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Trinity study discovers genetic mutation behind incurable childhood cancer

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Scientists in Trinity College Dublin have discovered how a specific genetic mutation causes an incurable childhood cancer, and have successfully reversed its effects by slowing cancer cell growth in laboratory conditions.

The treatment for diffuse midline glioma (DMG) is so effective using drugs already used on other cancers that they have called for immediate clinical trials in humans with a view to developing a new drug targeting the disease.

Their work on the mutation, known as H3K27M, sets out how “a new understanding of the genetics of DMG progression indicates [that] a highly promising, therapeutic approach may be realisable, offering significant hope of improved treatments in the future”.

There are five to 10 DMG cases in Ireland every year; with eight already this year. Brain tumours of various types affect 45-50 children annually.

The DMG findings were published in the scientific journal Nature Genetics on Thursday – the research is supported by Worldwide Cancer Research and the Brain Tumour Charity.

The scientists called for trials to begin on the already approved class of drugs called EZH2 inhibitors. These target the same key biological pathway involved in DMG, as they do successfully in lymphomas and sarcomas – two cancers common in adults.

“We’ve taken a huge step forward in our study of DMG tumours and hope that the insights will help us design and implement precision oncology-based treatment approaches in DMG patients in the future,” said Prof Adrian Bracken of the TCD School of Genetics and Microbiology, who led the research.

Crucially, EZH2 inhibitors have already received approval from the United States Food and Drug Administration for the treatment of two types of adult cancer.

“We propose these drugs could be impactful for children with DMG and, as a result, call for clinical trials to begin next.”

The successful targeting of the DMG tumour was achieved on human neural stem cells.

“Ultimately, we hope that our work – together with that of others focused in this area – will lead to curative clinical approaches for what is a truly terrible disease that can devastate families and for which there are currently no therapeutic options,” Prof Bracken added.

Challenge to treat

Paediatric gliomas like DMG are among the most devastating of childhood cancers. Tumours typically arise in the brain and are very challenging to treat, with prognosis extremely poor.

“As such, effective therapeutic options are urgently needed,” he underlined.

Dr Jane Pears, paediatric consultant oncologist at Our Lady’s Children’s Hospital, Crumlin, who treats children with this disease, said these tumours were a devastating diagnosis for children and their families.

“The best treatment we can currently offer may extend survival for a few months but is not curative. We are now entering an exciting era of expansion of our knowledge of this disease at a molecular level which, in turn, will lead us towards more targeted treatments,” she said.

Through collaboration between researchers and doctors in clinical settings, “this will hopefully lead to the improved outcomes that we all so dearly wish to see”, she said.

Maeve Lowery, professor of translational cancer medicine at Trinity and academic director of Trinity St James’s Cancer Institute, said: “This pivotal work illustrates the success of a precision oncology approach – where understanding how cancers develop on a genomic level can accelerate the development of more effective treatments with less side effects.”

The research programme led by Prof Bracken would build on this success to continue to develop new and innovative treatment strategies for adult and childhood cancers, she predicted.

Dr Becky Birch, head of research at the Brain Tumour Charity, hoped this “really promising discovery” would pave the way for new and targeted treatments to be developed for children with DMGs.

“With average survival still heartbreakingly short at less than 12 months, we urgently need to find new options to help slow the growth of this rare and often-inoperable cancer and give children diagnosed more time to live.”

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Higgins raises concerns over volume of legislation received in recent weeks

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Two Oireachtas committees are being convened at short notice to consider concerns raised by President Michael D. Higgins at the volume of legislation sent to his office in recent weeks.

In a letter to the Ceann Comhairle, the Cathaoirleach of the Seanad and the Department of the Taoiseach, Mr Higgins said an “overwhelming number of Bills” were presented for his consideration in the final two weeks before the Christmas and summer recesses.

“For example, in the three weeks since the beginning of July I have been asked to consider 19 separate Bills. Nine were presented on the one day, sharing a requirement to be considered and signed in the same seven-day period,” he wrote, pointing out that in the entire preceding six months, he was presented with 13 Bills for consideration.

Last year, 21 of the total of 32 Bills presented to him were sent in the weeks approaching summer and Christmas recesses.

