Exploration of Effective Spatial Performance of Accessible Neighbourhood Green (Ang), Including its Proportion and Standard Distance from User in Dhanmondi Residential Area, Dhaka

Urban physical context can be analyzed across three key matrixes (3-P) among others i.e. place, path, and people. So, pragmatic analysis of spatial effective performances connecting 3-P, require provoking frequency of people’s experience. Acknowledging this issue, the demand for accessible neighbourhood green (ANG) at an appropriate distance becomes the primary concern to enhance the quality of life and liveability in a city. However, with the continued urban growth and densification, the discrepancy between the demand and supply of open space continues to vary requiring adjustments to remain responsive. The real-life circumstance results in a shortage of parks and open areas in terms of demand and supply within accessible distance in Dhaka city. This paper intends to examine this issue through the case of the planned Dhanmondi Residential Area (DRA) in Dhaka. Despite having provision of multiple open spaces in DRA, visitor’s frequency varies due to age and gender group accessibility conditions and varying distances. Considering existing spatial norms set by Detail Area Plan (DAP), Dhaka structure plan (DSP), and numerous research works on Dhaka open spaces, the major inquiry posed here is whether these open spaces are appropriate for DRA or not. Therefore, the objective of this paper focuses on examining the quality of the physical environment of Neighbourhood public open spaces termed here as accessible neighbourhood green (ANG) in DRA to examine their adequacy concerning proportion and distance synchronized with the frequency of visits. The initial part of the paper focuses on conceptualizing the problem vis-à-vis the existing scenario.  Surveys and interviews have been conducted to assess people’s perceptions in terms of comfort, accessibility, sociability, and user frequency aligned with proximity. The result indicates that the provision of one appropriate ANG within two or three standard blocks apart contribute to enhancing the quality of life for the city dwellers and their liveability

Manipulation of both virus- and cell-specific factors is required for robust transient replication of a hepatitis C virus genotype 3a sub-genomic replicon

Hepatitis C virus (HCV) genotype (GT) 3 is the second most prevalent of the seven HCV genotypes and exhibits the greatest resistance to the highly potent, direct-acting antivirals (DAAs) that are currently in use. Previously a stable cell line harbouring the S52 GT3 subgenomic replicon (SGR) was established, but this SGR was unable to robustly replicate transiently. As transient SGRs are a critical tool in the development of DAAs, and the study of viral resistance, we sought to establish a transient SGR system based on S52. Next generation sequencing was used to identify putative culture-adaptive substitutions that had arisen during long term selection of the S52 SGR. A subset of these substitutions were built back into the S52 SGR in the context of a CpG/UpA-low luciferase reporter, with a single point mutation in NS4A conferring the greatest replication capability upon S52. Modification of the innate immune-sensing pathways of Huh7.5 hepatoma cells by expression of the parainfluenza virus type 5 V protein and SEC14L2 resulted in a further enhancement of S52 replication. Furthermore, this transiently-replicating SGR showed genotype-specific differences in sensitivity to two clinically-relevant NS5A DAAs. In conclusion, we report that a single substitution in NS4A, coupled with host cell modifications, enabled robust levels of transient replication by the GT3 S52 SGR. This system will have beneficial uses in both basic research into the unique aspects of GT3 biology and drug discovery

Calibration of the LIGO displacement actuators via laser frequency modulation

We present a frequency modulation technique for calibration of the displacement actuators of the LIGO 4-km-long interferometric gravitational-wave detectors. With the interferometer locked in a single-arm configuration, we modulate the frequency of the laser light, creating an effective length variation that we calibrate by measuring the amplitude of the frequency modulation. By simultaneously driving the voice coil actuators that control the length of the arm cavity, we calibrate the voice coil actuation coefficient with an estimated 1-sigma uncertainty of less than one percent. This technique enables a force-free, single-step actuator calibration using a displacement fiducial that is fundamentally different from those employed in other calibration methods.Comment: 10 pages, 5 figures, submitted to Classical and Quantum Gravit

Controlling calibration errors in gravitational-wave detectors by precise location of calibration forces

We present results of finite element analysis simulations which could lead to more accurate calibration of interferometric gravitational wave detectors. Calibration and actuation forces applied to the interferometer test masses cause elastic deformation, inducing errors in the calibration. These errors increase with actuation frequency, and can be greater than 50% at frequencies above a few kilohertz. We show that they can be reduced significantly by optimizing the position at which the forces are applied. The Advanced LIGO [1] photon calibrators use a two-beam configuration to reduce the impact of local deformations of the test mass surface. The position of the beams over the test mass can be chosen such both the local and the bulk induced elastic deformation are minimized. Our finite element modeling indicates that with two beams positioned within ±1 mm of their optimal locations, calibration errors due to test mass elastic deformation can be kept below 1% for frequencies up to 3.5 kHz. We thus show that precise control of the location of calibration forces could considerably improve calibration accuracy, especially at high frequencies

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody lateral flow assay for antibody prevalence studies following vaccination: a diagnostic accuracy study

