Weight-loss jabs are the latest craze for shedding a few pounds. Their effect has been dramatic with drugs such as Ozempic and Wegovy (semaglutide) causing users to lose up to 15% of their body fat on average.

Semaglutide, which is a glucagon-like peptide 1 (GLP-1 receptor agonist drug), mimics the action of a natural gut hormone which is released after we eat.

This gut hormone triggers multiple physiological responses that play a role in regulating body weight, such as releasing insulin to help control blood sugar levels, slowing stomach emptying (so we feel fuller for longer) and even telling the brain’s hunger centres to suppress appetite.

But as effective as GLP-1 drugs are, not everyone who uses them will lose a significant amount of weight. So-called “non-responders” are people who lose less than 5% of their body weight after roughly six months of treatment on the highest tolerated dose. Research suggests that between 10% and 30% of patients fit into this group.

Many people labelled as non-responders to GLP-1 receptor agonists such as semaglutide do not take the medication correctly or discontinue treatment before adequate therapeutic effect can be achieved. Studies show up to 20-60% of people people stop treatment within the first year, and widespread use of the drug in doses below the recommended amounts.

Certain metabolic issues such as insulin resistance, where the body’s cells stop responding properly to insulin, may also block semaglutide’s actions. Sleep disruption could inhibit the drug’s actions as well, as poor sleep is shown to delay the release of the body’s natural GLP-1 hormone.

People taking other medications, such as corticosteroids and psychotropic drugs (such as antidepressants) which can cause weight gain, may also find GLP-1 drugs don’t work very well for them.

But these aren’t the only reasons a person may be labelled a non-responder.

Interestingly, sex may play a role in how a person responds to these drugs, with research showing women taking semaglutide consistently lose more weight compared to men.

A review of 47 randomised controlled trials involving over 23,000 patients found that the greatest weight-loss effect from GLP-1 drugs was shown in participants who were young, female and not diagnosed with diabetes (so they therefore had better insulin sensitivity).

One reason why women react better could be their higher oestrogen levels. This hormone improves insulin sensitivity and stimulates GLP-1 secretion.

Another reason some people respond poorly to GLP-1 drugs is because of their genetic makeup.

Scientists have identified variants in the gene coding for the enzyme PAM (peptidyl-glycine alpha-amidating monooxygenase) that appears to cause GLP-1 resistance. This genetic change is carried by approximately 10% of the population.

People with this genetic change have higher circulating levels of GLP-1 but without the expected biological effect. This means that more GLP-1 hormone is needed to achieve the same response in people without the mutation. This suggests a clear resistance to the hormone.

Research which looked at the genetics of nearly 28,000 people taking a GLP-1 drug also identified genetic issues in another set of receptor genes called GLP-1R and GIPR.

This genetic issue caused differences in both weight loss and side effects. Those who had these genetic issues had higher body mass index (BMI) and body mass on average, and were more likely to have type 1 diabetes and other metabolic issues. Such genetic differences may explain why some people fail to lose any weight when taking a GLP-1 drug.

Another factor that may contribute for non-responders relates to the causes of obesity itself. Our body operates based on four distinct types of hunger. If a medication targets something that is not the primary cause of a person’s obesity, the response seen will be small.

The first type is our baseline slow-burn hunger, which is the minimum number of calories our body absolutely must consume in order to function (also known as our metabolic rate). Another type of hunger is hungry gut, relates to a genuine, physiological need to eat. The way we eat can also be driven by our brain (known as a hungry brain, where we eat from habit or stress) or our emotions (known as emotional hunger, where we eat to cope with how we feel).

For patients with emotional hunger, GLP-1 drugs do not address the root cause of the anxiety and depression driving that person’s overeating. According to one observational study carried out in Japan, emotional eaters were less likely to see significant weight changes when using a GLP-1 drug treatment.

Integrating cognitive behavioural therapy may therefore be important for people who struggle with emotional hunger and are using as GLP-1 drug. For hungry gut patients, a high-protein, high-fibre diet can enhance the drug’s effectiveness.

For patients with a hungry brain, switching to dual agonists such as tirzepatide (commercially known as Mounjaro), which targets two digestive hormones, GLP-1 and glucose-dependent insulinotropic peptide (GIP) may be useful. For slow-burn hunger, resistance training can increase resting metabolic rate.

While weight-loss drugs have proven effective for many, the fact that they don’t work for everyone shows how important it is to move towards developing precision obesity medicine. This would involve analysing a patient’s unique genes and lifestyle patterns to match them with the correct medication. While genetic testing for variants linked to non response is not common, it represents the next step in helping ensure patients are given therapies that work better for them.

