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Knowledge of the status of ecosystems is vital to help develop and implement conservation strategies. This is particularly relevant to the Arctic where the need for biodiversity conservation and monitoring has long been recognised, but where issues of local capacity and logistic barriers make surveys challenging. This paper demonstrates how long-term monitoring programmes outside the Arctic can contribute to developing composite trend indicators, using monitoring of annual abundance and population-level reproduction of species of migratory Arctic-breeding waterbirds on their temperate non-breeding areas. Using data from the UK and the Netherlands, countries with year-round waterbird monitoring schemes and supporting relevant shares of Arctic-breeding populations of waterbirds, we present example multi-species abundance and productivity indicators related to the migratory pathways used by different biogeographical populations of Arctic-breeding wildfowl and wader species in the East Atlantic Flyway. These composite trend indicators show that long-term increases in population size have slowed markedly in recent years and in several cases show declines over, at least, the last decade. These results constitute proof of concept. Some other non-Arctic countries located on the flyways of Arctic-breeding waterbirds also annually monitor abundance and breeding success, and we advocate that future development of “Arctic waterbird indicators” should be as inclusive of data as possible to derive the most robust outputs and help account for effects of current changes in non-breeding waterbird distributions. The incorporation of non-Arctic datasets into assessments of the status of Arctic biodiversity is recognised as highly desirable, because logistic constraints in monitoring within the Arctic region limit effective population-scale monitoring there, in effect enabling “monitoring at a distance”.
The heterogeneity of chronic post-COVID neuropsychiatric symptoms (PCNPS), especially after infection by the Omicron strain, has not been adequately explored.
Aims
To explore the clustering pattern of chronic PCNPS in a cohort of patients having their first COVID infection during the ‘Omicron wave’ and discover phenotypes of patients based on their symptoms’ patterns using a pre-registered protocol.
Method
We assessed 1205 eligible subjects in Hong Kong using app-based questionnaires and cognitive tasks.
Results
Partial network analysis of chronic PCNPS in this cohort produced two major symptom clusters (cognitive complaint–fatigue and anxiety–depression) and a minor headache–dizziness cluster, like our pre-Omicron cohort. Participants with high numbers of symptoms could be further grouped into two distinct phenotypes: a cognitive complaint–fatigue predominant phenotype and another with symptoms across multiple clusters. Multiple logistic regression showed that both phenotypes were predicted by the level of pre-infection deprivation (adjusted P-values of 0.025 and 0.0054, respectively). The severity of acute COVID (adjusted P = 0.023) and the number of pre-existing medical conditions predicted only the cognitive complaint–fatigue predominant phenotype (adjusted P = 0.003), and past suicidal ideas predicted only the symptoms across multiple clusters phenotype (adjusted P < 0.001). Pre-infection vaccination status did not predict either phenotype.
Conclusions
Our findings suggest that we should pursue a phenotype-driven approach with holistic biopsychosocial perspectives in disentangling the heterogeneity under the umbrella of chronic PCNPS. Management of patients complaining of chronic PCNPS should be stratified according to their phenotypes. Clinicians should recognise that depression and anxiety cannot explain all chronic post-COVID cognitive symptoms.
Background: Our prior six-year review (n=2165) revealed 24% of patients undergoing posterior decompression surgeries (laminectomy or discectomy) sought emergency department (ED) care within three months post-surgery. We established an integrated Spine Assessment Clinic (SAC) to enhance patient outcomes and minimize unnecessary ED visits through pre-operative education, targeted QI interventions, and early post-operative follow-up. Methods: We reviewed 13 months of posterior decompression data (n=205) following SAC implementation. These patients received individualized, comprehensive pre-operative education and follow-up phone calls within 7 days post-surgery. ED visits within 90 days post-surgery were tracked using provincial databases and compared to our pre-SAC implementation data. Results: Out of 205 patients, 24 (11.6%) accounted for 34 ED visits within 90 days post-op, showing a significant reduction in ED visits from 24% to 11.6%, and decreased overall ED utilization from 42.1% to 16.6% (when accounting for multiple visits by the same patient). Early interventions including wound monitoring, outpatient bloodwork, and prescription adjustments for pain management, helped mitigate ED visits. Patient satisfaction surveys (n=62) indicated 92% were “highly satisfied” and 100% would recommend the SAC. Conclusions: The SAC reduced ED visits after posterior decompression surgery by over 50%, with pre-operative education, focused QI initiatives, and its individualized, proactive approach.
Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).
Aims
We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.
Method
Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.
Results
Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.
Conclusions
We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.
Recent theories have implicated inflammatory biology in the development of psychopathology and maladaptive behaviors in adolescence, including suicidal thoughts and behaviors (STB). Examining specific biological markers related to inflammation is thus warranted to better understand risk for STB in adolescents, for whom suicide is a leading cause of death.
Method:
Participants were 211 adolescent females (ages 9–14 years; Mage = 11.8 years, SD = 1.8 years) at increased risk for STB. This study examined the prospective association between basal levels of inflammatory gene expression (average of 15 proinflammatory mRNA transcripts) and subsequent risk for suicidal ideation and suicidal behavior over a 12-month follow-up period.
Results:
Controlling for past levels of STB, greater proinflammatory gene expression was associated with prospective risk for STB in these youth. Similar effects were observed for CD14 mRNA level, a marker of monocyte abundance within the blood sample. Sensitivity analyses controlling for other relevant covariates, including history of trauma, depressive symptoms, and STB prior to data collection, yielded similar patterns of results.
Conclusions:
Upregulated inflammatory signaling in the immune system is prospectively associated with STB among at-risk adolescent females, even after controlling for history of trauma, depressive symptoms, and STB prior to data collection. Additional research is needed to identify the sources of inflammatory up-regulation in adolescents (e.g., stress psychobiology, physiological development, microbial exposures) and strategies for mitigating such effects to reduce STB.
Household survey estimates of retirement income suffer from substantial underreporting which biases downward measures of elderly financial well-being. Using data from both the 2016 Current Population Survey Annual Social and Economic Supplement (CPS ASEC) and the Health and Retirement Study (HRS), matched with administrative records, we examine to what extent underreporting of retirement income affects key statistics: elderly reliance on social security benefits and poverty. We find that retirement income is underreported in both the CPS ASEC and the HRS. Consequently, the relative importance of social security income remains overstated – 53 percent of elderly beneficiaries in the CPS ASEC and 49 percent in the HRS rely on social security for the majority of their incomes compared to 42 percent in the administrative data. The elderly poverty rate is also overstated – 8.8 percent in the CPS ASEC and 7.4 percent in the HRS compared to 6.4 percent in the administrative data.
Marsupials give birth to immunologically naïve young after a relatively short gestation period compared with eutherians. Consequently, the joey relies significantly on maternal protection, which is the focus of the present review. The milk and the pouch environment are essential contributors to maternal protection for the healthy development of joeys. In this review, we discuss bioactive components found in the marsupial pouch and milk that form cornerstones of maternal protection. These bioactive components include immune cells, immunoglobulins, the S100 family of calcium-binding proteins, lysozymes, whey proteins, antimicrobial peptides and other immune proteins. Furthermore, we investigated the possibility of the presence of plurifunctional components in milk and pouches that are potentially bioactive. These compounds include caseins, vitamins and minerals, oligosaccharides, lipids and microRNAs. Where applicable, this review addresses variability in bioactive components during different phases of lactation, designed to fulfil the immunological needs of the growing pouch young. Yet, there are numerous additional research opportunities to pursue, including uncovering novel bioactive components and investigating their modes of action, dynamics, stability and ability to penetrate the gut epithelium to facilitate systemic effects.
