Risk reduction and diversification in UK commercial property portfolios

The issue of diversification in direct real estate investment portfolios has been one of the most widely studied topics in academic and practitioner literature. Most work, however, has been done using mean returns and risks for broad market segments as inputs to asset allocation models, or in a few cases using data from small sets of individual properties. This paper reports results from a comprehensive testing of asset allocation modelling drawing on records of 10,000+ UK properties tracked by Investment Property Databank. It provides for the first time robust estimates of the diversification gains attainable given return, risk and cross-correlations across individual properties actually available to fund managers. The discussion of results covers implications for the number of assets and amount of money needed to construct “balanced” portfolios by direct investment, or via indirect specialist vehicles.Publisher PD

Final Report

Forest products provide essential resources for human civilization, including energy and materials. In processing forest products, however, unwanted byproducts, such as volatile organic compounds (VOCs) and hazardous air pollutants (HAPs) are generated. The goal of this study was to develop a cost effective and reliable air pollution control system to reduce VOC and HAP emissions from pulp, paper and paperboard mills and solid wood product facilities. Specifically, this work focused on the removal of VOCs and HAPs from high volume low concentration (HVLC) gases, particularly methanol since it is the largest HAP constituent in these gases. Three technologies were developed and tested at the bench-scale: (1) A novel composite material of activated carbon coated with a photocatalyst titanium dioxide (TiO{sub 2}) (referred to as TiO{sub 2}-coated activated carbon or TiO{sub 2}/AC), (2) a novel silica gel impregnated with nanosized TiO{sub 2} (referred to as silica-titania composites or STC), and (3) biofiltration. A pilot-scale reactor was also fabricated and tested for methanol removal using the TiO{sub 2}/AC and STC. The technical feasibility of removing methanol with TiO{sub 2}/AC was studied using a composite synthesized via a spay desiccation method. The removal of methanol consists of two consecutive operation steps: removal of methanol using fixed-bed activated carbon adsorption and regeneration of spent activated carbon using in-situ photocatalytic oxidation. Regeneration using photocatalytic oxidation employed irradiation of the TiO{sub 2} catalyst with low-energy ultraviolet (UV) light. Results of this technical feasibility study showed that photocatalytic oxidation can be used to regenerate a spent TiO{sub 2}/AC adsorbent. A TiO{sub 2}/AC adsorbent was then developed using a dry impregnation method, which performed better than the TiO{sub 2}/AC synthesized using the spray desiccation method. The enhanced performance was likely a result of the better distribution of TiO2 particles on the activated carbon surface. A method for pore volume impregnation using microwave irradiation was also developed. A commercial microwave oven (800 W) was used as the microwave source. Under 2450 MHz microwave irradiation, TTIP was quickly hydrolyzed and anatase TiO2 was formed in a short time (< 20 minutes). Due to the volumetric heating and selective heating of microwave, the solvent and by-products were quickly removed which reduced energy consumption and processing time. Activated carbon and TiO{sub 2}/AC were also tested for the removal of hydrogen sulfide, which was chosen as the representative total reduced sulfur (TRS) species. The BioNuchar AC support itself was a good H{sub 2}S remover. After coating TiO{sub 2} by dry impregnation, H{sub 2}S removal efficiency of TiO{sub 2}/AC decreased compared with the virgin AC due to the change of surface pH. Under UV light irradiation, H{sub 2}S removal efficiency of TiO{sub 2}/AC composite doubled, and its sulfate conversion efficiency was higher than that of AC. The formation of sulfate is preferred since the sulfate can be removed from the composite by rising with water. A pilot-scale fluidized bed reactor was designed to test the efficiency of methanol oxidation with TiO{sub 2}/AC in the presence of UV light. TiO{sub 2}/AC was prepared using the spray desiccation method. The TiO{sub 2}/AC was pre-loaded with (1) methanol (equivalent to about 2%wt) and (2) methanol and water. When the TiO{sub 2}/AC loaded with methanol only was exposed to UV light for one hour in the reactor, most of the methanol remained in the carbon pores and, thus, was not oxidized. The TiO{sub 2}/AC loaded with methanol and water desorbed about 2/3 of the methanol from its pores during fluidization, however, only a small portion of this desorbed methanol was oxidized. A biofilter system employing biological activated carbon was developed for methanol removal. The biofilter contained a mixed packing with Westvaco BioNuchar granular activated carbon, perlite, Osmocote slow release ammonium nitrate pellets, and Agrasoke water crystals in a 4:2:1:1 ratio by volume. The biofilter was inoculated with a bacterial culture collected from a Florida pulp and paperboard plant. A non-inoculated biofilter column was also tested. Use of a biological inoculum enriched from biofilm in the pulp and paper process has the potential to enhance the performance of a GAC biofilter. During testing, packing material was removed from the inlet and oulet of the biofilters and analyzed for genetic diversity using molecular techniques. The biofilter inoculated with specifically-enhanced inoculum showed higher bacterial diversity for methylotrophs and all bacteria, as compared to a non-inoculated biofilter. Mixed methylotrophic cultures, selected as potential biofilter inocula, showed increased methanol removal with highest concentrations of nitrogen provided as nitrate