The sight of Rice being substituted is a rare one for club or country, particularly at such a crucial point in the game when England, dominant after a chaotic first half, were leading 3-2 but struggling to put the game beyond doubt despite creating numerous golden chances as they found Croatia goalkeeper Dominik Livakovic in inspired form.

Caleb Yirenkyi scored a stoppage-time winner to earn Ghana a 1-0 win over Panama in a chilly and lively World Cup 2026 game in which the African ⁠side were forced to play the second half without starting goalkeeper Lawrence Ati Zigi on Wednesday.

After a lightning-quick counter-attack, Brandon Thomas-Asante charged forward before playing a precise pass into the area for Yirenkyi, who tapped home for his first competitive international goal.

Ghana, competing in their fifth World Cup and looking to improve on their run to the quarter-finals in 2010, were forced to play the match without Thomas Partey after the midfielder was denied entry into Canada and lost a visa appeal.

Panama, bolstered by a vociferous red-clad contingent of supporters, ⁠were energetic, purposeful and threatening in the final third while Ghana were unable to find their ​rhythm ⁠until the second half.

Ati Zigi was by far Ghana’s best player in the first half, commanding his area impressively while his teammates were unable to manage a single attempt on the Panama goal, but he did not come out for the second half after a collision.

Cecilio Waterman nearly ‌put Panama in front in the second minute with a slick first-time strike from a brilliant pass from Amir Murillo but was denied by a diving save from Ati Zigi.

Shortly after a hydration break that was loudly booed by spectators as light rain fell, Panama threw everything they could at the Ghana goal but failed to find a way through.

Panama demanded a penalty after Cristian Martinez went down in the box but their claims that there was contact from Jerome Opoku did not convince the referee.

Ati Zigi received treatment following a collision near the end of the first half and was replaced by Benjamin Asare when the game started to open up and Ghana found their stride. Panama nearly opened ‌the scoring in the 60th minute but Martinez lashed his attempt from close ​range into the side-netting from a tight angle.

Jonas Adjetey almost scored for Ghana when he rose high to meet a cross with a header that forced a smart stop from Orlando Mosquera. Thomas-Asante sent a gorgeous ⁠low cross into the box for Jordan Ayew but Panama defender Jiovany managed to poke it just wide of the post ‌before the night’s second ​hydration break was booed.

Ghana will look forward to ‌having Partey available for their June 23 match ​against England in Boston while Panama meet Croatia later that day in Toronto.

A species of bacteria living in the icy waters surrounding Antarctica could hold clues to future cancer treatment, especially for those battling melanoma, scientists say.

Researchers found that the melanoma-killing bacterium was growing on marine organisms called ascidians, or sea squirts, during a six-week expedition to one of the most remote environments on the planet.

“We first discovered this ascidian produces a bacterium that contains a toxic compound that kills melanoma cancer cells while not harming normal human cells,” said Bill Baker, a professor of chemistry at the University of South Florida.

“That selectivity is critical in drug development because you want to treat the disease without harming the patient,” Dr Baker said.

Many marine organisms in the frigid Antarctic waters rely on chemical defences to survive in the harsh environment, producing compounds that can deter predators and disease.

“The continent is unique because it has been geographically and environmentally isolated for millions of years,” Dr Baker said.

“As a result, species in Antarctica have had time to evolve independently, leading to highly specialised organisms. The ascidians we study are adapted specifically to this environment and are not found anywhere else,” he explained.

One of the compounds found to act effectively against melanoma cells is “palmerolide A” produced by the bacterium Candidatus Synoicihabitans palmerolidicus.

The latest expedition sought to find where the melanoma-killing bacterium occurs in the Antarctic and how widespread it is.

“We also wanted to understand how it lives inside the organism [sea squirt] and how that connects to the compounds linked to melanoma research,” Dr Baker said.

Researchers hope to further understand how the compounds are produced naturally and whether they can eventually be harnessed for medical applications.

Sea squirts harbouring the melanoma-killing bacteria are typically found at depths between about 18 and 24m (60 and 80ft), often along sloped or vertical seafloor surfaces where water currents are strong, scientists found.

At these depths, currents help deliver nutrients that sustain the organisms, they say.

Researchers conducted multiple dives and used two remotely operated vehicles to explore deeper waters.

The dives were carefully planned to ensure the safety of the scientists and the samples, they say.

“This research is important both environmentally and medically. We are learning how organisms use symbiosis to survive in extreme conditions, which is still largely unknown in cold-water ecosystems like Antarctica,” Dr Baker said.