Palmer amaranth with resistance to dicamba, glufosinate, and protoporphyrinogen oxidase inhibitors has been documented in several southern states. With extensive use of these and other herbicides in South Carolina, a survey was initiated in fall 2020 and repeated in fall 2021 and 2022 to determine the relative response of Palmer amaranth accessions to selected preemergence and postemergence herbicides. A greenhouse screening experiment was conducted in which accessions were treated with three preemergence (atrazine, S-metolachlor, and isoxaflutole) and six postemergence (glyphosate, thifensulfuron-methyl, fomesafen, glufosinate, dicamba, and 2,4-D) herbicides at the 1× and 2× use rates. Herbicides were applied shortly after planting (preemergence) or at the 2- to 4-leaf growth stage (postemergence). Percent survival was evaluated 5 to 14 d after application depending on herbicide activity. Sensitivity to atrazine preemergence was lower for 49 and 33 accessions out of 115 to atrazine applied preemergence at the 1× and 2× rate, respectively. Most of the accessions (90%) were controlled by isoxaflutole applied preemergence at the 1× rate. Response to S-metolachlor applied preemergence indicated that 34% of the Palmer amaranth accessions survived the 1× rate (>60% survival). Eleven accessions exhibited reduced sensitivity to fomesafen applied postemergence; however, these percentages were not different from the 0% survivor group. Glyphosate applied postemergence at the 1× rate did not control most accessions (79%). Palmer amaranth response to thifensulfuron-methyl applied postemergence varied across the accessions, with only 36% and 28% controlled at the 1× rate and 2× rate, respectively. All accessions were controlled by 2,4-D, dicamba, or glufosinate when they were applied postemergence. Palmer amaranth accessions from this survey exhibited reduced susceptibility to several herbicides commonly used in agronomic crops in South Carolina. Therefore, growers should use multiple management tactics to minimize the evolution of herbicide resistance in Palmer amaranth in South Carolina.
The increased severity and frequency of bushfires accompanying human-induced global warming have dire implications for biodiversity conservation. Here we investigate the response of a cryptic, cool-climate elapid, the mustard-bellied snake Drysdalia rhodogaster, to the extensive Black Summer fires of 2019/2020 in south-eastern Australia. The species is categorized as Least Concern on the IUCN Red List (last assessed in 2017), but because a large part of its range was burnt during the Black Summer and little was known about its ecology, D. rhodogaster was identified as a priority species for post-fire impact assessment. We evaluated three lines of evidence to assess the impact of the Black Summer fires on D. rhodogaster. Habitat suitability modelling indicated that c. 46% of the predicted range of the species was affected by bushfire. Field surveys conducted 9–36 months post-fire and collation of records from public databases submitted 0–24 months post-fire indicated that D. rhodogaster persisted in burnt landscapes. Fire severity and proportion of the landscape that was burnt within a 1,000-m radius of survey sites were poor predictors of site occupancy by D. rhodogaster. Although conclusions regarding the effects of fire on D. rhodogaster are limited because of the lack of baseline data, it is evident that the species has persisted across the landscape in the wake of extensive bushfires. Our work highlights the need for baseline knowledge on cryptic species even when they are categorized as Least Concern, as otherwise assessments of the impacts of catastrophic events will be constrained.
Associations between adversity and youth psychopathology likely vary based on the types and timing of experiences. Major theories suggest that the impact of childhood adversity may either be cumulative in type (the more types of adversity, the worse outcomes) or in timing (the longer exposure, the worse outcomes) or, alternatively, specific concerning the type (e.g., parenting, home, neighborhood) or the timing of adversity (e.g., specific developmental periods). In a longitudinal sample from the Future of Families and Wellbeing Study (N = 4,210), we evaluated these competing hypotheses using a data-driven structured life-course modeling approach using risk factors examined at child age 1 (infancy), 3 (toddlerhood), 5 (early childhood), and 9 (middle childhood). Results showed that exposures to more types of adversity for longer durations (i.e., cumulative in both type and timing) best predicted youth psychopathology. Adversities that occurred at age 9 were better predictors of youth psychopathology as compared to those experienced earlier, except for neglect, which was predictive of internalizing symptoms when experienced at age 3. Throughout childhood (across ages 1–9), aside from the accumulation of all adversities, parental stress and low collective efficacy were the strongest predictors of internalizing symptoms, whereas psychological aggression was predictive of externalizing symptoms.
