Carotenoid cleavage enzymes evolved convergently to generate the visual chromophore.

The retinal light response in animals originates from the photoisomerization of an opsin-coupled 11-cis-retinaldehyde chromophore. This visual chromophore is enzymatically produced through the action of carotenoid cleavage dioxygenases. Vertebrates require two carotenoid cleavage dioxygenases, ß-carotene oxygenase 1 and retinal pigment epithelium 65 (RPE65), to form 11-cis-retinaldehyde from carotenoid substrates, whereas invertebrates such as insects use a single enzyme known as Neither Inactivation Nor Afterpotential B (NinaB). RPE65 and NinaB couple trans-cis isomerization with hydrolysis and oxygenation, respectively, but the mechanistic relationship of their isomerase activities remains unknown. Here we report the structure of NinaB, revealing details of its active site architecture and mode of membrane binding. Structure-guided mutagenesis studies identify a residue cluster deep within the NinaB substrate-binding cleft that controls its isomerization activity. Our data demonstrate that isomerization activity is mediated by distinct active site regions in NinaB and RPE65-an evolutionary convergence that deepens our understanding of visual system diversity.

COVID-19 Burden in Adult Correctional or Detention Facilities and the Surrounding Communities, January 1, 2020-July 20, 2021.

We estimated the COVID-19 burden in adult correctional or detention facilities and associated counties by state, facility jurisdiction, and county urbanicity. COVID-19 cumulative incidence (cases per 1,000 persons) for each U.S. correctional or detention facility and people ages 18 years and older in the associated county was estimated between January 1, 2020 and July 20, 2021. Across 46 U.S. states, 1,083 correctional or detention facilities in 718 counties were included. The median COVID-19 incidence rate was higher in facilities than in associated counties for 42 of 46 states and for all facility jurisdictions and county urbanicity categories. COVID-19 burden was higher in most facilities than in associated counties. Implementing COVID-19 mitigation measures in correctional settings is needed to prevent SARS-CoV-2 transmission in facilities and associated counties.

Evaluation of Veterinary Medical Student Retention of Pre-clinical Concepts with Various Experiential Learning Methods.

Many veterinary medical colleges have undergone curricular changes that have moved away from traditional lecture-based teaching in favor of evidence-based, experiential methods of instruction. Such a curricular reinvention occurred in 2018 at Michigan State University's College of Veterinary Medicine, with individual courses using numerous instructional and learning methods. In the present study, three courses were assessed, two of which used a method of experiential learning, and the other utilizing a traditional lecture approach. The purpose of this study was to determine if the method of instruction impacted exam grades, content retention, and student perspective. Methods of teaching and learning were quantified for each course using the Classroom Observation Protocol for Undergraduate STEM. Following completion of each course, participants (n = 27) retook the same final examination and participated in a survey to evaluate their perspective 5 weeks later. Mean scores on the initial examinations in the experiential learning courses were significantly higher than the mean score of the traditional lecture course (p = .01). However, mean retake examination scores were similar for all courses (p = .76). Students reported more confidence with course materials and examinations in courses that incorporated active learning strategies. Although true retention is difficult to assess in veterinary medicine, evaluation of student perspectives suggests the use of experiential learning methods primarily or in combination with lecture-based material to support student learning of pre-clinical concepts. Future controlled studies are needed to evaluate veterinary students' short- and long-term learning and retention.

Life Expectancy and COVID-19 in Florida State Prisons.

INTRODUCTION: The heightened risk of COVID-19 infection and mortality in prisons is well documented, but COVID-19's impact on all-cause mortality in incarcerated populations has not yet been studied. This study analyzed mortality records from the Florida State Department of Corrections prison system population to evaluate the impact COVID-19 had on all-cause mortality and compare mortality rates and life expectancy with that of the overall state of Florida population. METHODS: Population age and sex data for Florida State Department of Corrections were ascertained from the Florida State Department of Corrections Offender Based Information System. Death data by age, sex, and cause of death were acquired from medical records and Florida State Department of Corrections offender reports. The state of Florida demographic and death data were collected from the Census Bureau, Florida Department of Health, and Centers for Disease Control and Prevention. Age- and sex-standardized life table measures were calculated, and COVID-19 contributions to changes in life expectancy were assessed using Arriaga's decomposition. RESULTS: The standardized mortality rate in the Florida State Department of Corrections population increased by 45% between 2019 and 2020, causing an overall 4.0-year decline in life expectancy. Over the same period, the state of Florida population's standardized mortality increased by 19%, resulting in an overall 2.7-year decline. Within the Florida State Department of Corrections population, life expectancy decline could be attributed exclusively to COVID-19 mortality. CONCLUSIONS: The state of Florida prison population saw a substantial increase in mortality driven solely by COVID-19 mortality, leading to an overall 4-year decline in life expectancy. Given the findings and continued threat of COVID-19 outbreaks, Florida State Department of Corrections and other prison systems should strive to increase vaccination uptake, decrease prison populations, and commit to COVID-19 data transparency.

