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Daily Archives: May 25, 2022
New study shows genes can predict response to arthritis treatment and paves the way for future drug development – QMUL
Posted: May 25, 2022 at 4:40 am
Published on:
The researchers also identified specific genes associated with resistance to most available drugs therapies, commonly referred to as refractory disease, which could provide the key to developing new, successful drugs to help these people.
While there has been much progress made over the past decades in treating arthritis, a significant number of patients (approximately 40%) do not respond to specific drug therapies, and 5-20% of people with the disease are resistant to all current forms of medication.
The researchers carried out a biopsy-based clinical trial, involving 164 arthritis patients, in which their responses to either rituximab or tocilizumab two drugs commonly used to treat RA were tested. The results of the original trial published in The Lancet in 2021 demonstrated that in those patients with a low synovial B-cell molecular signature only 12% responded to a medication that targets B cells (rituximab), whereas 50% responded to an alternative medication (tocilizumab). When patients had high levels of this genetic signature, the two drugs were similarly effective.
As part of the first-of-its-kind study, funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership, the Queen Mary team also looked at the cases where patients did not respond to treatment via any of the drugs and found that there were 1,277 genes that were unique to them specifically.
Building on this, the researchers applied a data analyses technique called machine learning models to develop computer algorithms which could predict drug response in individual patients. The machine learning algorithms, which included gene profiling from biopsies, performed considerably better at predicting which treatment would work best compared to a model which used only tissue pathology or clinical factors.
The study strongly supports the case for performing gene profiling of biopsies from arthritic joints before prescribing expensive so-called biologic targeted therapies. This could save the NHS and society considerable time and money and help avoid potential unwanted side-effects, joint damage, and worse outcomes which are common amongst patients. As well as influencing treatment prescription, such testing could also shed light on which people may not respond to any of the current drugs on the market, emphasising the need for developing alternative medications.
Professor Costantino Pitzalis, Versus Arthritis Professor of Rheumatology at Queen Mary University of London, said: Incorporating molecular information prior to prescribing arthritis treatments to patients could forever change the way we treat the condition. Patients would benefit from a personalised approach that has a far greater chance of success, rather than the trial-and-error drug prescription that is currently the norm.
These results are incredibly exciting in demonstrating the potential at our fingertips, however, the field is still in its infancy and additional confirmatory studies will be required to fully realise the promise of precision medicine in RA.
The results are also important in finding solutions for those people who unfortunately dont have a treatment that helps them presently. Knowing which specific molecular profiles impact this, and which pathways continue to drive disease activity in these patients, can help in developing new drugs to bring better results and much-needed relief from pain and suffering.
The incorporation of these signatures in future diagnostic tests will be a necessary step to translate these findings into routine clinical care.
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These Medications are Best for New Variant Symptoms Eat This Not That – Eat This, Not That
Posted: at 4:40 am
Most people withCOVID-19will experience a mild illness, and they'll be able to take care of themselves at home. But someespecially those withunderlying health conditionscould benefit from one of several COVID-19 treatments. Some of these are available in pill form and others are given intravenously or by injectionand all of them must be prescribed by a health care provider.
It's important to remember that while new treatments are effective at reducing the severity of symptoms and helping prevent hospitalization and death in people who become infected with COVID-19, they are not a substitute forvaccination, which remains the single most effective strategy to prevent serious disease. Read on to find outYale Medicine's guide to COVID-19 treatmentsand to ensure your health and the health of others, don't miss these Sure Signs You've Already Had COVID.
What is it?Paxlovidis Pfizer's brand name for an antiviral oral medication (in pill form) that combines two generic drugs, nirmatrelvir and ritonavir. It was the first COVID-19 antiviral pill to receive Food and Drug Administration (FDA)emergency use authorization (EUA), and the National Institutes of Health (NIH) has prioritized its use over other treatments for eligible patients. It is meant for people who have a current COVID-19 infection.
When it was authorized:December 2021.
Who can get it:People ages 12 and up who weigh at least 88 pounds, who have a positive COVID-19 test result, have symptoms, and are at high risk for developing severe COVID-19.
How you take it:For most people, the dose is three pills twice daily for five days, and it must be started within five days of developing COVID-19 symptoms.
Side effects:They're usually mild, and may include altered or impaired sense of taste, diarrhea, increased blood pressure, or muscle aches. Because Paxlovid is still being studied, it's possible that all of the risksaren't yet known.
How it works:Paxlovid is an antiviral medication, a type of drug that stops viruses from replicating inside the body's cells. Two of the pills in the three-pill dose are nirmatrelvir, which prevents the SARS-CoV-2 virus from replicating. The other medication is ritonavir, which gives the first drug's levels a boost by essentially shutting down its metabolism in the liver, so that nirmatrelvir levels remain high and can work longer to fight the infection.
How well it works:89% efficacy against hospitalization and death in theclinical trialin which all participants were unvaccinated.Though the trial was conducted beforeOmicronbecame the predominant variant, Pfizer says that the treatment appears to work well against it. This is backed up bythree laboratory-based studies(all of which involved Pfizer) that have not yet been published in peer-reviewed medical journals.
What else you should know:Paxlovid interacts with many medications, including common ones that are sold over the counter like St. John's Wort, blood thinners, cholesterol medicines, and many more. In some cases, this can cause complications that are serious enough to justify not taking it. So, it's important for doctors to have an up-to-date medication list, including over-the-counter medications and supplements; they may consider other treatments for some patients.
There is no experience treating pregnant women or breastfeeding mothers with Paxlovid. Women who are pregnant should discuss their options with their health care provider. It is also recommended that patients use effective barrier contraception or do not have sexual activity while taking Paxlovid.
Paxlovid is also not recommended for patients with severe liver or kidney disease and those withHIVwho are not on treatment.
