Background: CHAMPION-NMOSD (NCT04201262) is an ongoing global, open-label, phase 3 study evaluating ravulizumab in AQP4+ NMOSD. Methods: Adult patients received an intravenous, weight-based loading dose of ravulizumab on day 1 and a maintenance dose on day 15 and every 8 weeks thereafter. Following a primary treatment period (PTP; up to 2.5 years), patients could enter a long-term extension (LTE). Results: 58 patients completed the PTP; 56/2 entered/completed the LTE. As of June 16, 2023, median (range) follow-up was 138.4 (11.0-183.1) weeks for ravulizumab (n=58), with 153.9 patient-years. Across the PTP and LTE, no patients had an adjudicated on-trial relapse during ravulizumab treatment. 91.4% (53/58 patients) had stable or improved Hauser Ambulation Index score. 91.4% (53/58 patients) had no clinically important worsening in Expanded Disability Status Scale score. The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events was 94.8% and 25.9%, respectively. Most TEAEs were mild to moderate in severity and unrelated to ravulizumab. TEAEs leading to withdrawal from ravulizumab occurred in 1 patient. Conclusions: Ravulizumab demonstrated long-term clinical benefit in the prevention of relapses in AQP4+ NMOSD with a safety profile consistent with prior analyses.

A new magnetic mirror machine named KAIMIR (KAIST mirror) has been designed and constructed at the Korea Advanced Institute of Science and Technology (KAIST) to study mirror plasma physics and simulate the boundary regions of magnetic fusion plasmas such as in a tokamak. The purpose of this paper is to introduce the characteristics and initial experimental results of KAIMIR. The cylindrical vacuum chamber has a length of 2.48 m and a diameter of 0.5 m and consists of three sub-chambers, namely the source, centre and expander chambers. A magnetic mirror configuration is achieved by electromagnetic coils with a maximum magnetic field strength of 0.4 T at the mirror nozzles and 0.1 T at the centre. The source plasma is generated by a plasma washer gun installed in the source chamber with a pulse forming network system. The typical discharge time is ~12 ms with a ~6 ms (1–7 ms) steady period. Initial results show that the on-axis electron density at the centre is 1019–20 m−3 and the electron temperature is 4–7 eV. Two parameters were varied in this initial phase, the source power and the mirror ratio, which is the ratio of highest to lowest magnetic field strength in the mirror-confined region. We observed that the increase of the electron density was mitigated for a source power above 0.2 MW. It was also found that the electron density increases almost linearly with the mirror ratio. Accordingly, the stored electron energy was also linearly proportional to the mirror ratio, similar to the scaling of the gas dynamic trap.

As the scale of cosmological surveys increases, so does the complexity in the analyses. This complexity can often make it difficult to derive the underlying principles, necessitating statistically rigorous testing to ensure the results of an analysis are consistent and reasonable. This is particularly important in multi-probe cosmological analyses like those used in the Dark Energy Survey (DES) and the upcoming Legacy Survey of Space and Time, where accurate uncertainties are vital. In this paper, we present a statistically rigorous method to test the consistency of contours produced in these analyses and apply this method to the Pippin cosmological pipeline used for type Ia supernova cosmology with the DES. We make use of the Neyman construction, a frequentist methodology that leverages extensive simulations to calculate confidence intervals, to perform this consistency check. A true Neyman construction is too computationally expensive for supernova cosmology, so we develop a method for approximating a Neyman construction with far fewer simulations. We find that for a simulated dataset, the 68% contour reported by the Pippin pipeline and the 68% confidence region produced by our approximate Neyman construction differ by less than a percent near the input cosmology; however, they show more significant differences far from the input cosmology, with a maximal difference of 0.05 in $\Omega_{M}$ and 0.07 in w. This divergence is most impactful for analyses of cosmological tensions, but its impact is mitigated when combining supernovae with other cross-cutting cosmological probes, such as the cosmic microwave background.

