Background: We aim to assess the resting state functional connectivity (RSFC) and reactivity with functional near-infrared spectroscopy (fNIRS) in patients with acute stroke compared to age, sex and comorbidity-matched subjects. Methods: Patients with acute anterior circulation stroke syndrome localizing to the right (RH) or left hemisphere (LH) were enrolled. RSFC was assessed using group-level seed-based (Primary Motor cortex,PMC) correlation analysis. Finger-tapping-associated relative oxygen Hemoglobin (ΔHbO) changes were analyzed with generalized linear model regression. Results: 127 participants (RH stroke, 51; LH stroke, 43; control, 33) enrolled at a median of 21 (15,29) hours after symptom onset. Compared to the control group, the RSFC with the affected PMC (LH stroke) was reduced over the affected somatosensory cortex (SSC) in the minor ischemic stroke (IS) (r = -0.14 (-0.3,-0.01)), minor intracerebral hemorrhage (ICH) (-0.48 (-0.78,-0.18)) and major ICH groups (-0.2 (-0.4,-0.01). In the FT task compared to the control groups in LH stroke, ΔHbO was increased over the affected SSC in minor IS (β11.2(1.9,20.5)) and major ICH group (β11.7 (1.4,22.1)). In the FT task in RH stroke, ΔHbO was increased over the unaffected PMC in minor IS (β12.1(2.3,21.8)), major IS (β14.9 (0.3,29.5)), minor ICH (β25.7 (10.1,41.2)) and major ICH (β13.4 (1.1,25.6). Conclusions: Motor cortex dysconnectivity may be worse over the LH stroke. In RH stroke, there is early compensatory increased neuronal activity over the unaffected PMC. These results suggest differential acute remodelling in RH and LH strokes.

Objectives/Goals: This work aims to identify functional brain networks that differentiate opioid use disorder (OUD) subjects from healthy controls (HC) using machine learning (ML) analysis of resting-state fMRI (rs-fMRI). We investigate the default mode network (DMN), salience network (SN), and executive control network (ECN), as well as demographic features. Methods/Study Population: This work uses high-resolution rs-fMRI data from a National Institute on Drug Abuse study (IRB #HM20023630) with 31 OUD and 45 HC subjects. We extract rs-fMRI blood oxygenation level-dependent (BOLD) features from the DMN, SN, and ECN. The Boruta ML algorithm identifies statistically significant features and brain activity mapping visualizes regions of heightened neural activity for OUD. We conduct fivefold cross-validation classification experiments (OUD vs. HC) to assess the discriminative power of functional network features with and without incorporating demographic features. Demographic features are ranked based on ML classification importance. Follow-up Boruta analysis is performed to study the medial prefrontal cortex (mPFC), posterior cingulate cortex, and temporoparietal junctions in the DMN. Results/Anticipated Results: Boruta ML analysis identifies the DMN as the most salient functional network for differentiating OUD from HC, with 33% of DMN features found significant (p < 0.05), compared to 10% and 0% for the SN and ECN, respectively. The Boruta ML algorithm identifies age and education as the most significant demographic features. Brain activity mapping shows heightened neural activity in the DMN for OUD. The DMN exhibits the greatest discriminative power, with a mean AUC of 69.74%, compared to 47.14% and 54.15% for the SN and ECN, respectively. Fusing DMN BOLD features with the most important demographic features improves the mean AUC to 80.91% and the F1 score to 73.97%. Follow-up Boruta analysis highlights the mPFC as the most important functional hub within the DMN, with 65% significant features. Discussion/Significance of Impact: Our study enhances the understanding of OUD neurobiology, identifying the DMN as the most significant network using ML rs-fMRI BOLD feature analysis. Ethnicity, education, and age rank are the most important demographic features and the mPFC emerges as a key functional hub for OUD. Future research can build on these findings to inform treatment of OUD.

Evidence-based insertion and maintenance bundles are effective in reducing the incidence of central line-associated bloodstream infections (CLABSI) in intensive care unit (ICU) settings. We studied the adoption and compliance of CLABSI prevention bundle programs and CLABSI rates in ICUs in a large network of acute care hospitals across Canada.

Objectives: Studies in PD have traditionally focused on motor features, however, interest in non-motor manifestations has increased resulting in improved knowledge regarding the prognosis of the disease. Although several studies have explored the incidence of dementia in PD cohorts, these studies have been conducted mainly in reference centers in high-income countries (HIC). In this study we aimed to analyze the prevalence of cognitive impairment in people with parkinsonism and PD and its association with incident dementia in a population- based study, of elderly from six Latin American countries.

