The evolution of honest and dishonest signals of fighting ability.

Competition over resources is often decided via aggressive interactions, which may or may not escalate to all-out fights. Weapons and body size play important roles in such interactions, as they often provide reliable cues of an individual's fighting ability. In contrast, traits like nonfunctional display "weapons" may dishonestly exaggerate fighting ability in order to intimidate opponents into retreating.

Search for Leptonic Decays of Dark Photons at NA62.

The NA62 experiment at CERN, configured in beam-dump mode, has searched for dark photon decays in flight to electron-positron pairs using a sample of 1.4×10^{17} protons on dump collected in 2021. No evidence for a dark photon signal is observed.

Blood biodistribution and vector shedding of valoctocogene roxaparvovec in people with severe hemophilia A.

Following systemically administered adeno-associated virus gene therapy, vector particles are widely distributed, raising concerns about horizontal or germline vector transmission. Characterization of biodistribution and kinetics of vector DNA in body fluids can address these concerns and provide insights into vector behavior in accessible samples. We investigated biodistribution and vector shedding profile of valoctocogene roxaparvovec in men with severe hemophilia A enrolled in the phase 3 GENEr8-1 trial.

Clinical immunogenicity outcomes from GENEr8-1, a phase 3 study of valoctocogene roxaparvovec, an AAV5-vectored gene therapy for hemophilia A.

Gene transfer therapies utilizing adeno-associated virus (AAV) vectors involve a complex drug design with multiple components that may impact immunogenicity. Valoctocogene roxaparvovec is an AAV serotype 5 (AAV5)-vectored gene therapy for the treatment of hemophilia A that encodes a B-domain-deleted human factor VIII (FVIII) protein controlled by a hepatocyte-selective promoter. Following previous results from the first-in-human phase 1/2 clinical trial, we assessed AAV5-capsid- and transgene-derived FVIII-specific immune responses with 2 years of follow-up data from GENEr8-1, a phase 3, single-arm, open-label study in 134 adult men with severe hemophilia A.

Is biased mutation sufficient to save runaway sexual selection?

In the 1980s, groundbreaking theoretical studies showed that ornaments displayed during courtship can coevolve with preferences for such ornaments, leading to extreme exaggeration of both traits. Later models cast doubt on such "runaway" sexual selection, showing that even a small cost of preferences can prevent exaggerated ornaments from persisting long-term. It was subsequently shown that if mutations acting on the ornament are biased-tending to produce smaller rather than larger ornaments-then exaggeration can persist even in the presence of preference costs, seemingly vindicating the original models.

Transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec gene therapy: A simulation study for individuals with severe haemophilia A.

Introduction: Valoctocogene roxaparvovec, a gene therapy evaluated in the phase 3 GENEr8-1 trial, supports endogenous factor VIII (FVIII) production to prevent bleeding in people with severe haemophilia A. Individuals receiving emicizumab, an antibody mimicking the function of activated FVIII, were excluded from GENEr8-1 enrolment since emicizumab was an investigational therapy at the time of trial initiation.

Aim: Utilize pharmacokinetic simulations to provide guidance on best practices for maintaining haemostatic control while transitioning from emicizumab prophylaxis to valoctocogene roxaparvovec.

Development of a Weight-Band Dosing Approach for Vosoritide in Children with Achondroplasia Using a Population Pharmacokinetic Model.

Background And Objective: Vosoritide is a recently approved therapy for achondroplasia, the most common form of disproportionate short stature, that has been shown to be well tolerated and effective in increasing linear growth. This study aimed to develop a population pharmacokinetic (PPK) model to characterize pharmacokinetics (PK) of vosoritide and establish a weight-band dosing regimen.

Methods: A PPK model was developed using data from five clinical trials in children with achondroplasia (aged 0.

Control of Quantized Spontaneous Emission from Single GaAs Quantum Dots Embedded in Huygens' Metasurfaces.

Advancements in photonic quantum information systems (QIS) have driven the development of high-brightness, on-demand, and indistinguishable semiconductor epitaxial quantum dots (QDs) as single photon sources. Strain-free, monodisperse, and spatially sparse local-droplet-etched (LDE) QDs have recently been demonstrated as a superior alternative to traditional Stranski-Krastanov QDs. However, integration of LDE QDs into nanophotonic architectures with the ability to scale to many interacting QDs is yet to be demonstrated.

Fitness as the organismal performance measure guiding adaptive evolution.

A long-standing problem in evolutionary theory is to clarify in what sense (if any) natural selection cumulatively improves the design of organisms. Various concepts, such as fitness and inclusive fitness, have been proposed to resolve this problem. In addition, there have been attempts to replace the original problem with more tractable questions, such as whether a given gene or trait is favored by selection.

A probable Keplerian disk feeding an optically revealed massive young star.

The canonical picture of star formation involves disk-mediated accretion, with Keplerian accretion disks and associated bipolar jets primarily observed in nearby, low-mass young stellar objects (YSOs). Recently, rotating gaseous structures and Keplerian disks have been detected around several massive (M > 8 M) YSOs (MYSOs), including several disk-jet systems. All the known MYSO systems are in the Milky Way, and all are embedded in their natal material.

Intralipid infusion therapy as an adjunct treatment in women experiencing adenomyosis-related infertility.