What is it?The antiviral treatment remdesivir, sold under the brand name Veklury, was the first COVID-19 therapy to get full FDA approval, and, so far, it's still the only one. Although originally used in COVID-19 patients only after they were hospitalized, new data suggests it can be helpful in outpatients who become infected and who are at high risk for severe disease.It is meant for people who have a current COVID-19 infection.
When it was authorized:Full approval was granted in October 2020. (It was first authorized in May 2020 for critically ill patients who were being treated with oxygen for COVID-19.) The authorization was later expanded to include other groups, and it was authorized to treat non-hospitalized patients in January 2022.
Who can get it:Fully approved for children and adultswho are at high risk for severe disease. Infants and children must be at least 28 days old, weigh over 6.5 pounds or more, and be either hospitalized or at high risk for severe illness.
How you take it:Via injection or IV and administered only in a health care setting by a health care professional. For outpatients, the treatment is a three-day course of infusions that must be initiated within seven days of symptom onset.
Side effects:Nausea is the most common side effect. Hypersensitivity, including infusion-related and anaphylactic reactions, has been observed following treatment. There is insufficient data on the safety of using remdesivir in pregnant women or women who are breastfeeding; patients should speak with their health care provider.
How it works:Administered intravenously to patients who are in the hospital or in an ambulatory setting, the drug inserts itself into new viral genes to block replication of the virus, shortening the time it takes seriously ill patients to recover. A number of experts believe that the drug may work best early in the course of an infection.
How well it works:87% reduction in risk of hospitalization in non-hospitalized patients given a three-day course, according to a study published inThe New England Journal of Medicinein December 2021.
What else you should know:For hospitalized patients, research in early 2020 showed that the therapy reduced length of stay (the number of days in the hospital) from 15 days to 12. However, questions have been raised about remdesivir's trial results for hospitalized patients. In late 2021, the World Health Organization (WHO) recommended against remdesivir after releasingdatathat showed disappointing results. Still, many U.S. hospitals continue to provide this medication.
This is one of two NIH-preferred therapies (after Paxlovid) for COVID-19.
What is it?Bebtelovimab is an FDA-authorized investigational monoclonal antibody treatment that was developed by Eli Lilly. Not all authorized monoclonal antibodies have worked against all of the SARS-CoV-2 variants. However, data showing bebtelovimab's efficacy againstOmicron and its BA.2 subvariantprompted the FDA to authorize the drug through an EUA.It is meant for people who have a current COVID-19 infection.
When it was authorized:February 2022.
Who can get it:Adults and children ages 12 and up who weigh at least 88 pounds. They must have a positive COVID-19 test result and be at high risk for developing severe COVID-19.
How you take it:An intravenous injection is given for at least 30 seconds. Patients are observed by a health care provider for at least an hour after injection. Bebtelovimab must be given within seven days of symptom onset.
Side effects:There is limited information known about the safety and effectiveness of bebtelovimab for the treatment of mild-to-moderate COVID-19, according to theFDA fact sheet.The sheetalso provides a list of potential side effects the FDArecommends reporting to a medical provider, and reports that allergic reactions can happen during and after injection. Because bebtelovimab is still being studied, it's possible that all of the risks aren't yet known.
How it works:It binds to the spike protein that causes COVID-19, similar to other monoclonal antibodies that have shown efficacy against hospitalization and death from the disease.
How well it works:The EUA for bebtelovimab was supported by clinical and nonclinical data that showed it has efficacy against Omicron and its BA.2 subvariant.The clinical data was based on a Phase 2 trial that treated non-hospitalized patients with bebtelovimab alone or together with another drug called etesevimab. That study is available in apreprint, whichhas not yet been peer-reviewed.
What else you should know:There is limited experience treating pregnant women or breastfeeding mothers. So, those patientsshould discuss their options and specific situation with their health care provider.
The NIH considers this to be an alternative treatment, whichshould be usedonly when neither of the NIH-preferred therapies (Paxlovid and remdesivir)are available, feasible to use, or clinically appropriate.
What is it?Molnupiravir, also known by the brand name Lagevrio, was developed by Merck and Ridgeback Biotherapeutics. It was heralded as a potential game-changer when the companies announced their initial clinical trial results in 2021. But when the data was finalized, it showed the drug to have lower efficacy than originally reported. Its FDA authorization came after a close vote that took into account the lowered efficacy and safety profile. The Centers for Disease Control & Prevention (CDC) now recommends that this drug should be used when the above-mentioned treatments aren't available.
When it was authorized:December 2021.
Who can get it:People ages 18 and up who are at high risk for hospitalization and death from COVID-19.
How you take it:Four capsules every 12 hours (for example, at 8 a.m. and 8 p.m.) for five days. It must be taken as soon as possible, within five days of symptom onset.
How it works:When the drug enters the bloodstream, it blocks the ability of the SARS-CoV-2 virus to replicate.
How well it works:30% efficacy against hospitalization and death. Merck initially reported the efficacy as 50%, but later adjusted that figure. Some laboratory studies from Merck have shown that molnupiravir is effective against the Omicron variant.
Side effects:Diarrhea, nausea, and dizziness are the most common side effects. You should stop taking the pills right away if you have an allergic reaction. Because molnupiravir is still being studied, it's possible that all of the risks aren't yet known.
What else you should know:Molnupiravir is not recommended during pregnancy, since it has not been studied in pregnant women and has shown potential harm inin vitrostudiestherefore, the true risk for harm to an unborn baby is unknown.
Individuals who are able to become pregnant should use reliable birth control during treatment and for four days after their last dose. It is also not known if molnupiravir could affect sperm, so individuals who are taking molnupiravir and who are sexually active with partners who are able to become pregnant should use reliable birth control during treatment and for three months after the last dose. (Studies to understand the risk to sperm beyond three months are ongoing.)