A Mechanism‐based Pharmacokinetic Model of Remdesivir Leveraging Interspecies Scaling to Simulate COVID‐19 Treatment in Humans

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak initiated the global COVID-19 pandemic resulting in 42.9 million confirmed infections and >1.1 million deaths worldwide as of October 26, 2020. Remdesivir is a broad-spectrum nucleotide prodrug shown to be effective against enzootic coronaviruses. The pharmacokinetics (PK) of remdesivir in plasma have recently been described. However, the distribution of its active metabolite nucleoside triphosphate (NTP) to the site of pulmonary infection is unknown in humans. Our objective was to use existing in vivo mouse PK data for remdesivir and its metabolites to develop a mechanism-based model to allometrically scale and simulate the human PK of remdesivir in plasma and NTP in lung homogenate. Remdesivir and GS-441524 concentrations in plasma and total phosphorylated nucleoside concentrations in lung homogenate from Ces1c-/- mice administered 25 or 50 mg/kg of remdesivir subcutaneously were simultaneously fit to estimate PK parameters. The mouse PK model was allometrically scaled to predict human PK parameters to simulate the clinically recommended 200 mg loading dose followed by 100 mg daily maintenance doses administered as 30-minute intravenous infusions. Simulations of unbound remdesivir concentrations in human plasma were below 2.48 μM, the 90% maximal inhibitory concentration for SARS-CoV-2 inhibition in vitro. Simulations of NTP in lung were below high efficacy in vitro thresholds. We have identified a need for alternative dosing strategies to achieve more efficacious concentrations of NTP in human lung, perhaps by reformulating remdesivir for direct pulmonary delivery

Neuroendocrine regulation of dry matter intake in grazing dairy cows

Supplementary feeds are offered to grazing dairy cows to increase dry matter and metabolizable energy intakes; however, offering feed supplements reduces pasture dry matter intake, a phenomenon known as substitution. The objective of this research was to understand variations in grazing behaviour in pasture-fed cows and the effects of supplementation on grazing time and feeding intake rate throughout the day and to investigate humoral profiles of factors known to be associated with intake regulation in monogastric species and quantify their role in ruminant species. Grazing occurred predominately during daylight hours, with minimal grazing during the hours of darkness. Distinct grazing bouts were evident post sunrise and pre-sunset. Supplementation reduced time spent grazing; however, this was an accumulation of reduced grazing time throughout the day and was not restricted to the period following the consumption of supplement, as fundamentally, the profile of grazing behaviour in supplemented cows followed the same pattern as unsupplemented cows. The effects of supplementation on time spent grazing differed depending on the time of day. Time spent grazing linearly reduced with increasing supplement in the a.m., whereas, time spent grazing was unaffected by supplementation during the pre-sunset grazing bout, irrespective of supplement level or timing of sunset. The differences in grazing behaviour during the major post-sunrise and pre-sunset grazing events lead to the hypothesis that different factors regulate dry matter intake at these times. In the a.m., products of digestion and associated physiological factors regulate grazing behaviour. Whereas, in the p.m., environmental cues (i.e. sunset) override physiological signals that regulate grazing behaviour in the a.m. to ensure maximal grazing occurs prior to darkness, irrespective of supplementation or energy balance status. Humoral profiles of factors implicated in intake regulation in monogastric species were similar in the dairy cow. Humoral factors associated with a fasted or pre-prandial state were elevated and declined after meal initiation, whereas, factors indicating a change from a negative to a positive energy state increased after meal initiation. Despite the similar humoral profiles, the profile of plasma ghrelin during the major p.m. feeding event differed from its reported decrease in concentration after feeding, establishing a unique profile for ghrelin. Plasma ghrelin increased in the p.m. despite intensive grazing/feeding and cows being in a positive energy state prior to the p.m. feeding event, which had not been previously reported in ruminant species. The increase in ghrelin was coincident with an increase in the intensity of grazing/feeding that lead to the hypothesis that ghrelin increases in diurnal species ensuring animals maximise dry matter intake prior to darkness, which is a major environmental cue to cease grazing/feeding

