Background: Recent research has demonstrated that DBS sites in Alzheimer’s (AD) and Parkinson’s (PD) influencing cognition are functionally connected to the subiculum. However, the results are mixed, and it is unclear how or if DBS site-subiculum connectivity can be optimized to improve patient cognition. Methods: We studied how subiculum connectivity influenced cognitive outcomes in both PD (subthalamic nucleus) and AD (fornix) DBS patients (total n = 110). We first confirmed DBS site-subiculum connectivity had opposite cognitive effects in each disease. We next investigated patient factors underlying these opposing effects. Lastly, we related our findings back to clinical practice to guide DBS programming in PD and AD. Results: DBS site-subiculum connectivity correlated with cognitive improvement in AD but decline in PD. This was dependent upon hippocampal atrophy; such that higher subiculum connectivity was beneficial when the hippocampus was atrophic but deleterious when it was intact. Finally, we related our findings back to anatomy with cadaveric dissections and present how DBS stimulation can be optimized to improve patient cognition. Conclusions: DBS site-subiculum connectivity influences cognition but depends on patient factors. Thus, to optimize cognition based on patient factors, DBS electrodes can be programmed to stimulate subregions with higher or lower subiculum connectivity.

Background: Pain in a common symptom in adult-onset idiopathic dystonia (AOID). An appropriate tool to understand this symptom is needed to improve AOID patients’ care. We developed a rating instrument for pain in AOID and validated it in cervical dystonia (CD). Methods: Development and validation of the Pain in Dystonia Scale (PIDS) in three phases: 1. International experts and participants generated and evaluated the preliminary items for content validity; 2. The PIDS was drafted and revised, followed by cognitive interviews to ensure suitability for self-administration; and 3. the clinimetric properties of the final PIDS were assessed in 85 participants. Results: PIDS evaluates pain severity (by body part), functional impact and external modulating factors. It showed high test-retest reliability the total score (0.9, p<0.001), intraclass correlation coefficients higher than 0.7 for all items and high internal consistency (Cronbach’s alpha 0.9). Convergent validity analysis revealed a strong correlation between the PIDS severity score and the TWSTRS pain subscale (0.8, p<0.001), the brief pain inventory short form (0.7, p<0.001) and impact of pain on daily functioning (0.7, p<0.001). Conclusions: The PIDS is the first specific questionnaire developed to evaluate pain in patients with AOID with high-level clinimetric properties in people with CD.

OBJECTIVES/GOALS: Adolescents with congenital heart defects (CHD) have an elevated risk for future cardiovascular events, but information about their risk for e-cigarette use (“vaping”) is unknown. This study aims to present preliminary findings on gender differences in the association of impulsive behavior and vaping susceptibility from an ongoing investigation. METHODS/STUDY POPULATION: Adolescents with CHD (12-18 years; N=63) reported their vaping susceptibility and completed subjective (UPPS-P)/objective (Iowa Gambling Task; IGT) assessments of impulsive behavior previously associated with tobacco use. The UPPS-P includes 5 facets: 1) negative urgency (impulsivity under negative emotions), 2) positive urgency (impulsivity under positive emotions), 3) lack of premeditation (acting without thinking), 4) lack of perseverance (inability to focus), and 5) sensation seeking (seeking thrilling experiences). The IGT is a computerized task that creates conflict between immediate reward and delayed punishment via selections from advantageous/disadvantageous card decks. Linear regressions stratified by gender determined associations between vaping susceptibility and impulsivity. RESULTS/ANTICIPATED RESULTS: Nearly 30% (29.7%) of adolescents with CHD were susceptible to vaping. Negative urgency was associated with vaping susceptibility among females (β = 0.44, p = .035) but not males (β = 0.25, p = .128). Positive urgency was associated with vaping susceptibility among males (β = 0.37, p = .021) and trended toward significance among females (β = 0.40, p = .058). Lack of premeditation was associated with vaping susceptibility among males (β = 0.36, p = .025) but not females (β = 0.15, p = .490). The association between lack of perseverance and vaping susceptibility trended toward significance among males (β = 0.30, p = .064) but not females (β = -0.18, p = .413). IGT performance was not associated with susceptibility to vaping among either gender. UPPS-P facets and IGT performance were not significantly correlated. DISCUSSION/SIGNIFICANCE: The association of impulsivity and vaping susceptibility appears to be characterized by emotion-based rash action (positive/negative urgency) for females and by decreased conscientiousness (lack of premeditation/perseverance) for males. If replicated, the findings have implications for assessment of vaping risk and tailored intervention.