Certifiable Robustness to Adversarial State Uncertainty in Deep Reinforcement Learning.

Deep neural network-based systems are now state-of-the-art in many robotics tasks, but their application in safety-critical domains remains dangerous without formal guarantees on network robustness. Small perturbations to sensor inputs (from noise or adversarial examples) are often enough to change network-based decisions, which was recently shown to cause an autonomous vehicle to swerve into another lane. In light of these dangers, numerous algorithms have been developed as defensive mechanisms from these adversarial inputs, some of which provide formal robustness guarantees or certificates. This work leverages research on certified adversarial robustness to develop an online certifiably robust for deep reinforcement learning algorithms. The proposed defense computes guaranteed lower bounds on state-action values during execution to identify and choose a robust action under a worst case deviation in input space due to possible adversaries or noise. Moreover, the resulting policy comes with a certificate of solution quality, even though the true state and optimal action are unknown to the certifier due to the perturbations. The approach is demonstrated on a deep Q-network (DQN) policy and is shown to increase robustness to noise and adversaries in pedestrian collision avoidance scenarios, a classic control task, and Atari Pong. This article extends our prior work with new performance guarantees, extensions to other reinforcement learning algorithms, expanded results aggregated across more scenarios, an extension into scenarios with adversarial behavior, comparisons with a more computationally expensive method, and visualizations that provide intuition about the robustness algorithm.

Assessing the Mortality Impact of the COVID-19 Pandemic in Florida State Prisons.

BACKGROUND: The increased risk of COVID-19 infection among incarcerated individuals due to environmental hazards is well known and recent studies have highlighted the higher rates of infection and mortality prisoners in the United States face due to COVID-19. However, the impact of COVID-19 on all-cause mortality rates in incarcerated populations has not been studied. METHODS: Using data reported by the Florida Department of Corrections on prison populations and mortality events we conducted a retrospective cohort study of all individuals incarcerated in Florida state prisons between 2015 and 2020. We calculated excess deaths by estimating age-specific expected deaths from mortality trends in 2015 through 2019 and taking the difference between observed and expected deaths during the pandemic period. We calculated life table measures using standard demographic techniques and assessed significant yearly changes using bootstrapping. FINDINGS: The Florida Department of Corrections reported 510 total deaths from March 1, 2020 to December 31, 2020 among the state prison population. This was 42% higher (rate ratio 1.42, 95% CI 1.15 to 1.89) than the expected number of deaths in light of mortality rates for previous years. Reported COVID-19 deaths in a month were positively correlated with estimated excess deaths (80.4%, p <.01). Using age-specific mortality estimates, we found that life expectancy at age 20 declined by 4 years (95% CI 2.06-6.57) between 2019 and 2020 for the Florida prison population. INTERPRETATION: The Florida prison population saw a significant increase in all-cause mortality during the COVID-19 pandemic period, leading to a decrease in life expectancy of more than four years. Life years lost by the Florida prison population were likely far greater than those lost by the general United States population, as reported by other studies. This difference in years lost highlights the need for increased interventions to protect vulnerable incarcerated populations during pandemics. FUNDING: Vital Projects Fund, Arnold Ventures, US Centers for Disease Control, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

The medium, the message and the measure: a theory-driven review on the value of telehealth as a patient-facing digital health innovation.

