bluuebunny/crossref_metadata_2025 huggingface dataset:
RamBO: randomized blocky Occam, a practical algorithm for generating blocky models and associated uncertainties
Authors: Vargas Huitzil Eliana , Morzfeld Matthias , Constable Steven
Published: February 2025

We present new numerical tools for geophysical inversion and uncertainty quantification (UQ), with an emphasis on blocky (piecewise-constant) layered models that can reproduce sharp contrasts in geophysical or geological properties. The new tools are inspired by an ‘old’ and very successful inversion tool: regularized, nonlinear inversion. We combine Occam’s inversion with total variation regularization and a split Bregman method to obtain an inversion algorithm that we call blocky Occam, because it determines the blockiest model that fits the data adequately. To generate an UQ, we use a modified randomize-then-optimize approach (RTO) and call the resulting algorithm RamBO (randomized blocky Occam), because it essentially amounts to running blocky Occam in a randomized parallel for-loop. Blocky Occam and RamBO inherit computational advantages and stability from the combination of Occam’s inversion, split Bregman and RTO, and, therefore, can be expected to be robustly applicable across geophysics.
Ensemble Kalman Inversion for Geothermal Reservoir Modelling
Authors: de Beer Alex , Bjarkason Elvar K , Gravatt Michael , Nicholson Ruanui , O’Sullivan John P , O’Sullivan Michael J , Maclaren Oliver J
Published: February 2025

Numerical models of geothermal reservoirs typically depend on hundreds or thousands of unknown parameters, which must be estimated using sparse, noisy data. However, these models capture complex physical processes, which frequently results in long run-times and simulation failures, making the process of estimating the unknown parameters a challenging task. Conventional techniques for parameter estimation and uncertainty quantification, such as Markov chain Monte Carlo (MCMC), can require tens of thousands of simulations to provide accurate results and are therefore challenging to apply in this context. In this paper, we study the ensemble Kalman inversion (EKI) algorithm as an alternative technique for approximate parameter estimation and uncertainty quantification for geothermal reservoir models. EKI possesses several characteristics that make it well-suited to a geothermal setting; it is derivative-free, parallelisable, robust to simulation failures, and in many cases requires far fewer simulations to provide an accurate characterisation of the posterior than conventional uncertainty quantification techniques such as MCMC. We illustrate the use of EKI in a reservoir modelling context using a combination of synthetic and real-world case studies. Through these case studies, we also demonstrate how EKI can be paired with flexible parametrisation techniques capable of accurately representing prior knowledge of the characteristics of a reservoir and adhering to geological constraints, and how the algorithm can be made robust to simulation failures. Our results demonstrate that EKI provides a reliable and efficient means of obtaining accurate parameter estimates for large-scale, two-phase geothermal reservoir models, with appropriate characterisation of uncertainty.
The Chemistry of Behavior
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter explores the birth of a pharmaceutical problem, using the discovery of lysergic acid diethylamide (LSD) by Albert Hofmann as an example. Hofmann, working for Sandoz Pharmaceuticals, was researching compounds derived from ergot when he accidentally ingested a small amount of an experimental compound and experienced intense visual phenomena. This led to the realization that the substance could have profound effects on brain function, even in minute doses. The chapter delves into neurochemistry and neuropharmacology, explaining the structure and function of synapses, as well as how neurotransmitter mechanisms impact the nervous system. It discusses how drugs can alter brain chemistry, focusing on neurotransmitter receptors and their subtypes, and how drug development leverages this complexity to produce specific effects.
Life-Span Development of the Brain and Behavior
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter reviews of knowledge of the progress of brain development and the interplay between genetic and environmental factors in shaping neural growth. It begins with the story of Michael May, who, despite being blinded at a young age, achieved remarkable feats, including skiing and inventing equipment for blind individuals, before having his vision partially restored at age 46. The chapter then shifts to neural development, highlighting the complexity of the human brain, which contains over 80 billion neurons connected by quadrillions of synapses. It emphasizes that while genes play a crucial role in early brain development, environmental experiences, such as behavioral interactions, shape the brain's wiring. It outlines the six stages of brain development, from neurogenesis and cell migration to the critical processes of differentiation and myelination, which are key to establishing the brain's functions.
General Principles of Sensory Processing, Touch, and Pain
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter examines the fascinating case of Letizia, who experiences an unusual form of pain perception, where she feels only the immediate, acute pain from an injury but not the lingering, dull pain that typically follows. Letizia's ability to feel no pain from certain stimuli, such as capsaicin, sets her apart from others and raises questions about the mechanisms underlying pain and its role in survival. The chapter explores how sensory systems in animals, including humans, detect and process various forms of energy, like sound, light, and heat. It explains how sensory receptor organs convert particular types of stimuli into electrical signals that the brain interprets. This complex process involves various forms of sensory transduction and adaptation, helping organisms navigate their environments and survive.
Hearing, Balance, Taste, and Smell
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter describes the sensory systems that allow the detection and interpretation of sounds, beginning with an exploration of hearing or audition. It explains how pressure waves in the air are perceived as sound through the auditory system, including the roles of the external ear, middle ear, and inner ear in capturing, concentrating, and transducing sound energy into neural activity. It also delves into the anatomy of the cochlea and the organ of Corti, showing how vibrations are propagated and frequencies are encoded. The chapter discusses the evolutionary adaptations of various animals, from bats and owls to elephants and whales, which use sound for communication, navigation, and survival. This focus on auditory processing provides insights into how humans and animals rely on sound for interaction, reproduction, and environmental awareness.
Biological Rhythms, Sleep, and Dreaming
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter explores daily rhythms, particularly focusing on the sleep-waking cycle, and the significance of such rhythms in regulating behavior and physiology. It begins with the case of Barry, a freshman whose excessive sleepiness and episodes of sudden paralysis triggered by emotional surges indicated a deeper issue. The chapter introduces the concept of circadian rhythms, which govern many biological functions on a roughly 24-hour cycle. Circadian rhythms influence a wide range of physiological processes, such as hormone levels and body temperature, which fluctuate regularly throughout the day. It discusses how animals, including humans, follow these daily rhythms, adapting to environmental cues and the internal biological clock.
Learning and Memory
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter explores the mechanisms of learning and memory, highlighting the distinct types and their reliance on various brain regions. It reviews clinical studies, such as the case of Henry Molaison, that reveal how memory impairments can result from brain damage, shedding light on the differences between learning and memory. Researchers have uncovered that multiple brain areas contribute to specific memory functions, offering insights into how learning changes the brain at structural and cellular levels. The chapter highlights advances in research, including animal models and brain imaging, that continue to expand the understanding of how memories are stored, retrieved, and affected by neurological conditions. These findings emphasize the complexity of learning and memory and their essential role in shaping human behavior and individuality.
Language and Lateralization
Authors: Breedlove S. Marc , Watson Neil V.
Published: February 2025

