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  • The word ‘cancer’ leads to overtreatment and fear. Should we drop it?

    The word ‘cancer’ leads to overtreatment and fear. Should we drop it?

    The Oxford philosopher of language J L Austin died on 8 February 1960, just months after receiving a ‘grave’ diagnosis. His friend Isaiah Berlin called it a ‘dead secret’ – Austin himself had ‘no idea’ how little time was left. As Hilary term approached, Austin requested a mere four weeks’ leave until his glands ‘cleared up’. He died five weeks later.

    Today, Austin is best known for speech act theory, which teaches that language does not simply convey information but performs actions. In short, we do things with words. One word, however, is conspicuously absent from Austin’s late correspondence. Cancer. Lung cancer, Austin’s ‘grave’ diagnosis, claimed his life at age 48.

    Like many at the time, Austin’s doctors, family and friends avoided naming his disease. ‘Cancer’ was a whispered word, a taboo too terrible to speak. Physicians routinely withheld the diagnosis, fearing that merely uttering it would extinguish all hope and hasten death. As one writer observed:

    Cancer patients are lied to, not just because the disease is (or is thought to be) a death sentence, but because it is felt to be obscene – in the original meaning of that word: ill-omened, abominable, repugnant to the senses.

    That writer – Susan Sontag – like Austin, was an astute observer of the power of language. In Illness as Metaphor (1978), Sontag exposed how metaphors surrounding illness, especially cancer, do more than describe; they shape perception, reinforce stigma, and impose narratives that can harm. She called for a ‘liberation’ from these metaphors, arguing that we must stop treating cancer as ‘an evil, invincible predator’.

    Sontag died of cancer in 2004. By then, the narrative had shifted. When she was first diagnosed with breast cancer in 1975, there were no pink ribbons or ads urging early detection and treatment. By her death, however, cancer had moved from private affliction to public crusade. Women marched in solidarity; men grew moustaches for Movember; athletes donned pink jerseys, while coloured wristbands signalled support for everything from leukaemia to pancreatic cancer.

    Cancer was no longer a shameful obscenity but a rallying cry. Shattering the silence was undoubtedly progress. But with this shift came new metaphors – and new expectations. No longer an unspeakable fate, cancer became a battle to be fought, with patients cast as warriors, urged to ‘Fight Like Hell’. Drive through any major city in the United States, and you’ll pass billboards with slogans: ‘We Fight for You’; ‘Your Battle Begins Here.’ Cancer centres recruit patients, urging them to enlist. Public health campaigns preach constant vigilance against a lurking enemy needing to be stamped out before it takes root. What was once too fearsome to name became a call to action.

    Many now worry the pendulum has swung too far. Overtreatment – intervening where it’s unlikely to help and likely to harm – has become a major problem in modern oncology. Take prostate cancer. In the US alone, more than 50,000 men are diagnosed each year with a low-risk instance of the disease. These cancers rarely spread, and observation is a safe approach, with outcomes equivalent to surgery or radiation. Yet more than half of patients still undergo aggressive treatment, risking incontinence, impotence and other harms – without clear benefit.

    We treat not because it helps – but because the alternative feels like giving up

    Similar patterns play out in other cancers. More than 50,000 women in the US are diagnosed annually with ductal carcinoma in situ (DCIS), a non-invasive form of breast cancer with a low risk of progression. Yet nearly all undergo surgery, with a third receiving mastectomies. Trials have shown that observation can be a safe alternative, but they struggled to recruit patients – and, even when they did, many crossed over to surgery. As one commentator noted, clinicians are conditioned to act, and patients have been ‘brought up to expect “cancer” to be removed.’

    But overtreatment doesn’t stop at early stage disease. In the US, it’s estimated that nearly 700,000 people are living with advanced cancer. For many, the final stretch of life will be marked by intervention. One in three will receive aggressive treatment in their last months, and one in five will get chemotherapy in their final weeks. These treatments rarely prolong life and almost always diminish its quality, bringing exhaustion, nausea, hospital stays and lost time with loved ones. Despite guidelines discouraging such practices, the default remains action. We treat not because it helps – but because the alternative feels like giving up.

    As a physician, I see this firsthand. Patients hear the word ‘cancer’ and brace for battle. Some tell me they’ll accept anything – however toxic – if it means getting rid of the disease. Even when the evidence supports watching and waiting, the very idea can feel like surrender. And even when the evidence supports palliative care, many still choose to ‘fight to the bitter end’. To quote one patient: ‘Doing nothing is no choice.’ Clinicians, too, feel pressure to intervene. The urgency doesn’t come from disease biology – it comes from the weight of words.

    That’s why some oncologists now argue that we should drop the ‘dreaded C-word’: removing the cancer label from low-risk cases like early breast and prostate cancers could spare patients unnecessary treatment. We’ve come full circle – but for the opposite reason. What Austin’s doctors withheld to preserve hope, today’s oncologists would withhold to prevent us from doing too much. It’s a tempting solution to a serious problem. Cancer overtreatment harms millions and drains billions from healthcare systems every year. But is renaming really the answer?

