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Open Book Extracts Announces Completion of Largest Randomized Controlled Trial of Rare Cannabinoids for Pain

ROXBORO, N.C. — Open Book Extracts (OBX), a cGMP-certified manufacturer and distributor of the industry’s most innovative and highest quality cannabinoid ingredients and finished products, today announced the completion of its first […]

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Does Smoking Pot Make You Want to Drink Less?

It seems today, everyone wants to quit something, and not everyone is having an easy time of it. Whether you’re going to therapy, trying some quick fix being advertised on TV, or depending on will power, it’s hard to change from hard-set patterns. So, it’s always nice to know when a better method might be […]

The post Does Smoking Pot Make You Want to Drink Less? appeared first on CBD Testers.

The Pursuit of Uniqueness: Extending Valiant-Vazirani Theorem to the Probabilistic and Quantum Settings

Quantum 6, 668 (2022).

https://doi.org/10.22331/q-2022-03-17-668

Valiant-Vazirani showed in 1985 [45] that solving NP with the promise that "yes" instances have only one witness is powerful enough to solve the entire NP class (under randomized reductions). We are interested in extending this result to the quantum setting. We prove extensions to the classes Merlin-Arthur MA and Quantum-Classical-Merlin-Arthur QCMA [7]. Our results have implications for the complexity of approximating the ground state energy of a quantum local Hamiltonian with a unique ground state and an $textit{inverse polynomial}$ spectral gap. We show that the estimation (to within polynomial accuracy) of the ground state energy of poly-gapped 1-D local Hamiltonians is QCMA-hard, under randomized reductions. This is in stark contrast to the case of constant gapped 1-D Hamiltonians, which is in NP [24]. Moreover, it shows that unless QCMA can be reduced to NP by randomized reductions, there is no classical description of the ground state of every poly-gapped local Hamiltonian that allows efficient calculation of expectation values. Finally, we discuss a few of the obstacles to the establishment of an analogous result to the class Quantum-Merlin-Arthur (QMA). In particular, we show that random projections fail to provide a polynomial gap between two witnesses.

Time crystals on a quantum computer reach a record size

Results mark the beginning of a new phase in quantum simulation, say physicists

The post Time crystals on a quantum computer reach a record size appeared first on Physics World.

QubiC: An Open-Source FPGA-Based Control and Measurement System for Superconducting Quantum Information Processors

Lawrence Berkeley National Lab's new open source control & measurement system for superconducting quantum processors, bridging the quantum algorithm and the quantum hardware implementation layers of the computing stack.

The post QubiC: An Open-Source FPGA-Based Control and Measurement System for Superconducting Quantum Information Processors appeared first on Semiconductor Engineering.

Tiny Tina’s Wonderlands Endgame Chaos Chamber Mode Revealed

Once the end credits have rolled on Tiny Tina's Wonderlands, the real endgame begins with a mode that developer Gearbox Software calls Chaos Chamber. A replayable dungeon, each run in the Chaos Chamber will take place across several randomized rooms that feature boss fights and a loot stash waiting at the end.

The catch here is that each dungeon room will have two portals that players can choose between once the area has been cleared, with the new location activating one of several curse debuffs that are designed to make the journey that much more challenging.

Players can get around these curses by collecting crystals in each Chaos Chamber run, which can then be smashed against a rainbow-glowing die that spawns after completing a room. A normal Chaos Chamber run should take around 20-30 minutes to complete, and ends with a main boss fight as the grand finale.

"We have over 60 level layouts, which will mix and match throughout a dungeon run," lead game designer Kent Rochefort explained. "On top of that, all the many types of enemies from the game can show up, with up to three different kinds of armies in one room. There are also explosive barrels and traps that populate based on the room. Some are smaller, some are bigger. Our level designers went with what felt appropriate for each particular combat arena."

Completing side-objectives and activating an altar with crystals will also give players buffs that could be anything from increased critical damage, expanded ammo capacity, more powerful melee attacks, and more. The higher the risk, the better the reward at the end of a Chaos Chamber run, and players will also earn the in-game currency of Moon Orbs, which can be spent at an Enchantment Re-roller station to fine-tune their favorite gear.

For more details on Tiny Tina's Wonderlands ahead of tis March 25 launch on PC, PlayStation, and Xbox, you can check out our features showing off classes such as the Stabbomancer, Spellshot, and Spore Warden.