“Understanding the source and function of this compound is critical if we hope to develop it into a drug,” he said.

ARLINGTON, Texas (AP) — Hey, Jude, you and Harry didn’t let England down.

Harry Kane scored twice to equal the English record for World Cup goals, and Jude Bellingham put England in front for good two minutes into the second half of a 4-2 victory over Croatia on Wednesday.

Martin Baturina and Petar Musa answered each of Kane’s first-half goals in a rematch of a 2018 semifinal won by Croatia. Musa’s goal came on the final play before the whistle ending the first half.

The even score didn’t last long once play resumed.

Bellingham took a long pass from Elliot Anderson and stayed clear of the defender the rest of the way, sending a shot past Dominik Livakovic and in off the far post. Marcus Rashford padded the lead in the 85th minute.

“He just told us to let the shackles off,” Kane said of coach Thomas Tuchel’s halftime message after Croatia pulled even so late before the break. “The way we conceded that second goal is not the team we want to be. He finally just said, ‘What’s the worst that can happen? We lose the match, first group game, we get on with it.’ We move on. Just go and kind of show the world who we can be.”

Kane, who won the Golden Boot at the 2018 World Cup in Russia by scoring six times, is up to 10 World Cup goals, tying Gary Lineker’s mark from the 1986 and 1990 tournaments.

The 32-year-old’s first goal came on his second chance on a penalty kick after Livakovic’s save on the first try was nullified by a video review that showed both his feet off the goal line as Kane was striking the ball.

Kane went the same way toward the right post with the second attempt, while Livakovic lunged the other direction, to his right.

The penalty was called when Luka Modric, the 40-year-old midfielder who extended his Croatian record by appearing in his fifth World Cup, kicked Noni Madueke in the thigh.

Kane matched Lineker’s mark when the Bayern Munich striker easily beat Livakovic with a powerful header off a corner kick from Declan Rice. Kane has 81 international goals.

“We scored two goals that were good actions and good situations, but they were too little,” Croatia coach Zlatco Dalic said through an interpreter. “England was very difficult, (we) also have to be strong on the defensive side.”

Bellingham almost immediately had another great scoring chance after the Real Madrid player’s seventh international goal. Livakovic made that save and about a half-dozen more in a matter of minutes during a frenetic English attack.

“We could have scored probably three goals in that 20-minute spell coming out (after halftime),” Kane said. “In the end, we just had too much for a great team that will probably go far in the tournament themselves.”

Musa scored the first World Cup goal for an active player from Dallas of Major League Soccer, which plays its home games about 40 miles from AT&T Stadium.

The retractable-roof venue that is home to the NFL’s Dallas Cowboys is giving World Cup fans an air-conditioned reprieve from the muggy Texas heat, this time for white-clad English fans and Croatian supporters who were mostly wearing their country’s familiar red-and-white checkered uniforms, not the blue kits the players had on.

Musa tracked a header from Ivan Perisic and put a one-timer past Jordan Pickford, who was also beaten in the 36th minute by Baturina. That shot into the left corner ticked off Pickford’s hand.

Bukayo Saka’s pass left plenty of room for Rashford as the Barcelona player entered the penalty area, faked a shot with his left foot and scored his 19th international goal with his right.

“I loved the second half, all of it,” Tuchel said. “I encouraged them to go for it. To play with more courage, to be brave, to be ourselves. And like I said, I loved their reaction.”

England next plays Ghana in Foxborough, Massachusetts, in Group L on Tuesday, the same day Croatia plays Panama in Toronto.

___

AP World Cup: https://apnews.com/hub/fifa-world-cup

Much-loved York fried chicken restaurant Clucking Oinks has announced it will be taking up residence at a popular York pub – The Fox in Holgate Road – ahead of summer.

This follows the closure of their Castlegate location at the end of last month, something that the owners said was due to the ‘climate situation of hospitality in the UK’ – adding that “it’s become clear the idea of a restaurant isn’t a viable one”.

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Their original location inside Spark:York will remain open, as will its other premises inside Stack – a similar venue to Spark – in Newcastle city centre.

The truck is set to open its hatch tonight, catering to pub quizzers and football fans who will be visiting the pub to watch the England v Croatia game.

In a post on Instagram, the restaurant dubbed the opening ‘the next episode’.

They said: “After closing Castlegate we promised something exciting was coming and here she is! Our stunning new truck will be at @foxpubyork Wednesday-Sunday through the summer!

