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Relationships between boreal wildfire emissions and day-to-day variations in meteorological variables are complex and have important implications for the sensitivity of high-latitude ecosystems to climate change. We examined the influence of environmental conditions on boreal fire emissions and fire contributions to regional trace gas variability in interior Alaska during the summer of 2013 using two types of analysis. First, we quantified the degree to which meteorological and fire weather indices explained regional variability in fire activity using four different products, including active fires, fire radiative power, burned area, and carbon emissions. Second, we combined daily emissions from the Alaskan Fire Emissions Database (AKFED) with the coupled Polar Weather Research and Forecasting/Stochastic Time-Inverted Lagrangian Transport model to estimate fire contributions to trace gas concentration measurements at the Carbon in Arctic Reservoirs Vulnerability Experiment-NOAA Global Monitoring Division (CRV) tower in interior Alaska. Tower observations during two high fire periods were used to estimate CO and CH4 emission factors. We found that vapor pressure deficit and temperature had a level of performance similar to more complex fire weather indices. Emission factors derived from CRV tower measurements were 134 ± 25 g CO per kg of combusted biomass and 7.74 ± 1.06 g CH4 per kg of combusted biomass. Predicted daily CO mole fractions from AKFED emissions were moderately correlated with CRV observations (r = 0.68) and had a high bias. The modeling system developed here allows for attribution of emission factors to individual fires and has the potential to improve our understanding of regional CO, CH4, and CO2 budgets.

Jacqueline MT Henderson,1 Neville M Blampied,1 Karyn G France2 1School of Psychology, Speech and Hearing, Te Kura Mahi ā-Hirikapo, College of Science, University of Canterbury, Te Whare Wānanga o Waitaha, Christchurch, New Zealand; 2School of Health Sciences, University of Canterbury, Te Whare Wānanga o Waitaha, Christchurch, New ZealandCorrespondence: Jacqueline MT HendersonSchool of Psychology, Speech and Hearing, Te Kura Mahi ā-Hirikapo, College of Science, University of Canterbury, Te Whare Wānanga o Waitaha, Private Bag 4800, Christchurch, New ZealandTel +64 33694358Email Jacki.henderson@canterbury.ac.nzBackground: An important developmental task for infants over their first few years of life is to learn to settle to sleep with a reasonably short latency, maintain sleep through the night and coordinate with family sleeping and waking schedules. A child who can reliably do this is exhibiting self-regulated sleep. Otherwise, children’s sleep may have to be other (non-self) regulated to some degree and they may exhibit pediatric sleep disturbances (e.g., extended sleep latency, and/or frequent nightwaking); these are reported by 36– 45% of parents of infants between ages four to 12 months.Purpose: To answer the question: Can infant and parent factors observed at 1 month of infant age predict which infants will have regulated sleep at 6- and 12-months of age? Prediction from 1 month has not previously been investigated.Methods: In a prospective longitudinal study, the mothers of 52 typically developing infants completed 6-day sleep diaries at 1, 3, 6, 9 and 12 months from which a composite sleep score (CSS) was derived for each child at each month. Diary reliability was assessed once (for 54% of families) using all-night videosomnography.Results: At 6 months, CSS scores were distributed bi-modally and thus differentiated into two groups by an empirically observed CSS cutoff score, with a majority (56%) of infants classified as self-sleep regulated (S-R) and the rest as non-self sleep-regulated (NS-R). At 12 months, 72% could similarly be classified as S-R, while 28% exhibited some continuing sleep disturbance. Discriminant function analysis investigated the predictors of S-R vs NS-R group membership at 6 and 12 months from parent and child variables recorded at 1 month. Parent presence at sleep onset and less total infant sleep time predicted group membership at 6 months with 94% classification accuracy, and parental presence at sleep onset and frequency of infant night wakings predicted group membership at 12 months with 85% accuracy. At 1 month, parents of infants later classified as NS-R at 6 and 12 months had higher frequencies of all settling activities than parents of those later classified as S-R.Conclusion: Variables measured at 1 month that predicted sleep status at 6 and 12 months were parental presence at sleep onset, frequency of infant night waking and total infant sleep time. The overall frequency of parent settling activities at 1 month also clearly differentiated the two sleep groups at the older ages. Parenting behaviours are modifiable factors and thus may have the potential for preventing pediatric sleep disturbances in children.Keywords: infant, sleep regulation, predictors, parent behavior

