ABSTRACT
The brain's remarkable properties arise from the collective activity of millions of neurons. Widespread application of dimensionality reduction to multi-neuron recordings implies that neural dynamics can be approximated by low-dimensional "latent" signals reflecting neural computations. However, can such low-dimensional representations truly explain the vast range of brain activity, and if not, what is the appropriate resolution and scale of recording to capture them? Imaging neural activity at cellular resolution and near-simultaneously across the mouse cortex, we demonstrate an unbounded scaling of dimensionality with neuron number in populations up to 1 million neurons. Although half of the neural variance is contained within sixteen dimensions correlated with behavior, our discovered scaling of dimensionality corresponds to an ever-increasing number of neuronal ensembles without immediate behavioral or sensory correlates. The activity patterns underlying these higher dimensions are fine grained and cortex wide, highlighting that large-scale, cellular-resolution recording is required to uncover the full substrates of neuronal computations.
Subject(s)
Neurons , Animals , Neurons/physiology , Mice , Cell Count , Models, Neurological , Cerebral Cortex/cytology , Cerebral Cortex/physiology , Action Potentials/physiology , Male , Mice, Inbred C57BLABSTRACT
Objective: To map ophthalmologist locations and surgical practices as they vary sub-nationally within Honduras to maximize the impact of efforts to develop cataract surgical capacity. Methods: An anonymous survey was sent to all Honduran ophthalmologists with questions on surgical volume, department-level location, type of facility in which they work, surgical methods, and age. Surgical volume, population, and poverty data sourced through the Oxford Poverty Human Development Initiative were mapped at the department level, and cataract surgical rates (CSR; surgeries per million population per year) were calculated and mapped. Results: Sixty-one of the 102 Honduran ophthalmologists contacted responded. Of those, 85% perform cataract surgery, and 49% work at least part time in a non-profit or governmental facility. Honduras has fewer surgical ophthalmologists per million than the global average, and though national CSR appears to be increasing, it varies significantly between departments. The correlation between CSR and poverty is complex, and outliers provide valuable insights. Conclusion: Mapping ophthalmological surgical practices as they relate to population and poverty at a sub-national level provides important insights into geographic trends in the need for and access to eye care. Such insights can be used to guide efficient and effective development of cataract surgical capacity.
Subject(s)
Cataract , Ophthalmology , Physicians , Humans , Honduras/epidemiology , Cataract/epidemiology , WorkforceABSTRACT
PURPOSE: To quantitatively assess postoperative rotational stability and visual acuity with the DFT/DATx15 extended depth of focus (EDOF) toric intraocular lens (IOL). METHODS: In this prospective case series, thirty-five patients with a calculated IOL power between + 15.0 D and + 25.0 D, corneal astigmatism between 0.75 D and 2.25 D, and no significant ocular pathology underwent cataract surgery. Primary outcome was rotational stability of the IOL at 1 month post-operatively. Secondary outcomes included residual refractive astigmatism, absolute residual astigmatism prediction error, and monocular distance and intermediate visual acuities. RESULTS: Mean absolute postoperative IOL rotation was 1.1 ± 0.2 degrees, with no rotation of more than 3 degrees at the final visit. Monocular mean best spectacle-corrected distance visual acuity (BSCDVA) improved from logMAR 0.27 ± 0.030 to 0.078 ± 0.017 (P < .001). Monocular uncorrected distance visual acuity (UCDVA) improved from 0.93 ± 0.096 to 0.18 ± 0.022 (P < .001). Best spectacle-corrected intermediate visual acuity (DSCIVA) was 0.17 ± 0.025, and uncorrected intermediate visual acuity (UCIVA) was 0.27 ± 0.040. Residual regular astigmatic refractive error was 0.21 ± 0.047 D. CONCLUSIONS: The toric DFT/DATx15 EDOF lens showed excellent rotational stability and effective and predictable correction of astigmatism. Its refractive outcomes and safety profile were similar to those identified in prior studies of the non-toric DFT/DAT015 EDOF IOL. A small difference in monocular BSCDVA, of uncertain clinical significance, was found when comparing these outcomes with prior DFT/DAT015 data. The trial was retrospectively registered on November 5, 2021 (TRN ââNCT05119127).