This chapter analyzes the neuroscience of cerebral lateralization, focusing on the specialized roles of the left and right hemispheres in language, spatial cognition, and communication. Human language, defined by its use of arbitrary symbols and strict grammar, sets people apart from non-humans by enabling the sharing of abstract concepts across time. The chapter outlines verbal abilities that are primarily linked to the left hemisphere, while the right hemisphere specializes in complex spatial cognition. The chapter highlights studies in brain injuries, such as the one of Tinna Geula Phillips, who experienced loss of both speech and her inner voice. Such studies reveal how disruptions in hemispheric functions can profoundly affect identity and cognitive processes. The chapter finally examines how both hemispheres work together seamlessly in healthy brains and challenges misconceptions about being “right-brained” or “left-brained”.
Spatial Vision: From Spots to Stripes
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter examines the journey that visual information takes from the retina to the brain, detailing the structures and processes involved in interpreting visual stimuli. It explores the visual acuity and the retina's ganglion cells, emphasizing how these cells respond to stripes and gratings of specific spatial frequencies. The lateral geniculate nucleus (LGN) acts as a relay station, segregating input by eye and type of information while preparing it for processing in the striate cortex. In the striate cortex, neurons organize into columns and hypercolumns, specialized units that process orientation, spatial frequency, and movement, forming a detailed map of the visual field. The chapter also highlights selective adaptation as a tool to study cortical responses in humans and the critical development of vision, showcasing how experience and environmental stimuli refine neural architecture. Lastly, the chapter links cellular mechanisms to perception, providing insights into how we see and interpret the world.
Visual Motion Perception
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter explores the intricate mechanisms of motion perception, emphasizing its significance as a primary perceptual dimension. It begins with motion aftereffects, such as the waterfall illusion, illustrating how direction-specific neural adaptations in the brain can create an illusory sense of movement in stationary objects. It explains the computation of visual motion through neural circuits that detect directional changes, addressing challenges like the aperture problem and showing how the middle temporal area (MT) integrates signals to resolve the global motion. Practical applications of motion information include navigation using optic flow and timing collisions via tau, while biological motion enables humans to interpret dynamic actions and intentions. The development of motion perception highlights the gradual maturation of motion sensitivity, from early reflexive eye movements in infancy to complex motion-processing capabilities in adulthood.
Hearing: Physiology and Psychoacoustics
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter explores hearing, a vital sense often overlooked, by examining sound, the auditory system's anatomy, psychoacoustics, and hearing loss. It defines sound as pressure fluctuations caused by vibrating objects traveling through various media as waves. The mammalian auditory system comprises the outer, middle, and inner ear, which work together to convert sound waves into neural signals processed by the brain. Psychoacoustics bridges physical sound properties and human perception, revealing complexities such as the subjective experience of loudness and pitch. Factors like age, noise exposure, or genetics cause hearing loss, disrupting this intricate process and often requiring interventions such as hearing aids or cochlear implants.
Hearing in the Environment
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter explores how the auditory system enables humans to interpret complex acoustic environments. It examines sound localization through cues such as interaural time difference and interaural level differences, which give a sense of spatial awareness despite the complexity of overlapping sound waves. The auditory system interprets complex sounds, such as harmonics and timbre, as a fundamental process for distinguishing environmental or musical sources. Auditory scene analysis describes how the brain separates sounds into streams, drawing on spatial, spectral, and temporal cues to identify sources amidst noise. Continuity effects and restoration effects illustrate the auditory system's ability to fill in masked sounds, creating perceptual completeness during interruptions. Together, these mechanisms highlight the intricacies of how humans process, organize, and respond to the dynamic auditory world.
Touch
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter examines the sense of touch, beginning with how physical stimuli activate neural pathways, which translate mechanical signal and thermal signals into brain responses. It describes the submodalities of touch, focusing on how discriminative touch supports object recognition, affective touch facilitates social and emotional communication, and proprioception enables humans to sense limb positions. Haptic perception links sensory input with action, enabling humans to explore and understand their surroundings through active touch. The chapter then emphasizes the essential role of touch in everyday life, from safety and thermoregulation to social bonding, illustrating its evolutionary and functional significance. Lastly, by integrating physiology, perception, and behavior, it underscores the importance of touch in shaping interactions with the physical and social environment.
Olfaction
Authors: Wolfe Jeremy M. , Levi Dennis M. , Holt Lori L. , Bartoshuk Linda M. , Herz Rachel S. , Klatzky Roberta L. , Merfeld Daniel M.
Published: February 2025