1. Current pharmacotherapies for the treatment of Parkinson's disease (PD) are largely symptomatic and do not attenuate the characteristic nigral (dopamine) cell loss. 2. Using the 6-hydroxydopamine (6-OHDA) rat model of PD, we investigated the novel, potentially neuroprotective compound BZAD-01, which is an N-methyl-D-aspartate (NMDA) glutamate receptor antagonist selective for the NR2B subunit. 3. Forty female Sprague-Dawley rats were pretreated with either 10 mg/kg BZAD-01 or vehicle (5% sucrose and 0.1% ascorbate) in their drinking water for 11 days prior to and for 3 days following 6-OHDA surgery. During surgery, rats received an injection of either a toxic dose of 16 µg 6-OHDA or a non-toxic dose of 1 µg 6-OHDA (sham) into the medial forebrain bundle. A series of behavioural tests, including curling (measuring body axis bias), head position bias and narrow beam, was performed fortnightly for 8 weeks after surgery to assess the effects of BZAD-01 pretreatment on parkinsonism. Drug-induced rotational asymmetry was also assessed just before rats were killed. Post-mortem immunohistochemistry was performed to quantify the degree of nigral dopamine cell loss. 4. Pretreatment of 6-OHDA-lesioned rats with BZAD-01 significantly reduced the amount of dopamine cell loss and significantly improved all behavioural measures. Furthermore, there was no significant difference in any of the behavioural measures between lesioned rats pretreated with BZAD-01 and rats that underwent sham surgery. [ABSTRACT FROM AUTHOR]

Nephronophthisis is a form of autosomal recessive hereditary cystic kidney disease that typically progresses to end-stage renal disease by early adulthood. Conversely, focal segmental glomerulosclerosis is a histological glomerular phenotype that can be familial, primary (idiopathic), or secondary to a multitude of pathological processes affecting the kidney, including such tubulointerstitial diseases as nephronophthisis. Mutations in 6 distinct nephronophthisis genes have been described to date. We describe a consanguineous Filipino family with 2 novel sequence variants in the NPHP4 gene. Affected individuals presented with end-stage renal disease and histological features of focal segmental glomerulosclerosis on biopsy. They also had atypical radiological findings, making the clinical diagnosis of the genetic syndrome difficult. Furthermore, although ocular abnormalities and hearing loss were described previously, this is the first report of hepatic disease in patients with mutations in NPHP4. The diagnosis of nephronophthisis was made by means of mutational analysis of the NPHP4 gene after isolation of a region of homozygosity in affected individuals by using whole-genome single-nucleotide polymorphism analysis. Because establishment of the correct diagnosis has implications for therapeutic interventions, prognosis, and, in the case of heritable diseases, appropriate genetic counseling for affected individuals and their families, this report emphasizes the importance of obtaining meticulous clinical information, considering alternative diagnoses, and, when possible, performing genetic evaluation to confirm the diagnosis. We outline an approach to patients with hereditary kidney disease, focusing specifically on the molecular genetic techniques available to evaluate such families and determine a chromosomal region of interest and, subsequently, the diagnosis. Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

PURPOSE: Nearly 40% of all-terrain vehicle (ATV) crash-related fatalities involve pediatric patients, with many of these patients dying from head and neck injuries. West Virginia is in a unique position to examine these injuries because of its high rate of ATV use. This study examines craniofacial ATV-related trauma in children. PATIENTS AND METHODS: We conducted a single-center, retrospective, descriptive study of 26 children presenting with a craniofacial injury(ies) resulting from an ATV crash from January 2001 to December 2004. RESULTS: Twenty-six children (65% boys) with a mean age of 13.1 years presented with craniofacial injuries during the study period. Two patients were helmeted. Mortality was 3.8% (n = 1, head injury related, postinjury day 3). Patients were most often drivers of the ATV (65%), although girls were more likely to be passengers (P = .03). Facial contusions, lacerations, and abrasions were highly prevalent (62%, 69%, 65%, respectively), as were fractures of the facial bones and skull (77%). Thirty-five percent sustained closed head injuries, which were significantly associated with mandible fractures (odds ratio 12.8%; 95% CI, 1.15-143). Mean length of hospital stay was 4.6 +/- 5 days, and 36% required an ICU stay (mean, 5.1 +/- 3 days). Twenty-four percent required ventilator support (mean, 107 +/- 43 hours; range, 48 to 168 hours). Operative intervention was required in 72% of patients (n = 18). CONCLUSION: Maxillofacial injury patterns from ATV-related crashes in children suggest a high percentage of significant facial injuries and closed head injuries. As new ATV legislation that addresses operator use is enacted, a decrease in the number and severity of craniofacial injuries may be seen. Copyright © 2006 by the American Association of Oral and Maxillofacial Surgeons. [ABSTRACT FROM AUTHOR]

