Direct contribution of the sensory cortex to the judgment of stimulus duration.

Decision making frequently depends on monitoring the duration of sensory events. To determine whether, and how, the perception of elapsed time derives from the neuronal representation of the stimulus itself, we recorded and optogenetically modulated vibrissal somatosensory cortical activity as male rats judged vibration duration. Perceived duration was dilated by optogenetic excitation. A second set of rats judged vibration intensity; here, optogenetic excitation amplified the intensity percept, demonstrating sensory cortex to be the common gateway both to time and to stimulus feature processing. A model beginning with the membrane currents evoked by vibrissal and optogenetic drive and culminating in the representation of perceived time successfully replicated rats' choices. Time perception is thus as deeply intermeshed within the sensory processing pathway as is the sense of touch itself, suggesting that the experience of time may be further investigated with the toolbox of sensory coding.

Climate migration amplifies demographic change and population aging.

The warnings of potential climate migration first appeared in the scientific literature in the late 1970s when increased recognition that disintegrating ice sheets could drive people to migrate from coastal cities. Since that time, scientists have modeled potential climate migration without integrating other population processes, potentially obscuring the demographic amplification of this migration. Climate migration could amplify demographic change-enhancing migration to destinations and suppressing migration to origins. Additionally, older populations are the least likely to migrate, and climate migration could accelerate population aging in origin areas. Here, we investigate climate migration under sea-level rise (SLR), a single climatic hazard, and examine both the potential demographic amplification effect and population aging by combining matrix population models, flood hazard models, and a migration model built on 40 y of environmental migration in the United States to project the US population distribution of US counties. We find that the demographic amplification of SLR for all feasible Representative Concentration Pathway-Shared Socioeconomic Pathway (RCP-SSP) scenarios in 2100 ranges between 8.6-28 M [5.7-53 M]-5.3 and 18 times the number of migrants (0.4-10 M). We also project significant aging of coastal areas as youthful populations migrate but older populations remain, accelerating population aging in origin areas. As the percentage of the population lost due to climate migration increases, the median age also increases-up to 10+ y older in some highly impacted coastal counties. Additionally, our population projection approach can be easily adapted to investigate additional or multiple climate hazards.

Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

Integrating climate change induced flood risk into future population projections.

Flood exposure has been linked to shifts in population sizes and composition. Traditionally, these changes have been observed at a local level providing insight to local dynamics but not general trends, or at a coarse resolution that does not capture localized shifts. Using historic flood data between 2000-2023 across the Contiguous United States (CONUS), we identify the relationships between flood exposure and population change. We demonstrate that observed declines in population are statistically associated with higher levels of historic flood exposure, which may be subsequently coupled with future population projections. Several locations have already begun to see population responses to observed flood exposure and are forecasted to have decreased future growth rates as a result. Finally, we find that exposure to high frequency flooding (5 and 20-year return periods) results in 2-7% lower growth rates than baseline projections. This is exacerbated in areas with relatively high exposure to frequent flooding where growth is expected to decline over the next 30 years.

Tactile cognition in rodents.

Since the discovery 50 years ago of the precisely ordered representation of the whiskers in somatosensory cortex, the rodent tactile sensory system has been a fertile ground for the study of sensory processing. With the growing sophistication of touch-based behavioral paradigms, together with advances in neurophysiological methodology, a new approach is emerging. By posing increasingly complex perceptual and memory problems, in many cases analogous to human psychophysical tasks, investigators now explore the operations underlying rodent problem solving. We define the neural basis of tactile cognition as the transformation from a stage in which neuronal activity encodes elemental features, local in space and in time, to a stage in which neuronal activity is an explicit representation of the behavioral operations underlying the current task. Selecting a set of whisker-based behavioral tasks, we show that rodents achieve high level performance through the workings of neuronal circuits that are accessible, decodable, and manipulatable. As a means towards exploring tactile cognition, this review presents leading psychophysical paradigms and, where known, their neural correlates.

Multiple factors co-limit short-term in situ soil carbon dioxide emissions.