The Variables and Slow Transients Survey (VAST) on the Australian Square Kilometre Array Pathfinder (ASKAP) is designed to detect highly variable and transient radio sources on timescales from 5 s to $\sim\!5$ yr. In this paper, we present the survey description, observation strategy and initial results from the VAST Phase I Pilot Survey. This pilot survey consists of $\sim\!162$ h of observations conducted at a central frequency of 888 MHz between 2019 August and 2020 August, with a typical rms sensitivity of $0.24\ \mathrm{mJy\ beam}^{-1}$ and angular resolution of $12-20$ arcseconds. There are 113 fields, each of which was observed for 12 min integration time, with between 5 and 13 repeats, with cadences between 1 day and 8 months. The total area of the pilot survey footprint is 5 131 square degrees, covering six distinct regions of the sky. An initial search of two of these regions, totalling 1 646 square degrees, revealed 28 highly variable and/or transient sources. Seven of these are known pulsars, including the millisecond pulsar J2039–5617. Another seven are stars, four of which have no previously reported radio detection (SCR J0533–4257, LEHPM 2-783, UCAC3 89–412162 and 2MASS J22414436–6119311). Of the remaining 14 sources, two are active galactic nuclei, six are associated with galaxies and the other six have no multi-wavelength counterparts and are yet to be identified.

Much of our current understanding about novel coronavirus disease 2019 (COVID-19) comes from hospitalised patients. However, the spectrum of mild and subclinical disease has implications for population-level screening and control. Forty-nine participants were recruited from a group of 99 adults repatriated from a cruise ship with a high incidence of COVID-19. Respiratory and rectal swabs were tested by polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sera were tested for anti-SARS-CoV-2 antibodies by enzyme-linked immunosorbent assay (ELISA) and microneutralisation assay. Symptoms, viral shedding and antibody response were examined. Forty-five participants (92%) were considered cases based on either positive PCR or positive ELISA for immunoglobulin G. Forty-two percent of cases were asymptomatic. Only 15% of symptomatic cases reported fever. Serial respiratory and rectal swabs were positive for 10% and 5% of participants respectively about 3 weeks after median symptom onset. Cycle threshold values were high (range 31–45). Attempts to isolate live virus were unsuccessful. The presence of symptoms was not associated with demographics, comorbidities or antibody response. In closed settings, incidence of COVID-19 could be almost double that suggested by symptom-based screening. Serology may be useful in diagnosis of mild disease and in aiding public health investigations.

The onset of magnetic reconnection in space, astrophysical and laboratory plasmas is reviewed discussing results from theory, numerical simulations and observations. After a brief introduction on magnetic reconnection and approach to the question of onset, we first discuss recent theoretical models and numerical simulations, followed by observations of reconnection and its effects in space and astrophysical plasmas from satellites and ground-based detectors, as well as measurements of reconnection in laboratory plasma experiments. Mechanisms allowing reconnection spanning from collisional resistivity to kinetic effects as well as partial ionization are described, providing a description valid over a wide range of plasma parameters, and therefore applicable in principle to many different astrophysical and laboratory environments. Finally, we summarize the implications of reconnection onset physics for plasma dynamics throughout the Universe and illustrate how capturing the dynamics correctly is important to understanding particle acceleration. The goal of this review is to give a view on the present status of this topic and future interesting investigations, offering a unified approach.

Screening tools that effectively predict which nonnative species are likely to become invasive are necessary because of the disproportionate ecological and economic costs associated with invaders. We tested the effectiveness of the Australian Weed Risk Assessment system (WRA) in distinguishing plant species that are major invaders, minor invaders, and noninvaders in Florida. The test included 158 annuals and perennials in six growth forms from 52 families in 27 orders. The WRA with a secondary screen met all hypothesized accuracy levels: it correctly rejected 92% of test species that have been documented to be invasive in Florida and correctly accepted 73% of the noninvaders. The incorrect rejection of noninvaders was 8% with the remaining 19% of noninvaders falling into the “evaluate further” outcome. Only 10% of the 158 species required further evaluation. Invaders of natural areas and agricultural systems were identified with equal accuracy. Receiver operating characteristic analysis demonstrated high separation of invaders from noninvaders. The degree to which the WRA is precautionary may be adjusted by altering the cutoff scores that define the “accept, evaluate further,” and “reject” outcomes. This approach could be adopted in Florida as a screening mechanism to reduce importation of new invaders.

Specific roles of individual CDPKs vary, but in general they mediate essential biological functions necessary for parasite survival. A comparative analysis of the structure-activity relationships (SAR) of Neospora caninum, Eimeria tenella and Babesia bovis calcium-dependent protein kinases (CDPKs) together with those of Plasmodium falciparum, Cryptosporidium parvum and Toxoplasma gondii was performed by screening against 333 bumped kinase inhibitors (BKIs). Structural modelling and experimental data revealed that residues other than the gatekeeper influence compound–protein interactions resulting in distinct sensitivity profiles. We subsequently defined potential amino-acid structural influences within the ATP-binding cavity for each orthologue necessary for consideration in the development of broad-spectrum apicomplexan CDPK inhibitors. Although the BKI library was developed for specific inhibition of glycine gatekeeper CDPKs combined with low inhibition of threonine gatekeeper human SRC kinase, some library compounds exhibit activity against serine- or threonine-containing CDPKs. Divergent BKI sensitivity of CDPK homologues could be explained on the basis of differences in the size and orientation of the hydrophobic pocket and specific variation at other amino-acid positions within the ATP-binding cavity. In particular, BbCDPK4 and PfCDPK1 are sensitive to a larger fraction of compounds than EtCDPK1 despite the presence of a threonine gatekeeper in all three CDPKs.