Methods: This report consists of the analysis of data from a follow-up of 12,865 elderly people aged 65 years or older, carried out by 10/66 Dementia Research Group. Residents of urban and rural areas, from six low and middle- income countries (Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico and Peru). Exposures include parkinsonism and PD defined according to the UK Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main exposure and dementia was measured through the dementia diagnosis algorithm from 10/66 DRG.

Results: At baseline, the overall prevalence of cognitive impairment was 14% (n = 1,581), in people with parkinsonism and PD, it was of 30.0% and 26.2%, respectively. Parkinsonism and PD were individually associated with prevalent and incident dementia after controlling for age, sex, and education. The pooled odds ratios from a fixed-effects meta-analysis were 2.2 (95% CI: 1.9 – 2.6) for parkinsonism and 1.9 (95% CI: 1.4 – 2.4) for PD. Regarding incident dementia, the pooled sub-Hazard ratio estimated using a competing risk model was 1.5 (95% CI: 1.2 –1.9) for parkinsonism and 1.5 (95% CI: 1.0 – 2.2) forPD.

Conclusions: Parkinsonism and PD were associated cross-sectionally with the presence of cognitive impairment, and prospectively with incident dementia in elderly people in the community population of Latin America studied. Systematic screening for cognitive impairment and dementia with valid tools in PD patients may help with earlier detection of those at highest risk for adverse outcomes. Identifying modifiable risk factors could potentially lead to efficient interventions even in advanced stages of PD.

Background: Limited knowledge exists about the association between Parkinsonism or Parkinson’s disease (PD) and cognitive impairment and dementia in Latin America.

Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country cohort in Latin America.

Methods: The 10/66 is a prospective, observational cohort study. This population-based cohort study was based in six Latin American countries: Cuba, Dominican Republic, Puerto Rico, Venezuela, Mexico, and Peru. The study includes 12,865 participants from six countries, including residents aged 65 years and living in urban and rural catchment areas. Exposures included diagnosed Parkinsonism and PD defined according to the United Kingdom Parkinson’s Disease Society Brain Bank diagnostic criteria. Cognitive impairment was the main outcome measure for cross-sectional analysis and dementia was used to measure the prospective association with the exposures. Logistic regression models were used to explore the association between Parkinsonism/PD with cognitive impairment at baseline. Competing risk models were used to assess the prospective association between Parkinsonism/PD with incident dementia accounting for competing risk of mortality. Individual country analyses were combined via fixed-effect meta-analysis.

Results: At baseline, the prevalence of cognitive impairment in people with Parkinsonism and PD was 30% and 26.2%, respectively. Parkinsonism (OR 2.2 (95%CI 1.9 – 2.6)) and PD (1.9 (95%CI 1.4 – 2.4)) were individually associated with baseline and incident cognitive impairment after accounting for age, sex, and education, after pooling. In competing risk models, the pooled sub- hazard ratios for dementia in the fixed effect metanalysis were 1.5 (95%CI 1.2 – 1.9) for parkinsonism and 1.5 (95%CI 1.0 – 2.2) for PD.

Conclusions: Parkinsonism and PD were cross-sectionally associated with cognitive impairment and prospectively associated with incident dementia in Latin America. Routine screening for cognitive impairment and dementia with validated tools in PD patients may aid earlier detection of those at greater risk ofadverseoutcomes.

Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.

Currently, 7 named Sarcocystis species infect cattle: Sarcocystis hirsuta, S. cruzi, S. hominis, S. bovifelis, S. heydorni, S. bovini and S. rommeli; other, unnamed species also infect cattle. Of these parasites of cattle, a complete life cycle description is known only for S. cruzi, the most pathogenic species in cattle. The life cycle of S. cruzi was completed experimentally in 1982, before related parasite species were structurally characterized, and before the advent of molecular diagnostics; to our knowledge, no archived frozen tissues from the cattle employed in the original descriptions remain for DNA characterization. Here, we isolated DNA from a paraffin-embedded kidney of a calf experimentally infected with S. cruzi in 1980; we then sequenced portions of 18S rRNA, 28S rRNA, COX1 and Acetyl CoA genes and verified that each shares 99–100% similarity to other available isolates attributed to S. cruzi from naturally infected cattle. We also reevaluated histological sections of tissues of calves experimentally infected with S. cruzi in the original description, exploiting improvements in photographic technology to render clearer morphological detail. Finally, we reviewed all available studies of the life cycle of S. cruzi, noting that S. cruzi was transmitted between bison (Bison bison) and cattle (Bos taurus) and that the strain of parasite derived from bison appeared more pathogenic than the cattle strain. Based on these newfound molecular, morphological and physiological data, we thereby redescribed S. cruzi and deposited reference material in the Smithsonian Museum for posterity.