Soil respiration is a major source of atmospheric CO2. If it increases with warming, it will counteract efforts to minimize climate change. To improve understanding of environmental controls over soil CO2 emission, we applied generalized linear modeling to a large dataset of in situ measurements of short-term soil respiration rate, with associated environmental attributes, which was gathered over multiple years from four locations that varied in climate, soil type, and vegetation. Soil respiration includes many CO2-producing processes: we theorized that different environmental factors could limit each process distinctly, thereby diminishing overall CO2 emissions. A baseline model that included soil temperature, soil volumetric water content, and their interaction was effective in estimating soil respiration at all four locations (p < 0.0001). Model fits, based on model log likelihoods, improved continuously as additional covariates were added, including mean daily air temperature, enhanced vegetation index (EVI), and quadratic terms for soil temperature and water content, and their interactions. The addition of land cover and its direct interactions with environmental variables further improved model fits. Significant interactions between covariates were observed at each location and at every stage of analysis, but the interaction terms varied among sites and models, and did not consistently maintain importance in more complex models. A main-effects model was therefore tested, which included soil temperature and water content, their quadratic effects, EVI, and air temperature, but no interactions. In that case all six covariates were significant (p < 0.0001) when applied across sites. We infer that local-scale soil-CO2 emissions are commonly co-limited by EVI and air temperature, in addition to soil temperature and water content. Importantly, the quadratic soil temperature and moisture terms were significantly negative: estimated soil-CO2 emissions declined when soil temperature exceeded 22.5°C, and as soil moisture differed from the optimum of 0.27 m3 m-3.

Neotropical Clavulina: Two new species from Mexico and a re-evaluation of Clavulina floridana.

Clavulina comprises ca. 90 described species distributed worldwide in both tropical and temperate regions. However, only one species (C. floridana) has been described so far from tropical North America. We used morphological and molecular data from three DNA loci (nuc rDNA internal transcribed spacer region ITS1-5.8S-ITS2 [ITS], a portion of nuc 28S rDNA [28S], and a fragment of DNA-directed RNA polymerase II second largest subunit [RPB2]) from basidiomata and ectomycorrhizas collected in tropical ecosystems from three biogeographic provinces of Mexico and one tropical province in the USA to investigate the phylogenetic and taxonomic diversity of Clavulina in the region. Nine new species-level clades were discovered, two of which are proposed as new species (C. arboreiparva and C. tuxtlasana). Specimens of C. floridana recently collected in Florida were included in our analyses, for which a modern description is provided. In addition, C. floridana is a new record for Mexico. The diversity of Clavulina in tropical North America is comparable to that found in lowland tropical South America. However, some of the species found in tropical deciduous forests produce small, rare, and inconspicuous basidiomata, which easily go unnoticed, and therefore are poorly represented in collections. Many species remain undescribed in tropical regions of North America.

Research Note: Demographic Change on the United States Coast, 2020-2100.

Prospective demographic information of the United States is limited to national-level analyses and subnational analyses of the total population. With nearly 40% of the U.S. population being residents of coastal areas, understanding the anticipated demographic changes in coastal counties is important for long-range planning purposes. In this research note, we use long-range, county-level population projections based on a simplified cohort-component method to discuss demographic changes by age, sex, and race and ethnicity for coastal counties between 2020 and the end of the century, and we compare these changes to inland counties. Presently, coastal counties are statistically significantly different from inland counties by race and ethnicity (more diverse) and sex (more women) but not by age, yet by 2025, we expect coastal counties to become significantly older than inland counties. We note several important trajectories of predicted demographic outcomes in coastal counties across the remainder of the century: (1) the non-Hispanic White population is expected to decrease, both numerically and as a percentage of the population; (2) the population older than 65 is projected to increase, both numerically and as a percentage of the population; and (3) the ratio of women to men remains constant over the century at 1.03. These trends combine to suggest that the future U.S. coastline will likely be both increasingly diverse racially and ethnically and significantly older than it is today.

Housing unit and urbanization estimates for the continental U.S. in consistent tract boundaries, 1940-2019.

Subcounty housing unit counts are important for studying geo-historical patterns of (sub)urbanization, land-use change, and residential loss and gain. The most commonly used subcounty geographical unit for social research in the United States is the census tract. However, the changing geometries and historically incomplete coverage of tracts present significant obstacles for longitudinal analysis that existing datasets do not sufficiently address. Overcoming these barriers, we provide housing unit estimates in consistent 2010 tract boundaries for every census year from 1940 to 2010 plus 2019 for the entire continental US. Moreover, we develop an "urbanization year" indicator that denotes if and when tracts became "urbanized" during this timeframe. We produce these data by blending existing interpolation techniques with a novel procedure we call "maximum reabsorption." Conducting out-of-sample validation, we find that our hybrid approach generally produces more reliable estimates than existing alternatives. The final dataset, Historical Housing Unit and Urbanization Database 2010 (HHUUD10), has myriad potential uses for research involving housing, population, and land-use change, as well as (sub)urbanization.

