not to attack normal, healthy cells, but can also prevent them from striking at cancerous or chronically infected cells. Blocking PD-1 with checkpoint-inhibiting drugs — and thereby restoring the cancer-killing zeal of T cells — has become one of the most successful new approaches to cancer treatment in nearly a decade. However, it has shown effectiveness in only about a quarter of cases.“Exhausted T cells display a variety of functional defects,” said Nicholas Haining of Dana-Farber/Boston Children’s, the senior author of the new paper. “They are paralyzed and don’t have the firepower to destroy cancer or virally infected cells. For us, the question in this study was, do exhausted cells represent a distinct type of T cell or are they merely a ‘groggy’ version of functional T cells?”With chronically infected mice as their model, the researchers used a new technology called ATAC-seq to map the regulatory regions of the genome — the sections of DNA involved in switching genes on and off — in the animals’ exhausted and functional CD8+ T cells. (CD8+ T cells are programmed to identify and eliminate cancerous and infected cells.)“We found the landscape of regulatory regions to be fundamentally different in exhausted and functional T cells,” Haining said. “There were thousands of instances where a regulatory region appeared in exhausted T cells but not in their functional counterparts, and vice versa. This tells us that the two types of cells use very different wiring diagrams to control their gene activity.”The researchers then tested whether removing a regulatory stretch of DNA that spurs the production of PD-1 would drive down expression of the protein. Using CRISPR/Cas9 technology, they snipped out that region and indeed, PD-1 expression dropped.The success of this experiment may offer the key to improving CAR T cell therapy. CAR T cells are T cells that are removed from a patient, genetically engineered to grow a protein “sensor” that targets them to tumor cells, and then reinjected into the patient. Although the retrofitted T cells have demonstrated effectiveness at tracking down cancer cells, particularly in leukemia, one of the shortcomings of CAR T cells is that they tend to become exhausted.The work described in the new study suggests that while T cells are being engineered to produce the sensor, they could also be retooled to delete the genetic wiring that causes them to express excessive levels of PD-1 or other exhaustion genes. The resulting CAR T cells not only would be better at stalking cancer, but also more aggressive about attacking it.In the companion paper, researchers explored whether blocking the PD-1 checkpoint rewired exhausted T cells to make them, from an epigenetic standpoint, more like functional T cells. Using chronically infected mouse models, as in the first study, the investigators found that while such gain of function does occur briefly, the epigenetic switches from its previous, exhausted state remain largely unchanged.“This suggests that the benefits achieved by checkpoint blockade result from a transient revving up of exhausted T cells, not a permanent reshaping of their state,” Haining said.The findings of the two studies point to the need for a comprehensive atlas of the regulatory regions that are active in exhausted and functional T cells, he continued. Such a guide would provide targets for rewiring T cells with genetic engineering or epigenetic drugs to make them more effective cancer killers.The first authors of the study are Debattama R. Sen of Dana-Farber and James Kaminski of the University of California, Berkeley. Co-authors are R. Anthony Barnitz, Ulrike Gerdemann, Kathleen B. Yates, Hsiao-Wei Tsao, Jernej Godec, Martin W. LaFleur, Flavian D. Brown of Dana-Farber; Makoto Kurachi and E. John Wherry of the University of Pennsylvania; Pierre Tonnerre, Raymond T. Chung, and Georg M. Lauer of Massachusetts General Hospital; Damien C. Tully and Todd M. Allen of the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University; and Nicole Frahm of the Fred Hutchinson Cancer Research Center.last_img read more