    To begin to unpack this, we can turn to Austin and his theory of speech acts. Imagine you’re diagnosed with a disease. It started with a yellowing toenail. Your doctor examines you, then says: ‘You have Disease X.’ It’s slow growing, she explains, though it may spread. There’s a treatment, but it has side-effects. Some patients, she says, choose to live with Disease X. You consider your options, opt for treatment, and are cured. You never think of Disease X again.

    Now imagine a different diagnosis. This one began with a lump in your groin. Your doctor runs some tests, then breaks the news: ‘You have Disease Y.’ You shudder at the words. She tries to reassure you: it’s slow growing but can spread over time. The treatment has side-effects. But many patients, she adds, find it hard to live with Disease Y. She refers you to a support group, where you hear of patients who fought Disease Y and won. You choose treatment and achieve remission. You remain an active member of the Disease Y community. You see yourself as a Disease Y survivor.

    What’s the difference between Disease X and Y? Between onychomycosis, a fungal toenail infection, and an indolent lymphoma, a slow-growing cancer of the lymph nodes? Yes, they differ in prognosis. But perhaps the most striking difference lies elsewhere. It lies in what Austin calls illocutionary force.

    Illocutionary force is what words do in the very act of saying them – they create commitments, reshape roles, and influence identities. Take ‘I promise’: those two words don’t just express an intention; they create an obligation. Or take ‘You are guilty.’ Uttered by a judge, those words don’t just assign blame – they make you a criminal.

    The fighter effect is a powerful driver of overtreatment

    Likewise, the words ‘You have cancer’ do more than simply state a medical fact. A cancer diagnosis, like a guilty verdict, carries special illocutionary force. It doesn’t just describe a condition; it imposes a new identity. In short, it makes you a cancer patient.

    And not just a patient – a fighter. ‘Conquer Cancer.’ ‘Fight Like Hell.’ These slogans don’t just inspire; they instruct. They set expectations: show strength, not weakness; determination, not passivity; persistence, not surrender; action, not inaction. Cancer isn’t just a diagnosis – it’s a call to arms. We can give this special illocutionary force a name. Let’s call it the fighter effect.

    The fighter effect is a powerful driver of overtreatment. It’s what leads men with low-risk prostate cancer to undergo unnecessary prostatectomies. It’s what drives women with indolent breast lesions to receive mastectomies they may not need. And it’s what pushes patients with advanced disease to trade precious time for ineffective treatments at the end of life. The word ‘cancer’ demands action. In the words of one patient: ‘Something has got to be done.’

    Recognising cancer’s illocutionary force brings into focus two competing strategies for tackling overtreatment: renaming versus reframing. Proponents of renaming – those who argue that we should drop the ‘dreaded C-word’ and simply call early cancers something else – focus on blocking the immediate impact of cancer’s illocutionary force. By leaving the word unsaid, they aim to prevent the fighter effect from taking hold.

    But it’s a bit like building dams to stop flooding. It may protect some areas, but it doesn’t address the source of rising waters. The social and cultural currents that drive overtreatment remain, ready to surge again. To truly tackle overtreatment, we need a different strategy. Instead of building local dams, we must quell the rising waters. Rather than renaming the diagnosis, we must reframe its force.

    To reframe cancer’s illocutionary force means shifting the linguistic and social practices that give the word its power. It rejects the narrative that cancer demands a fight, aiming to disarm – rather than simply block – its illocutionary force. It creates space for treatment decisions to be guided by risks, benefits and patient preferences rather than by bellicose expectations.

    Why reframe rather than simply rename? There are at least three compelling reasons. The first is that reframing targets the root cause of overtreatment. Studies suggest that renaming early cancers with terms like IDLE (‘indolent lesion of epithelial origin’) may lead fewer patients to choose unnecessary treatment. But this is like trying to solve vaccine hesitancy by simply replacing the word ‘vaccine’ with a catchy acronym – say, BIBBLES (‘biological immunity boosting with bonafide, longitudinally established safety’). Clearly, that just skirts the issue. Renaming may block overtreatment in one instance, but it leaves the underlying misperception intact: that every cancer, regardless of risk, must be treated aggressively.

    What’s more, renaming doesn’t just leave the misperception intact but reinforces it. Avoiding the term ‘cancer’ only feeds the narrative – shared by Austin’s doctors and critiqued by Sontag – that it’s something too terrible to name. Just as calling Voldemort He-Who-Must-Not-Be-Named only intensifies his infamy, shying away from the C-word cements cancer’s power. Renaming some cancers, while reserving the word for cases where ‘fighting’ is deemed appropriate, ultimately reinforces the very expectations that efforts to tackle overtreatment ought to challenge.