The NIH considers this to bean alternativetreatment, whichshould be usedonly when neither of the NIH-preferred therapies (Paxlovid and remdesivir)are available, feasible to use, or clinically appropriate.
What is it?Evusheld is a monoclonal antibody, but different than the other medications listed above. It combines two drugs, tixagevimab and cilgavimab. It is not designed to treat COVID-19; rather, its purpose is to keepimmunocompromised peoplewho do not respond to vaccination from getting sick. Developed by AstraZeneca, it is the first long-acting antibody to receive an EUA for pre-exposure prevention of COVID-19.6254a4d1642c605c54bf1cab17d50f1e
When it was authorized:December 2021.
Who can take it:Anyone 12 years or older who weighs at least 88 pounds and is at risk for severe illnessor those who cannot receive COVID-19 vaccines. Anyone taking the medication should have neither an active COVID-19 infection norbeen recently exposed to a close contact who is infected.
How you take it:A health care provider will give one dose of Evusheld in the buttocks in two separate injections (of tixagevimab and cilgavimab, respectively), one after the other, with repeat doses every six months, while SARS-CoV-2 remains in circulation.Patients will be monitored for an hour after each injection. In March, the dosage for Evusheld was doubled, so patients who received the two injections prior to the change in dosage recommendations should talk to their doctor about the need to repeat treatment.
Side effects:Any intramuscular injection can cause hypersensitivity, pain, bruising, soreness, swelling, possible bleeding, or infection at the injection site. Tell your health care provider if you experience any allergic reactions during and after an injection. Serious but uncommon cardiac adverse events have occurred in the clinical trial.
Contact your health care provider or get medical help right away if you have any symptoms of cardiac events, including pain, pressure, or discomfort in the chest, arms, neck, back, stomach, or jaw, as well as shortness of breath, feeling tired or weak (fatigue), feeling sick (nausea), or swelling in your ankles or lower legs. Because Evusheld is still being studied, it's possible that all of the risks aren't yet known.
How it works:It combines two antibodies with differentand complementaryactivities against the SARS-CoV-2 virus.
How well it works:According to a clinical trial, there was a 77% reduction in chances of getting COVID-19 initially; 83% six months after the treatment, according to theFDA news release. AstraZeneca says the drug should be effective for a year. It's important to note that the exact efficacy against the latest variants is still unclear. (Note: Because the trial did not include immunocompromised patients, it is also unclear If the 77% reduction would apply to those who are immunosuppressed.)
What else you should know:Evusheld is intended as an additional benefit for those who may not respond to vaccination or who cannot be vaccinated. People who get Evusheld may need to receive additional doses for ongoing protection if new variants emerge. The best timing for additional doses, if needed, is not yet known; it will depend on which SARS-CoV-2 variant is in circulation.
Note: If you are experiencingsymptoms of COVID-19and think you are eligible for a treatment, you can visit the governmentTest-to-Treat Locator. You can use the site to search for places near you where you can fill a COVID-19 prescription or identify sites that provide testing, medical care, and COVID-19 medications.
Follow the fundamentals and help end this pandemic, no matter where you liveget vaccinated ASAP; if you live in an area with low vaccination rates, wear an N95 face mask, don't travel, social distance, avoid large crowds, don't go indoors with people you're not sheltering with (especially in bars), practice good hand hygiene, and to protect your life and the lives of others, don't visit any of these 35 Places You're Most Likely to Catch COVID.
This article has been published in Yale's Medicine.
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These Medications are Best for New Variant Symptoms Eat This Not That - Eat This, Not That
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The Aya Neo Air Is An OLED-Packing Handheld That Can Run Cyberpunk 2077 And GTA V – Nintendo Life
Posted: at 4:39 am
Image: Aya Neo
Chinese firm Aya Neo has already made something of a splash in the handheld gaming arena thanks to its Windows-based portables, but they've always been held back by the fact that they're so expensive, often costing over $1000.
However, the firm is expanding its lineup to include the Aya Neo Air, which will cost just CNY 4,399 (~US$649) when it launches later this year. That's still a big chunk of change, but that price point makes this a more realistic rival for the Switch although it's worth noting that it's still more expensive than Valve's recently-released Steam Deck.
Announced alongside the more powerful Aya Neo 2 and Aya Neo Slide, the Air will serve as the company's entry-level handheld and is powered by an AMD Barcelo APU which includes RX Vega graphics architecture. This means it will have less processing muscle than its siblings, both of which boast the Ryzen 7 6800U chipset with RDNA 2 graphics but those products will also cost more.
However, the company still claims that the Air will be capable of running the likes of GTA V, Forza Horizon 5 and Cyberpunk 2077 (with low graphical settings, as seen in the video below) and the fact that it has an OLED panel means it is superior to its stablemates in that regard Aya Neo's other products all use IPS screens.
It has also been confirmed that the Air lives up to its name by weighing just 420g, which makes it lighter than the Switch OLED Model.
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The Aya Neo Air Is An OLED-Packing Handheld That Can Run Cyberpunk 2077 And GTA V - Nintendo Life
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How to Build a Culture That Honors Quiet Time – HBR.org Daily
Posted: at 4:38 am
If you could travel back in time to Philadelphia in the summer of 1787 to visit the legendary meeting hall where the delegates to the Constitutional Convention were doing their work, youd find something rather strange.
The street in front of Independence Hall was covered with a giant mound of dirt.
The framers of the U.S. Constitution had ordered the construction of this earthen sound barrier because they were concerned that the noises of horse-drawn carriages, street vendors, and conversations outside would disturb the intense concentration that would be necessary for completing their task. The delegates werent going for total monastic silence. The historical records show that there was plenty of vocal debate and disagreement. But there was an underlying recognition that the group needed a quiet container for doing their extremely challenging work. That was the point of the big dirt mound.