Exercise: It’s all about timing

first_imgNumerous studies have demonstrated the role of physical activity in improving heart health for patients with Type 2 diabetes. But whether exercising at a certain time of the day promised an added health bonus for this population was still largely unknown.New research published in Diabetes Care reports a correlation between the timing of moderate-to-vigorous physical activity and cardiovascular fitness and health risks for individuals who have Type 2 diabetes and obesity or overweight.The research team from Brigham and Women’s Hospital and Joslin Diabetes Center investigators, along with collaborators found that, in its study of 2,035 people, men who performed physical activity in the morning had the highest risks of developing coronary heart disease (CHD), independent of the amount and intensity of weekly physical activity. Men most active midday had lower cardiorespiratory fitness levels. In women, the investigators did not find an association between specific activity timing and CHD risk or cardiorespiratory fitness.“The general message for our patient population remains that you should exercise whenever you can as regular exercise provides significant benefits for health,” said corresponding author Jingyi Qian of the Division of Sleep and Circadian Disorders at the Brigham and an instructor of medicine at Harvard Medical School. “But researchers studying the effects of physical activity should take into account timing as an additional consideration so that we can give better recommendations to the general public about how time of day may affect the relationship between exercise and cardiovascular health.”The researchers analyzed baseline data from the Look AHEAD (Action for Health in Diabetes) study, a multi-site, randomized clinical investigation that began in 2001 and monitored the health of more than 5,000 individuals with Type 2 diabetes and overweight or obesity. Among them, over 2,000 individuals had objectively measured physical activity at baseline.“The study population was very well characterized at baseline, with detailed metabolic and physical activity measurements, which was an advantage of using this dataset for our work,” said corresponding author Roeland Middelbeek of the Joslin Diabetes Center, who is a co-investigator of the Look AHEAD study.For the Diabetes Care article, the researchers reviewed data from hip-mounted accelerometers that participants wore for one week at the beginning of the Look AHEAD study. The researchers tracked the “clock-time” of daily moderate-to-vigorous activity, including labor-intensive work that extends beyond more traditionally defined forms of exercise. To assess the participants’ risk level of experiencing CHD over the next four years, the researchers used the well-known, sex-specific Framingham risk score algorithm.Sex-specific physiological differences may help explain the more prominent correlations seen in males, who tend to be at risk of CHD earlier in life. However, the researchers note that other factors could also be at play. It remains unclear why time-specific activity may be associated with different levels of health and fitness.The researchers also could not account for participants’ varying circadian rhythms: whereas a jog at 6 p.m. for one participant may be “evening exercise,” another participant prone to waking later in the day may, biologically, consider it to be “afternoon,” regardless of how the clock-time of the activity was recorded in the study.“Interest in the interaction between physical activity and the circadian system is still just emerging,” Qian said. “We formed a methodology for quantifying and characterizing participants based on the clock-time of their physical activity, which allows researchers to carry out other studies on other cohorts.”Beyond further integrating circadian biology with exercise physiology, the researchers are also excited to use longitudinal data to investigate how exercise timing relates to cardiovascular health outcomes, particularly among diabetes patients more vulnerable to cardiovascular events.Other contributors to the research include Michael P. Walkup, Shyh-Huei Chen, Peter H. Brubaker, Dale S. Bond, Phyllis A. Richey, John M. Jakicic, Kun Hu, Frank A.J.L. Scheer, and the Look AHEAD Research Group.Funding was provided by the National Institutes of Health. National Heart, Lung, and Blood Institute (K99HL148500). The Look AHEAD trial was supported by the Department of Health and Human Services through the following cooperative agreements from the National Institutes of Health (DK57136, DK57149, DK56990, DK57177, DK57171, DK57151, DK57182, DK57131, DK57002, DK57078, DK57154, DK57178, DK57219, DK57008, DK57135, and DK56992). The Indian Health Service (I.H.S.) provided personnel, medical oversight, and use of facilities.last_img read more