“It would strike me, as President and from my years as a parliamentarian, that there must be a more orderly approach to arranging the legislative timetable that allows all legislators the time to consider and contribute to proposals before the Oireachtas without unnecessary time constraints and an unseemly end-of-term haste to have Bills concluded,” the President wrote.

“Having this vital work concentrated into four weeks of the year strikes me as being less than ideal and, I believe, unnecessary.”

Mr Higgins noted that little time was being given over in the Oireachtas to debate often “very important and far-reaching legislative proposals”.

He said the process has “been curtailed through the imposition of restrictions on time in one or both Houses”.

He said amendments put down by Oireachtas members were often not discussed, and those proposed by the Government were at times “carried without an opportunity for scrutiny or debate”.

The President noted an “unseemly end-of-term haste”to pass legislation and said a “real prospect” of having to convene the Council of State in the days after Christmas day to consider Bills had arisen more than once.

Seán Ó Fearghaíl, the Ceann Comhairle, told The Irish Times that the Dáil’s Business Committee and the Seanad’s Committee on Procedures would meet on Friday to consider the letter, and actions open to the Oireachtas to consider.

There have been renewed concerns during the lifetime of this Dáil about the use of the guillotine to force Government legislation through without extensive oversight, with several heavyweight pieces of legislation passed in a matter of days before the Oireachtas rose for its summer break earlier this month.

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Who do I need to notify if I move home?

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Moving house is frequently said to be one of the most stressful things anyone can do.

The massive investment both financially and emotionally can take its toll, especially if the process takes months to complete.

It is why anything that helps to elevate some of the stress along the way can be hugely beneficial. This includes addressing some of the practicalities in advance, and having a list of who to notify when you move can help. 

We look at some of the organisations and companies who you may need to contact when you move home

We look at some of the organisations and companies who you may need to contact when you move home

Dozens of companies will need to know your new address, whether this is an insurer who may use them to help calculate your insurance premiums or a retailer who need to know where to send the clothing you ordered online.

Without updating them, you may endure a bigger headache from moving home than you had anticipated.

North London estate agent Jeremy Leaf, said: ‘When moving home, it is vital to plan ahead. Moving day can come upon you very quickly, particularly if there is a short time between exchange and completion.

‘Buildings insurance is the most important thing that needs arranging on your new property as soon as you have exchanged contracts.

‘Confirm your moving date with your removals firm and make a list of who needs notifying about your impending change of address – the electoral roll, the DVLA, Amazon and other delivery firms, particularly supermarket deliveries. The last thing you want is for your orders to turn up at your ‘old’ address once you have moved.

‘Don’t forget to change your council tax, while utility providers will also need informing, and given final meter readings. The more you plan ahead, the smoother the process will be.’ 

A checklist for who to notify when you change address can help to elevate some of the stress of moving home

A checklist for who to notify when you change address can help to elevate some of the stress of moving home

Tom Parker, of property website Zoopla, agreed: ‘Moving home can be overwhelming with so much to do. When it comes to notifying organisations, it’s best to divide it into digestible categories like work, household and vehicle.

‘Notifying your employer is a top priority, especially if your payslips are sent to your home. If you own a vehicle, ensure you update your driving licence, insurance providers and vehicle logbook.  

‘Make sure you also notify organisations like your broadband, utilities, insurance providers and council tax. Finally, don’t forget the small things like magazine subscriptions and store cards.’

Here we look at some of the organisations and companies who you may need to contact when you move home.

Employment 

Perhaps one of the most important and probably most overlooked places that need to be notified of your change of address is HMRC, which needs to know for tax purposes.  

Similarly, your employer needs to know when you change address for your payroll, so that it can update your contact details.

In addition, your National Insurance number helps the Government to identify you and is used by the organisations such as the DVLA and HMRC, so this will need your new address attached. 

Household

There are various companies providing services to your household that will need to know about your move so that they can update your contact information.

In some cases, you may end up continuing to pay for a service in your former home that you are no longer using if you fail to update these companies.

They include your cable or satellite provider, your phone and broadband company. It is also important to update your TV licence contact details, which can be done up to three months before a move.

Vehicles

You can update DVLA via its website and within two to four weeks, you should receive an updated licence and V5C log book documents for your car. Failing to update the log book could lead to a fine of up to £1,000.