This chapter explores the intricate mechanisms and experiences of olfaction, beginning with the physiological and neural basis of smell perception. It examines olfactory physiology, focusing on how odorant molecules interact with the olfactory epithelium and how neural pathways in the brain interpret odors. The chapter then explains the neurophysiology of olfaction by describing how the brain processes olfactory signals and how receptor activation patterns transform chemical stimuli into distinct odor perceptions. It discusses psychological aspects, such as odor identification, adaptation, and the impact of hedonic preferences on smell perception, showing how olfactory experiences connect to emotions, memories, and individual differences. The role of the vomeronasal organ and human pheromones in detecting chemosignals underscores olfaction's relevance to social communication, while a forward-looking perspective considers technological and scientific advancements poised to deepen our understanding of this essential sense.
Hormones and Sex
Authors: Watson Neil V. , Breedlove S. Marc
Published: February 2025

This chapter explores how hormones influence development, behavior, and biological processes across species, focusing on their diverse roles throughout the body. It identifies how hormonal mechanisms regulate reproductive behavior, emphasizing the brain's role in directing mating and parenting. Experimental studies reveal how individual differences in mating behavior arise from genetic and hormonal factors, shaping both physical structures and brain function. The chapter also examines the conditions like androgen insensitivity and congenital adrenal hyperplasia, highlighting how genetic and hormonal interactions guide sexual differentiation. The chapter concludes by analyzing how society and biology intersect in defining sex, presenting the complexities of developmental processes and their impact on identity and behavior.
Biological Rhythms and Sleep
Authors: Watson Neil V. , Breedlove S. Marc
Published: February 2025

This chapter examines how biological rhythms, such as circadian rhythms, organize behavior and synchronize internal cycles with external cues through a molecular clock located in the suprachiasmatic nucleus (SCN). It validates the SCN's role in circadian regulation by demonstrating its rhythmic metabolic activity and restoring rhythms in transplant studies. The chapter then presents sleep as an active and complex process, with distinct stages (REM and non-REM) that evolve throughout the lifespan, from REM-heavy infant sleep to reduced slow-wave sleep (SWS) in older adults. Studies reveal that total sleep deprivation disrupts immunity and cognition and can lead to death in mammals, while partial deprivation impairs memory and focus. The chapter concludes by highlighting the seriousness of sleep disorders, including narcolepsy and rapid eye movement (REM) behavior disorder, and advocating for good sleep hygiene to improve health and quality of life.
Suggested solutions for Chapter 4
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 4 of Clayden, Greeves & Warren Organic Chemistry, second edition, on the structure of molecules.
Suggested solutions for Chapter 7
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 7 of Clayden, Greeves & Warren Organic Chemistry, second edition, on delocalization and conjugation.
Suggested solutions for Chapter 9
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 9 of Clayden, Greeves & Warren Organic Chemistry, second edition, on using organometallic reagents to make C−C bonds.
Suggested solutions for Chapter 13
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 13 of Clayden, Greeves & Warren Organic Chemistry, second edition, on 1H NMR: proton nuclear magnetic resonance.
Suggested solutions for Chapter 25
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 25 of Clayden, Greeves & Warren Organic Chemistry, second edition, on alkylation of enolates.
Suggested solutions for Chapter 35
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 35 of Clayden, Greeves & Warren Organic Chemistry, second edition, on pericyclic reactions 2: sigmatropic and electrocyclic reactions.
Suggested solutions for Chapter 36
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 36 of Clayden, Greeves & Warren Organic Chemistry, second edition, on participation, rearrangement, and fragmentation.
Suggested solutions for Chapter 40
Authors: Clayden Jonathan , Greeves Nick , Warren Stuart
Published: February 2025