Australia name Bancroft in Ashes squad to face England

first_imgAUSTRALIA have recalled opening batsman Cameron Bancroft to their 17-man squad for the Ashes series against England.It is the first time Bancroft, 26, has been named in an Australia squad since a nine-month ban for his role in the ball-tampering scandal.Former captain Steve Smith and opener David Warner are set to play their first Test since year-long bans for their part in the scandal.The first Test in the five-match series starts on August 1 at Edgbaston.Chairman of selectors, Trevor Hohns, told BBC Radio 5 live he had spoken to Warner, Bancroft and Smith about the hostile reception they may receive at Edgbaston.“When it was their turn, I reiterated what to expect. They’ll be prepared and they’ll have good support around them,” he said.“They know what to expect. I’m sure the crowd will try to get under their skin, but it was only common sense that we included them.“They have served their time and it would be nice if everyone could just get on with it and let them play the game.”Tim Paine will captain Australia, with Matthew Wade recalled as back-up wicketkeeper, but Alex Carey, who impressed during the recent World Cup, misses out.The tourists have named a very strong pace attack including Patrick Cummins, Josh Hazlewood, Michael Neser, James Pattinson and Mitchell Starc, while Essex seamer Peter Siddle, 34, could appear in his sixth Ashes series.Pattinson, 29, is set to make his first Test appearance since 2016 following a series of injuries.Smith, 30, and Warner, 32, both returned to international cricket during the recent World Cup after their suspensions ended in March.Smith remains banned from leading Australia for another year, while former vice-captain Warner will not be considered for any team leadership positions in the future.Bancroft was caught on camera putting a piece of sandpaper down his trousers during the third Test against South Africa in March 2018 and subsequently lied that it was a piece of yellow tape.He returned from his ban in December and was appointed captain by Durham for their County Championship and One-Day cup campaigns this season.The Western Australian has scored 726 runs, including two centuries, at an average of 45.38 in nine Division Two matches this year and hit 93 not out in an a warm-up match between two Australia sides in Southampton on Thursday.It will be between Bancroft and Marcus Harris to open alongside Warner, with Joe Burns having been left out.Off-spinner Nathan Lyon is the only frontline spinner selected, with all-rounder Marnus Labuschagne, who has scored 1 100 Championship runs for Glamorgan this season, providing another option with his leg-spin.Pat Cummins and Travis Head will continue as joint vice-captains of the Test side.“We probably do think we’ve a chance at the moment – I’m very aware of the record, of having not won a series here since 2001,” Hohns added.“It would be something if we can pull it off.”Australia Ashes squad: Tim Paine (capt), Cameron Bancroft, Patrick Cummins, Marcus Harris, Josh Hazlewood, Travis Head, Usman Khawaja, Marnus Labuschagne, Nathan Lyon, Mitchell Marsh, Michael Neser, James Pattinson, Peter Siddle, Steven Smith, Mitchell Starc, Matthew Wade, David Warner.Ashes schedule (all Tests start at 11:00hrs BST)AUGUST1-5: 1st Test, Edgbaston14-18: 2nd Test, Lord’s22-26: 3rd Test, HeadingleySEPTEMBER4-8: 4th Test, Old Trafford12-16: 5th Test, The Ovallast_img read more


first_imgFinn Harps have announced the launch of a voucher promotion for the Christmas Gift market. Vouchers can be used to purchase, or as part exchange, for Season Tickets, Annual Lotto Membership and Club Merchandise.The Club will announce Season Ticket prices early in 2012, when the format and fixtures for next season are confirmed by the FAI.Gift certificates can be purchased from Committee members or from the Club Office (074-9130070).  FINN HARPS ANNOUNCE VOUCHER SCHEME was last modified: December 8th, 2011 by StephenShare this:Click to share on Facebook (Opens in new window)Click to share on Twitter (Opens in new window)Click to share on LinkedIn (Opens in new window)Click to share on Reddit (Opens in new window)Click to share on Pocket (Opens in new window)Click to share on Telegram (Opens in new window)Click to share on WhatsApp (Opens in new window)Click to share on Skype (Opens in new window)Click to print (Opens in new window) Tags:finn harpslast_img read more

A’s spring training preview: Kyler Murray, Jesus Luzardo among biggest questions

first_imgMESA, Ariz. — When the A’s gather at Hohokam Stadium on Monday for their first workout of the spring, they’ll be kicking off a season with something they havent had for a while: confidence.This isn’t the hope-we-make-the-playoffs type of confidence. This is the we’ve-been-there-before type of confidence.The A’s are coming off a season in which they not only reached the playoffs for the first time since 2014, but also went blow-for-blow with the Houston Astros, winning 97 games and earning …last_img

