Local Restrictions Research Articles

EpiCass and CassavaNet4Dev Advanced Bioinformatics Workshop

EpiCass and CassavaNet4Dev are collaborative projects funded by the Swedish Research Council between the Swedish University of Agriculture (SLU) and the International Institute of Tropical Agriculture (IITA). The projects aim to investigate the influence of epigenetic changes on agricultural traits such as yield and virus resistance while also providing African students and researchers with advanced bioinformatics training and opportunities to participate in big data analysis events. The first advanced bioinformatics training workshop took place from May 16th to May 18th, 2022, followed by an online mini-symposium titled "Epigenetics and crop improvement" on May 19th. The symposium featured international speakers covering a wide range of topics related to plant epigenetics, cassava viral diseases, and cassava breeding strategies. A new online and on-site teaching concept was developed for the three-day workshop to ensure maximum student participation across Western, Eastern, and Southern Africa. Initially planned in Nigeria, Kenya, Ethiopia, Tanzania, and Zambia, the workshop ultimately focused on Nigeria, Kenya, and Ethiopia due to a lack of qualified candidates in the other countries. Each classroom hosted 20 to 25 students, with at least one bioinformatician present for support. The classrooms were connected via video conferencing, whereas teachers located in different places in Africa and Europe joined the video stream to conduct teaching sessions. The workshop was divided into theoretical classes and hands-on sessions, where participants could run data analysis with support from online teachers and local bioinformaticians. To enable participants to run guided, CPU and RAM-intensive data analysis workflows and overcome local computing and internet access restrictions, a system of virtual machines (VMs) hosted in the cloud was developed. The teaching platform provided teaching and exercise materials to support the use of the VMs. Although some students could not run heavy data analysis workflows due to unforeseen restrictions in the cloud, these issues were solved. All participants had the opportunity to run the analysis steps independently in the cloud using the protocols hosted on the teaching platform.

Trajectory Planning for Autonomous Valet Parking in Narrow Environments With Enhanced Hybrid A* Search and Nonlinear Optimization

This paper focuses on the problem of autonomous valet parking trajectory planning in complex environments. The task normally can be well described by an optimal control problem (OCP) for the rapid, accurate, and optimal trajectory generation. Appropriate initial guesses obtained by sampling or searching-based methods are important for the numerical optimization procedure. Still, in highly complex environments with narrow passages, it may incur high computational costs or fail to find the proper initial guess. To address this challenge, an enhanced hybrid A* (EHA) algorithm is proposed to address the issue. The EHA includes four steps. The first step is to quickly obtain the global coarse trajectory using a traditional A* search. The second step is constructing a series of driving corridors along the rough trajectory, then evaluating and extracting nodes from each wide or narrow passage based on the length of the box's side. The third step is to extract each passage's boundary points. The final step is connecting boundary points by hybrid A* and generating a feasible initial guess for OCP. To reduce safety risks, vehicles in particular areas (Fig. 1b) should travel as slowly as possible. The global and local speed restrictions are distinct, and local restrictions are only activated when the vehicle enters a particular area. This “if-else” structure makes the optimization problem difficult. A novel approximation formulation for these local state constraints is introduced to overcome this issue. The experimental results demonstrate that the proposed method for trajectory planning is effective and robust.

Conducting a full-scale emergency management exercise during COVID-19: A case study of Puyallup Chill Out 2021

The COVID-19 public health emergency severely limited the ability of emergency managers to conduct emergency exercises, particularly at the functional or full-scale level. Throughout the COVID-19 pandemic response, other emergencies continued, and local emergency management was called to respond, ensuring that local guidelines and COVID-19 restrictions were observed. This paper describes how the pandemic impacted on the City of Puyallup’s emergency management training and exercise programme and how the City adapted to conduct a full-scale exercise in the autumn of 2021. Multiple delays, planning partners overwhelmed by COVID-19, and emergencies that occurred prior to the exercise were all addressed and included in the exercise scenario. The City of Puyallup and its planning partners built in contingencies in the run-up to the exercise, all the way through to the day of exercise play. Providing a safe, realistic and timely opportunity for the City of Puyallup and partners to conduct the exercise has resulted in a far-reaching after-action report and improvement plan to guide the preparedness and planning efforts of the City and its partners.

Effect of voluntary human mobility restrictions on vector-borne diseases during the COVID-19 pandemic in Japan: A descriptive epidemiological study using a national database (2016 to 2021).