Evaluation of pharmacogenomics and hepatic nuclear imaging-related covariates by population pharmacokinetic models of irinotecan and its metabolites.

BACKGROUND: Body surface area (BSA)-based dosing of irinotecan (IR) does not account for its pharmacokinetic (PK) and pharmacodynamic (PD) variabilities. Functional hepatic nuclear imaging (HNI) and excretory/metabolic/PD pharmacogenomics have shown correlations with IR disposition and toxicity/efficacy. This study reports the development of a nonlinear mixed-effect population model to identify pharmacogenomic and HNI-related covariates that impact on IR disposition to support dosage optimization. METHODS: Patients had advanced colorectal cancer treated with IR combination therapy. Baseline blood was analysed by Affymetrix DMET™ Plus Array and, for PD, single nucleotide polymorphisms (SNPs) by Sanger sequencing. For HNI, patients underwent 99mTc-IDA hepatic imaging, and data was analysed for hepatic extraction/excretion parameters. Blood was taken for IR and metabolite (SN38, SN38G) analysis on day 1 cycle 1. Population modelling utilised NONMEM version 7.2.0, with structural PK models developed for each moiety. Covariates include patient demographics, HNI parameters and pharmacogenomic variants. RESULTS: Analysis included (i) PK data: 32 patients; (ii) pharmacogenomic data: 31 patients: 750 DMET and 22 PD variants; and (iii) HNI data: 32 patients. On initial analysis, overall five SNPs were identified as significant covariates for CLSN38. Only UGT1A3_c.31 T > C and ABCB1_c.3435C > T were included in the final model, whereby CLSN38 reduced from 76.8 to 55.1%. CONCLUSION: The identified UGT1A3_c.31 T > C and ABCB1_c.3435C > T variants, from wild type to homozygous, were included in the final model for SN38 clearance.

Assessing population exposure to coastal flooding due to sea level rise.

The exposure of populations to sea-level rise (SLR) is a leading indicator assessing the impact of future climate change on coastal regions. SLR exposes coastal populations to a spectrum of impacts with broad spatial and temporal heterogeneity, but exposure assessments often narrowly define the spatial zone of flooding. Here we show how choice of zone results in differential exposure estimates across space and time. Further, we apply a spatio-temporal flood-modeling approach that integrates across these spatial zones to assess the annual probability of population exposure. We apply our model to the coastal United States to demonstrate a more robust assessment of population exposure to flooding from SLR in any given year. Our results suggest that more explicit decisions regarding spatial zone (and associated temporal implication) will improve adaptation planning and policies by indicating the relative chance and magnitude of coastal populations to be affected by future SLR.

Time coding in rat dorsolateral striatum.

To assess the role of dorsolateral striatum (DLS) in time coding, we recorded neuronal activity in rats tasked with comparing the durations of two sequential vibrations. Bayesian decoding of population activity revealed a representation of the unfolding of the trial across time. However, further analyses demonstrated a distinction between the encoding of trial time and perceived time. First, DLS did not show a privileged representation of the stimulus durations compared with other time spans. Second, higher intensity vibrations were perceived as longer; however, time decoded from DLS was unaffected by vibration intensity. Third, DLS did not encode stimulus duration differently on correct versus incorrect trials. Finally, in rats trained to compare the intensities of two sequential vibrations, stimulus duration was encoded even though it was a perceptually irrelevant feature. These findings lead us to posit that temporal information is inherent to DLS activity irrespective of the rat's ongoing percept.

How we do it: 'tonsil swabs please' - an alternative use in open neck surgery.