Consumption of unpasteurised milk in the United States has presented a public health challenge for decades because of the increased risk of pathogen transmission causing illness outbreaks. We analysed Foodborne Disease Outbreak Surveillance System data to characterise unpasteurised milk outbreaks. Using Poisson and negative binomial regression, we compared the number of outbreaks and outbreak-associated illnesses between jurisdictions grouped by legal status of unpasteurised milk sale based on a May 2019 survey of state laws. During 2013–2018, 75 outbreaks with 675 illnesses occurred that were linked to unpasteurised milk; of these, 325 illnesses (48%) were among people aged 0–19 years. Of 74 single-state outbreaks, 58 (78%) occurred in states where the sale of unpasteurised milk was expressly allowed. Compared with jurisdictions where retail sales were prohibited (n = 24), those where sales were expressly allowed (n = 27) were estimated to have 3.2 (95% CI 1.4–7.6) times greater number of outbreaks; of these, jurisdictions where sale was allowed in retail stores (n = 14) had 3.6 (95% CI 1.3–9.6) times greater number of outbreaks compared with those where sale was allowed on-farm only (n = 13). This study supports findings of previously published reports indicating that state laws resulting in increased availability of unpasteurised milk are associated with more outbreak-associated illnesses and outbreaks.

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.

In this era of spatially resolved observations of planet-forming disks with Atacama Large Millimeter Array (ALMA) and large ground-based telescopes such as the Very Large Telescope (VLT), Keck, and Subaru, we still lack statistically relevant information on the quantity and composition of the material that is building the planets, such as the total disk gas mass, the ice content of dust, and the state of water in planetesimals. SPace Infrared telescope for Cosmology and Astrophysics (SPICA) is an infrared space mission concept developed jointly by Japan Aerospace Exploration Agency (JAXA) and European Space Agency (ESA) to address these questions. The key unique capabilities of SPICA that enable this research are (1) the wide spectral coverage $10{-}220\,\mu\mathrm{m}$ , (2) the high line detection sensitivity of $(1{-}2) \times 10^{-19}\,\mathrm{W\,m}^{-2}$ with $R \sim 2\,000{-}5\,000$ in the far-IR (SAFARI), and $10^{-20}\,\mathrm{W\,m}^{-2}$ with $R \sim 29\,000$ in the mid-IR (SPICA Mid-infrared Instrument (SMI), spectrally resolving line profiles), (3) the high far-IR continuum sensitivity of 0.45 mJy (SAFARI), and (4) the observing efficiency for point source surveys. This paper details how mid- to far-IR infrared spectra will be unique in measuring the gas masses and water/ice content of disks and how these quantities evolve during the planet-forming period. These observations will clarify the crucial transition when disks exhaust their primordial gas and further planet formation requires secondary gas produced from planetesimals. The high spectral resolution mid-IR is also unique for determining the location of the snowline dividing the rocky and icy mass reservoirs within the disk and how the divide evolves during the build-up of planetary systems. Infrared spectroscopy (mid- to far-IR) of key solid-state bands is crucial for assessing whether extensive radial mixing, which is part of our Solar System history, is a general process occurring in most planetary systems and whether extrasolar planetesimals are similar to our Solar System comets/asteroids. We demonstrate that the SPICA mission concept would allow us to achieve the above ambitious science goals through large surveys of several hundred disks within $\sim\!2.5$ months of observing time.

The Hawaiian archipelago was formerly home to one of the most species-rich land snail faunas (> 752 species), with levels of endemism > 99%. Many native Hawaiian land snail species are now extinct, and the remaining fauna is vulnerable. Unfortunately, lack of information on critical habitat requirements for Hawaiian land snails limits the development of effective conservation strategies. The purpose of this study was to examine the plant host preferences of native arboreal land snails in Puʻu Kukui Watershed, West Maui, Hawaiʻi, and compare these patterns to those from similar studies on the islands of Oʻahu and Hawaiʻi. Concordant with studies on other islands, we found that four species from three diverse families of snails in Puʻu Kukui Watershed had preferences for a few species of understorey plants. These were not the most abundant canopy or mid canopy species, indicating that forests without key understorey plants may not support the few remaining lineages of native snails. Preference for Broussaisia arguta among various island endemic snails across all studies indicates that this species is important for restoration to improve snail habitat. As studies examining host plant preferences are often incongruent with studies examining snail feeding, we suggest that we are in the infancy of defining what constitutes critical habitat for most Hawaiian arboreal snails. However, our results indicate that preserving diverse native plant assemblages, particularly understorey plant species, which facilitate key interactions, is critical to the goal of conserving the remaining threatened snail fauna.