You will also need to notify the supplier of your vehicle breakdown cover and your car insurer.

Insurance

Most insurers take postcodes into account when calculating premiums and the cost of insurance cover, so they will need to be notified of your change of address. 

You may need to contact those insurers who provide cover for household contents, health, life, travel and your pets.

Healthcare

As well as your health insurer, you will also need to provide your address to other healthcare organisations.

For example, if you change doctors when you move home, you will need to let your old doctor know so that your medical information can be forwarded to your new doctor. This may similarly apply to your dentists and opticians.

Utilities

Your gas, electricity and water suppliers will need your updated contact information, even if you are leaving them behind at the old property and taking on new suppliers.

It can take a couple of days for energy providers to update your information, so it is worth contacting your suppliers ahead of your move. However, you may be able to move your deal to your new property.

Make sure you take readings of your utilities on the day of your move so you can update your suppliers with these and only pay for the amounts you have used. 

Royal Mail’s redirection service may be worth considering as it forwards any post sent to your former address to your new address. You can apply for the redirection up to three months before your moving date.

Money

There are several companies and organisations that fall into this category and will need to know your new contact address.

They include bank and building societies, your pension providers, loan companies, credit card providers and store cards. If you are on a state pension, the Government will need to know your new details.

Similarly, you will need to update your address for council tax purposes.

Others include your accountant as you don’t want important tax documents going to your old address (if you are not using the a postal redirection service). And don’t forget updating NS&I with your new address if you put money into premium bonds.

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Ireland ‘one of world’s best five places’ to survive global societal collapse

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Ireland is one of the world’s five places best suited to survive a global collapse of society, according to a new study. The others are Iceland, Tasmania, the UK and, topping the list, New Zealand.

The researchers say human civilisation is “in a perilous state” because of the highly interconnected and energy-intensive society that has developed and the environmental damage this has caused.

A collapse could arise from shocks such as a severe financial crisis, the effects of the climate crisis, destruction of nature, an even worse pandemic than Covid-19 or a combination of these, the scientists says.

To assess which nations would be most resilient to such a collapse, countries were ranked according to their ability to grow food for their population, protect their borders from unwanted mass migration, and maintain an electrical grid and some manufacturing ability. Islands in temperate regions and mostly with low population densities have come out on top.

The researchers say their study highlights the factors that nations must improve to increase resilience. They say that a globalised society that prizes economic efficiency has damaged resilience, and that spare capacity needs to exist in food and other vital sectors.

Billionaires have been reported to be buying land for bunkers in New Zealand in preparation for an apocalypse. “We weren’t surprised New Zealand was on our list,” says Prof Aled Jones, at the Global Sustainability Institute, at Anglia Ruskin University, in the UK.

“We chose that you had to be able to protect borders and places had to be temperate. So with hindsight it’s quite obvious that large islands with complex societies on them already” make up the list.

The study, published in the journal Sustainability, says: “The globe-spanning, energy-intensive industrial civilisation that characterises the modern era represents an anomalous situation when it is considered against the majority of human history.”

The study also says that environmental destruction, limited resources and population growth mean civilisation “is in a perilous state, with large and growing risks developing in multiple spheres of the human endeavour”.

New Zealand was found to have the greatest potential to survive relatively unscathed due to its geothermal and hydroelectric energy, abundant agricultural land and low human population density.

Jones says major global food losses, a financial crisis and a pandemic have all happened in recent years, and “we’ve been lucky that things haven’t all happened at the same time – there’s no real reason why they can’t all happen in the same year”.

He adds: “As you start to see these events happening I get more worried, but I also hope we can learn more quickly than we have in the past that resilience is important. With everyone talking about ‘building back better’ from the pandemic, if we don’t lose that momentum I might be more optimistic than I have been in the past.”

He says the coronavirus pandemic has shown that governments can act quickly when needed. “It’s interesting how quickly we can close borders, and how quickly governments can make decisions to change things.”

But, he adds, “This drive for just-in-time, ever-more-efficient economies isn’t the thing you want to do for resilience. We need to build in some slack in the system, so that if there is a shock then you have the ability to respond because you’ve got spare capacity. We need to start thinking about resilience much more in global planning. But, obviously, the ideal thing is that a quick collapse doesn’t happen.” – Guardian

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