This chapter provides solutions to the problems posed in Chapter 40 of Clayden, Greeves & Warren Organic Chemistry, second edition, on organometallic chemistry.
Small Volume Bodies of Constant Width
Authors: Arman A , Bondarenko A , Nazarov F , Prymak A , Radchenko D
Published: February 2025

For every large enough $n$, we explicitly construct a body of constant width $2$ that has volume less than $0.9^{n} \textrm{Vol}(\mathbb{B}^{n}$), where ${{\mathbb{B}}}^{n}$ is the unit ball in $\mathbb{R}^{n}$. This answers a question of O. Schramm.
Pharmacokinetics and safety of rifapentine in children: dosing for latent tuberculosis infection
Authors: Liu Weijian , Xu Nuo , Li Wei , Mak Wen Yao , He Tian , Qin Hongjuan , Lu Shuihua , Lu Hongzhou , Xiang Xiaoqiang , Zhu Xiao , Zhang Peize
Published: February 2025

Objectives

To assess the safety of 4-week daily rifapentine-isoniazid regimen in latent tuberculosis for Chinese children, and to provide paediatric-specific evidence for extrapolating adult dosing strategies to children.

Methods

An open-label, prospective, single-arm clinical trial was conducted among eligible patients (aged <10 years old). Rifapentine concentrations and laboratory safety biomarker (total bilirubin) were analysed and used for population pharmacokinetic-toxicity model development. Simulations were performed to compare efficacy and safety of weight-based and flat-dosing strategy.

Results

Once-daily rifapentine treatment was well tolerated: 310 samples (rifapentine n = 139; total bilirubin n = 171) from 36 children (age range 0.89–10 years) were captured well by a joint one-compartment pharmacokinetic with time-varying clearance and an indirect response model. The model adequately described rifapentine autoinduction, reaching a plateau after 21 days and increasing clearance by 70.4%. Simulation suggested that weight-based dosing may cause underexposure in children under 14.5 kg. A flat-dosing strategy could ensure plasma levels within the therapeutic windows. Rifapentine’s impact on total bilirubin was within a 2-fold range, and the effect subsided within 5 days after discontinuation.

Conclusions

Our study suggested that a flat-dosing strategy of rifapentine was potentially safe and effective for latent tuberculosis infection treatment in Chinese children aged 1 to 10 years old.
Evaluating the impacts of grass and legume living mulches on arthropod pests and beneficials, yield, and fruit quality in cantaloupe
Authors: Nunez Demian A , Farcuh Macarena , Burghardt Karin T , McCluen Scott , Hooks Cerruti R R
Published: February 2025

Increasing plant diversity in agroecosystems is often proposed as a way to reduce arthropod pest pressure and support natural enemy populations to reduce reliance on traditional chemical controls. Over 2 field seasons, we examined the effects of interplanting cantaloupe (Cucumis melo L. var. cantalupensis) with alsike clover (Trifolium hybridum L.) and Virginia wildrye (Elymus virginicus L.) on arthropod populations, cantaloupe yield, and fruit quality. Arthropod sampling through visual counts, sticky cards, and pitfall traps focused on herbivores and natural enemies across feeding guilds, with more specialized pests in the cucurbit system being identified to lower taxonomic levels. Living mulches might have delayed initial crop colonization by striped cucumber beetles (Acalymma vittatum F.) but had limited impact on beetle counts, which remained similarly low throughout the study across treatments. Aphid populations were lowest in wildrye interplanted plots, suggesting species-specific impacts on pest suppression. Beneficial arthropods, such as spiders, piercing predators, and parasitoids, were often more abundant in clover than in wildrye or monoculture plots, especially early in the season. However, cantaloupe yield was highest in monoculture plots, where fruit showed increased weight, size, and favorable color metrics compared to those from living mulch plots. These results indicate that while living mulches can support beneficial arthropods and possibly reduce early pest pressure, they may also introduce trade-offs in yield and quality. Future studies should explore adjustments to living mulch management in cantaloupe, such as reduced density or narrower planting strips, to optimize pest suppression benefits while limiting competition with the cash crop.
Foreign Legionnaires and Military Mutinies
Authors: Escribà-Folch Abel , Faulkner Christopher , Mehrl Marius
Published: February 2025