“She debuted at @burger_fest_uk this weekend where we won The Best Chicken Burger Award which was judged by @wingfestuk”

The Three Lions are taking on Croatia in their opening game of the tournament stateside

There were joyous scenes as England opened their account at the 2026 World Cup tonight.

The Three Lions are taking are taking on Croatia in Dallas, Texas, in their first group game in the newlly expanded tournament being held in the USA, Mexico and Canada.

And it was a dream start when a foul by Luka Modric on Noni Madueke saw England awarded a penalty.

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Captain Harry Kane’s initial effort was saved by the Croatian goalkeeper Dominik Livakovic.

However the referre ordered it to be retaken due to encroachment from two Croatian players,. and Kane made no mistake second time around, slotting home to give England a 12th minute lead.

Watch: Harry Kane gives England the lead from the spot

At the ‘We Are Football festival’ in Freight Island, where more than 2,000 fans have packed in, chaos erupted as England opened their account.

Beer was launched through the air as a sea of bodies bounced around in joy.

Stunned silence as Croatia equalise

That joy was cut short, with the fans reduced to stunned silence when a thundering strike from Martin Baturina drew Croatia level in the 36th minute.

It took Kane just eight minutes to get them celebrating again.

Kane restore’s England’s lead

A powerful header from a corner sent the raucous venue into raptures again.

Croatia draw level

Following an action-packed first-half, Croatia levelled again, with Petar Musa volleying home seconds before the half-time whistle.

Jude Bellingham puts England 3-2 up

But after a bright start to the second period, Jude Bellingham slotted home after a surging run to put England back in front and sparked further scenes of delerium in the fanzone.

Marcus Rashford makes it 4

Manchester United striker wrapped up the victory as he slotted home Bukayo Saka’s pass to make it 4-2 and a very satisfactory night for England faithful.

There chants of ‘It’s Coming Home’ and a booming rendition of Sweet Caroline following the full-time whistle.

Ashfield Caravan Park, on the outskirts of Dalton Piercy, near Hartlepool, is on the market.

The park spans around 11 acres and includes planning permission for 37 static holiday caravans, with the potential to increase to 47 units, and storage for up to 143 touring caravans.

Ashfield Caravan Park (Image: GSC Grays, Farm Agency)

It also has planning permission for a four-bedroom detached house.

The caravan park is operational all year round, with each of the 105 touring pitches developed with hardcore bases and electric hook-up points.

The site is divided into three main areas.

The western side, which makes up almost five acres, is home to the touring caravan pitches.

The north eastern section, covering about 1.8 acres, has planning permission for the storage of up to 143 touring caravans and a four-bedroom dwelling for owner or manager accommodation.

To the south eastern section, covering just over three acres, there is planning permission for 37 static holiday caravans, with potential to increase to 47 units, subject to further surveys and planning guidelines.

The park also includes a central reception with a licensed social club, a fully equipped amenity block, and a single static caravan for staff use.

The amenity block, built in 2006, provides a reception foyer with space for a convenience store, staff amenities, a commercial kitchen, and rear access into the social club with a bar and seating.

The block also includes showers and toilets, baby changing facilities, and a pot-washing station for all touring pitches.

Part of the internal space is currently used for storage, but it could be converted to self-contained manager accommodation, subject to planning consents.

The park is located in a rural landscape close to the coast, offering a peaceful and scenic environment.

The sale of the park includes numerous vehicles, plant, and equipment, with an inventory to be provided to seriously interested parties.

The sale of the park, which is bordered predominantly by mature hedgerows and open farmland, is listed by GSC Grays, Farm Agency.

The prestigious golf club have announced a planning application for ‘modifications to the championship course’

Royal County Down is widely regarded as the finest golf course anywhere on the planet.

But as anyone in the sporting world knows, if you are standing still, you are falling behind.

The prestigious golf club have announced a planning application for ‘modifications to the championship course’.

It’s difficult to improve on perfection.

The course recently came top of Golf Digest’s annual top 100 courses in the world list, and has been hailed as the best there is by the likes of Rory McIlroy and others many times.

With the stunning Mourne Mountains as the backdrop – on a clear day – the links sit right against the Irish Sea on the edge of Newcastle, Co Down.

Old Tom Morris’ famous track is renowned for its natural, rugged look, devilishly deep bunkers and dramatic blind tee shots. That all combines for one of the toughest tests in the game.

However, change is afoot at the bottom of the Mournes.

The Golf Club has filed a pre-application planning notice, proposing modifications to its championship course.

The finer details of those changes will be revealed on August 26, online – through their consultancy firm Clydeshanks – and at a consultation meeting in Newcastle.