In a free viewing learning condition, participants were allowed to move their eyes naturally as they learned a set of new faces. In a restricted viewing learning condition, participants remained fixated in a single central location as they learned the new faces. Recognition of the learned faces was then tested following the two learning conditions. Eye movements were recorded during the free viewing learning condition, as well as during recognition. The recognition results showed a clear deficit following the restricted viewing condition, compared with the free viewing condition, demonstrating that eye movements play a functional role during human face learning. Furthermore, the features selected for fixation during recognition were similar following free viewing and restricted viewing learning, suggesting that the eye movements generated during recognition are not simply a recapitulation of those produced during learning. [ABSTRACT FROM AUTHOR]

Eye movements were monitored while participants performed a change detection task with images of natural scenes. An initial and a modified scene image were displayed in alternation, separated by a blank interval (flicker paradigm). In the modified image, a single target object was changed either by deleting that object from the scene or by rotating that object 90 degrees in depth. In Experiment 1, fixation position at detection was more likely to be in the target object region than in any other region of the scene. In Experiment 2, participants detected scene changes more accurately, with fewer false alarms, and more quickly when allowed to move their eyes in the scene than when required to maintain central fixation. These data suggest a major role for fixation position in the detection of changes to natural scenes across discrete views. [ABSTRACT FROM AUTHOR]

The purpose of this intervention study was to prove that increasing flexibility of the hamstring musculotendinous unit would decrease the number of lower extremity overuse injuries that occur in military infantry basic trainees. Two different companies going through basic training at the same time were used. Hamstring flexibility was checked at the beginning and at the end of the 13-week infantry basic training course. The control company (N = 148) proceeded through normal basic training. The intervention company (N = 150) followed the same program but added three hamstring stretching sessions to their already scheduled fitness program. All subsequent lower extremity overuse injuries were recorded through the troop medical clinic. Hamstring flexibility increased significantly in the intervention group compared with the control group. The number of injuries was also significantly lower in the intervention group. Forty-three injuries occurred in the control group for an incidence rate of 29.1%, compared with 25 injuries in the intervention group for an incidence rate of 16.7%. Thus, in this study, the number of lower extremity overuse injuries was significantly lower infantry basic trainees with increased hamstring flexibility. [ABSTRACT FROM AUTHOR]

Inhibitory control of prepotent responses has been examined by using the antisaccade task, during which a reflexive saccade toward a peripheral onset must be suppressed before an eye movement in the opposite direction from the onset can be executed. In the present experiments, we sought to determine whether older and younger adults would perform similarly on this task. Older adults had a harder time suppressing their reflexive responses, as measured by an increase in the proportion of saccade direction errors. Despite an age-related decline in saccade direction accuracy, the increase in saccade latency associated with the antisaccade condition was the same for both younger and older adults. These results support the view that the effectiveness of inhibitory control declines with age (Hasher & Zacks, 1988; Hasher, Zacks, & May, 1999). [ABSTRACT FROM AUTHOR]

