Background: Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease process that represents a significant health shock for thousands of patients each year. Return to work outcomes and associated factors require evaluation to counsel patients and identify domains on which to focus clinical efforts. Methods: A systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines was performed using MEDLINE, EMBASE and Cochrane databases from inception to February 2024. Proportion of patients returning to work was collected from included studies. Odds ratios were pooled from studies evaluating the association between pre-rupture demographic variables, post-rupture clinical variables and return to work following aSAH. Results: Literature search yielded 3861 studies, of which 40 studies were included in the final analysis for a total of 6888 patients. On average, 55% (SD 17%) of all patients returned to work after an aSAH. Female sex (male sex OR 1.75), high grade aSAH on presentation (OR 0.30), and need for permanent CSF diversion (OR 0.50) are significantly associated with unemployment after aSAH. Conclusions: Female sex, high grade presentation, and permanent CSF diversion are associated with unemployment after aSAH. About half of all patients that experience aSAH return to work.

Background: Neck vessel imaging is often performed in hyperacute stroke to allow neurointerventionalists to estimate access complexity. This study aimed to assess clinician agreement on catheterization strategies based on imaging in these scenarios. Methods: An electronic portfolio of 60 patients with acute ischemic stroke was sent to 53 clinicians. Respondents were asked: (1) the difficulty of catheterization through femoral access with a regular Vertebral catheter, (2) whether to use a Simmons or reverse-curve catheter initially, and (3) whether to consider an alternative access site. Agreement was assessed using Fleiss’ Kappa statistics. Results: Twenty-two respondents (7 neurologists, 15 neuroradiologists) completed the survey. Overall there was slight interrater agreement (κ=0.17, 95% CI: 0.10–0.25). Clinicians with >50 cases annually had better agreement (κ=0.22) for all questions than those with fewer cases (κ=0.07). Agreement did not significantly differ by imaging modality: CTA (κ=0.18) and MRA (κ=0.14). In 40/59 cases (67.80%), at least 25% of clinicians disagreed on whether to use a Simmons or reverse-curve catheter initially. Conclusions: Agreement on catheterization strategies remains fair at best. Our results suggest that visual assessment of pre-procedural vessels imaging is not reliable for the estimation of endovascular access complexity.

The Australian SKA Pathfinder (ASKAP) offers powerful new capabilities for studying the polarised and magnetised Universe at radio wavelengths. In this paper, we introduce the Polarisation Sky Survey of the Universe’s Magnetism (POSSUM), a groundbreaking survey with three primary objectives: (1) to create a comprehensive Faraday rotation measure (RM) grid of up to one million compact extragalactic sources across the southern $\sim50$% of the sky (20,630 deg$^2$); (2) to map the intrinsic polarisation and RM properties of a wide range of discrete extragalactic and Galactic objects over the same area; and (3) to contribute interferometric data with excellent surface brightness sensitivity, which can be combined with single-dish data to study the diffuse Galactic interstellar medium. Observations for the full POSSUM survey commenced in May 2023 and are expected to conclude by mid-2028. POSSUM will achieve an RM grid density of around 30–50 RMs per square degree with a median measurement uncertainty of $\sim$1 rad m$^{-2}$. The survey operates primarily over a frequency range of 800–1088 MHz, with an angular resolution of 20” and a typical RMS sensitivity in Stokes Q or U of 18 $\mu$Jy beam$^{-1}$. Additionally, the survey will be supplemented by similar observations covering 1296–1440 MHz over 38% of the sky. POSSUM will enable the discovery and detailed investigation of magnetised phenomena in a wide range of cosmic environments, including the intergalactic medium and cosmic web, galaxy clusters and groups, active galactic nuclei and radio galaxies, the Magellanic System and other nearby galaxies, galaxy halos and the circumgalactic medium, and the magnetic structure of the Milky Way across a very wide range of scales, as well as the interplay between these components. This paper reviews the current science case developed by the POSSUM Collaboration and provides an overview of POSSUM’s observations, data processing, outputs, and its complementarity with other radio and multi-wavelength surveys, including future work with the SKA.

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.

Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.