The coronavirus disease 2019 (COVID-19) pandemic not only encouraged people to practice good hygiene but also caused behavioral inhibitions and resulted reduction in both endemic and imported infectious diseases. However, the changing patterns of vector-borne diseases under human mobility restrictions remain unclear. Hence, we aimed to investigate the impact of transborder and local mobility restrictions on vector-borne diseases through a descriptive epidemiological study. The analysis was conducted using data from the National Epidemiological Surveillance of Infectious Diseases system in Japan. We defined the pre-pandemic period as the period between the 1st week of 2016 to the 52nd week of 2019 and defined the pandemic period as from the 1st week of 2020 to the 52nd week of 2021, with the assumption that human mobility was limited throughout the pandemic period. This study addressed 24 diseases among notifiable vector borne diseases. Datasets were obtained from weekly reports from the National Epidemiological Surveillance of Infectious Diseases, and the incidence of each vector-borne disease was examined. Interrupted time series analysis was conducted on the epidemic curves for the two periods. Between the pre- and post-pandemic periods, the incidence of dengue fever and malaria significantly decreased, which may be related to limited human transboundary mobility (p = 0.003/0.002). The incidence of severe fever with thrombocytopenia syndrome, scrub typhus, and Japanese spotted fever did not show changes between the two periods or no association with human mobility. This study suggests that behavioral control may reduce the incidence of new mosquito-borne diseases from endemic areas but may not affect tick-borne disease epidemics within an endemic area.

A prospective study of the impact of COVID-19-related restrictions on activities and mobility upon physical activity, travel behaviour and attitudes

Background and aimsPublic health measures adopted to contain the spread of COVID-19 included restrictions on activities and mobility as people were asked to stay at home and schools moved to online learning. This may have increased risk of non-communicable disease by limiting recreational and transport-related physical activity. Building on an existing study, we assessed changes in self-reported and device-measured physical activity and travel behaviour before, during and after the peak of local COVID-19 outbreak and restrictions (March–July 2020). We examined beliefs in effectiveness of strategies to increase active and public transport after restrictions were reduced. MethodsA longitudinal study of adult infrequent bus users (average ≤ 2 trips per week; n = 70; 67% women) in Hobart, Australia. One-week assessment periods at four separate timepoints (before, during, 0–3 months after, and 3–6 months after the peak restrictions period) involved wearing an accelerometer, daily transport diaries, online surveys and tracking bus smartcard boardings. ResultsPhysical activity (especially among older participants), bus use and private motor vehicle use declined significantly during or 0–3 months after the peak restrictions period and returned to pre-restrictions levels by 3–6 months after the peak restrictions period, except bus use which remained significantly lower. Retrospective surveys overstated declines in bus use and active transport and self-reports understated declines in physical activity. Social distancing and improving service efficiency and frequency were seen as effective strategies for increasing bus use after restrictions but belief in effectiveness of distancing decreased over time. ConclusionsWhen restrictions on mobility are increased, supportive health promotion measures are needed to prevent declines in physical activity, particularly for older adults. Public transport systems need capacity to implement temporary distancing measures to prevent communicable disease transmission. Providing convenient, flexible, and efficient options for public transport may help to replenish public transport use after restrictions are reduced.

Siponimod Stabilizes Physical Disability Scores in People Living With Secondary Progressive Multiple Sclerosis After 2 Years of Treatment: Analysis From the Novartis Global Managed Access Program (P8-3.010)