Although resilient youth provide an important model of successful adaptation to adversity, we know relatively little about the origins of their positive outcomes, particularly the role of biological mechanisms. The current study employed a series of methylome-wide association studies to identify methylomic biomarkers of resilience in a unique sample of 276 twins within 141 families residing in disadvantaged neighborhoods. Results revealed methylome-wide significant differentially methylated probes (DMPs) for social and academic resilience and suggestive DMPs for psychological resilience and resilience across domains. Pathway analyses informed our understanding of the biological underpinnings of significant differentially methylated probes. Monozygotic twin difference analyses were then employed to narrow in on DMPs that were specifically environmental in origin. Our findings suggest that alterations in the DNA methylome may be implicated in youth resilience to neighborhood adversity and that some of the suggestive DMPs may be environmentally engendered. Importantly, our ability to replicate our findings in a well-powered sample was hindered by the scarcity of twin samples with youth exposed to moderate to substantial levels of adversity. Thus, although preliminary, the present study is the first to identify DNA methylation biomarkers of academic and social resilience.
Evaluation of adult antibiotic order sets (AOSs) on antibiotic stewardship metrics has been limited. The primary outcome was to evaluate the standardized antimicrobial administration ratio (SAAR). Secondary outcomes included antibiotic days of therapy (DOT) per 1,000 patient days (PD); selected antibiotic use; AOS utilization; Clostridioides difficile infection (CDI) cases; and clinicians’ perceptions of the AOS via a survey following the final study phase.
Design:
This 5-year, single-center, quasi-experimental study comprised 5 phases from 2017 to 2022 over 10-month periods between August 1 and May 31.
Setting:
The study was conducted in a 752-bed tertiary care, academic medical center.
Intervention:
Our institution implemented AOSs in the electronic medical record (EMR) for common infections among hospitalized adults.
Results:
For the primary outcome, a statistically significant decreases in SAAR were detected from phase 1 to phase 5 (1.0 vs 0.90; P < .001). A statistically significant decreases were detected in DOT per 1,000 PD (4,884 vs 3,939; P = .001), fluoroquinolone orders (407 vs 175; P < .001), carbapenem orders (147 vs 106; P = .024), and clindamycin orders (113 vs 73; P = .01). No statistically significant change in mean vancomycin orders was detected (991 vs 902; P = .221). A statistically significant decrease in CDI cases was also detected (7.8, vs 2.4; P = .002) but may have been attributable to changes in CDI case diagnosis. Clinicians indicated that the AOSs were easy to use overall and that they helped them select the appropriate antibiotics.
Conclusions:
Implementing AOS into the EMR was associated with a statistically significant reduction in SAAR, antibiotic DOT per 1,000 PD, selected antibiotic orders, and CDI cases.
Persistent brain fog is common in adults with Post-Acute Sequelae of SARS-CoV-2 infection (PASC), in whom it causes distress and in many cases interferes with performance of instrumental activities of daily living (IADL) and return-to-work. There are no interventions with rigorous evidence of efficacy for this new, often disabling condition. The purpose of this pilot is to evaluate the efficacy, on a preliminary basis, of a new intervention for this condition termed Constraint-Induced Cognitive therapy (CICT). CICT combines features of two established therapeutic approaches: cognitive speed of processing training (SOPT) developed by the laboratory of K. Ball and the Transfer Package and task-oriented training components of Constraint-Induced Movement therapy developed by the laboratory of E. Taub and G. Uswatte.
Participants and Methods:
Participants were > 3 months after recovery from acute COVID symptoms and had substantial brain fog and impairment in IADL. Participants were randomized to CICT immediately or after a 3-month delay. CICT involved 36 hours of outpatient therapy distributed over 4-6 weeks. Sessions had three components: (a) videogamelike training designed to improve how quickly participants process sensory input (SOPT), (b) training on IADLs following shaping principles, and (c) a set of behavioral techniques designed to transfer gains from the treatment setting to daily life, i.e., the Transfer Package. The Transfer Package included (a) negotiating a behavioral contract with participants and one or more family members about the responsibilities of the participants, family members, and treatment team; (b) assigning homework during and after the treatment period; (c) monitoring participants’ out-of-session behavior; (d) supporting problem-solving by participants and family members about barriers to performance of IADL; and (e) making follow-up phone calls. IADL performance, brain fog severity, and cognitive impairment were assessed using validated, trans-diagnostic measures before and after treatment and three months afterwards in the immediate-CICT group and on parallel occasions in the delayed-CICT group (aka waitlist controls).