The proposal to the council states: “Information relating to the proposed development will also be available to be viewed at www.clydeshanks.com/public-consultations, where an online consultation magazine will be available from 26 August 2026, and will be available to view for a minimum of 28 days thereafter.

“The online consultation will display details of the proposed development and facilitate comments from members of the public, relating to the proposed development.”

A cover letter on the proposal also explains: “The community consultation will take place at Newcastle Centre, 10-14 Central Promenade, Newcastle, Co. Down, BT33 0AA on Wednesday 26 August 2026 from 4-7pm.

“It will comprise a number of large wallboards that will graphically explain what is proposed, enabling interested parties to understand the nature of the development and how the scheme may look when completed.”

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Retirement planning might seem like a thoroughly modern concern, with pensions, investments and annuities forming part of today’s financial toolkit. But these financial tools are much older than they appear. In the later Middle Ages, people were already exchanging lump sums for steady income streams – and, in cities like Vienna, these arrangements underpinned entire urban economies.

Less expected, perhaps, is who helped make this system work. Alongside merchants and elites, communities of nuns quietly emerged as some of the city’s most reliable financial operators.

Annuities existed in several forms, each suited to different needs. At their core, these contracts involved one party providing a lump sum in exchange for a regular payment, usually secured on property or urban revenues. The most common type in medieval Vienna – my area of research – was the perpetual annuity, which generated a fixed annual return without a set end date and could be transferred or sold.

Alongside these stood life annuities, which paid people an income for their lifetime. This arrangement provided security in old age and helped with managing inheritance. There were also public annuities issued by civic authorities, through which the city itself raised funds by promising regular payments backed by its revenues.

These different forms of annuity supported a wide range of financial strategies. Households used them to access liquidity, investors secured predictable income streams and institutions managed long-term assets.

In cities such as Vienna, this system formed the backbone of urban finance and enabled sustained economic activity in the absence of formal banking institutions.

Women, credit and the records of a city

My research in Vienna’s city records offers an unusually detailed view of this system. A data-set of more than 2,000 annuity contracts recorded in the Grundbücher, the city’s property registers, between about 1360 and 1450 makes it possible to trace who participated in these markets and how their activity evolved over time.

Women are especially visible in these records, appearing frequently as both borrowers and lenders. Wives participated in household finance alongside their husbands, widows managed and reinvested their assets and some women acted as independent economic agents in their own right. Far from being marginal, women were embedded in the everyday functioning of late medieval credit markets.

Over the course of the 15th century, however, these patterns began to change. Individual women appear less frequently in annuity transactions. In their place, a different kind of female economic actor becomes increasingly visible: the convent.

Life cycle stages shaped how women engaged with credit within Vienna’s legal framework. Urban regulations defined when women could control property, including widowhood, entry into a convent and recognised economic maturity later in life.

Within these conditions, women appear in the annuity market across different stages, sometimes acting independently and sometimes with spouses or kin. At the same time, wider institutional changes shaped how credit moved through the city. Women remained an integral part of this system, even as the forms of their participation evolved.

One of the most striking developments during this period is the growing importance of female religious houses as lenders. As individual women appear less in annuity transactions, convents emerge as increasingly active providers of credit.

This shift becomes particularly visible after 1420, when Vienna’s Jewish community – long an important source of credit – was expelled. As established channels of lending contracted, new opportunities opened up. Convents stepped into this space, expanding their lending activity and becoming key providers of urban credit.

Convents as lenders

Convents gathered resources through dowries, donations and rents, building up substantial pools of capital behind cloistered walls. They then deployed this wealth through annuity contracts, often over long periods, carefully spreading risk by lending to a wide range of borrowers.

Convent administrators tracked payments, negotiated contracts and cultivated reputations for reliability. In a world where trust underpinned financial exchange, nuns became known as dependable creditors.

Their borrowers varied too. Viennese private annuity records show households, artisans, elites and institutions all turning to convents for credit. These loans supported property transactions, the management of existing debts, household needs and investment. Convent lending formed part of the everyday functioning of Vienna’s economy.

Understanding these records reshapes how women’s economic history can be understood. Though individually women were less represented in the financial systems, there was a shift toward collective and institutional forms of financial participation. Women continued to shape economic life, often through structures that organised and amplified their resources.

At a time when discussions about financial inclusion and stability remain central, there are lessons to be learned from Vienna. Trust, adaptability and a diversity of participants are integral to any healthy financial system. When established sources of credit change, new ones can step forward to sustain the system. In this case, female religious communities played a central role in supporting economic resilience.