<h3>Objective:</h3> To describe demographic and clinical characteristics and characterize change in Expanded Disability Status Scale (EDSS) score in people living with secondary progressive multiple sclerosis (plwSPMS) receiving siponimod under the managed access program (MAP; Global Siponimod MAP cohort [BAF2001M cohort]). <h3>Background:</h3> Siponimod significantly reduced the risk of confirmed disability progression and worsening of cognitive processing speed vs placebo in the phase 3 EXPAND trial (NCT01665144). However, real-world effectiveness data for siponimod remain scarce. <h3>Design/Methods:</h3> The BAF2001M cohort is an umbrella program to facilitate access to siponimod when marketing authorization is pending (under physician request) in the absence of acceptable alternative treatments. The program started in March 2019 and is ongoing. The target population included adult patients with SPMS and an EDSS score &lt;7 from March 2019 to January 2021. After January 2021, access to the MAP required SPMS with active disease. Treatment selection and patient monitoring were based on physician assessment. Baseline characteristics included country, age, sex, relapse, MRI activity in the last 2 years, EDSS, and cognition evaluation. <h3>Results:</h3> A total of 632 cases were analyzed (153 excluded from analysis due to local country restrictions). Mean (SD) age was 52.3 (8.7) years, 60% of patients were female, and median (IQR) EDSS was 5.5 (4.5–6.5). Prior to siponimod start, ~51% experienced a relapse in the last 2 years, 54% had previous cognitive evaluation, and 52% had an MRI scan in the last 2 years (48% showed activity). Mean change in EDSS from baseline was approximately −0.02/−0.03 at Months 6, 12, 18, and 24 (not significantly different vs baseline). Approximately 94% (140/149) of patients improved or were stable at Month 24. <h3>Conclusions:</h3> Most plwSPMS demonstrated improved or stabilized EDSS scores over 2 years. This population was older than the EXPAND study population and around half demonstrated relapse/MRI activity. Results support the effectiveness of siponimod in SPMS. <b>Disclosure:</b> Dr. Mavrikis Cox has received personal compensation for serving as an employee of Novartis Pharmaceuticals. Dr. Mavrikis Cox has stock in Novartis Pharmaceuticals. Virginia DeLasHeras has nothing to disclose. Dr. Ryan has received personal compensation for serving as an employee of Novartis. Mrs. Istrate has nothing to disclose. Soudeh Ansari has received personal compensation for serving as an employee of Novartis. Sophie Arnould has nothing to disclose. Dr. Piani Meier has received personal compensation for serving as an employee of Novartis. Dr. Piani Meier has received personal compensation for serving as an employee of Merck Group.

Stroke Metrics During Covid-19: a Comprehensive Stroke Center Experience (P14-5.002)

<h3>Objective:</h3> Analyze changes in stroke presentation and in-hospital systems-of-care at a Comprehensive Stroke Center (CSC) during the first year of the SARS-CoV-2 pandemic. <h3>Background:</h3> Although studies have shown a decrease in hospital stroke admissions during the pandemic, population-based studies investigating the evolution of stroke metrics throughout the pandemic are lacking. <h3>Design/Methods:</h3> From March 2018 to May 18, 2021, data from 2400 stroke admissions to our CSC were obtained. The study duration was split into 4 periods according to changes in local case numbers and community restrictions: period 0 (prepandemic), period 1 (first wave), period 2 (lull), and period 3 (second wave). Monthly intravenous thrombolysis (IVT) and endovascular therapy (EVT) rates and workflow times were compared among periods. Analyses were adjusted for age, sex, comorbidities, and need for continuing care. <h3>Results:</h3> Stroke monthly admissions decreased in period 1 (β = −6.39, p &lt; 0.001), recovered in period 2 (β = 9.20, p &lt; 0.001), and dropped again in period 3 (β = −3.85, p = 0.04). Although admissions increased in period 2, they did not reach prepandemic levels. Incidence of IVT also significantly dropped on period 1 (β = −0.71, p = 0.04) and then rose in period 3 (β = 1.30, p &lt; 0.001). Compared with the prepandemic period, recipients of acute stroke therapies during period 2 had prolonged door-to-CT times (adjusted difference 25 min, 95%CI 4.69–36.09 min). Moreover, in-hospital door-to-needle and groin-to-reperfusion times were also delayed in periods 2 and 3. <h3>Conclusions:</h3> We observed a significant decrease in stroke admissions and IVT treatment during the first COVID-19 wave, reflecting less care-seeking in our community initially. Further, during the lull period and second wave, significant acute stroke in-hospital workflow delays occurred. Going forward, additional measures are needed to reduce barriers to workflow and hospital avoidance for stroke patients during pandemic or other local crisis periods. <b>Disclosure:</b> Mrs. Carvalho de Oliveira has nothing to disclose. Dr. Ponciano has nothing to disclose. Prof. Farias Da Guarda has nothing to disclose. Nima Kashani has nothing to disclose. Aravind Ganesh has nothing to disclose. Dr. Turner has nothing to disclose.

