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Model-Informed Dose Optimization of Spironolactone in Neonates and Infants

Background/Objectives: Spironolactone (SP) has been used off-label in pediatrics since its approval, but its use is challenged by limited pharmacokinetic (PK) data in adults and especially in children. Methods: Physiologically based pharmacokinetic (PBPK) models for SP and its active metabolites, canrenone (CAN) and 7α thio-methyl spironolactone (TMS), in adults were developed. These models aim to enhance understanding of SP’s PK and provide a basis for predicting PK and optimizing SP dosing in infants and neonates. Given SP’s complex metabolism, we assumed complete conversion to CAN and TMS by CES1 enzymes, fitting CES1-mediated metabolism to the parent-metabolite model using PK data. We incorporated ontogeny for CES1 and CYP3A4 and other age-related physiological changes into the model to anticipate PK in the pediatric population.

A cryogenic winter for tomorrow’s accelerator

Behind every particle collision generated at the Large Hadron Collider is a multitude of technical feats. One of these is refrigeration on an industrial scale. To guide the particles, the thousands of superconducting magnets in the accelerator must be cooled to a temperature of close to absolute zero. This makes the LHC the largest cryogenic installation in the world: 23 of its 27 kilometers are maintained at 1.9 Kelvin (−271°C) using refrigerators in which superfluid helium circulates.

This unique cooling system needs to be further strengthened in preparation for the High-Luminosity LHC (HL-LHC), a major upgrade to the LHC that is scheduled to begin operation in 2030. On both sides of the two large experiments, ATLAS and CMS, more powerful focusing magnets and new types of cavities will considerably increase the number of collisions at each beam crossing or, in other words, the luminosity. This ultra-sophisticated equipment requires increased cooling power. Two new refrigerators are therefore being installed, in addition to the eight that are already needed for the existing accelerator.

The LHC’s refrigerators work on the same principle as the one in your kitchen, except that they are gigantic installations that occupy several buildings. Located on the surface, they include large compressors and an enormous cold box that contains the heat exchangers and the expansion turbines. These installations lower the helium temperature to 4.5 Kelvin (−268.6°C). Six compression units were installed in October.

Why quantum computers have memory problems over time

A team of Australian and international scientists has, for the first time, created a full picture of how errors unfold over time inside a quantum computer—a breakthrough that could help make future quantum machines far more reliable.

The researchers, led by Macquarie University’s Dr. Christina Giarmatzi, found that the tiny errors that plague quantum computers don’t just appear randomly. Instead, they can linger, evolve and even link together across different moments in time.

The team has made its experimental data and code openly available, and the full study is published in Quantum.

Online psychoeducation underperforms existing digital cognitive behavioral therapy in trial

Big Health Inc, along with paid academic investigators, reports higher remission rates and lower anxiety symptom scores with their smartphone-delivered digital cognitive behavioral therapy, DaylightRx, compared with an online psychoeducation, also created by Big Health Inc.

Generalized anxiety disorder involves excessive, persistent, and uncontrollable anxiety with lifetime prevalence reported as 6%, alongside reduced quality of life, impaired social and occupational functioning, and increased health care utilization.

Cognitive behavioral therapy and pharmacotherapy are considered first-line treatments. Despite strong tolerability, efficacy, and cost-effectiveness, access remains limited due to a shortage of trained therapists, time burdens, and stigma.

Women are better at recognizing illness in faces compared to men, study finds

Most people have either been told that they don’t look well when they were sick, or thought that someone else looked ill at some point in their lives. People often use nonverbal facial cues, such as drooping eyelids and pale lips, to detect illness in others, potentially to prevent infection in themselves. A new study, published in Evolution and Human Behavior, finds that women are more sensitive to these subtle cues than men.

In past studies, participants have been asked to rate signs of illness in the faces of others, but some of these studies used manipulated photos or people who had artificially induced sicknesses in the photos. In the new study, the team wanted to see whether naturally sick individuals would be rated as sick-looking, or as having an expression of “lassitude,” by other individuals and whether the recognition differed by sex.