Results:
To date, five were enrolled in the immediate-CICT group; four were enrolled in the wait-list group. All had mild cognitive impairment, except for one with moderate impairment in the immediate-CICT group. Immediate-CICT participants, on average, had large reductions in brain fog severity on the Mental Clutter Scale (MCS, range = 0 to 10 points, mean change = -3.7, SD = 2.0); wait-list participants had small increases (mean change = 1.0, SD = 1.4). Notably, all five in the immediate-CICT group had clinically meaningful improvements (i.e., changes > 2 points) in performance of IADL outside the treatment setting as measured by the Canadian Occupational Performance Measure (COPM) Performance scale; only one did in the wait-list group. The advantage for the immediate-CICT group was very large on both the MCS and COPM (d’s = 1.7, p’s < .05). In follow-up, immediate-CICT group gains were retained or built-upon.
Conclusions:
These preliminary findings warrant confirmation by a large-scale randomized controlled trial. To date, CICT shows high promise as an efficacious therapy for brain fog due to PASC. CICT participants had large, meaningful improvements in IADL performance outside the treatment setting, in addition to large reductions in brain fog severity.
A significant proportion of the forested production area in South Carolina is managed using aerial applications of imazapyr. Cotton injury from off-target movement of imazapyr has been observed in South Carolina. Field experiments were conducted twice at the Edisto Research and Education Center (EREC) in 2021 and 2022, and once at the Pee Dee Research and Education Center (PDREC) in 2022, to evaluate the response of cotton at two growth stages to imazapyr at 0.1×, 0.05×, 0.025×, 0.0125×, and 0.00625× of the normal use rate of 0.84 kg ae ha−1. Injury to cotton at the vegetative stage was 86% and 74% at 0.1× and 0.05× imazapyr rates 28 d after application (DAA). Cotton height ranged from 23 to 93 cm at all three locations. Yield at the EREC location in 2021 was reduced by 79%, 48%, and 31% at the 0.1×, 0.05×, and 0.025× rates of imazapyr, respectively. Similar reductions from imazapyr were observed at both EREC and PDREC in 2022. Injury to cotton at the reproductive stage based on visual estimates at 28 DAA ranged from 95% to 64% for the 0.1× to 0.0125× rates, respectively. Cotton height at the reproductive stage was reduced to 59% of the untreated control 28 DAA when the 0.1× rate of imazapyr was applied. Seed cotton (which included both seed and lint) yield ranged from 0 to 2,880 kg ha−1 at the three locations in both years. Seed cotton yield was lowest when imazapyr was applied at the 0.1× to 0.025× rates. Cotton exposure to imazapyr at the vegetative and reproductive growth stages resulted in plant injury, height, and yield reductions, especially at the higher rates of imazapyr. The greatest reduction in cotton growth and yield was observed after exposure at the reproductive growth stage regardless of imazapyr rate. In summary, the magnitude of cotton response to imazapyr depends on crop growth stage and imazapyr concentration at the time of exposure with the greatest impact occurring at the reproductive growth stage.
CI Cognitive Therapy (CICT) is a combination of behavioral techniques derived from CI Movement Therapy (CIMT) modified to apply to the cognitive domain, and Speed of (Cognitive) Processing Training (SOPT). SOPT is effective in improving cognitive function in the treatment setting and driving ability in everyday situations. The data concerning the effect of SOPT on other cognition-based instrumental activities of daily living (IADL) in everyday situations is incomplete. The strengths of CIMT, based on its Transfer Package (TP), are to facilitate 1) transfer of improved function from the treatment setting to IADL in everyday settings, and 2) long-term retention of the improved performance of IADL. This study sought to determine in a preliminary case series whether the TP of CI Movement Therapy combined with SOPT would have the same effect on a wide range of impaired cognition-based ADL.