Predicting norovirus and rotavirus resurgence in the United States following the COVID-19 pandemic: a mathematical modelling study

BackgroundTo reduce the burden from the COVID-19 pandemic in the United States, federal and state local governments implemented restrictions such as limitations on gatherings, restaurant dining, and travel, and recommended non-pharmaceutical interventions including physical distancing, mask-wearing, surface disinfection, and increased hand hygiene. Resulting behavioral changes impacted other infectious diseases including enteropathogens such as norovirus and rotavirus, which had fairly regular seasonal patterns prior to the COVID-19 pandemic. The study objective was to project future incidence of norovirus and rotavirus gastroenteritis as contacts resumed and other NPIs are relaxed.MethodsWe fitted compartmental mathematical models to pre-pandemic U.S. surveillance data (2012–2019) for norovirus and rotavirus using maximum likelihood estimation. Then, we projected incidence for 2022–2030 under scenarios where the number of contacts a person has per day varies from70%, 80%, 90%, and full resumption (100%) of pre-pandemic levels.ResultsWe found that the population susceptibility to both viruses increased between March 2020 and November 2021. The 70–90% contact resumption scenarios led to lower incidence than observed pre-pandemic for both viruses. However, we found a greater than two-fold increase in community incidence relative to the pre-pandemic period under the 100% contact scenarios for both viruses. With rotavirus, for which population immunity is driven partially by vaccination, patterns settled into a new steady state quickly in 2022 under the 70–90% scenarios. For norovirus, for which immunity is relatively short-lasting and only acquired through infection, surged under the 100% contact scenario projection.ConclusionsThese results, which quantify the consequences of population susceptibility build-up, can help public health agencies prepare for potential resurgence of enteric viruses.

Perception and attitudes toward COVID- 19 vaccines in Jordan: lessons for future pandemics.

This study aimed to assess Jordanians' perception and attitudes toward COVID-19 vaccines authorized for use in Jordan. Another objective was to evaluate the population's confidence in vaccine efficacy, their fears of the vaccines, and their perceptions and attitudes after vaccination. This cross-sectional study was conducted over four months (August 2021- December 2021) and included the general Jordanian population above 18 years old. A total of 398 participants were included in the study, with the majority (around 81.0%) received at least one dose of any of COVID-19 vaccines approved for use in Jordan. Most non-vaccinated participants (67.4%) were either unwilling to receive the COVID-19 vaccine or unsure. The main reasons for receiving the vaccine were: family protection, self-protection, global efforts to fight the virus and local restrictions, with some variability between vaccinated and non-vaccinated. The major reasons for fear of COVID-19 vaccines were limited research, vaccine effectiveness, and vaccine side effects. Pfizer-BioNTech vaccine was the most trusted vaccine by vaccinated and non-vaccinated participants (47.8% and 57.9%, respectively), and Oxford-AstraZeneca was the most feared by them (42.2% and 57.9%, respectively). Internet websites (>85.0%), social media platforms (>70.0%), relatives and friends (>69.0%), and news applications (>60.0%) were the major sources of information about the COVID-19 vaccines among participants. Our results revealed that hesitation in receiving the vaccine remains a challenge in Jordan, as in other countries. The findings also show that participants, regardless of their vaccination status, had many concerns about the four types of vaccines approved for use in Jordan during the study conduction period. Moreover, the participants' perceptions and attitudes towards the vaccines were variable between vaccinated and non-vaccinated participants and were variable for the four types of vaccines.

Interferon‐inducible phospholipids govern IFITM3‐dependent endosomal antiviral immunity

The interferon‐induced transmembrane proteins (IFITM) are implicated in several biological processes, including antiviral defense, but their modes of action remain debated. Here, taking advantage of pseudotyped viral entry assays and replicating viruses, we uncover the requirement of host co‐factors for endosomal antiviral inhibition through high‐throughput proteomics and lipidomics in cellular models of IFITM restriction. Unlike plasma membrane (PM)‐localized IFITM restriction that targets infectious SARS‐CoV2 and other PM‐fusing viral envelopes, inhibition of endosomal viral entry depends on lysines within the conserved IFITM intracellular loop. These residues recruit Phosphatidylinositol 3,4,5‐trisphosphate (PIP3) that we show here to be required for endosomal IFITM activity. We identify PIP3 as an interferon‐inducible phospholipid that acts as a rheostat for endosomal antiviral immunity. PIP3 levels correlated with the potency of endosomal IFITM restriction and exogenous PIP3 enhanced inhibition of endocytic viruses, including the recent SARS‐CoV2 Omicron variant. Together, our results identify PIP3 as a critical regulator of endosomal IFITM restriction linking it to the Pi3K/Akt/mTORC pathway and elucidate cell‐compartment‐specific antiviral mechanisms with potential relevance for the development of broadly acting antiviral strategies.