Intracortical brain-computer interfaces (iBCIs) can restore movement and communication abilities to individuals with paralysis by decoding their intended behavior from neural activity recorded with an implanted device. While this activity yields high-performance decoding over short timescales, neural data are often nonstationary, which can lead to decoder failure if not accounted for. To maintain performance, users must frequently recalibrate decoders, which requires the arduous collection of new neural and behavioral data. Aiming to reduce this burden, several approaches have been developed that either limit recalibration data requirements (few-shot approaches) or eliminate explicit recalibration entirely (zero-shot approaches). However, progress is limited by a lack of standardized datasets and comparison metrics, causing methods to be compared in an ad hoc manner. Here we introduce the FALCON benchmark suite (Few-shot Algorithms for COnsistent Neural decoding) to standardize evaluation of iBCI robustness. FALCON curates five datasets of neural and behavioral data that span movement and communication tasks to focus on behaviors of interest to modern-day iBCIs. Each dataset includes calibration data, optional few-shot recalibration data, and private evaluation data. We implement a flexible evaluation platform which only requires user-submitted code to return behavioral predictions on unseen data. We also seed the benchmark by applying baseline methods spanning several classes of possible approaches. FALCON aims to provide rigorous selection criteria for robust iBCI decoders, easing their translation to real-world devices.

Intracortical brain-computer interfaces (iBCIs) enable people with tetraplegia to gain intuitive cursor control from movement intentions. To translate to practical use, iBCIs should provide reliable performance for extended periods of time. However, performance begins to degrade as the relationship between kinematic intention and recorded neural activity shifts compared to when the decoder was initially trained. In addition to developing decoders to better handle long-term instability, identifying when to recalibrate will also optimize performance. We propose a method, "MINDFUL", to measure instabilities in neural data for useful long-term iBCI, without needing labels of user intentions. Longitudinal data were analyzed from two BrainGate2 participants with tetraplegia as they used fixed decoders to control a computer cursor spanning 142 days and 28 days, respectively. We demonstrate a measure of instability that correlates with changes in closed-loop cursor performance solely based on the recorded neural activity (Pearson r = 0.93 and 0.72, respectively). This result suggests a strategy to infer online iBCI performance from neural data alone and to determine when recalibration should take place for practical long-term use., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Understanding how the body is represented in motor cortex is key to understanding how the brain controls movement. The precentral gyrus (PCG) has long been thought to contain largely distinct regions for the arm, leg and face (represented by the "motor homunculus"). However, mounting evidence has begun to reveal a more intermixed, interrelated and broadly tuned motor map. Here, we revisit the motor homunculus using microelectrode array recordings from 20 arrays that broadly sample PCG across 8 individuals, creating a comprehensive map of human motor cortex at single neuron resolution. We found whole-body representations throughout all sampled points of PCG, contradicting traditional leg/arm/face boundaries. We also found two speech-preferential areas with a broadly tuned, orofacial-dominant area in between them, previously unaccounted for by the homunculus. Throughout PCG, movement representations of the four limbs were interlinked, with homologous movements of different limbs (e.g., toe curl and hand close) having correlated representations. Our findings indicate that, while the classic homunculus aligns with each area's preferred body region at a coarse level, at a finer scale, PCG may be better described as a mosaic of functional zones, each with its own whole-body representation.

Age-related declines in episodic memory do not affect all types of mnemonic information equally: when to-be-remembered information is in line with one's prior knowledge, or schema-congruent, older adults often show no impairments. There are two major accounts of this effect: One proposes that schemas compensate for memory failures in aging, and the other proposes that schemas instead actively impair older adults' otherwise intact memory for incongruent information. However, the evidence thus far is inconclusive, likely due to methodological constraints in teasing apart these complex underlying dynamics. We developed a paradigm that separately examines the contributions of underlying memory and schema knowledge to a final memory decision, allowing these dynamics to be examined directly. In the present study, healthy older and younger adults first searched for target objects in congruent or incongruent locations within scenes. In a subsequent test, participants indicated where in each scene the target had been located previously, and provided confidence-based recognition memory judgments that indexed underlying memory, in terms of recollection and familiarity, for the background scenes. We found that age-related increases in schema effects on target location spatial recall were predicted and statistically mediated by age-related increases in underlying memory failures, specifically within recollection. We also found that, relative to younger adults, older adults had poorer spatial memory precision within recollected scenes but slightly better precision within familiar scenes-and age increases in schema bias were primarily exhibited within recollected scenes. Interestingly, however, there were also slight age-related increases in schema effects that could not be explained by memory deficits alone, outlining a role for active schema influences as well. Together, these findings support the account that age-related schema effects on memory are compensatory in that they are driven primarily by underlying memory failures, and further suggest that age-related deficits in memory precision may also drive schema effects., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Understanding the cortical activity patterns driving dexterous upper limb motion has the potential to benefit a broad clinical population living with limited mobility through the development of novel brain-computer interface (BCI) technology. The present study examines the activity of ensembles of motor cortical neurons recorded using microelectrode arrays in the dominant hemisphere of two BrainGate clinical trial participants with cervical spinal cord injury as they attempted to perform a set of 48 different hand gestures. Although each participant displayed a unique organization of their respective neural latent spaces, it was possible to achieve classification accuracies of ~70% for all 48 gestures (and ~90% for sets of 10). Our results show that single unit ensemble activity recorded in a single hemisphere of human precentral gyrus has the potential to generate a wide range of gesture-related signals across both hands, providing an intuitive and diverse set of potential command signals for intracortical BCI use.