BACKGROUND: Thyroid and parathyroid surgery often involves the use of heated instruments for dissection. Whilst these are beneficial, accidental thermal damage to the exposed skin edges can occur, resulting in an unsatisfactory cosmetic outcome. Tonsil swabs can be used in head and neck surgery intra-operatively to control bleeding. This paper describes an alternative use for them in protecting wound edges during the procedure. METHOD: Damp tonsil swabs are sutured onto the wound edges after the initial skin incision. They remain present for the duration of the surgery and are removed at the time of skin closure. RESULTS: The tonsil swabs provide protection and help avoid accidental injury to the skin. No complications with this technique have been experienced. CONCLUSION: This paper describes a simple, effective and practical technique for protecting the skin during neck procedures using resources readily available in a standard ENT operating theatre.

Conserved visual capacity of rats under red light.

Recent studies examine the behavioral capacities of rats and mice with and without visual input, and the neuronal mechanisms underlying such capacities. These animals are assumed to be functionally blind under red light, an assumption that might originate in the fact that they are dichromats who possess ultraviolet and green cones, but not red cones. But the inability to see red as a color does not necessarily rule out form vision based on red light absorption. We measured Long-Evans rats' capacity for visual form discrimination under red light of various wavelength bands. Upon viewing a black and white grating, they had to distinguish between two categories of orientation: horizontal and vertical. Psychometric curves plotting judged orientation versus angle demonstrate the conserved visual capacity of rats under red light. Investigations aiming to explore rodent physiological and behavioral functions in the absence of visual input should not assume red-light blindness.

The Effect of Fermentation of High- or Low-Tannin Fava Bean on Glucose Tolerance, Body Weight, Cardiovascular Function, and Blood Parameters in Dogs After 7 Days of Feeding: Comparison With Commercial Diets With Normal vs. High Protein.

Fava bean, which is available in high- and low-tannin varieties, is not an approved pet food ingredient and was not included in the "assumed to be safe" category based on its ability to cause favism and hemolytic anemia in susceptible humans. The effects of 7-day feeding of test canine diets containing moderate protein (~27%) were compared with two control commercial diets with normal (NP, grain-containing, ~25% protein) or high protein (HP, grain-free, ~41% protein). Fava bean diets were formulated either with or without Candida utilis fermentation processing to reduce antinutritional factors. Glucose tolerance, body weight, cardiovascular function, and blood parameters were investigated in beagles fed the NP or HP diets or a randomized, crossover, 2 × 2 Latin square design of the fava bean diets: unfermented high-tannin (UF-HT), fermented high-tannin (FM-HT), unfermented low-tannin (UF-LT), and fermented low-tannin (FM-LT). After 7 days, HP decreased red blood cells (RBC) (P < 0.05) compared with NP, while FM increased RBC compared with UF. HP increased blood bicarbonate, calcium, phosphorus, urea, cholesterol, and albumin:globulin ratio while decreasing bilirubin, liver enzymes, and total protein. Sodium:potassium ratio was increased in UF-HT, decreased in FM-HT, and intermediate in LT regardless of fermentation. Blood phosphorus was increased in HT. Blood amylase was increased in FM-HT and decreased in FM-LT, being intermediate in UF regardless of fava bean variety. Blood direct bilirubin was decreased in HT regardless of fermentation. Of note, left ventricular end-systolic volume and cardiac output were increased in NP compared with HP-fed dogs, but were normal and had no significant differences among the fava bean diets. As expected, plasma taurine, cystine, and cysteine levels were increased in HP- compared with NP-fed dogs. Plasma cysteine levels were increased in HT- compared with LT-fed dogs and in FM- compared with UF-fed dogs. Taken together, these results show that fava bean appears to be safe as a dog food ingredient at least in the short term, and its nutritional value appears improved by fermentation. Moreover, blood chemistry parameters and cardiovascular function were impacted by protein content which merits further investigation with longer term feeding trials.

Pharmacogenomics and functional imaging to predict irinotecan pharmacokinetics and pharmacodynamics: the predict IR study.