Study Finds Psilocybin Therapy Has Long-Lasting Results

If you’re new to the world of psychedelics, this is a pretty incredible headline. If you’re well versed in the power of hallucinogens, then you’re probably glad that the medical world of today took yet another step to catch up. No matter how you look at it, progress is progress, and this is definitely progress. […]

The post Study Finds Psilocybin Therapy Has Long-Lasting Results appeared first on CBD Testers.

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Social Media Platforms May Put Content Moderation Burden on Users

Last Thursday, on 3rd March 2022, Twitter Inc announced the expansion of its crowdsourced fact-checking and content moderation program “Birdwatch” in a blog post (1). It would make notes on potentially misleading tweets visible to more users on the platform. The micro-blogging platform launched the project named Birdwatch last year as an experiment that asked […]

LENVIMA in Combination with KEYTRUDA Approved In Taiwan for the Treatment of Patients with Advanced Endometrial Carcinoma

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TOKYO, Mar 7, 2022 - (JCN Newswire) - Eisai Co., Ltd. announced today that LENVIMA (generic name: lenvatinib mesylate), the multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A. (known as MSD outside the United States and Canada)'s KEYTRUDA (generic name: pembrolizumab) has been approved in Taiwan for the treatment of patients with advanced endometrial carcinoma who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation.

The approval is based on results from the pivotal Phase 3 Study 309/KEYNOTE-775 trial. These results were presented at the Society of Gynecologic Oncology (SGO) 2021 Annual Meeting on Women's Cancer in March 2021, and published in the New England Journal of Medicine in January 2022.(1)

In this trial, LENVIMA plus KEYTRUDA demonstrated statistically significant improvements in overall survival (OS), reducing the risk of death by 38% (HR=0.62 [95% CI, 0.51-0.75]; p<0.0001), and progression-free survival (PFS), reducing the risk of disease progression or death by 44% (HR=0.56 [95% CI, 0.47-0.66]; p<0.0001), versus chemotherapy (investigator's choice of doxorubicin or paclitaxel). The median OS was 18.3 months for LENVIMA plus KEYTRUDA versus 11.4 months for chemotherapy. The median PFS was 7.2 months for LENVIMA plus KEYTRUDA versus 3.8 months for chemotherapy. The objective response rate (ORR) was 32% (95% CI, 27-37) for patients treated with LENVIMA plus KEYTRUDA versus 15% (95% CI, 11-18) for patients treated with chemotherapy (p<0.0001). Patients treated with LENVIMA plus KEYTRUDA achieved a complete response (CR) rate of 7% and partial response (PR) rate of 25% versus a CR rate of 3% and a PR rate of 12% for patients treated with chemotherapy.(2) In this trial, the five most common adverse reactions (any grade) observed in the LENVIMA plus KEYTRUDA combination arm were hypothyroidism, hypertension, fatigue, diarrhea and musculoskeletal disorders.(2)

LENVIMA plus KEYTRUDA was previously approved under accelerated approval process in Taiwan, for the treatment of patients with advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR), who have disease progression following prior systemic therapy and are not candidates for curative surgery or radiation based on data from the Study 111/KEYNOTE-146 trial. In accordance with accelerated approval regulations, continued approval was contingent upon verification and description of clinical benefit; these accelerated approval requirements have been fulfilled with the data from Study 309/KEYNOTE-775.

Endometrial cancer is the most common type of uterine body cancer. It is considered that more than 90% of uterine body cancers occur in the endometrium.(3) Worldwide, it was estimated there were more than 417,000 new cases and more than 97,000 deaths from uterine body cancers in 2020.(4) In Taiwan, there were more than 2,700 new cases of uterine body cancer and nearly 400 deaths from the disease in 2018.(5) The five-year relative survival rate for metastatic endometrial cancer (stage IV) is estimated to be approximately 17%.(6)

Eisai positions oncology as a key therapeutic area and is aiming to discover innovative new medicines with the potential to cure cancer. Eisai is committed to expanding the potential clinical benefits of lenvatinib for cancer treatment, as it seeks to contribute to addressing the diverse needs of, and increasing the benefits provided to, patients with cancer, their families and healthcare professionals.