Report: iOS Could End iPhone Jailbreaking (Updated)

first_imgmarshall kirkpatrick Tags:#news#web 8 Best WordPress Hosting Solutions on the Market AddictiveTips, a tech blog with a small but growing profile online, has published what it says is leaked information from an anonymous employee at Apple alleging that the new iOS will, among other things, detect whether an iPhone has been jailbroken and unlocked – then require that factory approved software be re-installed. Jailbroken phones that don’t return to the fold will be shut off from receiving a signal from AT&T. Update: Upon further discussion, it’s unclear whether the code in question will shut off all jailbroken phones or just those that have been unlocked from AT&T to run on T-Mobile.IPhone owners jailbreak their phones so they can run unauthorized software and access parts of device (which they bought) that Apple prohibits customer use of, including the ability to turn the iPhone into a wifi hotspot without paying an additional fee. Though new versions of the OS regularly allow users to access functionality that required jailbreaking before, posts such as our nearly 2 year old Top 10 Apps Worth Jailbreaking Your iPhone to Get remain very, very popular. Jailbreaking advocates consider the tactic to be a matter of freedom, customer rights and tech innovation.See also: Why You Have to Jailbreak the iPhoneIn its post that we found via The Next Web, AddictiveTips quotes its anonymous source thusly:in the iOS4 there is a line of code we wrote that stands for OAU also known as “Over Air Updates”. How it works is every 7 to 14 days We (Apple) and AT&T send a message to your iPhone that gathers some data from your iPhone without you knowing and we see what is running, baseband and firmware. We then send a following message. “There are optional updates for your iPhone, Would you like to install them now?” two options “Yes” or “Later”. Those are what would would call “OPTIONAL UPDATES” Now there are things called “MANDATORY UPDATES”. They tend to work the same way, grab data from the iPhones sends it to AT&T and us then back to your iPhone with the message, “Your iPhone (name of iphone) must be updated to the current AT&T standards to run”, your only option is to “Accept” Now you can try to work your way around it until you get the second mandatory message again “You must plug iPhone into iTunes and update” If you don’t do this you will then receive no Signal from the network anymore and your iPhone will potentially lock up with no signs of use until you update your iPhone via iTunes. You all agreed to this terms and condition when you installed iTunes 9.2 and then again once you updated to iOS4.The article’s source seems to indicate that this is not just about unlocking the iPhone from AT&T as a carrier, but also about the easier hack of jailbreaking it to run unauthorized software. Those two are on occasion confused, however.Is This Credible?It’s not hard to believe that Apple would implement a technical step to back up the prohibition against jailbreaking that it has in its Terms of Service, but it’s also not hard to believe that few enough people jailbreak their phones that it wouldn’t really be worth the hassle.Do you buy it? The source, Addicting Tips, is a small blog that doesn’t appear to have a history of sensationalism. The site posts tips on things like how to remove background noise during VOIP calls in Skype and how to gain root access to various mobile devices. Previous posts have been linked-to by trusted bloggers like LifeHacker and SearchEngineWatch’s Danny Sullivan.Not everyone believes it, though. IPhone jailbreak software developer @musclenerd, of the hacking group iPhone Dev Team, said this afternoon, “So much of that article seems like nonsense. How would AT&T send an over-the-air lock command to an iPhone on T-Mobile’s network?”Others have said that any anti-jailbreaking steps Apple takes will simply fall in time to an arms race with jailbreaking hackers. Leading hacker George Hotz said at a conference in France this week that he has created an exploit that will “jailbreak for life” any iPhone, including one running the newest iOS.What do you think? Why Tech Companies Need Simpler Terms of Servic…center_img Top Reasons to Go With Managed WordPress Hosting Related Posts A Web Developer’s New Best Friend is the AI Wai…last_img read more