Background: Brain-computer interfaces can enable communication for people with paralysis by transforming cortical activity associated with attempted speech into text on a computer screen. Communication with brain-computer interfaces has been restricted by extensive training requirements and limited accuracy., Methods: A 45-year-old man with amyotrophic lateral sclerosis (ALS) with tetraparesis and severe dysarthria underwent surgical implantation of four microelectrode arrays into his left ventral precentral gyrus 5 years after the onset of the illness; these arrays recorded neural activity from 256 intracortical electrodes. We report the results of decoding his cortical neural activity as he attempted to speak in both prompted and unstructured conversational contexts. Decoded words were displayed on a screen and then vocalized with the use of text-to-speech software designed to sound like his pre-ALS voice., Results: On the first day of use (25 days after surgery), the neuroprosthesis achieved 99.6% accuracy with a 50-word vocabulary. Calibration of the neuroprosthesis required 30 minutes of cortical recordings while the participant attempted to speak, followed by subsequent processing. On the second day, after 1.4 additional hours of system training, the neuroprosthesis achieved 90.2% accuracy using a 125,000-word vocabulary. With further training data, the neuroprosthesis sustained 97.5% accuracy over a period of 8.4 months after surgical implantation, and the participant used it to communicate in self-paced conversations at a rate of approximately 32 words per minute for more than 248 cumulative hours., Conclusions: In a person with ALS and severe dysarthria, an intracortical speech neuroprosthesis reached a level of performance suitable to restore conversational communication after brief training. (Funded by the Office of the Assistant Secretary of Defense for Health Affairs and others; BrainGate2 ClinicalTrials.gov number, NCT00912041.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: The objective of this work was to establish sustainable systems for quality improvement in an Academic Medical Center and Safety Net Hospital., Method: High reliability principles of leadership engagement, a culture of safety, and sustainable performance improvement were used. Target areas for improvement were clinical outcomes for patients, public reputation scores, and lower cost of care. The system was based on annual focused goals with specific targets, improvement teams, transparent scorecards, and data driven work. Program visibility was championed by leaders. Consistent education on quality, safety, efficiency, and effectiveness for all employees created buy-in. Data review and accountability tracked progress, helped resource allocation, and defined next steps., Results: In the first 5 years, all patient quality and safety metrics improved between 10% and 60%. This improvement resulted in higher CMS Star Ranking and Leapfrog patient safety grade. The next phase included maximizing value by expanding into hospital operations and finance with a focus on improved clinical documentation and reduced length of stay and cost of care. Clinical documentation improvement led to a 15% increase in comorbidity capture. This positively impacted reported outcomes and hospital payment by appropriate risk adjustment. Length of stay was addressed with a new care coordination program and physician-driven utilization review., Conclusions: High reliability principles are applicable in a resource limited healthcare system. Improved clinical and operational results were achieved through goal setting, improvement teams, and data driven projects leading to creation of an office of operational excellence., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Transmission electron microscopy (TEM) images can visualize kidney glomerular filtration barrier ultrastructure, including the glomerular basement membrane (GBM) and podocyte foot processes (PFP). Podocytopathy is associated with glomerular filtration barrier morphological changes observed experimentally and clinically by measuring GBM or PFP width. However, these measurements are currently performed manually. This limits research on podocytopathy disease mechanisms and therapeutics due to labor intensiveness and inter-operator variability., Methods: We developed a deep learning-based digital pathology computational method to measure GBM and PFP width in TEM images from the kidneys of Integrin-Linked Kinase (ILK) podocyte-specific conditional knockout (cKO) mouse, an animal model of podocytopathy, compared to wild-type (WT) control mouse. We obtained TEM images from WT and ILK cKO littermate mice at 4 weeks old. Our automated method was composed of two stages: a U-Net model for GBM segmentation, followed by an image processing algorithm for GBM and PFP width measurement. We evaluated its performance with a 4-fold cross-validation study on WT and ILK cKO mouse kidney pairs., Results: Mean (95% confidence interval) GBM segmentation accuracy, calculated as Jaccard index, was 0.73 (0.70-0.76) for WT and 0.85 (0.83-0.87) for ILK cKO TEM images. Automated and manual GBM width measurements were similar for both WT (p=0.49) and ILK cKO (p=0.06) specimens. While automated and manual PFP width measurements were similar for WT (p=0.89), they differed for ILK cKO (p<0.05) specimens. WT and ILK cKO specimens were morphologically distinguishable by manual GBM (p<0.05) and PFP (p<0.05) width measurements. This phenotypic difference was reflected in the automated GBM (p<0.05) more than PFP (p=0.06) widths., Conclusions: These results suggest that certain automated measurements enabled via deep learning-based digital pathology tools could distinguish healthy kidneys from those with podocytopathy. Our proposed method provides high-throughput, objective morphological analysis and could facilitate podocytopathy research and translate into clinical diagnosis., Competing Interests: Disclosures The authors have declared that no conflict of interest exists for this work.