*In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of lenvatinib, both as monotherapy and in combination with the anti-PD-1 therapy pembrolizumab from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

About LENVIMA (lenvatinib mesylate)

LENVIMA, discovered and developed by Eisai, is an orally available kinase inhibitor that inhibits the kinase activities of vascular endothelial growth factor (VEGF) receptors VEGFR1 (FLT1), VEGFR2 (KDR), and VEGFR3 (FLT4). LENVIMA inhibits other kinases that have been implicated in pathogenic angiogenesis, tumor growth, and cancer progression in addition to their normal cellular functions, including fibroblast growth factor (FGF) receptors FGFR1-4, the platelet derived growth factor receptor alpha (PDGFR&#945;), KIT, and RET. In syngeneic mouse tumor models, LENVIMA decreased tumor-associated macrophages, increased activated cytotoxic T cells, and demonstrated greater antitumor activity in combination with an anti-PD-1 monoclonal antibody compared to either treatment alone.

Currently, LENVIMA has been approved for monotherapy as a treatment for thyroid cancer in over 75 countries including Japan, in Europe, China and in Asia, and in the United States for locally recurrent or metastatic, progressive, radioiodine-refractory differentiated thyroid cancer. In addition, LENVIMA has been approved for monotherapy as a treatment for unresectable hepatocellular carcinoma in over 70 countries including Japan, in Europe, China and in Asia, and in the United States for first-line unresectable hepatocellular carcinoma. LENVIMA has been approved for monotherapy as a treatment for unresectable thymic carcinoma in Japan. It is also approved in combination with everolimus as a treatment for renal cell carcinoma following prior antiangiogenic therapy in over 60 countries, including in Europe and Asia, and in the United States the treatment of adult patients with advanced renal cell carcinoma following one prior anti-angiogenic therapy. In Europe, the agent was launched under the brand name Kisplyx for renal cell carcinoma. LENVIMA has been approved in combination with KEYTRUDA (generic name: pembrolizumab), for the first-line treatment of adult patients with advanced renal cell carcinoma (RCC) in the United States and in Europe. LENVIMA has been approved in combination with KEYTRUDA as a treatment for advanced endometrial carcinoma that is not microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) who have disease progression following prior systemic therapy in any setting and are not candidates for curative surgery or radiation in the United States, and has been approved for the similar indication (including conditional approval) in over 10 countries such as Canada and Australia. In some regions, continued approval for this indication is contingent upon verification and description of clinical benefit in the confirmatory trials. In Europe, it has been approved in combination with KEYTRUDA as the treatment of advanced or recurrent endometrial carcinoma in adults who have disease progression on or following prior treatment with a platinum containing therapy in any setting and who are not candidates for curative surgery or radiation. In Japan, it has been approved in combination with KEYTRUDA as the treatment of patients with unresectable advanced or recurrent endometrial carcinoma that progressed after cancer chemotherapy and with radically unresectable or metastatic renal cell carcinoma.

About Study 309/KEYNOTE-775 Trial

The approval was based on data from Study 309/KEYNOTE-775 (ClinicalTrials.gov, NCT03517449), a Phase 3 multicenter, open-label, randomized, active-controlled study conducted in 827 patients with advanced endometrial carcinoma who had been previously treated with at least one prior platinum-based chemotherapy regimen in any setting, including in the neoadjuvant and adjuvant settings. The primary efficacy outcome measures were OS, and PFS as assessed by blinded independent central review (BICR) according to RECIST v1.1.

Patients were randomized 1:1 to receive LENVIMA (20 mg orally once daily) plus KEYTRUDA (200 mg intravenously every three weeks) or investigator's choice, consisting of either doxorubicin (60 mg/m2 every three weeks) or paclitaxel (80 mg/m2 given weekly, three weeks on/one week off). Treatment with LENVIMA plus KEYTRUDA continued until RECIST v1.1-defined progression of disease as verified by BICR, unacceptable toxicity, or for KEYTRUDA, a maximum of 24 months. Administration of LENVIMA plus KEYTRUDA was permitted beyond RECIST-defined disease progression if the treating investigator considered the patient to be deriving clinical benefit and the treatment was tolerated.

About the Merck & Co., Inc., Kenilworth, N.J., U.S.A. and Eisai Strategic Collaboration

In March 2018, Eisai and Merck & Co., Inc., Kenilworth, N.J., U.S.A., known as MSD outside the United States and Canada, through an affiliate, entered into a strategic collaboration for the worldwide co-development and co-commercialization of LENVIMA. Under the agreement, the companies will jointly develop, manufacture and commercialize LENVIMA, both as monotherapy and in combination with KEYTRUDA, the anti-PD-1 therapy from Merck & Co., Inc., Kenilworth, N.J., U.S.A.