For 147 hospital-onset bloodstream infections, we assessed the sensitivity, specificity, positive predictive value, and negative predictive value of the National Healthcare Safety Network surveillance definitions of central-line–associated bloodstream infections against the gold standard of physician review, examining the drivers of discrepancies and related implications for reporting and infection prevention.

The relationships between host phylogenetics, functional traits and parasites in wildlife remain poorly understood in the Neotropics, especially in habitats with marked seasonal variation. Here, we examined the effect of seasonality and host functional traits on the prevalence of avian haemosporidians (Plasmodium and Haemoproteus) in the Brazilian Caatinga, a seasonally dry tropical forest. 933 birds were evaluated for haemosporidian infections. We found a high parasitism prevalence (51.2%), which was correlated with phylogenetic relatedness among avian species. Prevalence varied drastically among the 20 well-sampled species, ranging from 0 to 70%. Seasonality was the main factor associated with infections, but how this abiotic condition influenced parasite prevalence varied according to the host-parasite system. Plasmodium prevalence increased during the rainy season and, after excluding the large sample size of Columbiformes (n = 462/933), Plasmodium infection rate was maintained high in the wet season and showed a negative association with host body mass. No association was found between non-Columbiform bird prevalence and seasonality or body mass when evaluating both Plasmodium and Haemoproteus or only Haemoproteus infections. Parasite community was composed of 32 lineages including 7 new lineages. We evidenced that even dry domains can harbour a high prevalence and diversity of vector-borne parasites and pointed out seasonality as a ruling factor.

Among nursing home outbreaks of coronavirus disease 2019 (COVID-19) with ≥3 breakthrough infections when the predominant severe acute respiratory coronavirus virus 2 (SARS-CoV-2) variant circulating was the SARS-CoV-2 δ (delta) variant, fully vaccinated residents were 28% less likely to be infected than were unvaccinated residents. Once infected, they had approximately half the risk for all-cause hospitalization and all-cause death compared with unvaccinated infected residents.

Translational research should examine racism and bias and improve health equity. We designed and implemented a course for the Master of Science in Clinical Investigation program of the Northwestern University Clinical and Translational Sciences Institute. We describe curriculum development, content, outcomes, and revisions involving 36 students in 2 years of “Anti-Racist Strategies for Clinical and Translational Science.” Ninety-six percent of students reported they would recommend the course. Many reported changes in research approaches based on course content. A course designed to teach anti-racist research design is feasible and has a positive short-term impact on learners.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

We report results and modelling of an experiment performed at the Target Area West Vulcan laser facility, aimed at investigating laser–plasma interaction in conditions that are of interest for the shock ignition scheme in inertial confinement fusion (ICF), that is, laser intensity higher than ${10}^{16}$ $\mathrm{W}/{\mathrm{cm}}^2$ impinging on a hot ($T>1$ keV), inhomogeneous and long scalelength pre-formed plasma. Measurements show a significant stimulated Raman scattering (SRS) backscattering ($\sim 4\%{-}20\%$ of laser energy) driven at low plasma densities and no signatures of two-plasmon decay (TPD)/SRS driven at the quarter critical density region. Results are satisfactorily reproduced by an analytical model accounting for the convective SRS growth in independent laser speckles, in conditions where the reflectivity is dominated by the contribution from the most intense speckles, where SRS becomes saturated. Analytical and kinetic simulations well reproduce the onset of SRS at low plasma densities in a regime strongly affected by non-linear Landau damping and by filamentation of the most intense laser speckles. The absence of TPD/SRS at higher densities is explained by pump depletion and plasma smoothing driven by filamentation. The prevalence of laser coupling in the low-density profile justifies the low temperature measured for hot electrons ($7\!{-}\!12$ keV), which is well reproduced by numerical simulations.

A developing application of laser-driven currents is the generation of magnetic fields of picosecond–nanosecond duration with magnitudes exceeding $B=10~\text{T}$. Single-loop and helical coil targets can direct laser-driven discharge currents along wires to generate spatially uniform, quasi-static magnetic fields on the millimetre scale. Here, we present proton deflectometry across two axes of a single-loop coil ranging from 1 to 2 mm in diameter. Comparison with proton tracking simulations shows that measured magnetic fields are the result of kiloampere currents in the coil and electric charges distributed around the coil target. Using this dual-axis platform for proton deflectometry, robust measurements can be made of the evolution of magnetic fields in a capacitor coil target.