To do this, the team recruited 280 undergraduate students, of which 140 were male and 140 were female, to rate 24 photos. The photos consisted of 12 different faces in times of sickness and health.

Why some brains switch gears more efficiently than others

The human brain is constantly processing information that unfolds at different speeds—from split-second reactions to sudden environmental changes to slower, more reflective processes such as understanding context or meaning.

A new study from Rutgers Health, published in Nature Communications, sheds light on how the brain integrates these fast and slow signals across its complex web of white matter connectivity pathways to support cognition and behavior.

Different regions of the brain are specialized for processing information over specific time windows, a property known as intrinsic neural timescales, or INTs for short.

Exposure to common air pollutants alters adolescent brain development, study finds

Physician-scientists at Oregon Health & Science University warn that exposure to air pollution may have serious implications for a child’s developing brain.

In a recent study published in the journal Environmental Research, researchers in OHSU’s Developmental Brain Imaging Lab found that air pollution is associated with structural changes in the adolescent brain, specifically in the frontal and temporal regions —the areas responsible for executive function, language, mood regulation and socioemotional processing.

Air pollution causes harmful contaminants, such as particulate matter, nitrogen dioxide and ozone, to circulate in the environment. It has been exacerbated over the past two centuries by industrialization, vehicle emissions, and, more recently, wildfires.

Merging nanopores with nanofluidic devices could transform medicine and diagnostics

When disease begins forming inside the human body, something subtle happens long before symptoms appear. Individual molecules such as DNA, RNA, peptides, or proteins begin shifting in quantity or shape. Detecting these tiny molecular changes early could dramatically change how cancer, infections, and other conditions are diagnosed.

For years, scientists have dreamed of reading these changes one molecule at a time. Nanopores, nanometer-sized holes that detect single molecules by sensing changes in electric current, have brought that dream closer to reality, but nanopore sensing has hit several scientific walls.

Molecules rush through too fast to analyze. Signals drown in electrical noise. Proteins stick to pore surfaces and single pores simply cannot provide the scale required for real-world clinical use. So what would it take to make nanopore sensing fast, precise, and robust enough for society?

Measuring how materials hotter than the sun’s surface conduct electricity

Warm dense matter is a state of matter that forms at extreme temperatures and pressures, like those found at the center of most stars and many planets, including Earth. It also plays a role in the generation of Earth’s magnetic field and in the process of nuclear fusion.

Although warm dense matter is found all over the universe, researchers don’t have many good theories to describe the physics of materials under those conditions. Measurements of a material’s electrical conductivity would help test and refine models of warm dense matter. However, classic probes for such measurements require contact with the material. These can’t be used because materials in a warm dense matter state are very hot, often as hot or even hotter than the surface of the sun. Consequently, information about the electrical conductivity has so far been inferred indirectly.

In other words, without direct measurements, “there’s a lot of stuff in the universe happening that we as physicists are still struggling to understand,” said Ben Ofori-Okai, assistant professor at the Department of Energy’s SLAC National Accelerator Laboratory and Stanford University and a researcher at the Stanford PULSE Institute.

Westerly jet stream emerges as key driver of mid-latitude hydroclimatic extremes

In recent years, the global climate has become increasingly extreme, with intensifying alternations of droughts and floods—particularly in ecologically vulnerable mid-latitude regions. But what is driving this hydroclimatic variability? Scientists have long debated the underlying mechanisms.

A research team led by Prof. Long Hao from the Nanjing Institute of Geography and Limnology of the Chinese Academy of Sciences, drilled a 300.8-meter-long lacustrine sediment core in the Datong Basin of Shanxi Province, located in mid-latitude East Asia (Northern China). By reconstructing more than 5.7 million years of Earth’s history, the researchers revealed that the “waviness” of the westerly jet stream is the primary driver of mid-latitude climate variability. The study was recently published in Nature Communications.

This sediment core acts as a detailed “climate archive,” documenting precipitation changes over approximately 5.7 million years—spanning the Pliocene and Pleistocene epochs. By analyzing chemical indicators within the core, the researchers obtained a high-resolution record of ancient precipitation patterns.

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