A Cultural Resources Survey for the Leon Valley Hike and Bike Trail Project, Bexar County, Texas

In early March, 2014, South Texas Archeological Research Services, LLC, conducted a cultural resources survey for the Leon Valley Hike and Bike Trail Project, Bexar County, Texas. The survey focused on discovery and preliminary assessment of archeological resources but also included an estimation of effect to the Huebner-Onion Homestead and Stage Coach Stop Site (41BX1429), which was listed in the National Register of Historic Places. Since the project area was owned by the City of Leon Valley and the project involved federal funding through the Texas Department of Transportation, compliance with the Antiquities Code of Texas and Section 106 of the National Historic Preservation Act was triggered for the project. The survey was conducted according to applicable professional standards and guidelines under Texas Antiquities Permit 6803. Portions of the project area that were previously investigated were not included in the survey, and portions of the area were revised or omitted after completion of the survey. The project, as ultimately revised, consisted of replacement of existing trails, additions of new trails, and construction of concrete bridges at three creek crossings. Not including portions previously examined, the final revised footprint of the area of potential effects to cultural resources for the project was about 1.6 acres of trail rightof-way about 3,500 feet long and 20 feet wide. Except at the creek crossings, where some deeper cutting and filling would be needed, the average anticipated depth of impact for the project was about 6-12 inches. The area of potential effects for indirect effects to non-archeological cultural resources was the area within about 100 feet of the final proposed trail routes not previously surveyed. Background searches revealed that except for prehistoric archeological site 41BX1879, found near the project area in 2012 and later determined ineligible, and the Huebner-Onion Site, no cultural resources were within a kilometer radius of the survey area. Field conditions within most of the area surveyed precluded effective visual surface examination, but patchy surface exposures in the uplands and exposed profiles along Huebner Creek were inspected. Because of shallow soils within most of the area and access limitations, archeological backhoe trenching was neither feasible nor warranted. Sixteen archeological shovel tests were excavated throughout the survey area. Shallow clay soils over limestone or caliche bedrock, or dense clay substrate, were encountered in most of the tests. No archeological evidence was found during the survey and nothing was collected or curated. The Principal Investigator believed that construction of the proposed trail, as finally revised, should not affect any archeological resources. Based on the research and findings a consulting architectural historian and on all revisions to the project plans made to time of this report in June, 2014, the Principal Investigator and architectural historian believed that the project would have no adverse effect on the Huebner-Onion Site. A local historical icon within the survey area, the marker for the presumed gravesite of prominent nineteenth-century settler and stockman Joseph Huebner (1823-1882), was neither listed nor eligible as a landmark. In May, 2014, the segment of the proposed trail leading from the main east-west trail southward to the marker was omitted from the project by the City of Leon Valley, thereby obviating the need for further cultural resource investigations for that segment. Prior to omission, visual inspection and excavation of two archeological shovel tests within the footprint of the segment found no cultural evidence. It was recommended to the City of Leon Valley and its consultants, the Texas Historical Commission, and the Texas Department of Transportation that the project as revised should proceed without further archeological or other cultural resource compliance work, except in the event that cultural resources not found during the survey were found during project-related construction activities. Per applicable statutes and regulations, it was also recommended that in the event of such finds, work should immediately be halted in the vicinity until the finds were examined and evaluated by a qualified archeological consultant and/or the Commission and the Department

Environmental contamination and hygienic measures after feline calicivirus field strain infections of cats in a research facility

Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the presence and viability of FCV in the environment after sequential oronasal infections of specified pathogen-free cats with two FCV field strains in a research facility. Replicating virus was detected in saliva swabs from all ten cats after the first and in four out of ten cats after the second FCV exposure using virus isolation to identify FCV shedders. In the environment, where cleaning, but no disinfection took place, FCV viral RNA was detectable using RT-qPCR on all tested items and surfaces, including cat hair. However, only very limited evidence was found of replicating virus using virus isolation. Viral RNA remained demonstrable for at least 28 days after shedding had ceased in all cats. Disinfection with 5% sodium bicarbonate (and IncidinTM Plus) and barrier measures were effective in that no viral RNA was detectable outside the cat rooms. Our findings are important for any multicat environment to optimize hygienic measures against FCV infection