Rationale: Early steps in glomerular injury are poorly understood in collagen IV nephropathies., Objectives: We characterized structural, functional, and biophysical properties of glomerular capillaries and podocytes in Col4α3-/- mice and analyzed kidney cortex transcriptional profiles at various disease stages. We investigated the effects of TUDCA (suppresses ER stress) on these parameters and used human FSGS transcriptomic data to identify pathways rescued by TUDCA., Findings: In Col4α3-/- mice, podocyte injury develops by 3 months, with maximum glomerular deformability and 40% podocyte loss at 4 months. This period is followed is followed by glomerular capillary stiffening, proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis. Bulk RNA sequencing at sequential time points revealed progressive increases in inflammatory and injury gene expression, and activation of the TNF pathway. Mapping Podocyte-enriched genes from FSGS patients to mice showed that TUDCA, which mitigated renal injury suppressed molecular pathways associated with podocyte stress, hypertrophy and tubulo-interstitial injury., Conclusions: Col4α3-/- nephropathy progresses in two phases. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. The response of podocytes to TUDCA treatment provides insights into signaling pathways in Alport and related nephropathies.

Complement-mediated diseases can be treated using systemic inhibitors. However, complement components are abundant in circulation, affecting systemic inhibitors' exposure and efficacy. Furthermore, because of complement's essential role in immunity, systemic treatments raise infection risk in patients. To address these challenges, we developed antibody fusion proteins combining the alternative-pathway complement inhibitor factor H (fH 1-5 ) with an anti-C3d monoclonal antibody (C3d-mAb-2fH). Because C3d is deposited at sites of complement activity, this molecule localizes to tissue complement while minimizing circulating complement engagement. These fusion proteins bind to deposited complement in diseased human skin sections and localize to activated complement in a primate skin injury model. We further explored the pharmacology of C3d-mAb-2fH proteins in rodent models with robust tissue complement activation. Doses of C3d-mAb-2fH >1 mg/kg achieved >75% tissue complement inhibition in mouse and rat injury models while avoiding circulating complement blockade. Glomerular-specific complement inhibition reduced proteinuria and preserved podocyte foot-process architecture in rat membranous nephropathy, indicating disease-modifying efficacy. These data indicate that targeting local tissue complement results in durable and efficacious complement blockade in skin and kidney while avoiding systemic inhibition, suggesting broad applicability of this approach in treating a range of complement-mediated diseases., Competing Interests: Declaration of interests This work was funded by Q32 Bio, Inc., which holds patents on ADX-097 and related molecules. Q32 Bio is currently conducting clinical trials using ADX-097. F.L., S.T.R., K.C.F., J.G.M., A.E.C., S.M.V., and S.W. are current employees and equity holders of Q32 Bio, Inc. M.J.S. and S.L.K. were employees of Q32 Bio, Inc. at the time of their contributions to the described work. J.M.T., and V.M.H. are co-founders of Q32 Bio, Inc. and retain equity in the company., (Copyright © 2024 Q32 Bio. Published by Elsevier Inc. All rights reserved.)