Participants and Methods:
Participants were 6 adults with chronic stroke: mean chronicity = 36.2 months, (range, 16-56 months); mean age = 59.7 years, (range, 47-55); 1 female; 3 African American and 3 European American. Five had mild cognitive impairment, while one had moderate impairment. Participants received 35 hours of outpatient treatment in 10-15 sessions distributed over 2-6 weeks, depending on the participants’ availability. Sessions began with 1 hour of SOPT training followed by training of cognition-based ADL by the process of shaping, a common method in the behavior analysis field. Other behavior analysis methods employed in the TP of CI Movement Therapy were used, including: 1) behavior contracting, daily assignment of homework, participation of a family member in the training and monitoring process, daily administration of a structured interview assessing amount and quality of performance of 30 IADL, problem solving to overcome perceived (or real) barriers to performance of IADL. Participants were given daily homework assignments in follow-up and were contacted in periodic, pre-arranged phone calls to determine status, compliance and problem-solve.
Results:
All six participants showed marked improvement on the SOPT test similar to that in the Ball et al studies. However, here transfer to IADL outside the treatment setting was substantial. On the main real-world outcome, the Canadian Occupational Performance Measure (COPM), there were increases of 2.7±1.3 and 2.1±1.6 on the two scales (d’s = 1.9 & 1.3, respectively). (Changes on the COPM > 2 points are considered clinically meaningful and changes in d’ >.8 are considered large). On two other real-word measures, the Cognitive Task Activity Log (CTAL) and inventory of Improved and New Cognitive Activities (INCA), there was a marked increase during the acquisition phase of training. There was no loss in retention over the 6-16 months (mean = 12.2) of follow-up to date. Instead, the INCA showed strong further improvement after the end of treatment-setting training, especially in the New Activities Not Performed Since Before Stroke Onset category, going from a mean of 8.2 after training to 14.6 at the end of follow-up.
Conclusions:
These very preliminary results suggest that CICT may be an efficacious therapy for mild to moderate cognitive impairment in chronic stroke and possibly other disorders.
Recent theoretical models have posited that increases in self-injurious thoughts and behaviors (SITBs) during adolescence may be linked to failures in biological stress regulation in contexts of social stress. However, there is a lack of data examining this hypothesis during the transition to adolescence, a sensitive period of development characterized by changes across socioaffective and psychophysiological domains. Building on principles from developmental psychopathology and the RDoC framework, the present study used a longitudinal design in a sample of 147 adolescents to test whether interactions among experiences of social (i.e., parent and peer) conflict and cardiac arousal (i.e., resting heart rate) predicted adolescents’ engagement in SITBs (i.e., nonsuicidal self-injury, NSSI; and suicidal ideation; SI) across 1-year follow-up. Prospective analyses revealed that adolescents experiencing a combination of greater peer, but not family, conflict and higher cardiac arousal at baseline showed significant longitudinal increases in NSSI. In contrast, social conflict did not interact with cardiac arousal to predict future SI. Findings indicate that greater peer-related interpersonal stress in adolescents may increase risk for future NSSI among youth with physiological vulnerabilities (i.e., higher resting heart rate) that may be markers of maladaptive stress responses. Future research should examine these processes at finer timescales to elucidate whether these factors are proximal predictors of within-day SITBs.
OBJECTIVES/GOALS: In a familial case where 10 of 17 members inherited EA/LVNC in an autosomal dominant pattern, we discovered a novel, damaging missense variant in the gene KLHL26 that segregates with disease and comprises an altered electrostatic surface profile, likely decoupling the CUL3-interactome. We hypothesize that this KLHL26 variant is etiologic of EA/LVNC. METHODS/STUDY POPULATION: We differentiated a family trio (a heart-healthy daughter and EA/LVNC-affected mother and daughter) of induced pluripotent stem cells into cardiomyocytes (iPSC-CMs) in a blinded manner on three iPSC clones per subject. Using flow cytometry, immunofluorescence, and biomechanical, electrophysiological, and automated contraction methods, we investigated iPSC-CM differentiation efficiency between D10-20, contractility analysis and cell cycle regulation at D20, and sarcomere organization at D60. We further conducted differential analyses following label-free protein and RNA-Seq quantification at D20. Via CRISPR-Cas9 gene editing, we plan to characterize KLHL26 variant-specific iPSC-CM alterations and connect findings to discoveries from patient-specific studies. RESULTS/ANTICIPATED RESULTS: All iPSC lines differentiated into CMs with an increased percentage of cTnT+ cells in the affected daughter line. In comparison to the unaffected, affected iPSC-CMs had fewer contractions per minute and altered calcium transients, mainly a higher amount of total calcium release, faster rate of rise and faster rate of fall. The affected daughter line further had shorter shortening and relaxation times, higher proliferation, lower apoptosis, and a smaller cell surface area per cardiac nucleus. The affected mother line trended in a similar direction to the affected daughter line. There were no gross differences in sarcomere organization between the lines. We also discovered differential expression of candidate proteins such as kinase VRK1 and collagen COL5A1 from proteomic profiling. DISCUSSION/SIGNIFICANCE: These discoveries suggest that EA/LVNC characteristics or pathogenesis may result from decreased contractile ability, altered calcium transients, and cell cycle dysregulation. Through the KLHL26 variant correction and introduction in the daughter lines, we will build upon this understanding to inform exploration of critical clinical targets.