By what measure should a policy maker choose between two mediums that deliver the same or similar message or service? Between, say, video consultation or a remote patient monitoring application (i.e. patient-facing digital health innovations) and in-person consultation? To answer this question, we sought to identify measures which are used in randomised controlled trials. But first we used two theories to frame the effects of patient-facing digital health innovations on - 1) transaction costs (i.e. the effort, time and costs required to complete a clinical interaction); and 2) process outcomes and clinical outcomes along the care cascade or information value chain, such that the 'value of information' (VoI) is different at each point in the care cascade or value chain. From the trials, we identified three categories of measures: outcome (process or clinical), satisfaction, and cost. We found that although patient-facing digital health innovations tend to confer much of their value by altering process outcomes, satisfaction, and transaction costs, these measures are inconsistently assessed. Efforts to determine the relative value of and choose between mediums of service delivery should adopt a metric (i.e. mathematical combination of measures) that capture all dimensions of value. We argue that 'value of information' (VoI) is such a metric - it is calculated as the difference between the 'expected utility' (EU) of alternative options. But for patient-facing digital health innovations, 'expected utility' (EU) should incorporate the probability of achieving not only a clinical outcome, but also process outcomes (depending on the innovation under consideration); and the measures of utility should include satisfaction and transaction costs; and also changes in population access to services, and health system capacity to deliver more services, which may result from reduction in transaction costs.

On the same page: Co-designing the logic model of a telehealth service for children in rural and remote Australia.

The value of programme logic models as a tool for planning, evaluation, and communication is well recognised. However, the value of its development process is less discussed. In this paper, we describe how we used a combination of literature review and organisational stakeholder consultations to develop a logic model for a telehealth programme for children in rural and remote Australia. Our aim was to use this process to further embed the programme within its implementing organisation, and by so doing to promote its sustainability and scale-up; a major challenge of telehealth programmes, especially those involving reorganisation of processes. Our efforts to describe the components of this complex intervention on the one-page logic model allowed for debates and discussions within the implementing organisation which then facilitated an improved cross-organisational understanding of the telehealth programme; a real time face-to-face (video-link) service which requires the reorganisation of existing service delivery platforms. The process helped to embed the telehealth programme within existing services. We conclude that stakeholder engagement in developing logic models can transform them from being only a tool that provides the picture of why and how a programme works, to one that plays a role in embedding programmes within implementing organisations.

Physical fitness and performance. Training for old age: production functions for the aerobic exercise inputs.

PURPOSE: This paper attempts to develop production functions (PF) between aerobic exercise inputs and long-run health outputs. Future studies could use such PF for estimating the benefits and costs (broadly defined) of different exercise programs to help develop optimal (utility maximizing) ones. METHODS: To develop the PF, the paper reviewed the biomedical literature for the major dose-response relations between health, physical fitness, and exercise. Where relevant, the paper converted the dose-response relationships from relative risks to absolute probabilities and standardized terminology and units of measures. RESULTS: The paper develops a clear set of biological PF that illustrate, quantitatively, how increases in peak cardiorespiratory (CR) fitness as measured by a short stress test reduce the probability of all-cause mortality; how increasing intensities of short (approximately 30 min, three to five times a week) exercise sessions increase peak CR fitness or retard its age-related decline; and how consistent exercise reduces the risk of myocardial infarctions (MI). CONCLUSIONS: The exercise-long-run health PF developed in this paper should provide a useful framework for other studies to estimate the broadly defined costs and benefits of different exercise programs and to help develop optimal ones.

Chemical alteration of poly(tetrafluoroethylene) TFE teflon induced by exposure to electrons and inert-gas ions.

In this study the chemical alterations of poly(tetrafluoroethylene) (TFE Teflon) by approximately 1.0-keV electrons and 1.0-keV He and Ar ions have been examined using X-ray photoelectron spectroscopy (XPS). The initial F/C atom ratio of 1.99 decreases to a steady-state value of 1.48 after 48 h of electron exposure. Exposure to either He+ or Ar+ decreases the initial F/C atom ratio from approximately 2 to a steady-state value of 1.12. The high-resolution XPS C 1s data indicate that new chemical states of carbon form as the F is removed and that the relative amounts of these states depend on the F content of the near-surface region. These states are most likely due to C bonded only to one F atom, C bonded only to other C atoms and C that have lost a pair of electrons through emission of F-. Exposures of the electron-damaged and He+- or Ar+-damaged surfaces to research-grade O2 result in chemisorption of very small amounts of O indicating that large quantities of reactive sites are not formed during the chemical erosion. Further exposure to the electron or ion fluxes quickly removes this chemisorbed oxygen. Exposure of the He+-damaged surface to air at room temperature results in the chemisorption of a larger amount of O than the O2 exposure but no N is adsorbed. The chemical alterations due to electrons and ions are compared with those caused by hyperthermal (approximately 5 eV) atomic oxygen (AO) and vacuum ultraviolet (VUV) radiation. The largest amount of damage is caused by AO followed by VUV, inert-gas ions, and then electrons.