The composition of the armed forces is, by now, well established as a major factor determining the risk of coups d’état. However, military discontent not only manifests in the form of coups but also as mutinies. This latter form of troop rebellion has received little empirical attention. We examine how the practice of recruiting foreigners into the armed forces affects the likelihood of such events and develop two arguments regarding a direct and a moderating effect of legionnaires on mutiny risk. First, we contend that the recruitment of legionnaires is likely to cause material-based grievances, hence be perceived as detrimental to the corporate interests, wages, and promotion prospects of the rank-and-file, and thus troops will oppose the introduction of such recruitment policies. We hence expect the onset of legionnaire recruitment policies to be associated with an increased risk of mutinies. However, once such policies are in place, the presence of legionnaires can mitigate the effects of other mutiny drivers as foreign recruits impede local soldiers’ task-related grievances and thus incentives to mutiny in reaction to them. Using global data over the period 1948–2015, we find empirical support for the expectations derived from both arguments.
Trinity VI: Connection between Galaxy Star Formation Rates and Supermassive Black Hole Accretion Rates from z = 0 − 10
Authors: Zhang Haowen , Behroozi Peter , Volonteri Marta , Silk Joseph , Fan Xiaohui , Aird James , Yang Jinyi , Wang Feige , Hopkins Philip F
Published: February 2025

We infer supermassive black hole (SMBH) accretion rates and Eddington ratios as a function of SMBH/host galaxy mass and redshift with the empirical Trinity model of dark matter halo–galaxy–SMBH connection. The galaxy–SMBH mass and growth rate connection from Trinity match galaxy observables from 0 < z < 13 and SMBH observables from 0 < z < 6.5. Key findings include: 1) the ratio between cosmic SMBH accretion rate and galaxy star formation rate stays constant at ∼2 × 10−3 from z = 0 − 4, and decreases by 2 orders of magnitude from z = 4 − 10; 2) the average SMBH Eddington ratio $\overline{\eta }$ increases towards higher redshifts, nearly reaching $\overline{\eta }=1$ at z ∼ 10; 3) at fixed redshift for z < 3, SMBHs/galaxies with higher masses have lower $\overline{\eta }$, consistent with AGN downsizing; 4) the average ratio of specific SMBH accretion rate ($\overline{\mathrm{SBHAR}}$) to average specific star formation rate ($\overline{\mathrm{SSFR}}$) is nearly mass-independent, with a value $\overline{\mathrm{SBHAR}}/\overline{\mathrm{SSFR}}\sim 1$, which decreases slightly from z = 10 to z = 0; 5) similar to galaxies, SMBHs reach their peak efficiency to convert baryons into mass when host halos reach 1012M⊙; 6) given galaxy and SMBH growth histories from Trinity, the local descendants of 1 < z < 11 overmassive JWST AGNs will remain outliers from the local SMBH mass–galaxy mass relation. These findings combine to give a simple explanation for massive (109 − 1010M⊙) quasars at z > 6: at these redshifts, dark matter halos grow with an e-folding time of ∼45 Myrs, driving similar growth in both galaxies and SMBHs.
The relation between black hole spin and star formation in massive star-forming galaxies
Authors: Chen Yongyun , Gu Qiusheng , Fan Junhui , Xiong Dingrong , Yu Xiaoling , Ding Nan , Guo Xiaotong
Published: February 2025

It has always been believed that feedback from active galactic nuclei (AGNs) has an important impact on star formation in massive galaxies. Black hole spin is an important physical parameter of AGN. We use a large sample of massive star-forming galaxies to study the effects of AGN on star formation. Our main results are as follows: (i) there are significant correlations between black hole spin and star formation rate, specific star formation rate, and star formation activity parameter for massive star-forming early- and late-type galaxies, respectively. These results indicate that the spin of supermassive black holes regulates the star formation of massive star-forming early- and late-type galaxies. (2) The slopes of the relationship between black hole spin and star formation rate, specific star formation rate, and star formation activity parameter for massive star-forming early- and late-type galaxies are similar within the error range. These results imply that the mechanism of black hole spin regulating star formation may be similar in massive star-forming early-type and late-type galaxies.
Efficacy of the Rho-Kinase Inhibitor for Corneal Endothelial Protection in Fuchs Endothelial Corneal Dystrophy After Phacoemulsification
Authors: Keeratidamkerngsakul Benjama , Puangsricharern Vilavun , Chokesuwattanaskul Susama , Pongpirul Krit , Kittipibul Thanachaporn
Published: February 2025

Purpose:

To evaluate the efficacy of Rho-kinase (ROCK) inhibitors in corneal endothelial protection in Fuchs endothelial corneal dystrophy (FECD) after phacoemulsification.

Methods:

Forty-eight eyes from 31 patients with FECD and cataracts were randomly assigned to receive either the topical ROCK inhibitor (or ripasudil) or placebo 4 times a day, in addition to the standard antibiotic and antiinflammatory eye drops, for 1 month after phacoemulsification. Endothelial cell density (ECD), central corneal thickness (CCT), and corneal densitometry were measured. The primary outcome was the central ECD (C-ECD) loss percentage 3 months after phacoemulsification. Secondary outcomes included C-ECD loss and paracentral ECD loss percentages and the CCT change ratio at different time points after phacoemulsification. Adverse events were evaluated.