    Reframing seeks to transform the norms and expectations around the diagnosis

    The second reason to prefer reframing is that it respects patient autonomy. Imagine you have an American friend, Amy, who hates zucchini. She’s not allergic or intolerant. She simply fears that eating zucchini will make her sick. Worried that Amy’s missing out on zucchini’s culinary delights, you prepare your finest ratatouille. Knowing she hates zucchini, you strategically tell her your ratatouille is made with ‘courgette’. (Schooled in American English, Amy is unfamiliar with zucchini’s British synonym.) She eats your ratatouille.

    In this scenario, it’s plain that you’ve deceived Amy. You’ve prevented her from making an autonomous decision about whether to eat your ratatouille given her preferences. Even if you believe her fear is baseless, your deceit isn’t justified. A better friend would help Amy understand that zucchini won’t harm her so she can confidently enjoy the vegetable.

    Reframing aims to do just that: it addresses the fear directly, helping Amy see zucchini for what it really is. Renaming, by contrast, would have Amy eat ‘courgette’. This might be appropriate if she were your four-year-old daughter but it’s not appropriate for your friend.

    Critics argue that renaming early cancers is paternalistic, infringing on patients’ right to make autonomous decisions. Members of the public have echoed these concerns, worrying that renaming feels deceitful. Though paternalism rightly raises red flags in modern medicine, it can sometimes be justified. Proponents of renaming defend it as a way to spare patients the emotional burden of the C-word, nudging them towards better choices. Yet this approach is ultimately flawed. It concedes that the fighter effect is problematic but does nothing to address it. As a result, patients whose conditions remain labelled ‘cancer’ are still subject to its full force, pushing them towards overly aggressive interventions.

    Reframing offers a better path. Instead of sidestepping the problem, it seeks to transform the norms and expectations that surround the diagnosis. In so doing, it respects autonomy across the board – empowering all patients to make informed, proportionate decisions about their treatment.

    When patients discover that their so-called ‘lesion’ used to be called cancer, trust erodes

    The third reason to choose reframing is that it’s more robust. By robust, I mean resilient to shifting tides of medical practice, testing regimes and human behaviour that can undermine efforts to curb overtreatment.

    Consider cancer screening. Recently, attempts to restrict mammography to women over 50 to prevent overdiagnosis and overtreatment sparked widespread controversy, with conflicting guidelines, professional disputes and media uproar – what became dubbed ‘the mammography wars’. Even where restrictive screening guidelines are adopted, adherence is patchy, influenced by personal biases and patient pressures. Meanwhile, emerging technologies like blood-based cancer-detection tests introduce new avenues for overdiagnosis, further complicating efforts to address overtreatment.

    Renaming might seem more robust: if we can’t stop doctors from finding early cancers that don’t require treatment, we could at least change what they’re called. Replacing ‘cancer’ with ‘lesion’ or ‘IDLE’ might sidestep the fighter effect and thereby reduce unnecessary interventions. But this strategy, too, is fragile. As any physician knows, and as I’ve seen time and again in my own practice, such euphemisms inevitably prompt the further question. To borrow a line from the 1960 movie Ocean’s Eleven: ‘Look, doc. Give it to me straight. Is this the big casino?’

    Moreover, when patients discover that their so-called ‘lesion’ used to be called cancer, trust erodes. And, in that moment of discovery, the full illocutionary force of the C-word re-enters – often with a vengeance. When Amy Googles ‘courgette’, she won’t be pleased.

    Reframing is a more robust solution. Instead of relying on fragile euphemisms, it directly challenges the fighter effect – the underlying social forces that drive overtreatment. Rather than waging battles over labels, it aims to change the way we think and talk about cancer altogether.

    Changing the way we think and talk about cancer might seem like a lofty, even impossible goal. But as Austin scholars have pointed out, illocutionary forces are not immutable. They are shaped and sustained by social conventions. A promise carries weight because society enforces the expectation to keep one’s word. A guilty verdict gains significance through laws and institutions, and through how society views the crime. These are not set in stone. Change is possible.

    The same is true of a cancer diagnosis. Shifting illocutionary force means changing the conventions that give it power – moving away from seeing every cancer as a battle to be won at all costs, and toward treating it like other diseases, where decisions carefully consider a patient’s preferences, along with the risks and benefits of different options. That shift requires action across many fronts. Doctors must reconsider how they present the diagnosis, replacing militarised metaphors with language that emphasises patient agency. Public health campaigns must move beyond combative imagery, crafting messages that inform and empower without resorting to fear to drive decisions. Cancer centres, research institutions and media outlets all have a role to play in dismantling norms that perpetuate the fighter effect.

    Since Sontag, many have called for such changes. Austin’s insights lend new clarity to these calls, showing us why and how change should occur. Seeing the diagnosis of cancer as a speech act with powerful illocutionary force – capable of shaping norms, expectations, even identity – reveals that overtreatment can’t simply be contained by renaming specific cancers. Overtreatment isn’t just a medical issue, but a social and cultural one too. To change how we treat cancer, we must rethink the illocutionary force that surrounds the diagnosis.