Farmer and market vendor perceptions of COVID-19 impacts on horticultural fresh food systems in Tonga, Fiji, and Samoa

BackgroundWhen the global COVID-19 pandemic and state of emergency was declared in early 2020, South Pacific Island nations rapidly closed their borders resulting in significant socio-economic upheaval. With the South Pacific region highly vulnerable to external shocks, there was concern amongst Pacific governments and international donors as to the implications of COVID-19 restrictions on the local food system.MethodsHorticultural farmers and market vendors (n = 825) were surveyed in Fiji, Tonga, and Samoa, using local enumerators, over a five-month period (July to November 2020), which represented the initial phase of COVID-19 restrictions in the region. Data were disaggregated based on location, farmer and vendor impacts, and postharvest loss.ResultsFarmers in Fiji (86%) were more likely to experience difficulties in selling their crops during the initial stages of COVID-19 restrictions, compared to farmers on the smaller Pacific Island nations of Tonga (10%) or Samoa (53%). While market vendors in Fiji (73.2%) and Tonga (56.8%) were similarly impacted, few vendors (22%) in Samoa were affected. Farmers and market vendors on the islands of Viti Levu (Fiji) and Upolu (Samoa), specifically those supplying or located in the key urban centres were more likely to experience elevated postharvest loss. Elevated postharvest loss due to COVID-19 was more prevalent amongst municipal market vendors, peri-urban farms and vendors sourcing from larger commercial farms. Road-side vendors and vendors in the rural areas were less likely to incur elevated loss.ConclusionsWhile fresh horticultural food systems in Fiji, Tonga, and Samoa were all adversely effected by COVID-19 restrictions, these impacts were more acute in Fiji. Given value chains associated with main urban centres were more likely to incur elevated postharvest loss, this would imply consumers were avoiding town centres and alternatively sourcing fresh fruit and vegetable from rural road-side vendors. Pacific road-side vendors appear to have provided an important fresh food distribution capacity during local COVID-19 travel restrictions.

Digital Livelihoods Undone

A decade into the Syrian war, Lebanon remains the country hosting the largest number of refugees per capita worldwide, limiting their work to three sectors of the economy. Most of the employed refugees have therefore been active in the informal market under indecent and insecure working conditions. One solution currently being promoted by humanitarian and development organisations and the private sector is that digital work in web-based labour markets can provide an alternative that circumvents these local restrictions, offering refugees a way to make a livelihood online. This field report contests this assumption, based on analysis of the impact and experience of a digital skills training programme that reached some 3000 beneficiaries by 2021. The report critically examines how a context of regulatory restriction and economic crisis in Lebanon undermines the feasibility of digital refugee livelihoods, thereby offering a critique of the idea that web-based income opportunities transcend local markets, policies and regulations. Due to discriminatory policies, ICT-related exclusion, and financial exclusion, the programme’s objective shifted from online work to local work. Ironically, most of those graduates who found work did so in the local informal labour market once more, having failed to secure any form of sustainable online income opportunity.

Is social media the new wet market? Social media platforms facilitate the online sale of bushmeat in West Africa

Social media provides a platform for wildlife crime syndicates to access a global consumer-driven market. Whilst studies have uncovered the online trade in wildlife, the availability of wild meat (bushmeat) has not been assessed. To investigate the sale of wild meat online, we analysed 563 posts published between 2018 and 2022 from six West African Facebook pages selected using predetermined search criteria. Across 1511 images and 18 videos, we visually identified 25 bushmeat species-level taxa including mammals (six Rodentia, five Artiodactyla, three Carnivora, two Pholidota, one Primate, two Lagomorpha, one Hyracoidea), birds (three Galliformes) and reptiles (two Squamata), predominately advertised as smoked (63%) or fresh (30%) whole carcasses or portions. Among the species identified, 16% feature a status of concern on the International Union for Conservation of Nature (IUCN) Red List (Near Threatened to Endangered), 16% are listed on the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES; Appendix I and II) and 24% are either fully or partially protected by local legislation. Images were commonly used as propaganda rather than to display inventory, where additional taxa protected from game hunting in West Africa, such as hornbill, were exclusively listed in captions. The advertisement of these protected and vulnerable species on the surface web indicates weak local and international legislative enforcement. Comparatively, when the same search criteria were applied to the deep web browser Tor no results were generated, reinforcing the idea that bushmeat vendors have no need to hide their activities online. Despite local and international trade restrictions, the taxa advertised feature similarities with bushmeat seizures reported in Europe, alluding to the interconnectedness of the trade facilitated by social media. We conclude that enhanced policy enforcement is essential to combat the online sale of bushmeat and mitigate the potential biodiversity and public health impacts.