In cataract surgery, the natural lens of the eye is replaced with an artificial lens implant. In many cases, the patient's glasses prescription in the operated eye can be reduced or eliminated through careful choice of a lens implant. There are many types of lens implants available. Toric lens implants are used to reduce one component of the glasses prescription, called regular astigmatism (or often just "astigmatism"). To maintain the full astigmatism-reducing effect of the toric lens, the lens implant must not rotate significantly within the eye after the surgery. The DFT/DATx15 (Vivity™) is a relatively new type of lens implant designed to offer patients good spectacle-free vision at far distances and improved glasses-free vision at arm's length ("intermediate") compared to a more traditional lens implant that is designed to maximize spectacle-free distance vision only. This study reports one surgeon's experience with measuring the amount of rotation of DFT/DATx15 lenses after surgery. This study also assessed the ability of the DFT/DATx15 to reduce regular astigmatism and improve glasses-free vision at far and intermediate distances. The results show that this lens did not rotate significantly within the eye and was effective at reducing the regular astigmatism as intended.
Subject(s)
Astigmatism , Cataract , Lenses, Intraocular , Phacoemulsification , Humans , Lens Implantation, Intraocular , Astigmatism/surgery , Astigmatism/complications , Prospective Studies , Refraction, Ocular , Cataract/complicationsABSTRACT
Prior research has shown that Social Anxiety Disorder (SAD) is associated with significantly diminished positive affect (PA). Few studies have examined PA reactivity to pleasant experimental stimuli in individuals with SAD and whether emotional responses might be moderated by social context. Here, we investigated repeated measures of PA reactivity among individuals with SAD (n = 46) and healthy controls (HC; n = 39) in response to standardized neutral images, pleasant music, and social versus nonsocial guided imagery. Primary analyses revealed that SAD and HC participants did not differ in their PA reactivity when PA was conceptualized as a unitary construct. Exploratory analyses examining discrete subfacets of PA revealed potential deficits for SAD participants in relaxed and content PA, but not activated PA. Although participants with SAD reported relatively lower levels of relaxed and content PA overall compared with controls, they exhibited normal increases in all PA subfacets in response to pleasant music as well as pleasant social and nonsocial stimuli. These findings support a more nuanced conclusion about PA deficits in SAD than is described in the extant literature, suggesting that detecting PA deficits in SAD may depend upon how PA is conceptualized, evoked, and measured. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
Subject(s)
Music , Phobia, Social , Humans , Phobia, Social/psychology , Emotions/physiology , Imagery, Psychotherapy , Anxiety/psychologyABSTRACT
What drives positive affective and interpersonal experiences during social interaction? Undergraduates with high (nâ¯=â¯63) or low (nâ¯=â¯56) trait social anxiety (SA) were paired with unfamiliar low SA partners in a 45-minute conversation task. Throughout the task, participants and their conversation partners completed measures of affiliative goals, affect, curiosity, authenticity, and attentional focus. Both affective and interpersonal outcomes were assessed. Dyadic analyses revealed that participants' affiliative goals during the social interaction predicted positive outcomes for both themselves and their partners, although the link between affiliative goals and positive affect was weaker for participants with high SA. Mediation analyses demonstrated that adopting affiliative goals may promote more positive outcomes by increasing participants' curiosity and felt authenticity. Taken together, results illuminate the pathways through which people with varying levels of trait SA may derive interpersonally generated positive affect and positive social outcomes, with implications for clinical theory and practice.