Construction in Cambodia

first_img Start Free Trial Already a member? Log in Sign up for a free trial and get instant access to this article as well as GBA’s complete library of premium articles and construction details. This article is only available to GBA Prime Memberscenter_img A few weeks ago, I accompanied my wife Karyn, who is a pediatrician, on a three-week trip to Cambodia. She volunteered her services at the Angkor Children’s Hospital in Siem Reap, in response to a request from hospital administrators. The hospital invited her to Cambodia to provide two weeks of specialized medical training for the hospital staff.Lucky me: I got to tag along.Siem Reap is a bustling town in northwest Cambodia, only a few miles away from the world-famous temples of Angkor Wat. A typical lumberyard in Siem Reap, Cambodia. These lumberyards sell boards and planks (mostly tropical hardwoods, of course) as well as wood poles (used to support the forms used for suspended concrete floors) and bamboo poles (visible on the right side of the photo). Bamboo is used for many purposes, including staging. The tropical hardwood boards sold by Cambodian lumberyards are gorgeous, but it’s hard to look at these boards without wondering whether local logging practices are sustainable. One lumberyard I visited had a tablesaw powered by a gasoline engine. The saw is apparently used to rip boards to order. Power tools can be quickly repaired in Siem Reap. This worker is rewinding an electric motor. To deliver construction materials, tools, and equipment to the job site, most Cambodian builders use a tuk tuk (a trailer pulled by a motorcycle). Tuk tuks are used to deliver lumber and steel profiles, as well as anything that can be delivered in a Sheetrock bucket. At a demolition job in Siem Reap, I saw two workers loading a tuk tuk trailer with broken bricks and mortar. The weight that these tuk tuks can handle is impressive. This welding shop delivers steel with a very long tuk tuk trailer. Windows being delivered in Siem Reap. Strictly speaking,… last_img read more

Negre asserts Hockey India is the national body

first_imgInternational Hockey Federation (FIH) president Leandro Negre has expressed the hope that the Supreme Court of India would eventually rule in favour of the “democratically elected” Hockey India (HI), the national body that FIH recognises.Leandro NegreAlso, Negre categorically said that there was no question of the FIH recognising the KPS Gill-headed Indian Hockey Federation (IHF) as it has been suspended for not adhering to the world governing body’s guidelines on the merger of men’s and women’s bodies.”I would like to remind you that so far the Supreme Court has given good results (verdicts) to us in all cases. Recently, when India had to field a team at the women’s World Cup in Argentina, they allowed HI to send the team.For the Commonwealth Games (CWG) too, it was HI. I am quite sure the result of this case will be in favour of HI. If it doesn’t happen that will be a big damage (to the game in India),” Negre told MAIL TODAY in an interview.HI and IHF are locked in a bitter and messy battle over who controls the game in the country, with the sports ministry being a third party involved in the court cases being fought in Delhi and Patna. IHF had called for AGM/election on October 3 but the Patna High Court put a stay on it when a Bihar hockey official challenged the holding of the AGM.”At this moment, HI has all the authority to be the sole body of hockey in India. For the FIH, it’s very clear: the only body we can recognise in India is HI, no other one. The International Olympic Committee is doing the same,” he stressed. “The future of hockey in India is fantastic, incredible. People will have to stop all these small political issues – it’s egos of some political people – for the best of hockey. These are only personal issues; people have to have a vision for the future.”advertisementAbout the status of the IHF, the FIH president said that for the world body it doesn’t exist. “The IHF was suspended by us three years ago because they didn’t merge with the women’s hockey, and that’s against our constitution. They created a new body called Indian Hockey Confederation but again there was no real merger. Finally, the confederation was also suspended,” he pointed out.”For FIH, it’s a big surprise that after three years IHF has risen again. Why? I submitted this question to many people, but I haven’t got any good answer until now. If some people are looking to damage Indian hockey, go ahead. But they will never be recognised by the FIH. The IHF is past and HI is the future,” he emphasised.Former India captain Pargat Singh lost to Vidya Stokes for the top HI post, but Negre said he would not oppose anyone. “I met Pargat and he told me that he would support HI,” he said.The Spaniard said he’s ready to visit India again if that helps in resolving the complex issues. The FIH, at its congress in Montreux, near Lausanne, next month, is set to amend its constitution vis–vis the upper age limit for its executive board members.”We are reviewing the size of our executive board, and one of the main points is the upper age limit of 70 for its members. I fully support that. If this rule is in the FIH statutes, I have to agree to such a limit for HI (too, as per the new guidelines of the sports ministry),” he said.”I’m sure all the continental federations will abide by the same solution about the age issue. We’d love if all national federations abide by the same steps.” Negre revealed that at next year’s Champions Trophy, the first ever wild cards will be issued to the hosts and Pakistan, though they would be in different pools.”It will be held in three cities. Two of these will be picked from amongst Jalandhar, Mohali, Chandigarh, and Amritsar. There will be a change in format. Instead of two pools, teams will play in a round robin format, there will now be three. The two top teams from each pool will advance to the next stage, a third pool,” he explained.”These two teams will not play against each other again but their results [points] will be counted. This will be followed by the semi-finals and the final.”last_img read more