Fast forward about 240 years, and youll find that lawmakers in the United States have a rather different attitude toward noise. One of us, Justin, worked for several years as a legislative director in the U.S. House of Representatives, and he consistently found that it was too noisy to think. With cable news blasting, Twitter notifications dinging, high-decibel alarms signaling votes, to say nothing of the informational noise that pervades Capitol Hill: endless time-sensitive emails and the constant pressures of networking, politicking, and media management.
The example of this radical shift over 240 years illustrates a simple fact: An organizational culture can be noisy, or it can be quiet.
Theres empirical evidence that life is noisier than ever before there are louder and more ubiquitous TVs, speakers, and electronic device notifications in public spaces and open-plan offices. Across Europe, an estimated 450 million people, roughly 65% of the population, live with noise levels that the World Health Organization deems hazardous to health. All this has serious implications for our mental health, our physical health, and our ability to generate creative work.
The meaning of noise can sometimes be subjective. One persons symphony is another persons annoyance. We define noise as all the unwanted sound and mental stimulation that interferes with our capacity to make sense of the world and our ability to act upon our intentions. In this sense, noise is more than a nuisance. Its a primary barrier to being able to identify and implement solutions to the challenges we face as individuals, organizations, and even whole societies.
So, how do we transform norms of noisiness? On our teams and in our broader organizations, how can we build cultures that honor the importance of silence?
If we want organizational cultures that honor quiet, there are a few general principles we need to apply to make the transformation. The first is that we have to deliberately talk about it; we need to have clear conversations about our expectations around constant connectivity, when its permissible to be offline, and when its acceptable to reserve spaces of uninterrupted attention. These conversations can get into deeper cultural questions like whether its possible to be comfortable in silence together rather than always trying to fill the space, or whether its OK to be multitasking when another person is sharing something with you.
Weve found that, across different settings and situations, answering the following three questions can help teams begin to honor quiet time.
Starting a conversation about shared quiet doesnt just mean seizing the opportunity to point fingers at other peoples noisy habits. The best starting point for a conversation on group norms is a check-in with yourself. How are you contributing to the auditory and informational noise facing the greater collective?
Maybe you unwittingly leave ringers and notifications on full blast. Maybe you think out loud or habitually interrupt others. Perhaps you impulsively post on social media or send excessive texts or emails that require responses. Maybe you play music or podcasts in common spaces without checking in with others or jump on important work calls while your daughter is sitting next to you doing her homework.
Take some time to question whether any given habit thats generating noise is necessary or if its really just an unexamined impulse a default that needs to be reset. If your self-observation doesnt yield clear insights, ask a truth-teller in your life for observations about how you could do better.
Susan Griffin-Black, the co-CEO of EO Products, a natural personal care product company, tells us that she made a vow years ago to, never be on my phone or computer when someone is talking to me, no multitasking when Im with someone else. She upholds her golden rule, despite having hundreds of employees, a family, and a lot of social commitments.
Like Susan Griffin-Blacks commitment to not multitask in the presence of others, you can set a golden rule for mitigating noise or bringing in more deliberate quiet. Model what you want to see more of in the world. Stop to consider what you value most when it comes to mitigating noise and finding quiet. What personal golden rule reflects that? Or, alternatively, consider what noisy habits bother you most. What golden rule would address those?
In the 1990s, as an executive with Citysearch (now a division of Ticketmaster), Michael Barton noticed a problem. Workers, particularly programmers and developers, were struggling with noise and frequent interruptions in the open plan office. A young analyst at the company offered him an idea: Give each team member a red sash a three-foot-long/three-inch-wide strip of bright red fabric to wear as a do not disturb sign. There would be no stigma involved with wearing it if everyone knew they could simply open their drawer, take out their red sash, put it over their neck, and be considered out of the office. Barton took the idea up the chain, and the company decided to try it.
The red sash was not a panacea. It didnt eliminate many of the problems of noise and interruption. But it was a start. It led to several other experiments, including quiet phone-booth-sized mini-workstations and a hermetic tech cave for coding work. More importantly, however, the red sash intervention raised the issue of noise and distraction and opened an important dialogue.
Where its appropriate, and when its within your influence, consider how you can be a champion for quiet not just in the whole organization, but specifically for the people who lack the power or autonomy to structure their own circumstances. Maybe youre in a position in your company where you can call out the plight of an engineer or copywriter who obviously needs a sanctuary from the workplace din. In the personal sphere, maybe you suspect your introverted nephew could use an occasional break from boisterous family events, and you can gently raise the issue with your sibling.
While you cant set the overall group norms and culture unilaterally on the basis of what you think is right, you can be on the lookout for new ideas to propose or new possibilities for managing the soundscape or enhancing the ambiance, especially ones that serve the interests of those who lack influence.
The participants in the 1787 Constitutional Convention had norms that honored quiet deliberation. Facilitating pristine attention was a shared goal. That big mound of dirt reminded them and the public that the point of their gathering was to get beyond distraction in order to do important work. While a mound of dirt would not solve todays problems (the noise is so often inside our offices and homes), there are ways, as weve seen above, to shift organizational cultures with respect to noise and quiet.
At Citysearch, it was the red sash. For Susan Griffin-Black, its adhering to a golden rule. But there are many more ways to help create cultures of quiet. At some organizations, its no email Fridays or no meeting Wednesdays. At others, its eliminating the expectation of being available and on electronic devices during weekends or after 5 pm. For some workplaces, a redesign of the floor plan might help specific kinds of workers get the focus that they need. One solution might be authorizing uninterrupted blocks of time during the workday. Another might be giving up on the open floor plan and moving the whole office to a new building. For others still, its eliminating email as the primary means of communication and turning instead to a twice-daily team update meetings or an electronic system that preserves quiet headspace.