PURPOSE: Irinotecan (IR) displays significant PK/PD variability. This study evaluated functional hepatic imaging (HNI) and extensive pharmacogenomics (PGs) to explore associations with IR PK and PD (toxicity and response). METHODS: Eligible patients (pts) suitable for Irinotecan-based therapy. At baseline: (i) PGs: blood analyzed by the Affymetrix-DMET™-Plus-Array (1936 variants: 1931 single nucleotide polymorphisms [SNPs] and 5 copy number variants in 225 genes, including 47 phase I, 80 phase II enzymes, and membrane transporters) and Sanger sequencing (variants in HNF1A, Topo-1, XRCC1, PARP1, TDP, CDC45L, NKFB1, and MTHFR), (ii) HNI: pts given IV 250 MBq-99mTc-IDA, data derived for hepatic extraction/excretion parameters (CLHNI, T1/2-HNI, 1hRET, HEF, Td1/2). In cycle 1, blood was taken for IR analysis and PK parameters were derived by non-compartmental methods. Associations were evaluated between HNI and PGs, with IR PK, toxicity, objective response rate (ORR) and progression-free survival (PFS). RESULTS: N = 31 pts. The two most significant associations between PK and PD with gene variants or HNI parameters (P < 0.05) included: (1) PK: SN38-Metabolic Ratio with CLHNI, 1hRET, (2) Grade 3+ diarrhea with SLC22A2 (rs 316019), GSTM5 (rs 1296954), (3) Grade 3+ neutropenia with CLHNI, 1hRET, SLC22A2 (rs 316019), CYP4F2 (rs2074900) (4) ORR with ALDH2 (rs 886205), MTHFR (rs 1801133). (5) PFS with T1/2-HNI, XDH (rs 207440), and ABCB11 (rs 4148777). CONCLUSIONS: Exploratory associations were observed between Irinotecan PK/PD with hepatic functional imaging and extensive pharmacogenomics. Further work is required to confirm and validate these findings in a larger cohort of patients. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY (ANZCTR) NUMBER: ACTRN12610000897066, Date registered: 21/10/2010.

A sensory integration account for time perception.

The connection between stimulus perception and time perception remains unknown. The present study combines human and rat psychophysics with sensory cortical neuronal firing to construct a computational model for the percept of elapsed time embedded within sense of touch. When subjects judged the duration of a vibration applied to the fingertip (human) or whiskers (rat), increasing stimulus intensity led to increasing perceived duration. Symmetrically, increasing vibration duration led to increasing perceived intensity. We modeled real spike trains recorded from vibrissal somatosensory cortex as input to dual leaky integrators-an intensity integrator with short time constant and a duration integrator with long time constant-generating neurometric functions that replicated the actual psychophysical functions of rats. Returning to human psychophysics, we then confirmed specific predictions of the dual leaky integrator model. This study offers a framework, based on sensory coding and subsequent accumulation of sensory drive, to account for how a feeling of the passage of time accompanies the tactile sensory experience.

Spine Surgery in Italy in the COVID-19 Era: Proposal for Assessing and Responding to the Regional State of Emergency.

In December 2019, coronavirus disease 2019 (COVID-19) was discovered in Wuhan, Hubei province, from where it spread rapidly worldwide. COVID-19 characteristics (increased infectivity, rapid spread, and general population susceptibility) pose a great challenge to hospitals. Infectious disease, pulmonology, and intensive care units have been strengthened and expanded. All other specialties have been compelled to suspend or reduce clinical and elective surgical activities. The profound effects on spine surgery call for systematic approaches to optimizing the diagnosis and treatment of spinal diseases. Based on the experience of one Italian region, we draw an archetype for assessing the current and predicted level of stress in the health care system, with the aim of enabling hospitals to make better decisions during the pandemic. Further, we provide a framework that may help guide strategies for adapting surgical spine care to the conditions of epidemic surge.

State-Dependent Changes in Perception and Coding in the Mouse Somatosensory Cortex.

An animal's behavioral state is reflected in the dynamics of cortical population activity and its capacity to process sensory information. To better understand the relationship between behavioral states and information processing, mice are trained to detect varying amplitudes of whisker-deflection under two-photon calcium imaging. Layer 2/3 neurons in the vibrissal primary somatosensory cortex are imaged across different behavioral states, defined based on detection performance (low to high-state) and pupil diameter. The neurometric curve in each behavioral state mirrors the corresponding psychometric performance, with calcium signals predictive of the animal's choice. High behavioral states are associated with lower network synchrony, extending over shorter cortical distances. The decrease in correlation across neurons in high state results in enhanced information transmission capacity at the population level. The observed state-dependent changes suggest that the coding regime within the first stage of cortical processing may underlie adaptive routing of relevant information through the sensorimotor system.