Timing of supplementation alters grazing behavior and milk production response in dairy cows

Offering feed supplements to grazing dairy cows results in substitution of pasture; however, previous data indicate that the time at which concentrate supplements are offered might affect the level of substitution. These data indicated that cows grazed more intensely presunset, regardless of the amount of supplement offered. It was, therefore, hypothesized that substitution rate would be less, and response to supplement greater if cows received their supplement at the p.m. rather than the a.m. milking. Forty-eight multiparous, nonpregnant, Holstein-Friesian cows, approximately 60 d in milk, were randomly allocated to 1 of 3 treatments in an incomplete crossover arrangement. Treatments were pasture only, pasture + 3 kg of concentrate supplement dry matter (DM) offered during the a.m. milking (AM-SUP), and pasture + 3. kg of concentrate supplement DM offered during the p.m. milking (PM-SUP). Time spent grazing and calculated pasture DM intake did not differ between the AM-SUP and PM-SUP cows. However, a tendency (0.18 kg of milk/kg of concentrate DM) was observed for an increased marginal milk response (kg of milk/kg of DM supplement) for the AM-SUP cows when compared with PM-SUP cows. Irrespective of when supplements were offered, supplementation reduced total grazing time by a similar amount, and the reduction in time spent grazing was evident throughout the day. Cows in the PM-SUP group ruminated for longer and cows in the AM-SUP group spent more time idle compared with the pasture only groups. Cows in the AM-SUP group grazed for less time during the major a.m. grazing bout following a.m. milking compared with PM-SUP cows; in comparison, the major p.m. grazing bout following p.m. milking was unaffected by supplementation. The results indicated possible improvements in marginal milk response to supplements from altering the timing of delivery. © 2013 American Dairy Science Association

Immunogenicity and safety of SARS-CoV-2 recombinant protein nanoparticle vaccine GBP510 adjuvanted with AS03: interim results of a randomised, active-controlled, observer-blinded, phase 3 trialResearch in context

Summary: Background: GBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) in healthy adults aged ≥18 years, up to 6 months after the second dose. Methods: This was a randomised, active-controlled, observer-blinded, parallel group, phase 3 study, conducted at 38 sites across six countries (South Korea, Philippines, Thailand, Vietnam, Ukraine and New Zealand). Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination) was randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety), while Cohort 2 (regardless of baseline serostatus) was randomised 5:1 (safety). Primary objectives were to demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 vs. ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity (long-term 6 months cut-off date: 09 August 2022). This study was registered on ClinicalTrials.gov (NCT05007951). Findings: Between 30 August 2021 and 11 January 2022, a total of 4913 participants were screened and 4036 participants (1956 in Cohort 1 and 2080 in Cohort 2) who met eligibility criteria were enrolled and randomised to receive 2 doses of GBP510/AS03 (n = 3039) or ChAdOx1-S (n = 997). Most participants were Southeast Asian (81.5%) and aged 18–64 years (94.7%). The primary objectives assessed in per-protocol set included 877 participants in GBP510/AS03 and 441 in ChAdOx1-S group: at 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03/ChAdOx1-S) in per-protocol set was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1) of GBP510/AS03; the between-group SCR difference of 10.8% (95% CI 7.68–14.32) also satisfied the non-inferiority criterion (95% CI lower limit > −5%). Neutralizing antibody titres sustained higher for the GBP510/AS03 group compared to the ChAdOx1-S group through 6 months after the second vaccination. In Safety analysis (Cohort 1 & 2), the proportion of participants with adverse events (AEs) after any vaccination was higher with GBP510/AS03 vs. ChAdOx1-S for solicited local AEs (56.7% vs. 49.2%), but was similar for solicited systemic AEs (51.2% vs. 53.5%) and unsolicited AEs (13.3% vs. 14.6%) up to 28 days after the second vaccination. No safety concerns were identified during follow-up for 6 months after the second vaccination. Interpretation: Our interim findings suggested that GBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study