Across our society today, norms of noisiness run deep. Demands like constant connectivity and maintaining a competitive advantage still prevail in most office cultures. Few organizations prize or prioritize pristine human attention. But there are simple strategies we can employ in order to find our own personal sanctuaries and to shift broader cultures. By reclaiming silence in the workplace, we can create the conditions for reducing burnout and enhancing creative problem solving.
Even in an increasingly noisy world, we can be quiet together.
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How to Build a Culture That Honors Quiet Time - HBR.org Daily
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He wants to stay, Broke the golden rule, Dont think Ange liked his demand Celtic fans react to trophy day footage of star – Vital Celtic
Posted: at 4:38 am
Trophy day was magic wasnt it? To see the manager so happy after all the stick he had taken from the media over the course of the season was just brilliant.
It was a proverbial eff you to those that had lambasted him in the press after just seven games into the job.
And you know what?
It says a lot about those journalist that claimed he was under serious pressure and could be sacked in October that they havent had the balls or courage to come out and say I was wrong.
The players? Well every single one of them should take a bow.
And most of them did on Saturday. Except one notable exception.
Christopher Jullien seemed a forlorn figure on the lap of honour and when Celtic podcaster Ryan McGinlay tweeted out footage of the big defender:
Hes definitely away, isnt he? https://t.co/LxOb0fDRyL
McGinlay (@TheRyanMcGinlay) May 16, 2022
It sparked a debate amongst the Celtic fans:
He wants to stay but he needs game time.
Gareth Turner (@GarethTurner1) May 16, 2022
I think hell be away I dont see him being near the team next season either unfortunately hes too slow tracking back and just wouldnt suit Anges style of play maybe a different story if he didnt get the injury.
John (@John1888P) May 16, 2022
Broke the golden rule and went very public with his whines and moans. No way back I feel.
Grandude (@BrianMc81) May 16, 2022
Dont think Ange liked his demand for game timekept him out the squad altogether
Rebel86 (@Bludwulf1888) May 16, 2022
Id say so and judging by his pre match comments about asking to play the full 90 and not even being selected for the bench was a clear message from Ange. . Watched a B game when he played, definitely did not stand out. We move on #CelticFamily
Craig Wilkinson (@coach_wilki) May 16, 2022
Hell be away because our manager obviously doesnt rate the player post injury. Thats football. His wages will free up money for another defender. Clubs dont pay high salaries to players who arent in the squad much. Simple. Best of luck to him, Ange knows best.
kia (@idiotexposer1) May 17, 2022
No loss injuries a big worry for the big man,just give him a free
TBB Brimmer (@BrimmerTbb) May 17, 2022
Julliens comments last week certainly never helped his cause.
I said, in fact, I asked at the time what he thought he was playing at?
It seems whatever his thought process was, if it was to encourage the manager to give him more playing time, it doesnt seem to have worked.
Up Next: It may not be only players Ange will need in the transfer window
Could be an option Pundits stunning EPL move prediction for Celtic star
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JCPenney Builds on Long-standing Tradition of Diversity and Inclusion with Juneteenth Celebrations – Yahoo Finance
Posted: at 4:38 am
Events in partnership with Dr. Opal Lee the "Grandmother of Juneteenth" and Hope & Wonder Juneteenth Capsule Collection Will Benefit Unity Unlimited
LEWISVILLE, Texas, May 23, 2022--(BUSINESS WIRE)--JCPenney today unveils a multipoint celebration of Juneteenth honoring Dr. Opal Lee - the "Grandmother of Juneteenth" - and affirming the company's commitment to diversity, equity and inclusivitya tradition that hails back to the companys earliest days. Founded on the principle of The Golden Rule, JCPenney continues its emphasis on serving communities and diverse, working American families. For Juneteenth, JCPenney will put that mission into action with a mix of events, products and philanthropic commitments to honor the holiday and benefit the work of Dr. Opal Lee in Fort Worth and across the country.
"We are so honored to celebrate Juneteenth with special events and a new Hope & Wonder collection that allows us to give back and help Opal Lee spread her message of freedom and unity," says Val Harris, senior vice president, design, brand management and trend at JCPenney. "These efforts are the result of creative collaboration across many parts of the organization and JCPenney is so pleased to come together to honor this moment."
JCPenney has announced several initiatives to mark this years Juneteenth. Events to commemorate Juneteenth kicked off on May 17 with a virtual event featuring Opal Lee herself called, "Walking for Freedom: A Juneteenth Discussion with Dr. Opal Lee." The conversation reflected on the significance of Juneteenth and its designation as a federal holiday, Dr. Lees ongoing advocacy and community work, and the freedom journey that continues to this day. The broadcast streamed live on Facebook and YouTube and a replay can be viewed here.
On Saturday, June 18, a day before Juneteenth itself (Sunday, June 19), JCPenney will join Dr. Lee in Fort Worth, TX for Opals Walk for Freedom, building on a tradition she began in 2016 with 2.5-mile walks representing the 2.5 years it took Emancipation Proclamation enforcement to reach Texas. Now a nationwide event, Opals Walk for Freedom will be organized by community organizations in select cities across the country. JCPenney will also sponsor a "virtual" Opals Walk with JCPenney associates in other locations who want to join in with a self-directed 2.5-mile walk of their own.
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"JCPenneys Juneteenth Hope & Wonder Collection and national sponsorship of Opals Walk for Freedom speaks volumes about their commitment to diversity and inclusion," said Dione Sims, Executive Director of Unity Unlimited, Inc. the producers of the Walk and granddaughter of Dr. Lee. "Their generous donation will go a long way in supporting our mission to educate the country about the significance of Juneteenth as a national holiday that can bring people together and start the healing of America."