Background: Currently, there is some evidence that adenomyosis patients using gonadotropin-releasing hormone (GnRH) agonist long downregulation (LDR) prior to embryo transfer may improve in vitro fertilization (IVF) success rate, but not to the baseline expected success where there is no adenomyosis. Given the association between adenomyosis and an aberrant endometrial immune environment, many physicians also use prednisolone or Intralipid adjuvant treatments in combination with GnRH agonist therapy, despite neither being of proven benefit.

Objective: The purpose of this study was to investigate whether the addition of prednisolone or Intralipid immune therapy to GnRH agonist LDR improves fertility outcomes in patients with adenomyosis.

Seasonal variation in cuckoldry rates in the socially monogamous cichlid fish .

Unlabelled: Mating patterns in animal populations can respond to environmental conditions and consequently vary across time. To examine this variation in nature, studies must include temporal replicates from the same population. Here, we report temporal variation in genetic parentage in the socially monogamous cichlid from Lake Tanganyika, using samples of broods and their brood-tending parents that were collected across five field trips from the same study population.

A Bedside Equation to Estimate Endotracheal Tube Length for Infants.

Objective: To develop a bedside equation that can be used to estimate the ideal oral and nasal endotracheal tube (ETT) length for children younger than 1 year of age.

Study Design: Retrospective database analysis of 735 children younger than 1 year of age admitted to pediatric intensive care at Evelina London Children's Hospital from June 1, 2019, through August 31, 2021. ETT positions were determined by tube-tip superimposition over vertebral body on postintubation chest radiograph by trained medical students and pediatric radiologists with bedside assessment of ETT length at nostril or lip as recorded electronically by nursing staff.

Hermaphroditic origins of anisogamy.

Anisogamy-the size dimorphism of gametes-is the defining difference between the male and female sexual strategies. Game-theoretic thinking led to the first convincing explanation for the evolutionary origins of anisogamy in the 1970s. Since then, formal game-theoretic models have continued to refine our understanding of when and why anisogamy should evolve.

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB.

Two-Year Outcomes of Valoctocogene Roxaparvovec Therapy for Hemophilia A.

Background: Valoctocogene roxaparvovec delivers a B-domain-deleted factor VIII coding sequence with an adeno-associated virus vector to prevent bleeding in persons with severe hemophilia A. The findings of a phase 3 study of the efficacy and safety of valoctocogene roxaparvovec therapy evaluated after 52 weeks in men with severe hemophilia A have been published previously.

Methods: We conducted an open-label, single-group, multicenter, phase 3 trial in which 134 men with severe hemophilia A who were receiving factor VIII prophylaxis received a single infusion of 6×10 vector genomes of valoctocogene roxaparvovec per kilogram of body weight.

Spin Dynamics of a Solid-State Qubit in Proximity to a Superconductor.

A broad effort is underway to understand and harness the interaction between superconductors and spin-active color centers with an eye on hybrid quantum devices and novel imaging modalities of superconducting materials. Most work, however, overlooks the interplay between either system and the environment created by the color center host. Here we use a diamond scanning probe to investigate the spin dynamics of a single nitrogen-vacancy (NV) center proximal to a superconducting film.

Long-term persistence of exaggerated ornaments under Fisherian runaway despite costly mate search.

Exaggerated ornaments often evolve due to the mating preferences of the opposite sex. Genetic correlations between preferences and ornaments can lead both traits to elaborate dramatically in tandem, in a process known as 'Fisherian runaway'. However, in most previous models of Fisherian runaway, elaborate ornaments are not expected to persist when preferences are consistently costly to the choosing sex.

Frontal alpha asymmetry: A potential biomarker of approach-withdrawal motivation towards pain.

Pain-related catastrophising is a maladaptive coping strategy known to have a strong influence on clinical pain outcomes and treatment efficacy. Notwithstanding, little is known about its neurophysiological correlates. There is evidence to suggest catastrophising is associated with resting-state EEG frontal alpha asymmetry (FAA) patterns reflective of greater relative right frontal activity, which is known to be linked to withdrawal motivation and avoidance of aversive stimuli.

Electric current paths in a Si:P delta-doped device imaged by nitrogen-vacancy diamond magnetic microscopy.

The recently-developed ability to control phosphorous-doping of silicon at an atomic level using scanning tunneling microscopy, a technique known as atomic precision advanced manufacturing (APAM), has allowed us to tailor electronic devices with atomic precision, and thus has emerged as a way to explore new possibilities in Si electronics. In these applications, critical questions include where current flow is actually occurring in or near APAM structures as well as whether leakage currents are present. In general, detection and mapping of current flow in APAM structures are valuable diagnostic tools to obtain reliable devices in digital-enhanced applications.

Young mice administered adult doses of AAV5-hFVIII-SQ achieve therapeutic factor VIII expression into adulthood.

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) gene transfer provided reduced bleeding for adult clinical trial participants with severe hemophilia A. However, pediatric outcomes are unknown. Using a mouse model of hemophilia A, we investigated the effect of vector dose and age at treatment on transgene production and persistence.

The evolution of mating preferences for genetic attractiveness and quality in the presence of sensory bias.

The aesthetic preferences of potential mates have driven the evolution of a baffling diversity of elaborate ornaments. Which fitness benefit-if any-choosers gain from expressing such preferences is controversial, however. Here, we simulate the evolution of preferences for multiple ornament types (e.

Anisogamy explains why males benefit more from additional matings.

Why do males typically compete more intensely for mating opportunities than do females and how does this relate to sex differences in gamete size? A new study provides a formal evolutionary link between gamete size dimorphism and ‘Bateman gradients’, which describe how much individuals of each sex benefit from additional matings.