Background: Lateral flow immunoassays (LFIAs) are able to achieve affordable, large scale antibody testing and provide rapid results without the support of central laboratories. As part of the development of the REACT programme extensive evaluation of LFIA performance was undertaken with individuals following natural infection. Here we assess the performance of the selected LFIA to detect antibody responses in individuals who have received at least one dose of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: This was a prospective diagnostic accuracy study. Sampling was carried out at renal outpatient clinic and healthcare worker testing sites at Imperial College London NHS Trust. Two cohorts of patients were recruited; the first was a cohort of 108 renal transplant patients attending clinic following two doses of SARS-CoV-2 vaccine, the second cohort comprised 40 healthcare workers attending for first SARS-CoV-2 vaccination and subsequent follow up. During the participants visit, finger-prick blood samples were analysed on LFIA device, while paired venous sampling was sent for serological assessment of antibodies to the spike protein (anti-S) antibodies. Anti-S IgG was detected using the Abbott Architect SARS-CoV-2 IgG Quant II CMIA. A total of 186 paired samples were collected. The accuracy of Fortress LFIA in detecting IgG antibodies to SARS-CoV-2 compared to anti-spike protein detection on Abbott Assay Results: The LFIA had an estimated sensitivity of 92.0% (114/124; 95% confidence interval [CI] 85.7% to 96.1%) and specificity of 93.6% (58/62; 95% CI 84.3% to 98.2%) using the Abbott assay as reference standard (using the threshold for positivity of 7.10 BAU/ml) Conclusions: Fortress LFIA performs well in the detection of antibody responses for intended purpose of population level surveillance but does not meet criteria for individual testing

Single administration vaccines: delivery challenges, in vivo performance, and translational considerations

Introduction With a limited global supply of vaccines and an increasing vaccine hesitancy, improving vaccination coverage has become a priority. Current vaccination regimes require multiple doses to be administered in a defined schedule where missed doses may lead to incomplete vaccine coverage and failure of immunization programmes. As such, there is an ever-increasing demand to convert multi-dose injectable vaccines into single-dose formats, often called single administration vaccines (SAVs). Areas covered This review summarizes recent developments in the field of SAVs, with a focus on pulsatile or controlled-release formulations. It will identify the technical challenges, translational as well as commercial barriers to SAVs development. Furthermore, the progress of SAV formulations for hepatitis B and polio vaccines will be reviewed thoroughly as case studies, with a focus on the development challenges and the preclinical immunogenicity/reactogenicity data. Expert opinion Despite the efforts to develop SAVs, few attempts have advanced to Phase-I trials. Considering the SAV development journey and bottlenecks, including commercial barriers from the early stages, may overcome some of the hurdles around the technology. The renewed global focus on vaccines since the COVID-19 pandemic could facilitate development of a new generation of technologies for pandemic preparedness including strategies for SAVs

A systematic investigation of production of synthetic prions from recombinant prion protein

According to the protein-only hypothesis, infectious mammalian prions, which exist as distinct strains with discrete biological properties, consist of multichain assemblies of misfolded cellular prion protein (PrP). A critical test would be to produce prion strains synthetically from defined components. Crucially, high-titre 'synthetic' prions could then be used to determine the structural basis of infectivity and strain diversity at the atomic level. While there have been multiple reports of production of prions from bacterially expressed recombinant PrP using various methods, systematic production of high-titre material in a form suitable for structural analysis remains a key goal. Here, we report a novel high-throughput strategy for exploring a matrix of conditions, additives and potential cofactors that might generate high-titre prions from recombinant mouse PrP, with screening for infectivity using a sensitive automated cell-based bioassay. Overall, approximately 20 000 unique conditions were examined. While some resulted in apparently infected cell cultures, this was transient and not reproducible. We also adapted published methods that reported production of synthetic prions from recombinant hamster PrP, but again did not find evidence of significant infectious titre when using recombinant mouse PrP as substrate. Collectively, our findings are consistent with the formation of prion infectivity from recombinant mouse PrP being a rare stochastic event and we conclude that systematic generation of prions from recombinant PrP may only become possible once the detailed structure of authentic ex vivo prions is solved

Implementation, adoption and perceptions of telemental health during the COVID-19 pandemic: a systematic review

BACKGROUND: Early in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health, and to debates on its future use in routine mental health care. OBJECTIVE: To investigate the adoption and impacts of telemental health approaches during the COVID-19 Pandemic, and facilitators and barriers to optimal implementation. METHODS: Four databases (PubMed, PsycINFO, CINAHL and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesised using framework synthesis. RESULTS: A total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified. CONCLUSIONS: Implementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these. CLINICALTRIAL

Multiplexed detection of viral antigen and RNA using nanopore sensing and encoded molecular probes

We report on single-molecule nanopore sensing combined with position-encoded DNA molecular probes, with chemistry tuned to simultaneously identify various antigen proteins and multiple RNA gene fragments of SARS-CoV-2 with high sensitivity and selectivity. We show that this sensing strategy can directly detect spike (S) and nucleocapsid (N) proteins in unprocessed human saliva. Moreover, our approach enables the identification of RNA fragments from patient samples using nasal/throat swabs, enabling the identification of critical mutations such as D614G, G446S, or Y144del among viral variants. In particular, it can detect and discriminate between SARS-CoV-2 lineages of wild-type B.1.1.7 (Alpha), B.1.617.2 (Delta), and B.1.1.539 (Omicron) within a single measurement without the need for nucleic acid sequencing. The sensing strategy of the molecular probes is easily adaptable to other viral targets and diseases and can be expanded depending on the application required