The role of the ventrolateral frontal cortex in inhibitory oculomotor control

It has been proposed that the inferior/ventrolateral frontal cortex plays a critical role in the inhibitory control of action during cognitive tasks.However, the contribution of this region to the control of eye movements has not been clearly established.Here, we describe the performance of a group of 23 frontal lobe damaged patients in an oculomotor rule switching task for which the association between a centrally presented visual cue and the direction of a saccade could change from trial to trial. A subset of 16 patients also completed the standard antisaccade task.Ventrolateral damage was found to be a significant predictor of errors in both tasks. Analysis of the rate at which patients corrected errors in the rule switching task also revealed an important dissociation between left and right hemisphere damaged patients.Whilst patients with left ventrolateral damage usually corrected response errors with secondary saccades, those with right hemisphere lesions often failed to do so. The results suggest that the inferior frontal cortex forms part of a wider frontal network mediating inhibitory control over stimulus elicited eye movements. The critical role played by the right ventrolateral region in cognitive tasks may arise due to an additional functional specialization for the monitoring and updating of task rules

Quantification of Progesterone and 17-β Estradiol in Mouse Serum by Liquid Chromatography-Tandem Mass Spectrometry

Quantification of progesterone and 17-β estradiol in mouse serum by liquid chromatography-tandem mass spectrometry Authors: Benjamin Kennard, Allison Cobble, Amy Gravitte, Keleigh Galloway, Jen Kintner, Jennifer Hall, Stacy Brown Introduction: In the United States, Chlamydia trachomatis is a commonly appearing sexually transmitted infection1. It affects the U.S. healthcare system to a tune of about $500 million dollars annually2. In women, it generally appears asymptomatic and can lead to severe secondary complications such as pelvic inflammatory diseases or infertility1. Female sex hormones, estrogen and progesterone, are being identified to have a role in chlamydial infection. Specifically, this study aims to create quantification methods to detect levels of estrogen and progesterone in mice, infected with Chlamydia muridarum, plasma samples. Methods: Progesterone samples were prepared using solid-liquid extraction (SLE+) cartridges with ethyl acetate as the elution solvent. Estradiol samples were prepared using liquid-liquid extraction (LLE) with methyl tert-butyl ether and subsequent derivatization with DMIS. Following sample preparation, hormones were quantified in samples using LC-MS/MS with a gradient elution of 1 mM ammonium fluoride in water and acetonitrile. The separation was achieved using a UCT C18 column (100 x 21.mm, 1.8 μm particle size) maintained at 50oC. The mass spectrometer was set up to isolate molecular ions for progesterone (m/z 315.0910) and derivatized estradiol (m/z 431.1835). Quantification was facilitated by the use of deuterium-labeled internal standards and their corresponding molecular ions in the mass spectrometer (d9-progesterone; m/z 324.1230 and d5-estradiol; m/z 436.2922). Results: Several aspects of the assay presented have been optimized for maximum analyte recovery and analytical sensitivity, including column choice, mobile phase, derivatizing agents for estradiol, and extraction protocols for progesterone. The LC-MS/MS method was investigated for precision and accuracy over three separate days. The dynamic range of the progesterone assay was 5 – 100 ng/mL, with a limit of detection of 1 ng/mL. Likewise, the estradiol assay was linear in the range of 5 – 100 ng/mL, with a limit of detection of 0.5 ng/mL. The average precision, represented by % RSD was 0.74 – 8.5% and 6.3 – 13.4% for progesterone and estradiol, respectively. The accuracy of the method, represented by % error was 1.6 – 14.4% and 4.0 – 10.5% for progesterone and estradiol, respectively. Successful validation was defined as \u3c 15% RSD and error (\u3c 20% at the limit of quantification), per current FDA Guidelines. Conclusions: The developed LC-MS/MS method is specific for progesterone and estradiol, and the extraction is suitable for preparation of mouse serum samples. This assay could be successfully applied to hormone quantification in mouse samples to support the investigation of the link between chlamydia infection and hormone levels in female animals. References 1. Chlamydia - 2017 Sexually Transmitted Diseases Surveillance. https://www.cdc.gov/std/stats17/chlamydia.htm. Accessed October 23, 2018. 2. Owusu-Edusei K, Chesson HW, Gift TL, et al. The Estimated Direct Medical Cost of Selected Sexually Transmitted Infections in the United States, 2008. Sex Transm Dis. 2013;40(3):197-201. doi:10.1097/OLQ.0b013e318285c6d

COMBINE: COMpilation and Backend-INdependent vEctorization for Multi-Party Computation