Subject(s)
Exploratory Behavior , Interpersonal Relations , Anxiety , Emotions , Humans , Social InteractionABSTRACT
Objectives: To determine if mycophenolate mofetil reduces the incidence and severity of granulation tissue in-growth in canine tracheal stent patients. Study design: Randomized clinical trial. Animals: 111 dogs from the hospital population. Methods: Client-owned dogs that received an endoluminal self-expanding tracheal stent for canine tracheal collapse between 2014 and 2020 were randomly assigned into one of two treatment groups. Control group medication protocol consisted of prednisone 0.5 mg/kg PO BID/SID/EOD × 30 days, hydrocodone 0.25 mg/kg PO TID × 30 days, and cefovecin 8 mg/kg SQ post-placement. Mycophenolate group medication protocol was identical to the control group medication protocol with the addition of mycophenolate mofetil 10 mg/kg PO BID × 30 days, SID for life. Recheck tracheoscopy was performed at 1, 3, and 6 months post-stent placement. Presence and severity of granulation tissue were determined by tracheoscopy and were recorded as a percentage of tracheal lumen obstruction by blinded evaluators (none present, <25%, >25-50%, and >50%). Results: At none of the three time points was there a statistically significant difference in grade between controls and those receiving mycophenolate (p = 0.467, p = 0.330, and p = 0.410). Conclusions and Clinical Significance: Our results suggest that mycophenolate can be safely given to these patients but do not support that its administration will reduce the incidence and severity of granulation tissue. Although a difference was observed in the severity of granulation tissue between the two groups, loss to follow-up may have influenced conclusions. A larger study would be warranted to further evaluate the effect of mycophenolate on the development of granulation tissue.
ABSTRACT
Two-photon microscopy has enabled high-resolution imaging of neuroactivity at depth within scattering brain tissue. However, its various realizations have not overcome the tradeoffs between speed and spatiotemporal sampling that would be necessary to enable mesoscale volumetric recording of neuroactivity at cellular resolution and speed compatible with resolving calcium transients. Here, we introduce light beads microscopy (LBM), a scalable and spatiotemporally optimal acquisition approach limited only by fluorescence lifetime, where a set of axially separated and temporally distinct foci record the entire axial imaging range near-simultaneously, enabling volumetric recording at 1.41 × 108 voxels per second. Using LBM, we demonstrate mesoscopic and volumetric imaging at multiple scales in the mouse cortex, including cellular-resolution recordings within ~3 × 5 × 0.5 mm volumes containing >200,000 neurons at ~5 Hz and recordings of populations of ~1 million neurons within ~5.4 × 6 × 0.5 mm volumes at ~2 Hz, as well as higher speed (9.6 Hz) subcellular-resolution volumetric recordings. LBM provides an opportunity for discovering the neurocomputations underlying cortex-wide encoding and processing of information in the mammalian brain.
Subject(s)
Cerebral Cortex/cytology , Microscopy/methods , Animals , Calcium/analysis , Female , Lasers , Male , Mice , Mice, Inbred C57BL , Microspheres , Neurons/cytologyABSTRACT
We discuss a methodology to generate and study knockout gene-edited human intestinal organoids. We describe the generation of knockout human embryonic stem cell lines that we then differentiate into mature human intestinal organoid tissue in Matrigel using several growth factors. We also discuss a pair of assays that can be used to study the integrity of the intestinal epithelial barrier of the human intestinal organoids under inflammatory stress conditions.
Subject(s)
Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Intestinal Mucosa/cytology , Organoids/cytology , Organoids/metabolism , CRISPR-Cas Systems/genetics , Cells, Cultured , Gene Editing , Humans , TransfectionABSTRACT
The enteric nervous system (ENS) represents a vast network of neuronal and glial cell types that develops entirely from migratory neural crest (NC) progenitor cells. Considerable improvements in the understanding of the molecular mechanisms underlying NC induction and regional specification have recently led to the development of a robust method to re-create the process in vitro using human pluripotent stem cells (hPSCs). Directing the fate of hPSCs toward the enteric NC (ENC) results in an accessible and scalable in vitro model of ENS development. The application of hPSC-derived enteric neural lineages provides a powerful platform for ENS-related disease modeling and drug discovery. Here we present a detailed protocol for the induction of a regionally specific NC intermediate that occurs over the course of a 15-d interval and is an effective source for the in vitro derivation of functional enteric neurons (ENs) from hPSCs. Additionally, we introduce a new and improved protocol that we have developed to optimize the protocol for future applications in regenerative medicine, in which components of undefined activity have been replaced with fully defined culture conditions. This protocol provides access to a broad range of human ENS lineages within a 30-d period.