Results:

There was significantly less cell loss among those eyes treated with ripasudil. C-ECD significantly increased from a baseline of 2361 cells/mm2 (95% confidence interval, 2151–2571) to 2506 cells/mm2 (95% confidence interval, 2296–2716) 3 months after phacoemulsification. The paracentral ECD loss was 0.4% in the ripasudil group versus 7.3% in the control group. Corneal densitometry remained relatively unchanged in the ripasudil group but increased significantly over time in the control group. The mean CCT increased slightly in both groups from baseline to the final follow-up at 3 months, albeit without significant differences between the groups. In the ripasudil group, transient conjunctival erythema was the most common adverse event.

Conclusions:

The topical ROCK inhibitor, or ripasudil, demonstrated beneficial effects on preventing endothelial cell loss and improving endothelial function in patients with FECD undergoing phacoemulsification. Corneal densitometry showed reduced corneal light scattering in the ripasudil group after phacoemulsification, suggesting improved corneal endothelial function.
Risk of hospitalization or death does not differ in children exposed to HIV, yet uninfected compared to non-exposed peers in the Zambia Infant Cohort Study (ZICS)
Authors: Herlihy Julie M. , Zulu Ethan , Mwananyanda Lawrence , Forman Leah , Heeren Tim , Gill Christopher J. , Chilengi Roma , Namuziya Natasha , Payne-Lohman Barbara , Chavuma Roy , Duffy Cassandra R. , Thea Donald M.
Published: February 2025

Objective:

Increased mortality and morbidity has been observed among children who are HIV-exposed, uninfected (CHEU). It is unknown if health disparities remain despite promotion of exclusive breastfeeding and adoption of universal combination antiretroviral therapy (cART) for pregnant women.

Design:

We conducted a longitudinal cohort study among pregnant women with and without HIV [Zambia Infant Cohort (ZICS)] with the primary goal to measure the morbidity/mortality experienced by CHEU in first 6 months of life, and secondarily whether such disparities could be explained by timing of cART initiation or elevated maternal immune activation.

Methods:

Pregnant women with/without HIV (1 : 1) were enrolled prior to 26 weeks gestation by ultrasound and assessed twice antenatally. Infants were seen at birth, 6 days, 6, 10, 14, 20, and 24 weeks of age and assessed for illnesses, sick visits/hospitalizations, infant feeding, immunizations, and co-trimoxazole compliance.

Results:

From 1276 livebirths, there were 36 deaths and 89 hospitalizations over 6 months. Preconception cART uptake was 73%, and majority of pregnant women with HIV had suppressed viral loads at enrollment. There was no difference in hospitalization or death rates for CHEU as compared to HIV-unexposed children [incidence rate ratio (IRR) 1.27, 95% CI 0.79–2.04, P = 0.33]. This did not shift after adjusting for maternal immune activation prematurity or small for gestational age (SGA). Exclusive breastfeeding reduced risk of hospitalization by 43%.

Conclusion:

In this setting of moderate cART uptake, we found no evidence of increased hospitalizations or deaths among CHEU. We conclude that the observed increased morbidity among CHEU can be effectively mitigated through early initiation of cART and exclusive breastfeeding.
Short-course antibiotic strategies for ventilator-associated pneumonia
Authors: Tan Wei Cong , Quah Joan , Li Andrew Yunkai
Published: February 2025

Purpose of review

Evidence behind antibiotic duration while treating ventilator-associated pneumonia (VAP) remains unclear. There is a need to balance minimizing the development of antimicrobial resistance without compromising clinical outcomes given the high mortality.

Recent findings

Recent studies have suggested that shorter antibiotic courses, when individualized to clinical response, may be adequate for treating VAP without increasing the incidence of mortality or recurrence, regardless of pathogens. Moreover, shortening duration may reduce the risk of adverse events, including acute kidney injury.

Shortening the duration of antibiotic treatment for VAP, in the setting of appropriate clinical response, is a reasonable strategy to reduce costs and selective pressure driving antimicrobial resistance. This was demonstrated in the latest REGARD-VAP study, even among VAP patients with nonfermenting Gram-negative bacilli or carbapenem-resistant pathogens. Given the challenges in diagnosing VAP, such pragmatic approaches would be essential as part of overall antibiotic stewardship programmes. Further refinement to the criteria for antibiotic cessation may be possible.
Teasing out factors differentiating pathologic from benign pneumatosis intestinalis
Authors: Song Julia , Zhang Biqi , Mahvi David , Shariat Mahsa , Castillo-Angeles Manuel , Dey Tanujit , Askari Reza
Published: February 2025

BACKGROUND

Pneumatosis intestinalis (PI) is a rare radiographic finding that can range from being a benign process to needing emergency surgery. Sufficiently powered studies are lacking, and recommendations for management remain unclear. The purpose of this study was to identify key predictors of pathologic PI using physical examination, laboratory, and radiographic findings.

