Shrewsbury maternity scandal: Payout over boy’s brain injury

Adam Cheshire’s case formed part of a probe into the biggest maternity scandal in NHS history.

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Ambulance Strikes: Births suspended at Frome Birthing Centre

There is concern transfer to hospital from Frome Birthing Centre can not be guaranteed if required.

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‘Alexithymia means I can’t explain how I’m feeling’

A politics graduate reflects on life being autistic and experiencing alexithymia and aphantasia.

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Ambulance staff on strike in England and Wales

Life-threatening 999 calls will be attended to, but other emergencies may not be or could face delays.

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Technology can help the NHS, says AstraZeneca boss

AstraZeneca’s Leif Johansson says AI and screening could prevent costly treatment in hospitals.

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Harlow hospital suspends gas and air over nitrous oxide levels

Princess Alexandra Hospital in Harlow says use has been suspended in the maternity unit.

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Motion capture tech from Avatar films used in disease research

Motion capture suits used to create alien characters can track the onset of diseases of movement, researchers say.

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New genetic disorder that causes susceptibility to opportunistic infections

An international consortium co-led by Vanderbilt University Medical Center immunogeneticist Rubén Martínez-Barricarte, PhD, has discovered a new genetic disorder that causes immunodeficiency and profound susceptibility to opportunistic infections including a life-threatening fungal pneumonia.

The discovery, reported Jan. 20 in the journal Science Immunology, will help identify people who carry this in-born error of immunity (IEI). “Our findings will provide the basis for genetic diagnosis and preventive treatment for these groups of patients,” Martínez-Barricarte said.

IEIs, also known as primary immunodeficiencies, are genetic defects characterized by increased susceptibility to infectious diseases, autoimmunity, anti-inflammatory disorders, allergy, and in some cases, cancer.

To date, 485 different IEIs have been identified. It is now thought that they occur in one of every 1,000 to 5,000 births, making them as prevalent as other genetic disorders, including cystic fibrosis and Duchene’s muscular dystrophy.

Despite recent medical advances, about half of patients with IEIs still lack a genetic diagnosis that could help them avoid debilitating illness and death. That’s why this research is so important.

The error in this case is a mutation in the gene for the protein IRF4, a transcription factor that is pivotal for the development and function of B and T white blood cells, as well as other immune cells.

As a postdoctoral fellow at The Rockefeller University, Martínez-Barricarte was part of an international research team that, in 2018, identified an IRF4 mutation associated with Whipple’s disease, a rare bacterial infection of the intestine that causes diarrhea, weight loss, and abdominal and joint pain.

Martínez-Barricarte is now an assistant professor of Medicine in the Division of Genetic Medicine, and of Pathology, Microbiology & Immunology in the Division of Molecular Pathogenesis.

In 2020, after moving his lab to VUMC, he began collaborating with Aide Tamara Staines-Boone, MD, and her colleagues in Monterrey, Mexico. They were caring for a young boy who was suffering from severe and recurrent fungal, viral, mycobacterial, and other infections.

Martínez-Barricarte and his team sequenced the protein-encoding regions of the boy’s genome and discovered a de novo IRF4 mutation, which originated in the patient and was not inherited from his parents.

Upon consulting with IRF4 experts at the Imagine Institute for the study and treatment of genetic diseases in Paris, they were told that seven other groups were independently characterizing the same mutation. They now collaborate as the IRF4 International Consortium.

In the current study, the consortium identified seven patients from six unrelated families across four continents with profound combination immunodeficiency who experienced recurrent and serious infections, including pneumonia caused by the fungus Pneumocystis jirovecii. Each patient had the same mutation in the DNA-binding domain of IRF4.

Extensive phenotyping of patients’ blood cells revealed immune cell abnormalities associated with the disease, including impaired maturation of antibody-producing B cells, and reduced T-cell production of infection-fighting cytokines.

Two knock-in mouse models, in which the mutation was inserted into the mouse genome, exhibited a severe defect in antibody production consistent with the combined immune deficiency observed in the patients.

The researchers also discovered the mutation had a “multimorphic” effect detrimental to the activation and differentiation of immune cells.

While the mutant IRF4 binds to DNA with a higher affinity than the native form of the protein (in a hypermorphic way), its transcriptional activity in common, canonical genes is reduced (hypomorphic), and it binds to other DNA sites (in a neomorphic way), altering the protein’s normal gene expression profile.

This multimorphic activity is a new mechanism for human disease. “We anticipate that variants with multimorphic activity may be more widespread in health and disease,” the researchers concluded.

Co-authors from Martínez-Barricarte’s lab included graduate students Jareb Pérez Caraballo and Xin Zhen, and research assistant Linh Tran. His research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (grant #AI171466).

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The Beauty of Conflict

Conflict. It’s a word that can strike fear into the hearts of many, especially those who consider themselves “spiritual” people. After all, isn’t the goal of spirituality to move beyond conflict and find inner peace?

Conflict is not something to be feared or avoided. Conflict is a powerful aspect of human life to embrace and even celebrate.

The existence of conflict in this reality is not a mistake. Conflict has many benefits, both for our individual growth and for society as a whole. It helps us sculpt our characters, upgrade our thinking, and add more depth and nuance to our understanding of the world. It may be uncomfortable or destructive at times, but it’s also necessary for our growth and evolution.

You didn’t create the presence of conflict in this reality. It’s been around long before your current life, and it will continue to exist long afterwards. You’re not going to suppress or eliminate it. Conflict exists here for good reasons. If you don’t currently grasp or respect those reasons, that isn’t going to force reality to bend to your ignorance because plenty of other people do grasp and respect the value of conflict.