Subject(s)
Cell Culture Techniques , Enteric Nervous System/cytology , Intestine, Small/cytology , Neural Crest/cytology , Neurons/cytology , Pluripotent Stem Cells/cytology , Antigens, CD/genetics , Antigens, CD/metabolism , Biomarkers/metabolism , Cell Differentiation , Cell Lineage/physiology , Enteric Nervous System/metabolism , Gene Expression , Genes, Reporter , Homeodomain Proteins/genetics , Homeodomain Proteins/metabolism , Humans , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , Intestine, Small/metabolism , Neural Crest/metabolism , Neurons/metabolism , PAX3 Transcription Factor/genetics , PAX3 Transcription Factor/metabolism , Pluripotent Stem Cells/metabolism , Regenerative Medicine/methodsABSTRACT
Estimations of tropical insect diversity generally suffer from lack of known groups or faunas against which extrapolations can be made, and have seriously underestimated the diversity of some taxa. Here we report the intensive inventory of a four-hectare tropical cloud forest in Costa Rica for one year, which yielded 4332 species of Diptera, providing the first verifiable basis for diversity of a major group of insects at a single site in the tropics. In total 73 families were present, all of which were studied to the species level, providing potentially complete coverage of all families of the order likely to be present at the site. Even so, extrapolations based on our data indicate that with further sampling, the actual total for the site could be closer to 8000 species. Efforts to completely sample a site, although resource-intensive and time-consuming, are needed to better ground estimations of world biodiversity based on limited sampling.
ABSTRACT
Individuals with social anxiety disorder (SADs; nâ¯=â¯41) and healthy controls (HCs; nâ¯=â¯40) were administered the Waterloo Images and Memories Interview, in which they described mental images that they tend to experience in both anxiety-provoking and non-anxiety-provoking social situations. Participants then recalled, in as much detail as possible, specific autobiographical memories of salient aversive and non-aversive social experiences that they believed led to the formation of these images. Audio-recorded memory narratives were transcribed and coded based on the procedure of the Autobiographical Interview, which provides a precise measure of the degree of episodic detail contained within each memory. Participants also rated the subjective properties of their recalled memories. Results revealed that participants across the two groups retrieved equivalent rates of both aversive and non-aversive social memories. However, SAD participants' memories of aversive events contained significantly more episodic detail than those of HCs, suggesting that they may be more highly accessible. Moreover, participants with SAD appraised their memories of aversive experiences as more distressing and intrusive than HCs, and perceived them as having a significantly greater influence on their self-perception. In contrast, no group differences were observed for memories of non-aversive events. Findings have the potential to shed new light on autobiographical memory in SAD, with implications for psychotherapeutic intervention.
Subject(s)
Anxiety Disorders/psychology , Anxiety/psychology , Mental Recall/physiology , Adolescent , Adult , Female , Humans , Male , Memory, Episodic , Phobia, Social/psychology , Social Behavior , Young AdultABSTRACT
Pilot and open trials suggest that imagery-enhanced group cognitive behaviour therapy (CBT) is highly effective for social anxiety disorder (SAD). However, before being considered reliable and generalisable, the effects of the intervention need to be replicated by clinicians in a setting that is independent of the protocol developers. The current study compared outcomes from clients with a principal diagnosis of SAD at the Australian clinic where the protocol was developed (nâ¯=â¯123) to those from an independent Canadian clinic (nâ¯=â¯46) to investigate whether the large effects would generalise. Trainee clinicians from the independent clinic ran the groups using the treatment protocol without any input from its developers. The treatment involved 12 2-h group sessions plus a one-month follow-up. Treatment retention was comparable across both clinics (74% vs. 78%, ≥9/12 sessions) and the between-site effect size was very small and non-significant on the primary outcome (social interaction anxiety, dâ¯=â¯0.09, pâ¯=â¯.752). Within-group effect sizes were very large in both settings (dsâ¯=â¯2.05 vs. 2.19), and a substantial minority (41%-44%) achieved clinically significant improvement at follow-up. Replication of treatment effects within an independent clinic and with trainee clinicians increases confidence that outcomes are generalisable.