Recent years have witnessed significant advances in programming technology for multi-party computation (MPC), bringing MPC closer to practice and wider applicability. Typical MPC programming frameworks focus on either front-end language design (e.g., Wysteria, Viaduct, SPDZ), or back-end protocol implementation (e.g., ABY, MOTION, SPDZ). We propose a methodology for an MPC compilation toolchain, which by mimicking the compilation methodology of classical compilers enables middle-end (i.e., machine-independent) optimizations, yielding significant improvements. We advance an intermediate language, which we call MPC-IR that can be viewed as the analogue of (enriched) Static Single Assignment (SSA) form. MPC-IR enables backend-independent optimizations in a close analogy to machine-independent optimizations in classical compilers. To demonstrate our approach, we focus on a specific backend-independent optimization, SIMD-vectorization: We devise a novel classical-compiler-inspired automatic SIMD vectorization on MPC-IR. To demonstrate backend independence and quality of our optimization, we evaluate our approach with two mainstream backend frameworks that support multiple types of MPC protocols, namely MOTION and MP-SPDZ, and show significant improvements across the board

Performance of a Kinetic Inductance Phonon-Mediated Detector at the NEXUS Cryogenic Facility

Microcalorimeters that leverage microwave kinetic inductance detectors to read out phonon signals in the particle-absorbing target, referred to as kinetic inductance phonon-mediated (KIPM) detectors, offer an attractive detector architecture to probe dark matter (DM) down to the fermionic thermal relic mass limit. A prototype KIPM detector featuring a single aluminum resonator patterned onto a 1-gram silicon substrate was operated in the NEXUS low-background facility at Fermilab for characterization and evaluation of this detector architecture's efficacy for a dark matter search. An energy calibration was performed by exposing the bare substrate to a pulsed source of 470 nm photons, resulting in a baseline resolution on the energy absorbed by the phonon sensor of $2.1\pm0.2$ eV, a factor of two better than the current state-of-the-art, enabled by millisecond-scale quasiparticle lifetimes. However, due to the sub-percent phonon collection efficiency, the resolution on energy deposited in the substrate is limited to $\sigma_E=318 \pm 28$ eV. We further model the signal pulse shape as a function of device temperature to extract quasiparticle lifetimes, as well as the observed noise spectra, both of which impact the baseline resolution of the sensor

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

Background: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial

BackgroundThe safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population.MethodsPANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031.FindingsBetween Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir.InterpretationMolnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community

Conducting a College Prep Program During Covid-19: An Analysis on Austin Test Prep (ATP) at Austin High School

Austin Test Prep (ATP) is a Houston-based college preparation program that focuses on mentoring high-school students from disadvantaged communities to counteract the effects of income disparity on education. The program curriculum is divided into two parts: SAT preparation and college preparation. The mentoring is conducted in two-hour sessions every Monday from 4pm-6pm with the first 30 minutes being a presentation from an ATP mentor and the final hour and a half used to guide the students through example problems and worksheets on the topic. The project aims to achieve at least a 100-point increase of SAT scores of students who actively participate in the program. Objective data, in the form of SAT scores before and after the program, and subjective data, in the form of survey questions that ask students to state their confidence in their abilities as well as the effectiveness of the program, are both collected. The subjective data is recorded on a scale from 1 to 5 where 1 is least confident and 5 is most confident. The students self-evaluate their abilities in the three subject sections of the SAT and their relationship with their mentor. Due to the Coronavirus pandemic, this project has taken on an online approach via Microsoft Teams and has progressed through multiple barriers such as student attendance and commitment to the program. Through a logic model and falsifiable logic model, this presentation demonstrates the current program organization and explores the successes and setbacks to the program’s development.Psychological, Health, and Learning Sciences, Department ofHonors Colleg

Liquid Chromatography–Mass Spectrometry Applications for Quantification of Endogenous Sex Hormones

Liquid chromatography, coupled with tandem mass spectrometry, presents a powerful tool for the quantification of the sex steroid hormones 17-β estradiol, progesterone and testosterone from biological matrices. The importance of accurate quantification with these hormones, even at endogenous levels, has evolved with our understanding of the role these regulators play in human development, fertility and disease risk and manifestation. Routine monitoring of these analytes can be accomplished by immunoassay techniques, which face limitations on specificity and sensitivity, or using gas chromatography–mass spectrometry. LC–MS/MS is growing in capability and acceptance for clinically relevant quantification of sex steroid hormones in biological matrices and is able to overcome many of the limitations of immunoassays. Analyte specificity has improved through the use of novel derivatizing agents, and sensitivity has been refined through the use of high-resolution chromatography and mass spectrometric technology. This review highlights these innovations, among others, in LC–MS/MS steroid hormone analysis captured in the literature over the last decade