But wait… doesn’t everyone want a conflict-free world? Heck no! Not everyone here is conflict avoidant, and trying to create a peace-only, conflict-free world doesn’t serve them. In fact, such efforts will actively be opposed by many. Just try to create a conflict-free world – or even a microcosm of it – and you’ll see that the world resists your efforts. That’s not a mistake; it’s because conflict is incredibly useful.

I love peace, and I also love conflict. Both are different frequencies of this human experience, and I value and appreciate them essentially equally. If you’d assumed that one of my goals was to create a conflict-free world, you’d be mistaken. Blech! I don’t want that at all. I want conflict to remain very much a part of this world. If I want to change anything about it, I’d seek to upgrade how people relate to conflict, how they form intentions around it, and how they find purpose and meaning within it. That includes continuing to upgrade and improve how I relate to conflict.

Conflict can take many forms, from random and pointless to meaningful and purposeful. Take the example of a parent preventing their child from doing something really stupid or dangerous while the child resists such efforts. This is a purposeful and necessary step in the child’s growth and development. Or consider a sports team competing against a rival. This conflict fuels the growth and development of the team and the individual players – often in ways that impact their lives off the field too. And it can be very entertaining to watch as well. And then we have rich and meaningful social conflicts such as the Civil Rights Movement, which are still generating powerful ripples. We even have conflicts about conflicts, and we have some conflicts about conflicts about conflicts too.

Do you ever enjoy watching conflict? Do you really want it to go away entirely? Be honest.

I really don’t want a life or reality without conflict. That would be so incredibly boring.

At the very least, even when you’re engaging in a conflict that you’re resisting, you’re probably entertaining other people who are observing you, even when you aren’t aware of this.

How do you relate to the part of yourself that finds conflict attractive? Do you ever shame it or try to suppress it? Do you pretend that you’re really not that kind of person? What if you dropped the shame and guilt? Consider that your fascination with conflict, however big or small it may be, isn’t a mistake and that there are powerful and productive reasons that you’re secretly drawn to it.

Isn’t the goal of spirituality to avoid conflict and find inner peace? I’d agree that one aspect of spiritual development is to cultivate inner peace. But that doesn’t mean avoiding conflict. It actually includes making peace with the presence of conflict in this reality – and especially in your own life. Resisting, fearing, or avoiding conflict doesn’t actually help you align with peace.

Peace and conflict aren’t opposites. They actually arise together. You can’t have one without the other because each serves to define the other.

There’s a scene in the two-part “Redemption” episode of Star Trek: The Next Generation that provides a powerful and insightful – and fun – way to frame conflict, both on a physical and a spiritual level. In that episode the Klingons are engaged in a brutal civil war. But after a vicious battle, they all go to a neutral bar, drink blood wine, and hang out and celebrate their warrior fierceness together. On the battlefield they are bitter enemies, but at the bar they’re all friends and comrades. They get pretty drunk and rowdy celebrating the glory of conflict together. Then when they sober up the next day, they return to the battlefield and continue fighting.

One particular Klingon named Worf, however, goes to that bar and doesn’t get it. Worf was raised by humans and struggles to grasp how all these enemies could be foolishly celebrating together when they ought to be preparing for the next battle engagement. Worf wants to go back and make repairs to their ship, so they can be more battle-ready. But his brother Kurn explains it: “You and I will fight battles that others can only dream of. The time for glory is here. It is not a time to worry about stabilizers; it is a time to celebrate. For tomorrow we all may die!”

This is how I love to think about conflict in our human lives. On one level we may do battle, but on another level, we can also love and respect each other as co-warriors. When we die, the human conflict dissolves, but while we’re here on Earth, it may be very worthwhile to wholeheartedly engage in it. Every conflict we create and experience here is temporary. Every conflict has a limited lifespan, and one way or another it will end.

Conflict and peace go hand-in-hand. Again, they arise together, so I encourage you to embrace both aspects of life. One is not better than the other. Peace isn’t superior to conflict.

How would you like to deal with Trump supporters (i.e. supreme idiots) in your life? Do you want to make peace with them? Or would you rather fight? You can do both, you know. Some pretty intelligent people I know have tried to talk to them to develop an understanding, and they’ve returned dejected and disappointed for the most part. Then they vent about those encounters and give up on trying it again. And there are those who proclaim success in maintaining positive relationships with Trumpers, while adding, “but we avoid talking about politics at all costs,” as if that’s some kind of meaningful success. This reminds me of the “Massive Head Wound Harry” Saturday Night Live skit where everyone tries to avoid addressing the obvious. What head wound? Everything seems normal to me.

Embracing conflict doesn’t mean glorifying violence. It means fighting the good fights while we’re here. There are many good fights to be fought these days, so let’s get to fighting them. And then afterwards we can all go to that Klingon bar, drink blood wine, and celebrate our warrior fierceness.

I enjoy pushing back against racist and fascist idiocy these days. On the one hand, it seems odd that common sense still needs defenders, but it clearly does, so that one is an easy opt-in, is it not?

Yet I can still hug Trump supporters when we meet up at the bar – while we’re still here on Earth. The smell can be a bit rough, but I manage. 😉

Remember that we all die in the end. All our human conflicts will eventually be over and done with. We’re going to leave them all behind no matter what. But while we’re here, let’s embrace the conflicts that are the richest and most purposeful for us. Grab the sword and the armor that you like best, and play the role of warrior when it suits you. That is your path to peace.

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‘I’ve been given a do not resuscitate order but I want to live’

Marie McLean is scared to go to sleep after discovering her records tell medics not to attempt CPR.

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