JCPenney will also mark the holiday with the launch of a new Juneteenth collection from Hope & Wonder, a private label brand of collections designed to engage the community in a positive way and bring key cultural and seasonal moments to life. Hope & Wonder is a multifaceted private brand that leverages the Companys national platform to raise awareness, celebrate diversity and uplift our communities. This brand empowers our associates to design and create a product that best represents the moment, play a key role in selecting our nonprofit partners and even participate as models in marketing material. JCPenney donates 100% of net profits from the four cultural moment collections to nonprofit partners; the Juneteenth collection supports Opal's Walk for Freedom, presented by Unity Unlimited.
Introduced in January 2022, Hope & Wonder, a private brand exclusively at JCPenney, is the latest JCPenney initiative designed to make a positive impact on families and communities. In recent months, the Company has announced purpose-driven offerings and programs including the fully inclusive JCPenney Beauty, a shop-in-shop experience featuring products by Black and Brown founders with Thirteen Lune, the Young, Gifted and Black Design Challenge for HBCU students, a long-term charitable partnership with Muhammad Ali Enterprises and Thereabouts, an inclusive brand for kids that celebrates diversity of shapes, sizes, styles, and abilities. JCPenney will continue to be inspired by the uniqueness of its customers to create experiences and products that make a difference.
About JCPenney
JCPenney is the shopping destination for diverse, working American families. With inclusivity at its core, the Companys product assortment meets customers everyday needs and helps them commemorate every special occasion with style, quality and value. JCPenney offers a broad portfolio of fashion, apparel, home, beauty and jewelry from national and private brands and provides personal services including salon, portrait and optical. The Company and its 50,000 associates worldwide serve customers where, when and how they want to shop from jcp.com to more than 650 stores in the U.S. and Puerto Rico.
In 2022, JCPenney celebrates 120 years as an iconic American brand by continuing its legacy of connecting with customers through shopping and community engagement. Please visit JCPenneys Newsroom to learn more and follow JCPenney on Facebook, Instagram, Twitter and LinkedIn.
About Unity Unlimited
Founded in 2000, Unity Unlimited, Inc. is a non-profit organization that embodies the values and life service of Opal Lee throughout her seven decades as an educator, volunteer, civic leader, civil rights organizer, and national advocate for the Juneteenth National Holiday movement. The organizations main mission is providing educational activities and resources to foster unity and harmony within the community, the city, the state, the nation, and the world regardless of race, culture or denomination. Today, Unity Unlimited operates at the intersection of grass-roots social services, running programs in the Dallas-Fort Worth area such as the Ft. Worth Juneteenth celebration, Opals Farm, Your Voice Unleashed musical programming, Secret Santa, and Opals Walk for Freedom (national).
View source version on businesswire.com: https://www.businesswire.com/news/home/20220523005384/en/
Contacts
Nina Quatrino - Corporate Communications, JCPenneyjcpnews@jcp.com
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Dr. Williams Holmes Obituary – Times Record – SWTImes
Posted: at 4:38 am
Dr. Williams Holmes
On the morning of May 17, 2022, Dr. Williams C. "W.C." Holmes Jr. of Fort Smith, AR passed away at 92 years old. Williams was born to Dr. Williams C. Sr. and Mary Philomene Holmes in 1929 in Mobile, AL. He grew up in Foley, AL and later attended St. Stanislaus Catholic Boarding School for Boys in Bay St. Louis, MS. During his time in Bay St Louis, he met the love of his life, Rose Mary Dick. They were married in 1950 at Our Lady of the Gulf Catholic Church in Bay St. Louis. Williams studied medicine at the University of Alabama-Birmingham where he was a member of the DKE fraternity and attended the undergraduate program at University of Alabama-Tuscaloosa. He performed his surgical internship under Alton Ochsner, Sr., M.D. in New Orleans, LA. Williams served two years in the United States Air Force at Sheppard ABF in Wichita Falls, TX performing surgery for the duration of his service. Williams and Rose Mary moved their family to Fort Smith in 1964 where he joined the Cooper Clinic medical group. He was a general surgeon with Cooper Clinic and retired from St. Edwards Mercy Medical Center in 1996.
During his time living in Fort Smith Williams was a supporter of education and the arts, and at one time was president of the Fort Smith Symphony Orchestra. In his retirement Williams enjoyed sailing the Atlantic Ocean solo, with friends and family and performing as a charter captain. He enjoyed scuba diving and underwater photography. He was an avid listener of classical music and a fan of college football. He was a devout Catholic and attended mass at Immaculate Conception in Fort Smith, AR where he also served as a eucharistic minister. Williams was a volunteer at the Golden Rule Clothes Closet and a supporter of higher education through the scholarship program at Girls, Inc. He enjoyed swimming and exercise classes at Mercy Fitness Center as well as socializing and playing bingo with his fellow residents and staff at Brookdale Senior Living.
Williams is preceded in death by both parents, Williams and Philomene, his wife Rose Mary, and daughter Amy Schluterman. He is survived by two brothers, James S. Holmes of Slidell, LA and Broox G. Holmes of Mobile, AL; three children, Sibley Holmes-Pennington of Fort Smith, Mark Holmes of Abita Springs, LA, David Holmes of Fort Smith; 6 grandchildren, Desiree Williamson (Anthony), Heather Tarrant (Andy), Clayton Holmes (Victoria), Zachary Schluterman, Dustin Pennington (Renee), Leila Chavez (James); 4 great-grandchildren; Hadlie Schluterman, Kailyn Tarrant, Felix Williamson, Grace Lipham; and many nieces and nephews.
Visitation for friends and family will be held on Wednesday, May 25 from 5:30-6:30pm at Edward Funeral Home, 201 N 12th St, Fort Smith, AR, followed by the Rosary at 6:30pm. A funeral mass will be held Thursday, May 26 at 11:00am at Immaculate Conception Catholic Church, 22 N. 13th St., Fort Smith, AR followed by a funeral procession and interment at Calvary Cemetery. Reception to follow at Immaculate Conception.