Modified-live feline calicivirus vaccination elicits cellular immunity against a current feline calicivirus field strain in an experimental geline challenge study

Feline calicivirus (FCV) is a common cat virus associated with oral ulcerations and virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. The high genetic diversity of FCV poses a challenge in vaccine design. Protection against FCV has been related to humoral and cellular immunity; the latter has not been studied in detail. This study investigates the cellular and humoral immune response of specified pathogen-free (SPF) cats after modified-live FCV F9 vaccinations and two heterologous FCV challenges by the analysis of lymphocyte subsets, cytokine mRNA transcription levels, interferon (IFN)-γ release assays in peripheral blood mononuclear cells (PBMCs), anti-FCV antibodies, and neutralisation activity. Vaccinated cats developed a Th1 cytokine response after vaccination. Vaccination resulted in antibodies with neutralising activity against the vaccine but not the challenge viruses. Remarkably, IFN-γ-releasing PBMCs were detected in vaccinated cats upon stimulation with the vaccine strain and the first heterologous FCV challenge strain. After the first experimental infection, the mRNA transcription levels of perforin, granzyme B, INF-γ, and antiviral factor MX1 and the number of IFN-γ-releasing PBMCs when stimulated with the first challenge virus were higher in vaccinated cats compared to control cats. The first FCV challenge induced crossneutralising antibodies in all cats against the second challenge virus. Before the second challenge, vaccinated cats had a higher number of IFN-γ-releasing PBMCs when stimulated with the second challenge virus than control cats. After the second FCV challenge, there were less significant differences detected between the groups regarding lymphocyte subsets and cytokine mRNA transcription levels. In conclusion, modified-live FCV vaccination induced cellular but not humoral crossimmunity in SPF cats; innate immune mechanisms, secretory and membranolytic pathways, and IFN-γ-releasing PBMCs seem to be important in the host immune defence against FCV

Severe acute respiratory syndrome coronavirus 2 serosurveillance in a patient population reveals differences in virus exposure and antibody-mediated immunity according to host demography and healthcare setting

Identifying drivers of SARS-CoV-2 exposure and quantifying population immunity is crucial to prepare for future epidemics. We performed a serial cross-sectional serosurvey throughout the first pandemic wave among patients from the largest health board in Scotland. Screening of 7480 patient sera showed a weekly seroprevalence ranging from 0.10% to 8.23% in primary and 0.21% to 17.44% in secondary care, respectively. Neutralisation assays showed that around half of individuals who tested positive by ELISA assay, developed highly neutralising antibodies, mainly among secondary care patients. We estimated the individual probability of SARS-CoV-2 exposure and quantified associated risk factors. We show that secondary care patients, males and 45-64-year-olds exhibit a higher probability of being seropositive. The identification of risk factors and the differences in virus neutralisation activity between patient populations provided insights into the patterns of virus exposure during the first pandemic wave and shed light on what to expect in future waves

Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalisation

COVID‐19 is caused by a novel coronavirus called severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Virus cell entry is mediated through a protein‐protein interaction (PPI) between the SARS‐CoV‐2 spike protein and angiotensin‐converting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus S‐protein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and in‐vitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for S‐protein RBD binding and prevent virus internalization

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Early entry requirements of feline calicivirus of differing pathogenicities

Abstract not currently available

Incidence of acute respiratory failure cases in West Midlands Ambulance Service (WMAS) – sub-study of ACUTE (ambulance CPAP: use, treatment effect and economics) trial