METHODS

A retrospective cohort study was conducted at two quaternary academic centers (2010–2020). A total of 334 consecutive patients 18 years or older with radiographic evidence of PI were identified. Patients were excluded if they pursued comfort care or if there was concurrent radiographic evidence of vaso-occlusive process. Pathologic PI was defined as presence of ischemic and/or perforated bowel on exploratory laparotomy or death prior to planned surgery.

RESULTS

Of the 334 patients included in our study, 91 (27%) underwent exploratory laparotomy, of which 59 (65%) had ischemic and/or perforated bowel. These latter patients and 10 other patients who died before exploratory laparotomy defined the pathologic PI cohort. A stepwise model was created for predicting pathologic disease. Significant predictors were the presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, increasing leukocyte count, and end organ injury, which were used to construct a nomogram for clinical use.

CONCLUSION

A nomogram score based on presence of portal venous gas, multisegment PI, vasopressor use, peritonitis, leukocytosis, and end organ injury may help predict the probability of pathologic PI and therefore can inform surgical decision making.

LEVEL OF EVIDENCE

Epidemiologic Study; Level III.
American Clinical Neurophysiology Society Technical Standards for Electrical Stimulation With Intracranial Electrodes for Functional Brain Mapping and Seizure Induction
Authors: Arya Ravindra , Baumer Fiona M. , Chauvel Patrick , Frauscher Birgit , Jayakar Prasanna , Kheder Ammar , Lega Bradley , Lesser Ronald P. , Miller Kai J. , Nuwer Marc R. , Pedersen Nigel P. , Ritaccio Anthony L. , Sabsevitz David S. , Sinha Saurabh R. , So Elson L. , Tatum William O. , Templer Jessica W. , Schuele Stephan U.
Published: February 2025

Purpose:

These American Clinical Neurophysiology Society technical standards suggest best practices for electrical stimulation mapping (ESM) with subdural and stereotactic depth electrodes for seizure induction and mapping of brain function.

Methods:

A working group was convened from American Clinical Neurophysiology Society membership with expertise in ESM. PubMed searches were performed to identify pertinent peer-reviewed literature. Recurrent meetings reviewed progress, built consensus by discussion, and developed evidence-based recommendations to the extent possible.

Recommendations:

Stimulators used for ESM should have sufficient dynamic range, ability to interrupt a stimulus train, and ictal disrupt mechanism(s). Charge density should be calculated for the specific electrodes and ESM settings, the maximum safe limits being 52 to 57 μC/cm2/phase for subdural electrodes and not established for stereotactic depth electrodes. Subdural ESM for functional mapping is typically performed at 50-Hz pulse frequency, 200- to 300-µs pulse width, 2- to 8-s train duration, and 1- to 20-mA current strength. Stereo ESM is commonly performed using 2 different pulse frequencies: 1 Hz (300–500 µs pulse width, train duration up to 30 s, and often a constant current of 3–5 mA), and 50 Hz (100–500 µs pulse width, train duration 2-8 s, and 0.5–10 mA current intensity).

Conclusions:

This guideline provides technical standards for the performance of ESM, which will likely evolve over time with advances in technology and additional evidence (also see Graphical Abstract).
Delamination detection in layered waveguides using Ostrovsky wave packets
Authors: Tamber J. S. , Chappell D. J. , Tranter M. R.
Published: February 2025

We examine the scattering of Ostrovsky wave packets, generated from an incident solitary wave, in a two-layered waveguide with a delamination in the centre and soft (imperfect) bonding on either side of the centre. The layers of the waveguide are assumed to consist of different materials, and the strains are described by a system of coupled Boussinesq equations. A semi-analytical approach consisting of matched asymptotic multiple-scale expansions is applied, leading to Ostrovsky equations in soft-bonded regions and Korteweg−de Vries (KdV) equations in the delaminated region. This semi-analytical method has good agreement with direct numerical simulations, validating the approach as well as providing a significant reduction in the computation time. In the delaminated regions, Ostrovsky wave packets evolve into a train of solitary waves, which subsequently evolve into Ostrovsky wave packets in the second bonded region. Analysis of the phase shift in the wave packet, introduced from the delaminated region, allows us to predict both the position and the length of the delamination; the first time this has been achieved using nonlinear waves. These results motivate experiments to validate the theoretical results, with the aim of creating a tool to monitor the integrity of layered structures.
Challenges to the ΛCDM cosmology
Authors: Efstathiou George
Published: February 2025

Observations of the cosmic microwave background (CMB) radiation are described with remarkable accuracy by the six-parameter

Λ

CDM cosmology. However, the key ingredients of this model, namely dark matter, dark energy and cosmic inflation are not understood at a fundamental level. It is, therefore, important to investigate tensions between the CMB and other cosmological probes. I will review aspects of tensions with direct measurements of the Hubble constant

H
0

, measurements of weak gravitational lensing, and the recent hints of evolving dark energy reported by the Dark Energy Spectroscopic Instrument (DESI) collaboration.

