Covariate adjustment is an approach to improve the precision of trial analyses by adjusting for baseline variables that are prognostic of the primary endpoint. Motivated by the SEARCH Universal HIV Test-and-Treat Trial (2013-2017), we tell our story of developing, evaluating, and implementing a machine learning-based approach for covariate adjustment. We provide the rationale for as well as the practical concerns with such an approach for estimating marginal effects. Using schematics, we illustrate our procedure: targeted machine learning estimation (TMLE) with Adaptive Pre-specification. Briefly, sample-splitting is used to data-adaptively select the combination of estimators of the outcome regression (i.e., the conditional expectation of the outcome given the trial arm and covariates) and known propensity score (i.e., the conditional probability of being randomized to the intervention given the covariates) that minimizes the cross-validated variance estimate and, thereby, maximizes empirical efficiency. We discuss our approach for evaluating finite sample performance with parametric and plasmode simulations, pre-specifying the Statistical Analysis Plan, and unblinding in real-time on video conference with our colleagues from around the world. We present the results from applying our approach in the primary, pre-specified analysis of 8 recently published trials (2022-2024). We conclude with practical recommendations and an invitation to implement our approach in the primary analysis of your next trial.

In recent years, differentiable penalized likelihood methods have gained popularity, optimizing the causal structure by maximizing its likelihood with respect to the data. However, recent research has shown that errors in likelihood estimation, even on relatively large sample sizes, disallow the discovery of proper structures. We propose a new approach to amortized causal discovery that addresses the limitations of likelihood estimator accuracy. Our method leverages Prior-Fitted Networks (PFNs) to amortize data-dependent likelihood estimation, yielding more reliable scores for structure learning. Experiments on synthetic, simulated, and real-world datasets show significant gains in structure recovery compared to standard baselines. Furthermore, we demonstrate directly that PFNs provide more accurate likelihood estimates than conventional neural network-based approaches.

More UK families will know what sacrifice for our nation means as the nation seeks to deter a potential confrontation with Russia, the head of the military has said. Sir Richard Knighton said the country's security cannot be outsourced to the armed forces and requires a whole-of-society response, including harnessing UK universities and manufacturing. While the chief of the defence staff suggested there was only a remote chance of Russia directly attacking the UK, he told an event at the Royal United Services Institute that so-called hybrid attacks showed the threat was worsening . He referenced a Russian spy ship that was recently suspected of mapping undersea cables near UK waters. Every day the UK is subject to an onslaught of cyber-attacks from Russia and we know that Russian agents are seeking to conduct sabotage and have killed on our shores, he added.

How the US left Ukraine exposed to Russia's winter war Will Europe use frozen Russian assets to fund war? How can Ukraine rebuild China ties? Ukraine has carried out a successful underwater drone strike on a Russian submarine in the port of Novorossiysk, causing critical damage to the vessel, its domestic security service says. In a statement on Monday, the Security Service of Ukraine (SBU) said the Kilo-class submarine was knocked out of operation in the first such attack by Sea Baby drones. The SBU said the submarine "carried four Kalibr cruise missile launchers" used to strike Ukrainian territory.

Coldplay's Chris Martin made a surprise appearance at a couple's wedding to play the music for their first dance. The groom's mother had asked the singer for a video message to be played at the wedding of Abbie and James Hotchkiss from Stafford. He went one better, though, and said he would appear in person, with only the newlyweds and the groom's parents in on the secret. Surprised guests saw him walk into the wedding venue, Blithfield Lakeside Barns in Staffordshire, wearing a white beanie hat to perform All My Love at the piano while the couple danced. Guests took a while to notice it was actually him, but didn't want to ruin our wedding day so asked us loads of questions once he'd gone, Mrs Hotchkiss said.

The US firm behind the Roomba smart vacuum cleaner, iRobot, has filed for bankruptcy protection after facing competition from Chinese rivals and being hit by tariffs. Under the so-called pre-packaged Chapter 11 process, the main manufacturer of its devices, Shenzhen-based Picea Robotics, will take ownership of the firm. The tough commercial landscape had forced iRobot to cut its prices and make major investments in new technology, according to documents filed on Sunday. US import duties of 46% on goods from Vietnam, where most of iRobot's devices for the American market are made, increased its costs by $23m (£17.2m) this year, the firm said. The loss-making company was valued at $3.56bn in 2021 after the pandemic helped to drive strong demand for its products.

For four decades statistical physics has been providing a framework to analyse neural networks. A long-standing question remained on its capacity to tackle deep learning models capturing rich feature learning effects, thus going beyond the narrow networks or kernel methods analysed until now. We positively answer through the study of the supervised learning of a multi-layer perceptron. Importantly, (i) its width scales as the input dimension, making it more prone to feature learning than ultra wide networks, and more expressive than narrow ones or ones with fixed embedding layers; and (ii) we focus on the challenging interpolation regime where the number of trainable parameters and data are comparable, which forces the model to adapt to the task. We consider the matched teacher-student setting. Therefore, we provide the fundamental limits of learning random deep neural network targets and identify the sufficient statistics describing what is learnt by an optimally trained network as the data budget increases. A rich phenomenology emerges with various learning transitions. With enough data, optimal performance is attained through the model's "specialisation" towards the target, but it can be hard to reach for training algorithms which get attracted by sub-optimal solutions predicted by the theory. Specialisation occurs inhomogeneously across layers, propagating from shallow towards deep ones, but also across neurons in each layer. Furthermore, deeper targets are harder to learn. Despite its simplicity, the Bayes-optimal setting provides insights on how the depth, non-linearity and finite (proportional) width influence neural networks in the feature learning regime that are potentially relevant in much more general settings.

June Squibb sparkles opposite Cynthia Nixon in a futuristic drama, and Michelle Williams loses her way in Eugene O'Neill's Pulitzer Prize winner. Appropriately enough, Jordan Harrison's déjà-vu-inducing "Marjorie Prime" has been here before. The Off Broadway theatre Playwrights Horizons produced the poignant sci-fi play about hyperrealistic re-creations of the dead--so-called Primes, which are used as a supportive technology for the bereaved--in Anne Kauffman's spirited, delicately comic production, back in 2015. Lois Smith, then eighty-five years old, played Marjorie, a woman struggling with dementia. It's the early twenty-sixties, and so Marjorie is attended by a holographic Prime of her husband, Walter, who tells her stories from her own life.

'Hero' who wrestled gun from Bondi shooter named as Ahmed al Ahmed A hero bystander who was filmed wrestling a gun from one of the Bondi Beach attackers has been named as 43-year-old Ahmed al Ahmed. Video verified by the BBC showed Mr Ahmed run at the gunman and seize his weapon, before turning the gun round on him, forcing his retreat. Mr Ahmed, a fruit shop owner and father of two, remains in hospital, where he has undergone surgery for bullet wounds to his arm and hand, his family told 7News Australia. Eleven people were killed in the shooting on Sunday night, as more than 1,000 people attended an event to celebrate Hanukkah. The attack has since been declared by police as a terrorist incident targeting the Jewish community.

Australian police say a shooting at Bondi Beach, which killed 12 people - including one gunman - targeted the Jewish community on the first day of Hanukkah. Twenty-nine people were injured, with a second gunman in critical condition. Drone footage appears to show a gunman firing from a bridge in a nearby carpark. In the wake of a recent fatal shark attack, the BBC is off the coast in Sydney to learn how authorities are trying to protect people. The BBC's Katy Watson was in the courtroom as Erin Patterson was sentenced to life.