    Sontag herself saw this clearly. She even lived through an important shift in that force. The unspeakable, ‘grave’ diagnosis that killed Austin had, by the time it claimed Sontag, become nameable, visible – even public. That was progress. But it wasn’t the liberation she’d hoped for.

    Too many patients are convinced that stopping treatment or choosing palliation means surrender

    She’d incisively critiqued cancer’s earlier metaphors of silence and despair, yet wasn’t immune to its newer ones. As her son David Rieff recounts in his memoir Swimming in a Sea of Death (2008), following her diagnosis Sontag became a ‘militant propagandist for more rather than less treatment’, pursuing extraordinarily aggressive regimens – first for breast cancer, and later for the leukaemia that followed. Though ‘less is more’ captured her artistic sensibility, Rieff writes: ‘when it came to cancer treatments more was always better.’ By today’s standards, much of her treatment would be considered excessive – its toxicity likely contributing to the second cancer that ultimately claimed her life.

    Even after her bone marrow transplant failed, Sontag refused to stop. She remained determined to ‘fight for her life to the very end’, rejecting any talk of palliation and pressing her doctors to continue. As her son movingly recalls, it was ‘the opposite of an easy death’ – a slow, painful end, ‘stripped of her dignity’ and ‘unreconciled to her own extinction’.

    As a physician treating patients with blood cancers, I’ve seen how too many still face a similar fate, convinced that stopping treatment, choosing palliation – or even death itself – means surrender. As one patient with advanced cancer put it: ‘If I were to die, which I most likely will, then I’m a failure, I’m weak, I’m not a good fighter.’

    The metaphors have changed – but their force endures. Though stigma has given way to slogans, true liberation means casting off these narratives altogether. It means reframing cancer’s illocutionary force so that it’s no longer a death sentence or a battle cry but a diagnosis – one that, like any other, demands deliberation, not action by default.

    We should all be free to attach our own meanings to the experience of illness

    This isn’t to deny that a cancer diagnosis can be devastating. The words ‘You have cancer’ often signal life-altering challenges ahead. Cancer remains a leading cause of death, claiming far too many lives – many younger than Sontag and even Austin, whose enduring contributions to literature and philosophy were tragically cut short by the disease. Early detection and effective treatment – sadly, unavailable to Austin and ultimately unsuccessful for Sontag – can and do saves lives.

    Yet even with advances in therapy, most cancers remain difficult to cure, and treatments remain long and arduous. In the face of such hardships, some might see the fighter effect as a source of strength, helping them endure a difficult treatment cycle or pursue early intervention. Some patients may choose to embrace the identity of ‘fighter’; others of ‘traveller’; others of something entirely different. We should all be free to attach our own meanings to the experience of illness.

    To argue for reframing cancer’s illocutionary force is not to deny the gravity of the disease, the benefits of early treatment, or the hardships faced by patients. It’s to question whether the expectation to ‘fight’ should be baked into the very act of diagnosing cancer. Patients already grapple with complex decisions – navigating treatment options, weighing side-effects, and considering what it all means. They should not be further burdened by pressures to ‘fight’ because of the force of words. Decoupling the fighter effect from the cancer diagnosis allows patients to make their own informed choices – choices that weigh risks and benefits, not words. Only by shifting these norms can we achieve the kind of liberation that Sontag envisioned – it’s the only way to truly ‘de-mythicise’ cancer so that patients are free to shape their own identities and experiences.

    As Austin reminds us, we do things with words. Words have the power to create norms, establish expectations, and shape identities. This power is rooted in linguistic and social conventions – conventions that, as Austin and Sontag well knew, are never fixed. In Austin’s day, cancer was an unspeakable diagnosis; in Sontag’s, it became a battle cry. Both were shaped by the language of their time. And both, in different ways, suffered under its weight.

    Today, we stand at a different moment. Patients with cancer needn’t suffer in silence – but neither should they be summoned to war. If we are to carry forward Austin’s insights and realise Sontag’s vision, we must change not just the volume but the force of the word ‘cancer’. It shouldn’t be whispered. Nor shouted. It should be spoken clearly and calmly – so that patients can face a cancer diagnosis with autonomy, unburdened by expectation. To truly tackle overtreatment, we shouldn’t avoid the word ‘cancer’. We should transform what it means.

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  • The Strad News – Man arrested over theft of 285-year-old violin, worth £150k

    The Strad News – Man arrested over theft of 285-year-old violin, worth £150k

    Read more news stories here

    The Metropolitan Police has made an arrest in its search for a 1740 Lorenzo Carcassi violin that was stolen from a London pub in February this year.

    The violin belongs to David López Ibáñez, a member of the Philharmonia Orchestra. The instrument, along with three bows, were stolen in a black Riboni Unoeotto case at 7:30pm on Tuesday 18 February from the Marquess Tavern in Canonbury.

    In June, the Met Police released CCTV images of the suspect and appealed to the public to help trace the thief.

    Suspect pic 10 - violin theft

    A 43-year-old man was arrested on 25 June on suspicion of theft and was taken into custody. He was released on bail pending further inquiries.