Clinical trials are constantly evolving in the context of increasingly complex research questions and potentially limited resources. In this review article, we discuss the emergence of “adaptive” clinical trials that allow for the preplanned modification of an ongoing clinical trial based on the accumulating evidence with application across translational research. These modifications may include terminating a trial before completion due to futility or efficacy, re-estimating the needed sample size to ensure adequate power, enriching the target population enrolled in the study, selecting across multiple treatment arms, revising allocation ratios used for randomization, or selecting the most appropriate endpoint. Emerging topics related to borrowing information from historic or supplemental data sources, sequential multiple assignment randomized trials (SMART), master protocol and seamless designs, and phase I dose-finding studies are also presented. Each design element includes a brief overview with an accompanying case study to illustrate the design method in practice. We close with brief discussions relating to the statistical considerations for these contemporary designs.

As a typical plasma-based optical element that can sustain ultra-high light intensity, plasma density gratings driven by intense laser pulses have been extensively studied for wide applications. Here, we show that the plasma density grating driven by two intersecting driver laser pulses is not only nonuniform in space but also varies over time. Consequently, the probe laser pulse that passes through such a dynamic plasma density grating will be depolarized, that is, its polarization becomes spatially and temporally variable. More importantly, the laser depolarization may spontaneously take place for crossed laser beams if their polarization angles are arranged properly. The laser depolarization by a dynamic plasma density grating may find application in mitigating parametric instabilities in laser-driven inertial confinement fusion.

We present the most sensitive and detailed view of the neutral hydrogen (${\rm H\small I}$) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ($1.6\,\mathrm{mJy\ beam}^{-1}$) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ (${\sim}10\,\mathrm{pc}$). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

Background: Many studies have demonstrated improved arm pain (AP) following surgery for degenerative cervical radiculopathy (DCR); however, axial neck pain (NP) is generally not felt to improve. The purpose of this study was to determine whether surgery for DCR improves NP. Methods: A ambispective cohort study of the Canadian Spine Outcomes Research Network (CSORN) registry for patients

who received 1-level, 2-level, 3-level ADCF (anterior cervical discectomy and fusion) or cervical disc arthroplasty (CDA) for DCR. Outcomes: 12-month post-operative Visual Analogue Scale for NP (VAS-NP), Neck Disability Index (NDI), VAS for AP (VAS-AP), Short-Form Physical Health Composite Scale (SF36-PCS), and Mental Health Composite Scale (SF36-MCS). Results: We identified 603 patients with DCR. CDA patients were the youngest (ANOVA; p<0.001). Patients reported similar pre-operative AP, NP, disability, and health-related quality of life, regardless of procedure (ANOVA; all P>0.05). All procedures offered a statistically significant reduction in VAS-NP, VAS-AP, and NDI (ANOVA; all P<0.001). Mean change from baseline in NP, AP, and disability, were similar across procedures. At 12 months, mean reduction in VAS-AP, VAS-NP, and NDI exceeded minimal clinically important differences for nearly all procedures. Conclusions: Patients undergoing surgery for DCR can expect a clinically significant, approximate 50% reduction in NP, AP, and neck-related disability.

The excavation of a building in the village of Felanitx in the eastern part of the island of Mallorca (Balearic Islands) has revealed the existence of a small necropolis. The inhumations did not provide grave goods except for a bronze belt buckle for which the typological study suggests a Late Antique chronology. The stratigraphical sequence however seems to suggest a possible evolution of the space across time since some graves are cut by others. In order to obtain an absolute date for the necropolis and to verify if there are chronological differences between the graves, a total of 6 human bones samples have been 14C dated by AMS. The results of the radiocarbon dating confirm a Late Antique chronology (4th to 7th century AD) for the graves but do not suggest a chronological evolution. Despite the fact that the knowledge of the necropolis is still fragmentary, the results are extremely important because they provide an absolute date for a Late Antique necropolis in the Mallorcan rural area.

Ultraintense laser-driven relativistic electrons provide a way of heating matter to high energy density states related to many applications. However, the transport of relativistic electrons in solid targets has not been understood well yet, especially in dielectric targets. We present the first detailed two-dimensional particle-in-cell simulations of relativistic electron transport in a silicon target by including the field ionization and collisional ionization processes. An ionization wave is found propagating in the insulator, with a velocity dependent on laser intensity and slower than the relativistic electron velocity. Widely spread electric fields in front of the sheath fields are observed due to the collective effect of free electrons and ions. The electric fields are much weaker than the threshold electric field of field ionization. Two-stream instability behind the ionization front arises for the cases with laser intensity greater than $5\times 10^{19}~\text{W}/\text{cm}^{2}$ that produce high relativistic electron current densities.