As infants view visual scenes every day, they must shift their eye gaze and visual attention from location to location, sampling information to process and learn. Like adults, infants' gaze when viewing natural scenes (i.e., photographs of everyday scenes) is influenced by the physical features of the scene image and a general bias to look more centrally in a scene. However, it is unknown how infants' gaze while viewing such scenes is influenced by the semantic content of the scenes. Here, we tested the relative influence of local meaning, controlling for physical salience and center bias, on the eye gaze of 4- to 12-month-old infants (N = 92) as they viewed natural scenes. Overall, infants were more likely to fixate scene regions rated as higher in meaning, indicating that, like adults, the semantic content, or local meaning, of scenes influences where they look. More importantly, the effect of meaning on infant attention increased with age, providing the first evidence for an age-related increase in the impact of local meaning on infants' eye movements while viewing natural scenes., (© 2024 International Congress of Infant Studies.)

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination., (© 2024. The Author(s).)

Quantum algorithms provide an exponential speedup for solving certain classes of linear systems, including those that model geologic fracture flow. However, this revolutionary gain in efficiency does not come without difficulty. Quantum algorithms require that problems satisfy not only algorithm-specific constraints, but also application-specific ones. Otherwise, the quantum advantage carefully attained through algorithmic ingenuity can be entirely negated. Previous work addressing quantum algorithms for geologic fracture flow has illustrated core algorithmic approaches while incrementally removing assumptions. This work addresses two further requirements for solving geologic fracture flow systems with quantum algorithms: efficient system state preparation and efficient information extraction. Our approach to addressing each is consistent with an overall exponential speed-up., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

We investigated how sensitive visual processing is to spatiotemporal disruptions in ongoing visual events. Prior work has demonstrated that participants often miss spatiotemporal disruptions in videos presented in the form of scene edits or disruptions during saccades. Here, we asked whether this phenomenon generalizes to spatiotemporal disruptions that are not tied to saccades. In two flicker paradigm experiments, participants were instructed to identify spatiotemporal disruptions created when videos either jumped forward or backward in time. Participants often missed the jumps, and forward jumps were reported less frequently compared with backward jumps, demonstrating that a flicker paradigm produces effects similar to a saccade contingent disruption paradigm. These results suggest that difficulty detecting spatiotemporal disruptions is a general phenomenon that extends beyond trans-saccadic events., (© 2024. The Psychonomic Society, Inc.)

The Kidney Precision Medicine Project (KPMP) aims to create a kidney tissue atlas, define disease subgroups, and identify critical cells, pathways, and targets for novel therapies through molecular investigation of human kidney biopsies obtained from participants with AKI or CKD. We present the case of a 66-year-old woman with diabetic kidney disease who underwent a protocol KPMP kidney biopsy. Her clinical history included diabetes mellitus complicated by neuropathy and eye disease, increased insulin resistance, hypertension, albuminuria, and relatively preserved glomerular filtration rate (early CKD stage 3a). The patient's histopathology was consistent with diabetic nephropathy and arterial and arteriolar sclerosis. Three-dimensional, immunofluorescence imaging of the kidney biopsy specimen revealed extensive periglomerular neovascularization that was underestimated by standard histopathologic approaches. Spatial transcriptomics was performed to obtain gene expression signatures at discrete areas of the kidney biopsy. Gene expression in the areas of glomerular neovascularization revealed increased expression of genes involved in angiogenic signaling, proliferation, and survival of endothelial cells, as well as new vessel maturation and stability. This molecular correlation provides additional insights into the development of kidney disease in patients with diabetes and spotlights how novel molecular techniques used by the KPMP can supplement and enrich the histopathologic diagnosis obtained from a kidney biopsy., (Copyright © 2023 by the American Society of Nephrology.)