Memorial contributions in Dr. W.C. Holmes Jr.'s memory can be made to Immaculate Conception church for mass said in his memory or Girls Inc. of Fort Smith.
To view the online guestbook, please go to http://www.edwardsfuneralhome.com
Posted online on May 23, 2022
Published in Southwest Times Record
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Here’s exactly when to book a hotel to get the best deal – CNBC
Posted: at 4:38 am
This story is part of CNBC Make It's One-Minute Money Hacks series, which provides easy, straightforward tips and tricks to help you understand your finances and take control of your money.
As summer approaches, you might start looking toward your next vacation, and in some cases, setting your sights on a faraway destination. Roughly 50% of millennials and Gen Z are planning to travel internationally in 2022, according to Expedia's 2022 Travel Value Index outlook.
But whether you are taking a quick weekend trip or jet-setting across the world, the recent rise in inflation might put a damper on your plans.
If you want to maximize your trip budget, the golden rule of travel is typically to plan your trip well ahead of time.
With flights, typically the earlier you book, the more money you'll save. But with hotels or Airbnbs, it can be unclear how far in advance you should reserve a room to get the best deal.
One tip: If you're flexible, willing to wait or simply easy-going with travel planning, you could save on lodging by booking at the last minute. That's right, it can be cheaper to book your next home-away-from-home only days before you leave.
The ideal amount of time to book a hotel room is only 15 days before your trip, according to a 2021 NerdWallet study.
Looking at more than 2,500 hotel room rates between 2019 and 2021, NerdWallet found rates were about 13% cheaper when booked 15 days before compared to four months before.
On average, travelers saved about $30 per night by booking last-minute, which can really add up.
The savings were even higher for luxury hotels: About 22% cheaper when booked 15 days out.
However, if you're traveling to a popular destination or during a busy travel season, you risk not snagging your first-choice hotel. You may get stuck at a hotel further away from your destination the beach, Disney World or a sporting event may be a little harder to get to if you wait too long to book.
But with skyrocketing travel prices, booking your hotel at the right time could mean the difference in how much cash you have in your pocket for the rest of the trip.
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"Only team left that can win it all by Phil Jackson ‘s rule – Golden State Warriors": NBA Reddit comes up with… – The Sportsrush
Posted: at 4:38 am
Phil Jackson and his theory might have the Golden State Warriors as clear as the NBA champions of 2022.
Theres hardly any coach in the NBA who comes close to Phil Jacksons success, excluding Red Auerbach, who had something else in that 10x Champion Boston Celtics team.
Greg Popovic is the closest thing when you consider the fact that Phil only got success when he coached a team full of the best players in the league in multiple positions. Thats it, thats the list.
Also read: Yeah, I remember facing Steve, he had Michael Jordan: Jason Kidds hilarious response on facing the Warriors coach during their playing days
And when coaches of that stature use some tactics on a regularity that is comprehensible by the rest, it becomes something like a mathematical theorem.
Their tactics and theories used by them regularly in games get iced in basketball fanatics minds forever, as they get into the Basketball Hall of Fame. One such, Jacksons theory about a certain number of wins to start a season has given the NBA 36 of its last 40 Champions.
Thanks to a Redditor that got our attention to it the Golden State Warriors are the only team that could win the championship this season by Jacksons theory, which states that:-
If your team reaches 40 wins before it loses 20, they are contenders.
For the last 40 years, every championship-winning team has hit this mark except 4.
1995 Rockets
2004 Pistons
2006 Heat
The Redditor forgot to mention last years champion the Milwaukee Bucks who lost 24 games before they could win 40.
Of the teams left in the playoffs, Golden State is the only team left to have hit that mark. As of February 1st, when Miami lost its 20th game, the team records were as follows.
Miami Heat (32-20)
Boston Celtics (27-25)
Golden State Warriors (39-13)
Dallas Mavericks (29-22)
Lets see if it really turns out to be true. But we must again remind you that last year Milwaukee Bucks won the championship. Meanwhile, there were three teams in the West who started by Phils rule and couldnt win it all.
Also read: Love to go on the road, hit a bucket, and silence the crowd: Luka Doncic talks about facing Warriors X Factor, the Chase Center crowd
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TED NUGENT Wants To Know Why DEE SNIDER Celebrated His Sickness: ‘What Caused That Nasty, Nasty Hate?’ – BLABBERMOUTH.NET
Posted: at 4:38 am
Ted Nugent has once again blasted Dee Snider for seemingly celebrating the fact that the controversial rocker was diagnosed with coronavirus.
After Nugent went public with the fact that he was battling COVID-19 in April 2021, TESTAMENT guitarist Alex Skolnick shared a couple of headlines highlighting the fact that Nugent was previously spreading false information about the pandemic, only to contract the virus himself and become severely sick. Snider, who tested positive for COVID-19 last summer despite the fact that he was fully vaccinated, shared Skolnick's tweet and included the following message: "It's just...so...beautiful!"
Nugent, an outspoken conspiracy theorist who has refused to take the vaccine, touched upon Snider's comment during his May 20 YouTube livestream. He said (as transcribed by BLABBERMOUTH.NET): "Dee Snider a nice guy, I thought. But if you make fun of someone getting sick, you're not a nice guy, Dee. What happened to you? We always got along. And then you celebrated my sickness. And you don't know how rotten that is? Why don't you know how rot Dee, you're not a rotten guy.
"Dee, if you have a problem with Ted Nugent, there's only one person you should discuss that with: Ted Nugent," he continued. "If I have a problem with Dee Snider, I'm addressing you, Dee; I would like to talk to you.