When it comes to images, why does it always seem as if Mieke Bal has already been there, done that, and thought it through? This is a book that could have been called ‘How to Do Things with Images’, to echo J. L. Austin's study of words. But that would not have been enough, because Mieke's project also insists on noticing how images do things with and to us – how they affect us, lead us astray or towards insight and transformation. Do we carry images in our minds in memories and fantasies? Or do they carry us away, like the vehicles of metaphors that break through the guard rails of logic into ana-logic? When you pick up this book, you will have to be prepared to break out of some habitual ways of thinking about what it means to see a film, go to the theatre, visit an exhibition, read a book, hear a voice. Image-Thinking connects all these practices as image-performances across the boundaries of media in their involvement with the body of beholder/ participant.
Superficially, this is a book about Mieke Bal's practice as a filmmaker, with special emphasis on the phenomenon of madness. When read immersively, however, it reveals itself as a guide through a set of experimental image practices ranging across and beyond the arts. We know that Mieke's films are often staged within non-theatrical cinematic installations. The effect is a condensed and super-charged version of my own favourite renegade practice in American multiplex cinemas, roaming the hallways between action thrillers, moody melodramas and outrageous comedies. The viewer's decisions are part of the work, as are those of the filmmaker in sometimes allowing accidental intrusions into the mise en scène. A carnivalesque tolerance for improvisation and surprising juxtaposition makes the experience of her work into a labyrinth of discovery. Image-Thinking provides an Ariadne's thread through the maze, tracing Mieke's thought process as these works came together with teams of collaborators. Instead of treating the artwork as the finished product, assembled after a long ordeal of research and planning, Mieke emphasises the ‘search’ itself as the work, the ‘thought-image’ as the lamp that lights the way.
To analyze the spread of a novel sequence type (ST1478) of vancomycin-resistant Enterococcus faecium across Canadian hospitals.
Design:
Retrospective chart review of patients identified as having ST1478 VRE bloodstream infection.
Setting:
Canadian hospitals that participate in the Canadian Nosocomial Infection Surveillance Program (CNISP).
Methods:
From 2013 to 2018, VRE bloodstream isolates collected from participating CNISP hospitals were sent to the National Microbiology Laboratory (NML). ST1478 isolates were identified using multilocus sequence typing, and whole-genome sequencing was performed. Patient characteristics and location data were collected for patients with ST1478 bloodstream infection (BSI). The sequence and patient location information were used to generate clusters of infections and assess for intrahospital and interhospital spread.
Results:
ST1478 VRE BSI occurred predominantly in a small number of hospitals in central and western Canada. Within these hospitals, infections were clustered on certain wards, and isolates often had <20 single-nucleotide variants (SNV) differences from one another, suggesting a large component of intrahospital spread. Furthermore, some patients with bloodstream infections were identified as moving from one hospital to another, potentially having led to interhospital spread. Genomic analysis of all isolates revealed close relatedness between isolates at multiple different hospitals (<20 SNV) not predicted from our epidemiologic data.
Conclusions:
Both intrahospital and regional interhospital spread have contributed to the emergence of VRE ST1478 infections across Canada. Whole-genome sequencing provides evidence of spread that might be missed with epidemiologic investigation alone.