    However, the violin has not been recovered.

    Ibáñez described the violin, worth £150,000, as his ‘voice.’

    ’Aside of the actual monetary value of it, to me it really was priceless,’ he told the BBC.

    The violin has a distinct heart-shaped hole at the back of the scroll. Ibáñez urges anyone who may have seen the violin to get in touch with the police with the Crime Reference Number  01/7178074/25. 

    Best of Technique

    In The Best of Technique you’ll discover the top playing tips of the world’s leading string players and teachers. It’s packed full of exercises for students, plus examples from the standard repertoire to show you how to integrate the technique into your playing.

    Masterclass

    In the second volume of The Strad’s Masterclass series, soloists including James Ehnes, Jennifer Koh, Philippe Graffin, Daniel Hope and Arabella Steinbacher give their thoughts on some of the greatest works in the string repertoire. Each has annotated the sheet music with their own bowings, fingerings and comments.

    Calendars

    The Canada Council of the Arts’ Musical Instrument Bank is 40 years old in 2025. This year’s calendar celebrates some its treasures, including four instruments by Antonio Stradivari and priceless works by Montagnana, Gagliano, Pressenda and David Tecchler.

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  • Person-focused approach explains distinct autism genetic subtypes

    Person-focused approach explains distinct autism genetic subtypes

    New study shows that autism is not one condition, but four, each driven by different genes and brain development patterns, helping to reshape diagnosis and care.

    Study: Decomposition of phenotypic heterogeneity in autism reveals underlying genetic programs. Image credit: chrupka/Shutterstock.com

    A paper published in Nature Genetics provides a new glimpse into the role of genetic variation in the range of clinical symptoms found in autism spectrum disorder (ASD). The team of researchers found that autism classes can be clinically distinguished. Each is associated with unique patterns of gene dysregulation, reflecting distinct molecular-level perturbations caused by class-specific sets of mutations.

    Introduction

    ASD is a neurodevelopmental condition characterized by difficulties with social communication and interaction, often demonstrating restricted and repetitive behavior patterns, interests, or activities. With an increasing ASD burden each year, the phenotypic and genetic differences in the ASD pool are becoming more obvious.

    A systematic evidence-based association study of genetic and phenotypic data has not matched the genetic and phenotypic complexity of ASD. The current study used a large sample of autism phenotypes to reveal phenotypic classes and the underlying genetic heterogeneity.

    A person-centric method is essential in this analysis, rather than focusing on single traits, since each co-occurring trait inevitably affects the other. Only then can they be properly mapped to their genotypic origin. Such an approach provides a clearer picture of how these developmental disruptions interact and evolve, allowing for an informed prognosis.

    This approach avoids the limitation of traditional trait-centric analyses and better captures the complex, interacting nature of ASD symptoms in real individuals.

    About the study

    The current study used genotypic and phenotypic data from the SPARK cohort of 5,392 people. They collected phenotypic data from standard diagnostic questionnaires (the Social Communication Questionnaire-Lifetime (SCQ), Repetitive Behavior Scale-Revised (RBS-R), and the Child Behavior Checklist 6–18 (CBCL), combined with the developmental milestone history.

    Researchers applied a generative finite mixture modelling (GFMM) framework to analyze 239 features, allowing individuals to be grouped into clinically meaningful phenotypic classes based on their overall trait profiles.

    Study results

    The model distinguished autism classes using the seven core traits: limited social communication, restricted and/or repetitive behavior, attention deficit, disruptive behavior, anxiety and/or mood symptoms, developmental delay (DD), self-injury, and the severity of symptoms. They assigned each of 239 phenotype features associated or co-occurring with each trait.

    Four ASD phenotypic classes emerged. One class (Social/behavioral) had both severe social communication deficits and restricted or repetitive behavior, compared to other ASD children. They also showed disruptive behavior and attention deficit, with anxiety, but normal developmental rates.

    The Mixed ASD class distinctively shows developmental delay, despite some features of social communication deficits, restricted/repetitive behavior, and self-injury. The other two classes were Moderate challenges, with a lower ASD score for all seven core traits than other ASD children but above non-autistic siblings, and Broadly affected, with a higher score than other ASD children.

    These classes were validated by their agreement with the reported co-occurring conditions, parental narratives, and medical history. For instance, the Broadly affected class was much more likely to have all co-occurring conditions: attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), delayed language development, anxiety, and depression.

    Conversely, the Mixed ASD class had the lowest odds of anxiety, depression, or ADHD. Yet they were at high risk for language and intellectual delay, and motor abnormalities, concordant with their delayed development and high occurrence of restricted/repetitive behavior. In contrast, the Social/behavioral class had a higher risk of ASD-associated ADHD, anxiety, and depression diagnoses.

    Mixed ASD and Broadly affected classes were usually diagnosed the earliest. They were most likely to be receiving a variety of therapies, due to the highest cognitive impairment and poor language skills. The Broadly affected class also showed the most significant co-occurring conditions and the highest use of clinical interventions.