"What caused that nasty, nasty hate? 'Well, you said bad things about [former U.S. secretary of state] Hillary Clinton.' Because Hillary Clinton destroys everything she touches," Nugent explained. "She's a dishonest, tyrannical, oath-violating criminal. That's not mean; that's the truth. 'Well, you said [she should] suck my machine gun.' Dee, Dee, my friend have you ever said 'F.U.' to someone but not really intentionally pursuing sex with that person? Are you kidding me? Do you think I would ever want her lips anywhere near my firearms? You're not aware of street terms? You must be. You must be. 'Cause I understand you're a good father and a good husband. So why were you such a prick at that moment? I just don't get it."
Nugent previously addressed Snider's comment about his COVID-19 battle in a December 2021 interview with Sofa King Cool. At the time, Ted said: "What is that thought process? [Dee] and I have been friends. What horrible human impulse horrible, rotten, hateful, soulless impulse must exist in horrible people to take pleasure and celebrate a fellow man's illness. It went viral across the globe where the left said I got what I deserved. How did I deserve that? 'Well, you called it a hoax.' I never, ever used the 'H' word. I never used word 'hoax'; I never called it a hoax. I called [top infectious diseases doctor Anthony] Fauci a scam artist. I called [House Speaker Nancy] Pelosi, Fauci and [former U.S. president Barack] Obama at the Wuhan lab with our tax dollars to cultivate a communist Chinese weaponized virus? That's not a Ted Nugent supposition. We have the footage. And they took glee.
"A guy like Dee Snider how can you abandon your humanity and take pleasure in another person's sickness?" he continued. "What a horrible, horrible manifestation of societal human abandonment. So, I pray for the Dee Sniders to allow themselves to be that rotten. I expect Marxists and leftists, but not a Dee Snider and not otherwise reasonably decent people, 'cause he's a good guy. But, boy, he really showed a rotten, horrible side when he did that. And it didn't impact me at all because I know that there's always been bad, nasty people.
"So, if Dee Snider's watchin, Dee I think it was a hiccup; I don't think that's what you are," Ted added. "But when you're ready to be a man and apologize, I will expect and accept your apology, because that was a rotten moment in an otherwise nice life.
"How do you just decide to be a prick one day? It's sad."
Nugent went on to say that wishing people ill based on party politics or any other factors is never acceptable. "So, the little boys and girls that are getting leukemia, do they deserve that?" he said. "Are you kidding me? I suppose when someone gets cancer and they keep smoking and drinking and eating food that isn't food, I suppose at some point you do deserve that, because you know that that's bad for you and you keep doing it; that's when you deserve something. But what kind of mindless idiot would take pleasure in anybody, even if they hate my politics And if you hate my politics, you've gotta be a real dirtbag, 'cause my politics are freedom; my politics are self-evident truth based in God-given individual rights, God, family, country, the Constitution, Bill Of Rights, Declaration Of Independence, work ethic, law and order, the Ten Commandments, the Golden Rule. You have a problem with that? That's the foundation of America. So if you have a problem with Ted Nugent's politics, you are a bad, bad person."
Ted continued: "Even a guy like Tom Morello, who I love, and [Carlos] Santana, who I love, wearing a Che Guevara shirt? So you're a supporter of genocide? You're a supporter of a guy that would have killed you. Che would have killed Santana and Tom Morello if he had a chance. What the fuck? How many mind-altering chemicals do you have to consume to be that fucking stupid? What the fuck? Wearing a Che Guevara shirt is like wearing an Adolf Hitler shirt. What is wrong with these people? You can't explain it. You have to literally take your soul and put it in the garbage to be that stupid."
Last October, Nugent appeared on "Off The Record" where he once again said that he wouldn't take the COVID-19 vaccine because the shots that were available in the United States were developed in less than a year are probably fake.
"It's not a vaccine," he said. "It's an experimental shot. Now the FDA was forced to authorize it recently, but they were jabbing people with an experimental shot right up until that fake authorization.
"I don't believe it's a vaccine," he reiterated. "Most of America doesn't believe it's a vaccine. The only ones that are taking it are either gullible or being forced because they're gonna lose their job, lose their life and lose their livelihood."
Asked what he would say to the people who believe it's a worthwhile vaccine and it's saving lives, Ted said: "I appreciate the opportunity to speak to the people that went ahead and got the jab. I speak their language. I will speak to them thusly: Baaaaaah," he said, imitating a sheep. "Baaaaaah. Baaaaaah. Baaaaaah. They understand that."
When senior Capitol correspondent Tim Skubick asked Nugent point blank if he believes that the millions of people who got the shot are "just stupid," Ted replied: "Yup."
In April 2021, Nugent talked about the darkest days of his battle with COVID-19, saying that he had "never been so scared" in his entire life. The 73-year-old pro-gun activist, who had previously claimed the virus was "not a real pandemic," said: "It was really scary. I didn't think I was gonna make it. I literally couldn't function for about 20 hours, and then they came and they rescued me The six-foot-two, 225-pound headache [this time] was like nothing I have ever experienced. I mean, from my tip of my toes to the top of my hair, I literally was dizzy and weak and struggled to get up to go to the bathroom. And I would lay in the bathtub a couple of times a day with the water as hot as I could take it just to divert."
Ted also said that he was being treated for COVID-19 by a group of doctors who made a video in 2020 calling for the use of hydroxychloroquine to battle the novel coronavirus, despite warnings from public health experts. Nugent went on to detail his clinical management of COVID-19, saying he was taking hydroxychloroquine, "a proven drug for 65 years," as well as ivermectin, "another proven drug."
In the past, Nugent, a staunch Donald Trump supporter, had referred to the virus as a "leftist scam to destroy" America's 45th president. He had also repeated a narrative pushed by conservative media and disputed by health experts that suggests the official death count from the coronavirus is inflated.
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