At least seven companies investigated in bread pricefixing probe

first_imgVANCOUVER – The Competition Bureau’s investigation into allegations of bread price-fixing includes at least seven companies from bakery wholesalers and discount chains to Canada’s three major grocers, according to court documents.George Weston Ltd. (TSX:WN) and Loblaw Companies Ltd. (TSX:L) admitted Tuesday to participating in an industry-wide bread price-fixing arrangement for over a decade and tipping off the country’s competition watchdog.The Competition Bureau executed search warrants at the offices of a number of grocers earlier this fall, but has said there has been no conclusion of wrongdoing and no charges have been laid.The investigation began on Aug. 11 and was expanded on Oct. 23.The search warrants and information to obtain them were sealed because of concerns by the watchdog that the release of the information might compromise its investigation. However, the affidavits sworn by a Competition Bureau investigator to have them sealed were unsealed by the court this week.According to those affidavits, the regulator is also investigating the alleged involvement of Canada Bread, Walmart, Sobeys (TSX:EMP.A), Metro (TSX:MRU) and Giant Tiger as well as “other persons known and unknown.”“The bureau is collecting facts to determine the precise time frame of, and the participants in, the alleged conspiracy,” Simon Bessette, a senior competition law officer, swore in an affidavit on Oct. 26.“Analyzing the records the bureau obtains from the search warrants sought in the ITO will take time; however, it would only be after such analysis is performed that the bureau would be in a position to determine whether additional investigative steps are required.”“Should details of the bureau’s ongoing investigation be made available to the public, the integrity of the evidence available through further investigative steps and/or court authorizations may be compromised,” Bessette wrote.Metro said in a statement Tuesday that it continues to co-operate with authorities and it has launched an internal investigation.“Based on the information processed to date, we have found no evidence that Metro has violated the Competition Act and we do not believe that the bureau’s investigation will have a material adverse effect on the corporation’s business, results of operations or financial condition,” the statement said.Giant Tiger released a statement Wednesday saying they currently “have no reason to believe that Giant Tiger or any of our employees has violated the Competition Act.”Walmart Canada spokesman Alex Roberton said in an email that the company “takes its legal obligations very seriously.”Canada Bread spokeswoman Sylvia Sicuso said Tuesday that the company and its associates “operate with the highest ethical standards” and neither has been charged with any offences.Giant Tiger, Walmart Canada and Canada Bread all said they are co-operating fully with the investigation.Sobeys Inc. did not respond to a request for comment, but has previously said it is also co-operating.Weston and Loblaw said Tuesday they became aware of an arrangement involving the co-ordination of retail and wholesale prices of some packaged breads from late 2001 until March 2015.The companies said they established an independent compliance office earlier this year and provided training and re-certification to marketing personnel at Weston Bakeries and all merchants and store managers at Loblaw, as well as senior managers at both companies and at parent company George Weston.The employees responsible for the companies’ role in the arrangement are no longer employed there.Loblaw is also offering eligible customers a $25 gift card that can be used at its grocery stores across Canada.The Competition Act prohibits agreements that “prevent or unduly lessen competition or to unreasonably enhance the price of a product,” according to the bureau.That could include agreements between competitors to fix prices, or to restrict production of a product by setting quotas or other means, which would be considered cartel activities. Penalties for price fixing could include fines of up to $25 million, imprisonment to a maximum term of 14 years, or both.However, the bureau says price-fixing conspiracies are, by their nature, difficult to detect and prove.Follow @AleksSagan on Twitter.Note to readers: This is a corrected story. A previous version provided incorrect maximum fines and imprisonment terms for price-fixing agreements.last_img read more