    An independent cohort of autistic subjects also confirmed the validity of these classes. The model showed a high correlation in feature enrichment patterns across the SPARK and SSC cohorts, highlighting its robustness and generalizability.

    The scientists then investigated genetic influences using polygenic scores (PGS) for autism and five well-accepted genome-wide association studies (GWAS) for autism-related conditions or traits. They explored both inherited and newly arising genetic variations. The findings revealed genetic differences according to the four classes.

    The Broadly affected and Social/behavioral classes had higher ADHD PGS signals than for other classes or non-autistic siblings. Depression-related PGS and diagnosis rate were both highest in the Social/behavioral class. This class also had the highest number of high-impact variants in neuronal genes, mainly expressed after birth. However, ASD PGS did not differ significantly between classes due to high within-group variance, highlighting the limited explanatory power of current common-variant-based ASD scores.

    The Broadly affected class, which showed the highest rate of cognitive impairment, delayed development, and the lowest educational status, had the lowest IQ PGS. Thus, “co-occurring conditions were associated with common genetic variation that significantly differed among the four identified classes.”

    All four classes had more mutations than non-autistic siblings, and mutations were unevenly distributed between the classes. The Broadly affected class had excessive loss-of-function (LoF) or missense mutations, and the social/behavioral class was the least enriched.

    Whilst all four classes showed more mutations than non-ASD siblings, the Broadly affected class had the highest high-impact de novo mutations. In contrast, the Mixed ASD class showed increased rare inherited variation alongside de novo mutations, indicating a stronger inherited genetic component.

    ASD-specific gene set analysis showed a higher burden of new LoF mutations associated with developmental delay. High-impact mutations in a relatively small group of genes contribute to cognitive impairment. The greater the development delay in the class, the higher the odds for new LoF mutations.

    Fragile X mental retardation protein (FMRP) target gene mutations were especially enriched in the Broadly affected class and the Mixed ASD class. FMRP in both Broadly affected and Mixed ASD classes was linked to developmental delay and cognitive deficit. The Broadly affected class showed additional enrichment for mood and behavioral traits such as anxiety, hyperactivity, and aggression.

    Tracing the molecular pathways affected by these mutations showed that each class reflected specific pathway disruptions. For instance, disruption of microtubule activity, chromatin organization, and DNA repair was enriched in the Social/behavioral class, compared to neuronal action potential and membrane depolarization in Mixed ASD.

    In the Mixed ASD class, LoF mutations affected prefrontal cortical neuronal genes expressed primarily during fetal and early newborn life. This class, therefore, had the most developmental delay and the earliest diagnosis, compared to the Social/behavioral class, where postnatal gene expression was disrupted.

    The Broadly affected class showed gene dysregulation spanning all developmental stages and cell types, especially of FMRP target genes and highly constrained genes. In contrast, the Moderate challenges class had enrichment for variants in genes with lower evolutionary constraint, which may explain the milder developmental impact.

    Conclusions

    The study demonstrated the value of a person-centered rather than a trait-centric approach to ASD genotype-phenotype analysis. The four phenotype-based classes described here agreed with reported clinical features and can be applied to any clinical cohort. Importantly, it suggests that ASD phenotypes do not reflect a spectrum of intellectual disability.

    The classes also had separate genetic signals and differed in the timing of gene dysregulation during the developmental trajectory. These differences correlate with the degree of delay in development and the outcome.

    The study provides a framework to investigate the neurobiological mechanisms underlying distinct ASD presentations, supported by genetic and molecular data across developmental stages.

    These findings suggest new research directions to understand the neurobiological mechanisms underlying different ASD presentations, allowing for more precise diagnosis and management of these conditions.

    Download your PDF copy now!

    Journal reference:

    • Litman, A., Sauerwald, N., Snyder, L. G., et al. (2025). Decomposition of phenotypic heterogeneity in autism reveals underlying genetic program. Nature Genetics. Doi: https://doi.org/10.1038/s41588-025-02224-z. https://www.nature.com/articles/s41588-025-02224-z

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  • Severe Obesity Tied to DISH-Related Spinal Changes

    Severe Obesity Tied to DISH-Related Spinal Changes

    TOPLINE:

    This study linked severe obesity to diffuse idiopathic skeletal hyperostosis (DISH)-related spinal radiographic changes in patients with metabolic syndrome (MetS).

    METHODOLOGY:

    • Retrospective study of the effect of obesity on DISH-related spinal radiographic changes vs degenerative changes in patients with metabolic syndrome (MetS).
    • Overall, 124 MetS patients with diabetes, hypertension, and BMI of 25 or higher were categorized into four obesity classes: 0 (BMI, 25.0-29.9), I (BMI, 30.0-34.9), II (BMI, 35.0-39.9), and III (BMI ≥ 40).
    • Spine and chest radiographs were assessed to determine the presence of both DISH-related chunky spondylophytes and degenerative spondylophytes.
    • DISH was diagnosed when spondylophytes spanned at least four contiguous vertebrae.