This article is part of the discussion meeting issue ‘Challenging the standard cosmological model’.
Investigating ultra-large large-scale structures: potential implications for cosmology
Authors: Lopez Alexia M. , Clowes Roger , Williger Gerard
Published: February 2025

Large-scale structure (LSS) studies in cosmology map and analyse matter in the Universe on the largest scales. Understanding LSSs can provide observational support for the cosmological principle (CP) and the standard cosmological model (

Λ

CDM). In recent years, many discoveries have been made of LSSs that are so large that they become difficult to understand within

Λ

CDM. Reasons for this are that they potentially challenge the CP (i.e. the scale of homogeneity) and their formation and origin are not fully understood. In this article, we review two recent LSS discoveries: the Giant Arc (GA, approx. 1 Gpc) and the Big Ring (BR, approx. 400 Mpc). Both structures are in the same cosmological neighbourhood—at the same redshift (

z
∼
0.8

) and with a separation on the sky of approximately only

12

∘

. Both structures exceed the often-cited scale of homogeneity (Yadav+ 2010), so individually and together, these two intriguing structures raise more questions for the validity of the CP and potentially hint at new physics beyond the standard model. The GA and BR were discovered using a novel method of mapping faint matter at intermediate redshifts, interpreted from the Mg II absorption doublets seen in the spectra of background quasars.

This article is part of the discussion meeting issue ‘Challenging the standard cosmological model’.
Could sample variance be responsible for the parity-violating signal seen in the Baryon Oscillation Spectroscopic Survey?
Authors: Philcox O. H. E. , Ereza J.
Published: February 2025

Recent works have uncovered an excess signal in the parity-odd four-point correlation function measured from the Baryon Oscillation Spectroscopic Survey (BOSS) galaxy catalogue. If physical in origin, this could indicate new parity-breaking processes in inflation. At heart, these studies compare the observed four-point correlator with the distribution obtained from parity-conserving mock galaxy surveys; if the simulations underestimate the covariance of the data, noise fluctuations may be misinterpreted as a signal. To test this, we reanalyse the BOSS CMASS parity-odd dataset with the noise distribution model using the newly developed
GLAM-Uchuu
suite of mocks. These comprise full

N

-body simulations that follow the evolution of

2000
3

dark matter particles and represent a significant upgrade compared with the formerly used
MultiDark-Patchy
mocks, which were based on an alternative (non

N

-body) gravity solver. We find no significant evidence for parity-violation (with a baseline detection significance of

1.0
σ

), suggesting that the former signal (

2.9
σ

with our data cuts) could be caused by an underestimation of the covariance in MultiDark-Patchy. The significant differences between results obtained with the two sets of BOSS-calibrated galaxy catalogues (whose covariances differ at the

10
−

20
%

level) showcase the heightened sensitivity of beyond-two-point analyses to nonlinear effects and indicate that previous constraints may suffer from large systematic uncertainties.

This article is part of the discussion meeting issue ‘Challenging the standard cosmological model’.
Chiral Single Molecule Localization Microscopy (chiralSMLM)
Authors: Aravinth S , Pant Neeraj , Mondal Partha P.
Published: February 2025

Chiral fingerprints are unique to a molecule and convey information related to binding sites, conformation, and its immediate chemical environment. Deciphering these information is expected to aid a better understanding of the biological processes at the very molecular scale. Here, we present a new technique calledchiralSM LM, to selectively detect chiral enantiomers (left-handed and right-handed) of single molecules and generate a super-resolved map of their distribution in cell. Calibration, characterization, and optimization of the system is carried out using a polarized light source (left and right circularly) and by recording known structures (Actin filaments) in a cell. Subsequently, the distribution of Dendra2-Actin enantiomers on the actin filaments is mapped. Finally,chiralSM LMis employed to study the characteristic distribution of viral proteins (Hemaglutinin and NS3) in transfection studies of two diseases (Influenza type-A and Dengue type2) after 48 hrs of transfection. Single-molecule and cluster analysis reveals that left-handed HA and left-handed NS3 molecules have a larger footprint, suggesting the role of chiral molecules in promoting cluster formation during viral infection. This is amazing, considering the fact that Left-handed enantiomers are known to play a crucial role in a range of biological functions. The new classification of single molecules purely based on their chiral nature is expected to advance single-molecule imaging.

Summary & Significance

Deciphering the chirality of single molecules and studying its effect on the biological function of a cell is fabulous. This gives a new perspective for understanding functions purely based on the chiral nature of single biomolecules in a cell. We developed achiralSM LMmicroscopy system to demonstrate the effect of chirality on the clustering behavior of viral proteins in a cell-transfection study. Hence, the findings provide a new way of quantifying molecule-molecule and molecule-organelle interactions.