A Spatio-Temporal Approach For Determining Individual's Covid-19 Risks

Current state of art approaches such as the susceptible-infected-removed model and machine learning models are not optimized for modeling the risks of individuals and modeling the effects of local restrictions. To improve the drawback of these approaches, the feedback processing framework is proposed where previously accumulated global statistics and the model estimates generated from the spatial-temporal data are combined to improve the performance of the local prediction. The proposed framework is evaluated in three processing stages: generation of the simulation dataset, feedback analysis, and evaluation for the spatial-temporal and real-time pandemic analysis. In the data generation stage, the corresponding state of the illness for each person is modeled by a Markov stochastic process. In this stage, the parameters such as the reproduction rate, symptomatic rate, asymptomatic rate, population count, infected count, and the average mobility rate are used to update the individual's Covid-19 status and the individual's movements. The movement data of each person is generated randomly for several places of interest. In the feedback analysis stage, both the aggregated statistics and the local event data are combined in a linear model to infer a score for the Covid-19 probability of the person. In this respect, a stochastic model can be used to approximate the local statistics. In the evaluation stage, the result of the feedback analysis for all the interactions is used to classify the state of the individuals periodically. Later the accuracy of the evaluation for each person is obtained by comparing the individual's prediction with the real data generated in the same time interval. The Kappa scores independent from different populations, locations, and mobility rates obtained for every interaction indicate a significant difference from the random statistics.

Characterization of immunoglobulin loci in the gigantic genome of Ambystoma mexicanum.

The axolotl, Ambystoma mexicanum is a unique biological model for complete tissue regeneration. Is a neotenic endangered species and is highly susceptible to environmental stress, including infectious disease. In contrast to other amphibians, the axolotl is particularly vulnerable to certain viral infections. Like other salamanders, the axolotl genome is one of the largest (32 Gb) and the impact of genome size on Ig loci architecture is unknown. To better understand the immune response in axolotl, we aimed to characterize the immunoglobulin loci of A. mexicanum and compare it with other model vertebrates. The most recently published genome sequence of A. mexicanum (V6) was used for alignment-based annotation and manual curation using previously described axolotl Ig sequences or reference sequences from other vertebrates. Gene models were further curated using A. mexicanum spleen RNA-seq data. Human, Xenopus tropicalis, Danio rerio (zebrafish), and eight tetrapod reference genomes were used for comparison. Canonical A. mexicanum heavy chain (IGH), lambda (IGL), sigma (IGS), and the putative surrogate light chain (SLC) loci were identified. No kappa locus was found. More than half of the IGHV genes and the IGHF gene are pseudogenes and there is no clan I IGHV genes. Although the IGH locus size is proportional to genome size, we found local size restriction in the IGHM gene and the V gene intergenic distances. In addition, there were V genes with abnormally large V-intron sizes, which correlated with loss of gene functionality. The A. mexicanum immunoglobulin loci share the same general genome architecture as most studied tetrapods. Consistent with its large genome, Ig loci are larger; however, local size restrictions indicate evolutionary constraints likely to be imposed by high transcriptional demand of certain Ig genes, as well as the V(D)J recombination over very long genomic distance ranges. The A. mexicanum has undergone an extensive process of Ig gene loss which partially explains a reduced potential repertoire diversity that may contribute to its impaired antibody response.

Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: a randomized, multicenter, placebo-controlled trial Healthcare Worker Exposure Response and Outcomes of Hydroxychloroquine (HERO-HCQ)

To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCWs). In a 1: 1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCWs at risk for COVID-19 infection were enrolled between April and November 2020. Participants were randomized to HCQ or matched placebo. The HCQ dosing included a loading dose of HCQ 600 mg twice on day 1, followed by 400 mg daily for 29 days. The primary outcome was a composite of confirmed or suspected COVID-19 clinical infection by day 30, defined as new-onset fever, cough, or dyspnea and either a positive SARS-CoV-2 polymerase chain reaction test (confirmed) or a lack of confirmatory testing due to local restrictions (suspected). Study enrollment closed before full accrual due to recruitment challenges. The primary end point occurred in 41 (6.0%) participants receiving HCQ and 53 (7.8%) participants receiving placebo. No difference in the proportion of participants experiencing clinical infection (estimated difference of -1.8%, 95% confidence interval -4.6-0.9%, P=0.20) was identified nor any significant safety issues. Oral HCQ taken as prescribed appeared safe among HCWs. No significant clinical benefits were observed. The study was not powered to detect a small but potentially important reduction in infection. NCT04334148.

3D Point-Voxel Correlation Fields for Scene Flow Estimation.

In this paper, we propose Point-Voxel Correlation Fields to explore relations between two consecutive point clouds and estimate scene flow that represents 3D motions. Most existing works only consider local correlations, which are able to handle small movements but fail when there are large displacements. Therefore, it is essential to introduce all-pair correlation volumes that are free from local neighbor restrictions and cover both short- and long-term dependencies. However, it is challenging to efficiently extract correlation features from all-pairs fields in the 3D space, given the irregular and unordered nature of point clouds. To tackle this problem, we present point-voxel correlation fields, proposing distinct point and voxel branches to inquire about local and long-range correlations from all-pair fields respectively. To exploit point-based correlations, we adopt the K-Nearest Neighbors search that preserves fine-grained information in the local region, which guarantees the scene flow estimation precision. By voxelizing point clouds in a multi-scale manner, we construct pyramid correlation voxels to model long-range correspondences, which are utilized to handle fast-moving objects. Integrating these two types of correlations, we propose Point-Voxel Recurrent All-Pairs Field Transforms (PV-RAFT) architecture that employs an iterative scheme to estimate scene flow from point clouds. To adapt to different flow scope conditions and obtain more fine-grained results, we further propose Deformable PV-RAFT (DPV-RAFT), where the Spatial Deformation deforms the voxelized neighborhood, and the Temporal Deformation controls the iterative update process. We evaluate the proposed method on the FlyingThings3D and KITTI Scene Flow 2015 datasets and experimental results show that we outperform state-of-the-art methods by remarkable margins. The code is available at https://github.com/weiyithu/PV-RAFT.

Crossing numbers of complete bipartite graphs

The long standing Zarankiewicz's conjecture states that the crossing number cr(Km,n) of the complete bipartite graph is Z(m,n):= [m/2][m-1/2][n/2][n-1/2]. Using flag algebras we show that cr(Kn,n) ≥ 0.9118 • Z(n, n) + o(n4). We also show that the rectilinear crossing number cr-(Kn,n) of Kn,n is at least 0.987 • Z(n,n) + o(n4). Finally, we show that if a drawing of Kn,n has no K3,4 that has exactly two crossings, and these crossings share exactly one vertex, then it has at least Z(n,n) + o(n4) crossings. This is a local restriction inspired by Turán type problems that gives an asymptotically tight result.

'They're all individuals, none of them are on the same boat': barriers to weight management in general practice from the rural nurse perspective.

To explore nurses' experiences with, and barriers to, obesity healthcare in rural general practice. Obesity is a significant health risk worldwide, which can lead to many other physical and psychosocial health issues that contribute to a poor quality of life. Primary care is considered the most suitable context to deliver obesity management healthcare across the world, including New Zealand, which reportedly has 34% of all adults (and 51% Indigenous Māori) classed as obese. Nurses in primary care have a significant role in the multidisciplinary team and deliver obesity healthcare in general practice contexts. Yet, there is little focus on the nurse perspective of weight management, specifically in rural areas where medical staff and resources are limited, and obesity rates are high. This was a qualitative research design. Semi-structured interviews with 10 rural nurses from indigenous and non-indigenous health providers were analyzed guided by Braun and Clarke () approach to thematic analysis. Three themes were identified: limitations of a nurse role; patient-level barriers; and cultural barriers. Nurses reported experiencing significant barriers to delivering effective weight management in their practice due to factors outside the scope of their practice such as patient-level factors, social determinants of health, rural locality restrictions, and limitations to their role. While this study highlights that practice nurses are versatile with an invaluable skill repertoire, it also demonstrates the near impossibility for rural nurses to meet their rural patient's complex weight management needs, as there are many social determinants of health, sociocultural, and rural locality factors acting as barriers to effective weight management. Nurses experienced a lack of systemic support in the form of time, resources, funding, and effective weight management referral options. Future investigation should look to address the unique rural weight management healthcare needs that experience many barriers.