In addition to ongoing clinical studies evaluating the LENVIMA plus KEYTRUDA combination across several different tumor types, the companies have jointly initiated new clinical studies through the LEAP (LEnvatinib And Pembrolizumab) clinical program and are evaluating the combination in more than 10 different tumor types across more than 20 clinical trials.
In Taiwan, Eisai's pharmaceutical sales subsidiary Eisai Taiwan Inc. is marketing Lenvima and is co-commercializing it with a local branch of Merck & Co., Inc., Kenilworth, N.J., U.S.A.

(1) V. Makker. et al. Lenvatinib plus Pembrolizumab for Advanced Endometrial Cancer.
The New England Journal of Medicine. bit.ly/3HPQ59b
(2) The information listed in Taiwanese Package insert
(3) American Cancer Society, "Causes, Risks, Prevention." Endometrial Cancer. bit.ly/3HNy6jy
(4) International Agency for Research on Cancer, World Health Organization. "Corpus uteri Fact Sheet." Cancer Today, 2020. bit.ly/35tT3TP
(5) Taiwan Cancer Registry 2018 Report.
(6) American Cancer Society, "Survival Rates for Endometrial Cancer." bit.ly/3hLZe8i

Media Inquiries:
Public Relations Department,
Eisai Co., Ltd.
+81-(0)3-3817-5120


Copyright 2022 JCN Newswire. All rights reserved. www.jcnnewswire.comEisai Co., Ltd. announced today that LENVIMA (generic name: lenvatinib mesylate), the multiple receptor tyrosine kinase inhibitor discovered by Eisai, in combination with Merck & Co., Inc., Kenilworth, N.J., U.S.A.

Does cannabis help or worsen depression?

Many people use cannabis to ease symptoms of depression, but there haven't been any clinical studies done that examine whether or not it actually can treat the condition.

The post Does cannabis help or worsen depression? appeared first on Leafly.

Oculis Strengthens Leading Ophthalmology Pipeline by In-Licensing Neuroprotective Drug Candidate for Glaucoma from Accure Therapeutics

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Lausanne, Switzerland, and Barcelona, Spain, Mar 2, 2022 - (JCN Newswire) - Oculis S.A., (Oculis) a global ophthalmology company developing life-changing treatments to save sight and improve eye care with breakthrough innovations, and Accure Therapeutics, a private translational neuroscience R&D company, today announced a licensing agreement granting Oculis exclusive global rights to develop and commercialize ACT-01, a potentially disease-modifying therapy to protect and prevent damage to the optic nerve and retina.

ACT-01, which is being renamed OCS-05, is a first-in-class small molecule with neuroprotective activity that has shown positive results in animal models of neuroinflammation and neurodegeneration. Its mechanism of action is related to the activation of the trophic factor pathways such as IGF-1 and BDNF. In ophthalmology, this action can protect the nerve axons in conditions where the optic nerve is affected, such as in acute optic neuritis and glaucoma, where the OCS-05 could prevent chronic vision loss.

Based on positive preclinical data and results of a phase 1 safety and PK study in healthy volunteers, a phase 2a study was initiated (the ACUITY study).

ACUITY is a two-arm, randomized, double-blind, placebo-controlled, monocentric study to evaluate the safety and tolerability of OCS-05 compared to placebo in patients with acute optic neuritis. In addition to safety, secondary outcome measures will include optic nerve anatomical measures, as well as visual function measures. The study is ongoing at the La Pitie-Salpetriere hospital in Paris within the neurology-ophthalmology network of the Public University Hospital Group in Paris (APHP). One third of the planned sample size has been enrolled.
Oculis is currently planning the expansion of the program in ophthalmology working with the regulatory agencies in the US, EU and China amongst others.

Riad Sherif, M.D., CEO of Oculis, said: "We are excited about this agreement as it combines Oculis's ophthalmology expertise with Accure's unique neuroprotective approach to help transform the treatment of neurodegenerative diseases in ophthalmology. At Oculis, our focus is on building a highly innovative and differentiated pipeline providing life changing treatments for ocular unmet medical needs, and OCS-05 is a perfect fit for that ambition. Glaucoma is a leading global cause of irreversible blindness, and despite IOP lowering treatments, a significant proportion of patients still go blind. With OCS-05, we have the potential to bring to market the first neuroprotective for glaucoma and other optic neuropathies."