    TAKEAWAY:

    • Among patients with MetS, 33.9% were diagnosed with DISH.
    • Patients with DISH had significantly more DISH-related chunky spondylophytes (P < .0001) and fewer degenerative spondylophytes (P = .04) than those without.
    • Patients in obesity classes II and III had significantly more DISH-related chunky spondylophytes vs classes 0 and I (P = .02), with a comparable number of degenerative spondylophytes between groups.
    • DISH patients in obesity classes II and III had more DISH-related chunky spondylophytes than those in lower classes (14.1 vs 9.7); however, the difference was not statistically significant.

    IN PRACTICE:

    “Our results support the hypothesis that obesity may not only be a comorbid condition but also a driving factor in the formation of Drc [DISH-related chunky]-spondylophytes,” the authors wrote.

    “The strong association between obesity and DISH-related radiographic changes underscores the importance of integrating weight management strategies into the clinical care of MetS patients to potentially mitigate the progression of Drc-spondylophytes,” they added.

    SOURCE:

    This study was led by David Kiefer, MD, Ruhr-Universität Bochum, Herne, Germany. It was published online on July 1, 2025, in The Journal of Rheumatology.

    LIMITATIONS:

    The retrospective design of the study may have introduced selection bias. Additionally, the study cohort was limited to patients with MetS, which could have led to an overrepresentation of obesity and related comorbidities, potentially limiting generalizability to populations without MetS or with lower BMI.

    DISCLOSURES:

    This study received no financial or industrial support. The authors declared having no conflicts of interest.

    This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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  • Harassment complaint filed against suspended opposition MPAs in Punjab Assembly – Samaa TV

    1. Harassment complaint filed against suspended opposition MPAs in Punjab Assembly  Samaa TV
    2. No headway in talks on Punjab MPAs’ fate  Dawn
    3. Suspended MPAs to cast Senate votes  The Express Tribune
    4. PA speaker clarifies his constitutional role in disqualification references  nation.com.pk
    5. Protecting sanctity of the House highly important: PA Speaker  Associated Press of Pakistan

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  • Marathon legend Fauja Singh dies in road accident at 114

    Marathon legend Fauja Singh dies in road accident at 114

    Fauja Singh, believed to be the world’s oldest marathon runner, died in a road accident in Punjab on Monday at the age of 114.

    Singh was struck by a car on the Jalandhar-Pathankot highway on Monday afternoon and suffered a severe head injury. He was rushed to the hospital but succumbed to his injuries later that evening.

    Born on April 1, 1911, in Beas Pind, Jalandhar, Fauja Singh defied age and adversity throughout his life. He could not walk properly until he was five and was often dismissed as physically weak.

    However, after a life of farming and personal tragedy, including the loss of his wife and son in the early 1990s, he turned to running to cope with grief – a choice that would ultimately see him become a legend.

    Fauja Singh began running competitively at the age of 89 and completed his first marathon in London in 2000.

    He went on to run nine full marathons in London, Toronto, New York and Mumbai, achieving a personal best of 5:40:04 in the ‘over 90’ age category at the Toronto Waterfront Marathon in 2003.

    Known affectionately as the Turbaned Tornado, Fauja Singh became a beloved figure in the global athletics community.

    At 100, he became the first centenarian to complete a marathon, finishing the 2011 Toronto Waterfront Marathon in just over eight hours.

    Although the Guinness World Records did not officially recognise the feat due to a lack of a birth certificate, Fauja Singh’s passport marks his birth year as 1911.

    He also set five age-group world records in one day at a meet in Toronto in 2011.

    A torchbearer for the London 2012 Olympics, Fauja Singh used his platform to raise funds for charity and promote good values. He also appeared in international advertising campaigns alongside David Beckham and Muhammad Ali.

    Fauja Singh retired from competitive running in 2013 after completing a 10km race in Hong Kong China. A biography, Turbaned Tornado, was published in 2011.

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  • Air India Crash Findings Prompt Inspections of Boeing Fuel Switches – The New York Times

    1. Air India Crash Findings Prompt Inspections of Boeing Fuel Switches  The New York Times
    2. As theories swirl about Air India crash, key details remain unknown  BBC
    3. India orders airlines to inspect Boeing fuel switches after Air India crash  Al Jazeera
    4. 32 seconds to disaster: How a routine takeoff turned catastrophic  Reuters
    5. A crash probe, a flight of fancy  Dawn

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  • Supreme Court declares FBR recovery notices without due notice as illegal

    Supreme Court declares FBR recovery notices without due notice as illegal

    ISLAMABAD (Dunya News) – The Supreme Court of Pakistan has declared the issuance of recovery notices by the Federal Board of Revenue (FBR) without giving taxpayers appropriate time as illegal and against the principles of justice.

    A three-member bench headed by Justice Athar Minallah heard the case, and an 18-page judgment authored by Justice Ayesha Malik was issued. The court dismissed the intra-court appeals filed by FBR.