1727. Phase 1b Dose-ranging Study Demonstrates Tolerability and Pharmacokinetics (PK) of Oral Epetraborole at the Predicted Therapeutic Dosage for Mycobacterium avium Complex (MAC) Lung Disease

Abstract Background Epetraborole (EBO) — an orally available bacterial leucyl transfer RNA synthetase inhibitor with potent activity against nontuberculous mycobacteria — is under clinical development for treatment of MAC lung disease. We conducted a Phase 1b dose-ranging study of EBO tablets in healthy adult volunteers, to inform dose selection in the treatment of MAC lung disease. Methods In this double-blind, placebo-controlled trial, EBO or placebo tablets were administered (n=8/cohort, 3:1 randomization) at dosages of 250-1000 mg q24h or 500 mg or 1000 mg q48h for up to 28 days. Standard Ph1 clinical and laboratory evaluations and treatment-emergent adverse events (TEAEs) were assessed. Based on prior human studies using significantly higher EBO daily doses, gastrointestinal (GI) events and anemia were predetermined AEs of special interest (AESIs). Plasma concentrations of EBO were measured by validated LC-MS/MS methods. Plasma PK parameters were determined using non-compartmental methods. Results A total of 43 subjects were enrolled; the 1000 mg q24h cohort was terminated early due to local COVID restrictions. Overall, 80.6% EBO subjects and 83.3% placebo subjects experienced ≥1 TEAE, none of which was serious or severe (Table). Most TEAEs were mild in severity (90%), and the remainder were moderate (10%). No TEAE leading to withdrawal from study was reported. The most frequent types of TEAEs were GI events (48.4% EBO, 41.7% placebo subjects), the most common being mild nausea. Two subjects had premature discontinuation of EBO due to a TEAE (asymptomatic liver enzyme elevations in a 250 mg q24h subject and mild nausea in a 1000 mg q48h subject). One 1000mg q24h subject had a TEAE of anemia. No clinically significant findings or TEAEs were observed for physical examinations, ECGs, or urine laboratory tests. Plasma Cmax and AUC0-∞ of EBO increased in a linear, dose-proportional manner across cohorts. Tmax was observed at ∼1 h post dose; mean t1/2 ranged from 7.63 to 11.1 h. Conclusion Oral EBO administered for 28-day dosing was generally well tolerated at the predicted therapeutic dose (500mg q24h) Predictable PK characteristics facilitate its use in MAC lung disease Further evaluation in a Phase 2/3 treatment-refractory MAC lung disease study is planned Disclosures Paul B. Eckburg, MD, Paratek Pharmaceuticals, Inc.: Safety Review Board|Spero Therapeutics, Inc.: Advisor/Consultant Sanjay Chanda, PhD, AN2 Therapeutics: Stocks/Bonds George Talbot, MD, AN2 Therapeutics, Inc.: Advisor/Consultant|AN2 Therapeutics, Inc.: Co-founder Christopher M. Rubino, PharmD, Adagio Therapeutics: Grant/Research Support|Amplyx Pharmaceuticals, Inc: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Bravos Biosciences: Ownership Interest|Celdara Medical LLC: Grant/Research Support|Cidara Therapeutics Inc: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Evopoint Biosciences Co.: Grant/Research Support|Fedora Pharmaceuticals: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|ICPD Biosciences, LLC.: Ownership Interest|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Lassen Therapeutics: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Novartis Pharmaceuticals Corp.: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|PureTech Health: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics,: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|TauRx Therapeutics: Grant/Research Support|Tetraphase Pharmaceuticals: Grant/Research Support|tranScrip Partners: Grant/Research Support|Utility Therapeutics: Grant/Research Support|Valanbio Therapeutics, Inc.: Grant/Research Support|VenatoRx: Grant/Research Support|Wockhardt Bio AG: Grant/Research Support.