Subject(s)
Cognitive Behavioral Therapy/methods , Imagery, Psychotherapy/methods , Phobia, Social/therapy , Adolescent , Adult , Female , Humans , Male , Phobia, Social/psychology , Treatment Outcome , Young AdultABSTRACT
Study of all flies (Diptera) collected for one year from a four-hectare (150 x 266 meter) patch of cloud forest at 1,600 meters above sea level at Zurquí de Moravia, San José Province, Costa Rica (hereafter referred to as Zurquí), revealed an astounding 4,332 species. This amounts to more than half the number of named species of flies for all of Central America. Specimens were collected with two Malaise traps running continuously and with a wide array of supplementary collecting methods for three days of each month. All morphospecies from all 73 families recorded were fully curated by technicians before submission to an international team of 59 taxonomic experts for identification. Overall, a Malaise trap on the forest edge captured 1,988 species or 51% of all collected dipteran taxa (other than of Phoridae, subsampled only from this and one other Malaise trap). A Malaise trap in the forest sampled 906 species. Of other sampling methods, the combination of four other Malaise traps and an intercept trap, aerial/hand collecting, 10 emergence traps, and four CDC light traps added the greatest number of species to our inventory. This complement of sampling methods was an effective combination for retrieving substantial numbers of species of Diptera. Comparison of select sampling methods (considering 3,487 species of non-phorid Diptera) provided further details regarding how many species were sampled by various methods. Comparison of species numbers from each of two permanent Malaise traps from Zurquí with those of single Malaise traps at each of Tapantí and Las Alturas, 40 and 180 km distant from Zurquí respectively, suggested significant species turnover. Comparison of the greater number of species collected in all traps from Zurquí did not markedly change the degree of similarity between the three sites, although the actual number of species shared did increase. Comparisons of the total number of named and unnamed species of Diptera from four hectares at Zurquí is equivalent to 51% of all flies named from Central America, greater than all the named fly fauna of Colombia, equivalent to 14% of named Neotropical species and equal to about 2.7% of all named Diptera worldwide. Clearly the number of species of Diptera in tropical regions has been severely underestimated and the actual number may surpass the number of species of Coleoptera. Various published extrapolations from limited data to estimate total numbers of species of larger taxonomic categories (e.g., Hexapoda, Arthropoda, Eukaryota, etc.) are highly questionable, and certainly will remain uncertain until we have more exhaustive surveys of all and diverse taxa (like Diptera) from multiple tropical sites. Morphological characterization of species in inventories provides identifications placed in the context of taxonomy, phylogeny, form, and ecology. DNA barcoding species is a valuable tool to estimate species numbers but used alone fails to provide a broader context for the species identified.
Subject(s)
Diptera , Animals , Biodiversity , Central America , Colombia , Costa Rica , ForestsABSTRACT
OBJECTIVES: Ultrasound serves an important role in the prenatal diagnosis of fetal structural anomalies. Recently, there has been increased use of teleultrasound protocols. We aimed to evaluate the sensitivity and accuracy of teleultrasound. METHODS: We conducted an Institutional Review Board-approved retrospective cohort study determining the sensitivity and accuracy of teleultrasound. In addition, we evaluated the number of ultrasound examinations required to complete an anatomic survey. Only ultrasound examinations performed for anatomic surveys were included. Studies were excluded if performed before 16 completed weeks' gestation, if they had multiple gestations, or for reasons other than anatomy (eg, Doppler studies and fluid assessment). Prenatal diagnoses were compared with postnatal diagnoses obtained from a robust mandatory birth defects surveillance program that records all birth defects in the entire state, from deliveries before 20 weeks' gestation through infants up to 2 years of age. RESULTS: A total of 2499 studies were evaluated; 2368 were included. The teleultrasound cohort had a congenital anomaly prevalence of 5.66%. The sensitivity of teleultrasound was 57.46%; the specificity was 98.21%; and the accuracy was 95.9%. Anatomic surveys were completed after 1 visit in 82% of patients, whereas 63% and 61% of the remaining patients required 2 and 3 visits, respectively. CONCLUSIONS: Teleultrasound for prenatal diagnosis has similar sensitivity and accuracy as the published literature for on-site ultrasound. Further studies are needed to compare the sensitivity and accuracy within the same population and further validate this potentially cost-saving modality.