    The Supreme Court annulled an FBR recovery notice of Rs 2.92 billion issued to one private company and similarly declared void a withholding tax recovery notice of Rs 1.88 billion against another private entity. In both cases, the recovery notices were issued by tax officers on the very same day appeals were filed and decided.

    Upholding the decision of a single judge of the High Court, the Supreme Court ruled that issuing immediate payment orders under Section 140 of the Income Tax Ordinance contradicts legislative intent. It emphasized that the appeal decision by a tax officer must be duly served to the taxpayer before any recovery action is taken.

    The judgment clarified that the term “by the date” under the law implies providing “reasonable time” — not demanding payment “on the same day.” The court highlighted that protecting legal rights, ensuring a fair hearing, and preserving the dignity of taxpayers are essential before executing any recovery.

    Justice Ayesha Malik observed that the conduct of the Commissioner Inland Revenue amounted to an authoritarian misuse of power, violating fundamental rights including dignity, fair trial, and access to justice. The court further noted that coercive recoveries could severely damage the business reputation of companies.

    The verdict concluded that FBR failed to justify its actions and ruled that both the issuance of notices and the withdrawal of funds were unlawful. It emphasized the need to maintain a fair balance between tax collection efforts and citizens’ rights. 


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  • One in 10 children screened in UNRWA clinics are malnourished, UN Palestinian refugee agency says – Reuters

    1. One in 10 children screened in UNRWA clinics are malnourished, UN Palestinian refugee agency says  Reuters
    2. Food shortages in Gaza are pushing children to the brink: UNRWA  Dawn
    3. UNRWA demands immediate end to Gaza blockade as humanitarian crisis deepens  Ptv.com.pk
    4. Aid for Gaza’s starving children is right at the gates. Let it in  +972 Magazine
    5. Children in crisis: Protection realities and response in the State of Palestine (June 2025)  ReliefWeb

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  • Conan relishing career-high Lions Tour

    Conan relishing career-high Lions Tour

    Jack Conan is a two-time British & Irish Lion, a three-time Six Nations champion and five-time URC winner – but insists The Qatar Airways British & Irish Lions Tour to Australia 2025 is the biggest occasion of his career.

    The Ireland No.8 has started two games and appeared off the bench in a third on Tour so far and is in contention for a starting place for the first Test against Australia this weekend.

    If he makes the matchday 23, it will mark a fourth straight Lions Test appearance for the 32-year-old, who started all three matches against South Africa four years ago.

    The Lions were narrowly beaten by the Springboks in that Test series, which was played behind closed doors due to the impact of the Covid pandemic.

    However, the Sea of Red is out in force in Australia and Conan is loving every minute.

    “Yeah, it’s chalk and cheese but it’s been unbelievably special, unbelievably enjoyable,” he said.

    “It’s vastly different to four years ago. With no-one in the crowd, it felt eerie and strange not to have anyone there at what should be the biggest occasion of your career.

    “A few weeks with the lads getting to move about, see some of the different places and see a lot of red at the games.

    “The atmosphere [here] has been incredible. I thought the game in Adelaide was unbelievable.

    READ MORE: The Making of Jack Conan

    “I think everyone’s absolutely loved it and it’s been a great challenge so far. We’re looking forward to pushing on and being better than we have been in the last few weeks.

    “Everyone will be a bit nervous about selection but I think everyone’s gone incredibly well, especially in the back row.”

    The back row presents perhaps the toughest selection dilemma for Head Coach Andy Farrell, who has a plethora of options in all three positions.

    Jac Morgan and Josh van der Flier have excelled at openside flanker, Tom Curry, Ollie Chessum and Tadhg Beirne have all played blindside – while Ben Earl and Henry Pollock offer versatility across the line.

    Conan is loving the challenge and admits competition for places has helped him raise his game.

    “It’s tough for the coaches I’m sure and hopefully we’ve given them all plenty of headaches over the last while, because I think no matter who’s been out there they’ve taken their opportunity really well,” Conan said.

    “It’s about those lads who get to run out on the weekend to do right by the lads who aren’t playing – and the lads who are on the bench and making the most of their opportunity.

    “That level of talent pushes everyone on to be at your best. I don’t think anyone can say that they’ve been poor over the last few weeks and I think especially in the back row the standard’s been unbelievably high.

    “It’s been a joy to play with the lads and get to know them and I’ve absolutely loved it over the last few weeks.”

    While Conan is one of 11 players with past Tour experience, he is not resting on his laurels and knows the Lions face a huge task against Australia.

    The Wallabies beat England and Wales during the Autumn Nations Series last year and are improving under former Ireland head coach Joe Schmidt.

    “No-one can ever take away being a Lion for me and playing in three Tests – but four years ago is definitely not the same as now,” Conan said.

    “This has been an incredible joy and the best few weeks of my career and I think that’s a sentiment that’s shared throughout the squad.

    “Everyone’s loving it and loving the challenge. We are unbelievably excited for Saturday to hopefully we can go out and create a bit of history.”

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