OBJECTIVES/GOALS: To develop feasible screening methods for activity of the enzyme Glucose-6-phosphate dehydrogenase (G6PD) with point of care applicability. METHODS/STUDY POPULATION: Current knowledge establishes the relevance of G6PD as a critical therapeutic determinant for effective antimalarial therapy due to the occurrence of mutations that lead to post-treatment severe adverse effects. We present our findings on development of cost effective point-of-care screening methodologies to ascertain G6PD deficiency. RESULTS/ANTICIPATED RESULTS: Using Patient Cohort Explorer and data from the Department of Pathology, we established the prevalence of G6PD deficiency at the University of Mississippi Medical Center, Jackson, MS as high as 11.8% (African-American males in all population, n = 2518). Next, for selection of potential target groups, we set up a protocol for recruitment of volunteers based on ethnic background, parental ethnicity, and medical history. G6PD activity was evaluated using point of care methods [Trinity Biotech test or CareSTART Biosensor], and Gold Standard quantitative spectrophotometric assay (LabCorp). Determinations in >20 subjects have showed comparable concordance. If used with a conservative interpretation of the signal, the Trinity Biotech test showed superior potential for use in the field relative to the CareSTART Biosensor. DISCUSSION/SIGNIFICANCE OF IMPACT: We established the prevalence of G6PD deficiency in our medical center. We have also setup tests for point-of-care assessment of G6PD. Pending evaluation of the relative tests performance, we will be in position to screen individuals and select them for a prospective clinical trial to evaluate the safety of antimalarial agents on scope of G6PD deficiency.

OBJECTIVES/SPECIFIC AIMS: To introduce CCTS to the clinical and translational research community. METHODS/STUDY POPULATION: Established in the summer of 2017, the Center for Clinical and Translational Science (CCTS) fosters cooperative clinical and translational sciences between the University of Mississippi School of Pharmacy (UMSOP) and the University of Mississippi Medical Center (UMMC). CCTS facilitates the translation of basic research discoveries into clinically validated therapies to improve the health of populations in Mississippi and beyond. Priority areas of investigation in CCTS include Cardiometabolic disorders, Cancer, Neuroscience, Infectious diseases, Precision Medicine, and Community-Based Research. To accomplish CCTS mission three overarching goals have been defined: I) Develop progressive and sustainable capacity for clinical and translational research in Mississippi; II) Promote interprofessional engagement in clinical and translational science; and III) Foster research collaboration among stakeholders in and outside of Mississippi. RESULTS/ANTICIPATED RESULTS: To carry its CCTS’s mission three research units have been established: 1) The Pre-clinical Research Unit: Develops processes to move basic science discoveries towards translation into research in humans. This unit provides guidance in the development of Investigational New Drug (IND) applications; and identifies and pursues opportunities to develop progressive capacities for in vitro, ex vivo, in vivo, and in silico approaches for evaluating new pharmaceutical and therapeutic agents. 2) The Clinical Research Unit: Transitions projects that have received IND approval into the first phase of clinical trials. It also transitions clinical trials from Phase I to Phase II and to Phase III; develops standard operating procedures (SOPs), personnel training plans, and policies to guide clinical research; works with industry sponsors and governmental funding agencies; and assures compliance with regulatory requirements. 3) Community/population Research Unit: Develops, coordinates, and facilitates research activities and translation between clinical and community/population research stages. To do so, this unit works closely with community partners and Population Health programs on the Oxford and Jackson campuses. DISCUSSION/SIGNIFICANCE OF IMPACT: Since its inception, the CCTS has surpassed 1.5 million dollars in competitive funding. This early success positions the CCTS well to promote research collaboration between UMSOP and UMMC and to progress in becoming a national leader in clinical and translational investigation.