Background Acute respiratory failure (ARF) is a life-threatening emergency and pre-hospital CPAP may improve outcomes. A CPAP cost-effectiveness determinant is the incidence of eligible patients with ARF. This sub-study of the ACUTE trial aimed to determine the number of adults with ARF potentially suitable for CPAP, presenting to WMAS. Methods This observational study was conducted between 1stAugust 2017 and 31st July 2018. Adult patients presenting with SpO2 <94% were identified from WMAS electronic patient records. Electronic filters applied ACUTE trial inclusion and exclusion criteria, with subsequent manual clinical review by a research paramedic. A second research paramedic checked a sub-sample for inter-rater agreement. Overall and monthly incidence rates were calculated, census data provided the population denominator. Results 108,391 potential patients were identified from electronic patient records (EPR), after filter application 4,526 cases were eligible for review (Figure 1). After review, 1017 cases were considered CPAP candidates. Inter-rater agreement was 86%. Overall incidence was 17.35 per 100,000 population per year (95%CI 16.3–18.5). Marked seasonal variation was present, increasing over winter (Figure 2). Urban areas had the highest proportion of eligible patients (67.6% v 18.3% Rural v 14.2% semi-rural); and 53.0% of all eligible were male. Conclusions The incidence of eligible ARF patients impacts on the cost-effectiveness of pre-hospital CPAP, but previous reports have been variable, using sub-optimal methods or from non-UK settings. We report a valid NHS estimate of 17 patients per 100,000 who do not respond to current pre-hospital ARF management and could be candidates for CPAP., https://emj.bmj.com/content/36/10/e11.3. This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ DOI http://dx.doi.org/10.1136/emermed-2019-999abs.2

Environmental contamination and hygienic measures after feline calicivirus field strain infections of cats in a research facility

Feline calicivirus (FCV) can cause painful oral ulcerations, salivation, gingivitis/stomatitis, fever and depression in infected cats; highly virulent virus variants can lead to fatal epizootic outbreaks. Viral transmission occurs directly or indirectly via fomites. The aim of this study was to investigate the presence and viability of FCV in the environment after sequential oronasal infections of specified pathogen-free cats with two FCV field strains in a research facility. Replicating virus was detected in saliva swabs from all ten cats after the first and in four out of ten cats after the second FCV exposure using virus isolation to identify FCV shedders. In the environment, where cleaning, but no disinfection took place, FCV viral RNA was detectable using RT-qPCR on all tested items and surfaces, including cat hair. However, only very limited evidence was found of replicating virus using virus isolation. Viral RNA remained demonstrable for at least 28 days after shedding had ceased in all cats. Disinfection with 5% sodium bicarbonate (and Incidin$^{TM}$ Plus) and barrier measures were effective in that no viral RNA was detectable outside the cat rooms. Our findings are important for any multicat environment to optimize hygienic measures against FCV infection

Modified-Live Feline Calicivirus Vaccination Reduces Viral RNA Loads, Duration of RNAemia, and the Severity of Clinical Signs after Heterologous Feline Calicivirus Challenge.

Feline calicivirus (FCV) is a common cat virus causing clinical signs such as oral ulcerations, fever, reduced general condition, pneumonia, limping and occasionally virulent-systemic disease. Efficacious FCV vaccines protect against severe disease but not against infection. FCV is a highly mutagenic RNA virus whose high genetic diversity poses a challenge in vaccine design. The use of only one modified-live FCV strain over several decades might have driven the viral evolution towards more vaccine-resistant variants. The present study investigated the clinical signs, duration, and amount of FCV shedding, RNAemia, haematological changes and acute phase protein reaction in SPF cats after subcutaneous modified-live single strain FCV vaccination or placebo injection and two subsequent oronasal heterologous FCV challenge infections with two different field strains. Neither clinical signs nor FCV shedding from the oropharynx and FCV RNAemia were detected after vaccination. After the first experimental infection, vaccinated cats had significantly lower clinical scores, less increased body temperature and lower acute phase protein levels than control cats. The viral RNA loads from the oropharynx and duration and amount of RNAemia were significantly lower in the vaccinated animals. No clinical signs were observed in any of the cats after the second experimental infection. In conclusion, FCV vaccination was beneficial for protecting cats from severe clinical signs, reducing viral loads and inflammation after FCV challenge