Laurent Nguyen, M.D., Co-founder and Chief Executive Officer at Accure Therapeutics, said: "Having shown promising early data and potential in a number of ocular disease indications, the timing is right for a partnership between two like-minded companies committed to patients and driven by a passion for neuroscience. By leveraging its expertise in ophthalmology, Oculis has the potential to fulfill the promise of this exciting asset in a wide range of neurodegenerative diseases."

In reference experimental animal models of acute optic neuritis (acute inflammatory demyelinating disorder of the optic nerve) and high-pressure glaucoma (high eye pressure damaging the optic nerve and leading to permanent vision loss), OCS-05 reduces damage to the optic nerve and retina. It also decreases paralysis progression in an autoimmune encephalomyelitis animal model for multiple sclerosis (inflammation caused by the body's immune system, which destroys nerve cell processes and myelin in the brain and spinal cord).

Data from a completed phase 1 study show the safety and tolerability of single and multiple doses of OCS-05 in healthy volunteers.

Under the terms of the agreement, Accure Therapeutics will receive an upfront payment, potential milestone payments upon the achievement of certain development and commercial milestones, and tiered royalties on sales.

Anthony Rosenberg, Chairman of Oculis's Board of Directors, said: "The addition of OCS-05 to Oculis's pipeline is very much in line with the Company's strategy to develop transformative therapies that address the root cause of ocular disease to improve patients' sight and quality of life. There is a clear need for first-in-class therapies that can protect and prevent damage to the optic nerve and retina. Oculis has the team and expertise to bring OCS-05 through clinical trials and ultimately to patients around the world."

Montserrat Vendrell, Chairman of Accure Therapeutics and Partner at Alta Life Sciences added: "This licensing deal with Oculis is a proof-of-concept of the value creation that Accure Therapeutics brings as a translational R&D engine, taking forward truly unique science that spun-off from the University of Barcelona. This licensing agreement will enhance Accure's capabilities to accelerate and expand value potential for the rest of its pipeline."

About Oculis
Oculis is a global biopharmaceutical company purposefully driven to save sight, improve eye care and address significant unmet medical needs with breakthrough innovations. Oculis's highly differentiated pipeline includes candidates for topical retinal treatments, topical biologics and disease modifying treatments. With a presence in key international markets, Oculis is poised to deliver life-changing treatments to patients worldwide.

Headquartered in Lausanne, Switzerland and with operations in Europe, the U.S. and China, Oculis is led by an experienced management team with a successful track record and supported by leading international healthcare investors.

For more information, please visit: www.oculis.com

About Accure Therapeutics
Accure Therapeutics is a private translational neuroscience R&D company. Based in Barcelona (Spain), it was launched in 2020 with a Series A funding led by Alta Life Sciences Spain I and supported by the Centre for Technological and Industrial Development (CDTI). This European company with an international mindset boasts a unique portfolio of three new chemical entity programs pursuing innovative targets - with potential to accommodate others. Accure aims to develop new disease modifying drugs to treat serious conditions such as optic neuritis, multiple sclerosis, Parkinson's disease and epilepsy. With an experienced business and scientific team, Accure Therapeutics is one of the few companies that operate in an agnostic fashion on initial science to deliver cutting-edge drugs in CNS.

To learn more visit https://accure.health/



Copyright 2022 JCN Newswire. All rights reserved. www.jcnnewswire.comOculis S.A., (Oculis) a global ophthalmology company developing life-changing treatments to save sight and improve eye care with breakthrough innovations, and Accure Therapeutics, a private translational neuroscience R&D company

Elden Ring Co-Op: How To Play Multiplayer

Playing Elden Ring co-op is the optimal way to play for many players, but as usual, the system in place is a bit more complicated than you might be used to if you're not someone who tends to jump into From Software's games. The path to playing multiplayer in Elden Ring takes a few steps, but once you've got the process down, you'll be able to quickly join or invite friends and newfound allies alike. Here's all you need to know about how to play Elden Ring in co-op.

Elden Ring: How to play co-op

When you arrive in The Lands Between, you'll default to playing games in solo mode, but you can easily change this using an item you'll start the game with once you get past the tutorial.

The first thing you'll want to do is check your network settings under the game's system options menu. You'll see options for cross-region play, voice, chat, and more. Set these to your preferences, including possibly turning co-op off entirely by selecting your launch setting to offline. But since you're here, you're more likely looking to play in co-op, so here's what you need to know.