Subject(s)
Congenital Abnormalities/diagnostic imaging , Congenital Abnormalities/embryology , Telemedicine/methods , Ultrasonography, Prenatal/methods , Adult , Cohort Studies , Female , Humans , Pregnancy , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Telemedicine/standards , Ultrasonography, Prenatal/standardsABSTRACT
High-quality research in clinical psychology often depends on recruiting adequate samples of clinical participants with formally diagnosed difficulties. This challenge is readily met within the context of a large treatment center, but many clinical researchers work in academic settings that do not feature a medical school, hospital connections, or an in-house clinic. This article describes the model we developed at the University of Waterloo Centre for Mental Health Research for identifying and recruiting large samples of people from local communities with diagnosable mental health problems who are willing to participate in research but for whom treatment services are not offered. We compare the diagnostic composition, symptom profile, and demographic characteristics of our participants with treatment-seeking samples recruited from large Canadian and American treatment centers. We conclude that the Anxiety Studies Division model represents a viable and valuable method for recruiting clinical participants from the community for psychopathology research.
ABSTRACT
World representatives of the genus Arganthomyza Rohácek, 2009 (Diptera, Anthomyzidae) are reviewed, keyed and their relationships are discussed on the basis of a phylogenetic analysis of morphological characters. The Nearctic species of Arganthomyza are revised, described and illustrated, and first data about their biology and distribution are given. Five new species, A. carbo sp. n. (Canada, USA), A. acuticuspis sp. n. (USA), A. bivittata sp. n. (Canada, USA), A. duplex sp. n. (Canada, USA) and A. disjuncta sp. n. (Canada, USA) are described and A. socculata (Zetterstedt, 1847) is newly recorded from the Nearctic Region (USA: Alaska). Based on the phylogenetic analysis, four main clades/species groups are recognized within Arganthomyza, represented by the following species: A. barbarista Rohácek, 2009 (A. barbarista group); A. setiplanta (Rohácek, 1987), A. versitheca Rohácek, 2009 and A. carbo sp. n. (A. setiplanta group); A. acuticuspis sp. n., A. bivittata sp. n. and A. duplex sp. n. (A. duplex group); A. disjuncta sp. n. and A. socculata (Zetterstedt) (A. socculata group). Considering the contemporary distribution and relationships of Arganthomyza species, it is hypothesized that the A. barbarista group and A. setiplanta group originated in East Asia while the A. duplex group and the A. socculata group each has its origin in the Nearctic Region.
Subject(s)
Diptera/anatomy & histology , Diptera/classification , Animals , Female , Male , North America , PhylogenyABSTRACT
PREMISE OF THE STUDY: Lateral roots, responsible for water and nutrient uptake, maintain nonvertical angles throughout development. Soil phosphate is one limiting nutrient for plant growth that is known to induce changes to root system architecture, such as increased lateral root formation. This study seeks to determine whether phosphate concentration affects lateral root orientation in addition to its previously described influences on root architecture. METHODS: Images of intact Arabidopsis root systems were recorded for 24 h, and lateral root tip angles were measured for wild-type and mutant pgm-1 and pin3-1 roots on a full or low phosphate medium. Setpoint angles of unstimulated root systems were determined, as were gravitropic responses of lateral roots over time. KEY RESULTS: The root system setpoint angles of wild-type and mutant pin3-1 roots showed a shift toward a more vertical orientation on low orthophosphate (Pi) medium. The gravitropic responses of both pgm-1 and pin3-1 roots on low Pi medium was elevated relative to control Pi medium. Mutations in two phosphate transporters with high levels of expression in the root showed a gravitropic response similar to wild-type roots grown on low Pi, supporting a role for Pi status in regulating lateral root gravitropism. CONCLUSIONS: Lateral root orientation and gravitropism are affected by Pi status and may provide an important additional parameter for describing root responses to low Pi. The data also support the conclusion that gravitropic setpoint angle reacts to nutrient status and is under dynamic regulation.