In the game's menu--I hesitate to call it a pause menu since you can't actually pause Elden Ring--you'll see three strange items when you click on multiplayer: Finger Severer, Tarnished Furled Finger, and Small Gold Effigy. Each of these has specific purposes relating to multiplayer.

These gold summoning signs are essentially invitations to join co-op with other players.

Tarnished Furled Finger: Leaves a gold summoning sign to play cooperative multiplayer. You can only place one summoning sign, so when you place a new old, your previous gold summon sign will be removed. In other players' worlds, they may see your gold summon sign, and should they interact with it, they will join your game.

Small Gold Effigy: Sends a cooperative summon sign to several nearby summoning pools (activated pools only). In essence, this tells the game that you'd like to join a multiplayer session, and it may mean you're pulled into another player's world at any point once you've activated this.

Finger Severer: Allows you to disband a co-op session with your ally, sending them out of your multiplayer session and returning you both to solo play.

If you'd like to invite a specific player, you can set up a multiplayer password and you'll only be matched with other players using the same password. This works basically like a game invite, allowing you and other specific players to play together while keeping other randomized players from joining or taking you in as their co-op partner.

You can also create up to five group passwords that allow you to filter out the messages, summoning signs, bloodstains, phantoms, and other multiplayer elements from anyone not using your group passwords. This is useful because a lot of player messages can be deceiving or even absurd, so using a group password will help ensure you're only receiving environmental messages from players whom you trust.

Destiny 2 PSA: Xur Now Sells Hawkmoon And Dead Man’s Tale

Xur's inventory this week includes two of the rarer Destiny 2 Exotics, Hawkmoon and Dead Man's Tale, two weapons that were previously available from seasonal quests and challenging missions. While Xur has other Exotic gear for sale--such as Sunshot and Lucky Pants--these two items are well worth acquiring.

Dead Man's Tale is a lever-action scout rifle that combines classic style with satisfying perks if you're talented at landing headshots, while Hawkmoon is a hand cannon from the original Destiny that has been given a new lease on life in Destiny 2. The quests for both weapons are no longer active, due to the removal of the Tangled Shore location in Destiny 2. These Exotics are somewhat unique because you could previously run their missions again and again to receive new versions of the guns with different, random perks. While the missions are gone, you can still get randomized versions of Hawkmoon and Dead Man's Tale from Xur, who offers a new roll on the guns each week.

This week's roll of Dead Man's Tale has the Vorpal Weapon perk, which increases damage against bosses and Guardians using their Super abilities, while the Hawkmoon on offer is equipped with Eye of the Storm. That particular trait makes the weapon more accurate the lower your health is, which works well with setting up the hand cannon's powerful Paracausal Shot ability, which gives you a big-damage blast once you've landed some precision shots.

The downside of this situation is that Xur is charging a premium for these rare guns. Here's how much you'll need to spend for each of them:

Get 'em while they're hot.
  • 125,000 Glimmer
  • 200 Legendary Shards
  • 1 x Exotic Cipher
  • 1 x Ascendant Shard

That's a hefty price to pay for each weapon, let alone both. You'll essentially need the maximum amount of Glimmer that you can hold, a sizable number of Legendary Shards, and two exceedingly rare materials. An Exotic Cipher can be earned at Rank 55 on the Season pass, or you can spend time in the Crucible and Gambit as part of Xur's Xenology quest that the vendor offers, allowing you to earn one per week. Exotic Ciphers are usually required to purchase an Exotic weapon from the dedicated kiosk in the Tower, which contains several years' worth of previously-released Exotics.

Ascendant Shards are somewhat easier to obtain. You can earn several of them on the premium tier of the season pass, dismantling tier 10 Exotic armor, or through resets of the Vanguard, Crucible, and Gambit reputation ranks. Master-difficulty Nightfall Strikes also have a chance to drop them as rewards and Grandmaster Nightfalls will drop one Ascendant Shard for achieving a platinum completion. Banshee-44 also sells Ascendant Shards for a combination of enhancement prisms, planetary materials, and 50,000 Glimmer.

You'll need to be quick to grab these rolls, as Xur will only hang around until the weekly reset on Tuesday, at 9 AM PT / 12 PM ET. If you're looking to see where Xur is this week, you can also check out our weekly guide to see what the Agent of the Nine and occasional game show host has to offer.

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