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

SARS coronavirus pathogenesis and therapeutic treatment design

Through the study of the viral pathogenesis, the mechanisms of disease can be elucidated providing specific targets for therapeutic intervention intended to prevent the development of disease. We conducted four studies to gain a better understanding of SARS-CoV disease pathogenesis and therapeutic design. We conducted two studies to investigate SARS-CoV evolution and adaptation to the human host. We have also investigated the importance of the innate immunity in protection from SARS-CoV disease. Lastly, we evaluated the protective efficacy of vaccination in senescent populations. The prototypic civet SZ16 spike (S) gene was engineered into our epidemic strain infectious clone (icSARS) to create the recombinant icSZ16-S virus. A mutant of icSZ16-S (icSZ16-S K479N) was passaged on human airway epithelial cells (HAE) and resultant "evolved" viruses contained mutations in S that enhanced interactions with the receptor (hACE2) though adaptive mutations differed from those seen during the epidemic. icSARS grew equally well in cells expressing the civet or human receptor while icSZ16-S only grew within civet expressing cells. Dual species tropism is retained by the epidemic strain suggesting it evolved through repeated passage between human and civet hosts. Mice deficient in MyD88 (MyD88-/-), an adapter protein that mediates Toll-like receptor (TLR), IL-1R, and IL-18R signaling, are far more susceptible to mouse adapted SARS-CoV (rMA15) infection. Despite increased viral loads, the expression of multiple proinflammatory cytokines and chemokines within lung tissue was significantly reduced in MyD88-/- mice compared to wild-type mice suggesting that MyD88-mediated innate immune signaling and inflammatory cell recruitment to the lung are required for protection from lethal rMA15 infection. We have developed a senescent BABL/c mouse model of SARS-CoV pathogenesis where infection with the mouse adapted SARS-CoV bearing a GD03 S glycoprotein (rMA15 GD03-S) mortality in senescent mice. We vaccinated senescent mice with Venezuelan equine encephalitis virus replicon particles (VRP) expressing Urbani-S, GD03-S, SZ16-S, a pool of all three S expressing VRPs or control VRPs in a prime/boost regimen. After rMA15 GD03-S infection, all mice in the VRP HA and SZ16-S groups died while Urbani-S, GD03-S and Pool-S groups demonstrated 11, 29, 33% survival rates, respectively

Investigating factors that improve golf scores by comparing statistics of amateur golfers in repeat scramble strokes and one-ball conditions

This study investigated how scores and statistics of amateur golfers changed when self-scramble (SC) was compared to normal play. Participants took two (SC2) to three (SC3) golf strokes each. Scores under these conditions were compared with those from normal round (NR) play to determine to what extent the scores and statistics would improve. Means, standard deviations, repeated measures one-way ANOVA, and a forward stepwise multiple regression analysis were performed for data analysis. The mean total score over nine holes by NR plays was 46.6 strokes, with a significant reduction of 7.7 strokes and 10.6 strokes under SC2 and SC3 conditions, respectively. Even when the three play conditions’ total scores decreased significantly for all subjects, the putt rate was around 38%, suggesting that the ratio of the number of putts per score did not change when play conditions changed. Stepwise multiple regression analysis for NR and SC2 using total score as the dependent variable and each statistic as the independent variables showed that greens in regulation (GIR) predicted 51.2% of the total score for NR; GIR and the One-Putt rate predicted 87.3% of the total score for SC2. These findings indicate that GIR is the most important factor for reducing non-professional golfers’ total scores. This study suggests that players gain experience in reducing their golf scores in a format that is similar to an actual game of golf

Use of intraoperative neural monitoring for prognostication of recovery of vocal mobility and reduction of permanent vocal paralysis after thyroidectomy

Introduction: The benefits of intraoperative neural monitoring (IONM) of recurrent laryngeal nerve (RLN) on post-thyroidectomy vocal cord palsy (VCP) rates are contentious. We wished to study impact of IONM on permanent VCP after thyroidectomy. Methods: Retrospective review of prospective series of 1011 (1539 nerves-at-risk) patients undergoing thyroidectomy without (418, group 1) and with (583, group 2) IONM. Results: There were three recognized nerve injuries in group 1, vs one in group 2 (P =.3). There were no differences in overall VCP rates. However, patients in group 2 with immediate postoperative VCP had higher likelihood of full recovery than patients in group 1 (55 of 56 vs 23 of 29 patients, P =.01), and lower incidence of total permanent VCP (2 of 917 vs 9 of 647 patients, P =.01). Conclusion: Among patients with immediate postoperative VCP after thyroidectomy, IONM is associated with a higher likelihood of regaining normal vocal function. This may be related to better identification of RLN branching in IONM cases

Prognostic performance of TNM8 staging rules in oral cavity squamous cell carcinoma

Background: Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination. Methods: Retrospective study of 297 patients with OCSCC who underwent surgery at our institution. Clinical and pathological data were previously populated from review of medical charts and histological reports. Slides were re-reviewed for depth of invasion measurements. Patients were staged using both TNM7 and TNM8 with overall survival statistics analysed. Results: Overall 118 patients (39.7%) were upstaged using TNM8. Both TNM7 and TNM8 stage categories were highly significant for OS (all p values < 0.0001). Hazard discrimination analysis showed that TNM7 could only differentiate stage III from stage IV disease with significance (OS p = 0.01). In comparison TNM8 could distinguish between stage II and III disease (OS p = 0.047) and between stage III and IV disease (OS p = 0.004). Subsite analysis suggested that both editions of the staging system perform best for tongue primaries. Conclusions: Although TNM8 showed improved hazard discrimination in comparison to TNM7, problems with discriminative ability persisted with 8th edition staging criteria. Large scale validation studies will be required to direct future refinement of the staging rules and to establish if the continued use of a single staging system for all oral cavity subsites is appropriate

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

Anaplastic thyroid cancer: outcomes of trimodal therapy

BACKROUND: The purpose of this study is to assess the impact of trimodal therapy [surgery, chemotherapy and external beam radiotherapy (EBRT)] in patients with anaplastic thyroid cancer (ATC) treated with curative intent. MATERIALS AND METHODS: Retrospective review of patients with ATC treated at a tertiary referral centre between January 2009 and June 2020. Data were collected regarding demographics, histology, staging, treatment and outcomes. RESULTS: Seven patients (4 female) were identified. Median age was 58 years (range 52–83 years). All patients received EBRT with concurrent doxorubicin. Six patients received surgery followed by chemoradiotherapy (CRT), and one underwent neoadjuvant CRT followed by surgery. Median radiological tumour size was 50mm (range 40–90 mm). Six patients had gross extrathyroidal extension and three had N1b disease. Prescribed radiotherapy schedules were 46.4 Gy in 29 bidaily fractions (n = 2, treated 2010), 60 Gy in 30 daily fractions (n = 2), 66Gy in 30 fractions (n = 2) and 70 Gy in 35 fractions (n = 1; patient received neoadjuvant CRT). CRT was discontinued early for two patients due to toxicities. At median follow up of 5.8 months, 42.9% (3/7) patients were alive and disease-free. Only one patient developed a local failure. Three patients died from distant metastases without locoregional recurrence. CONCLUSIONS: Despite poor prognosis of ATC, selected patients with operable tumours may achieve high locoregional control rates with trimodal therapy, with possibility of long-term survival in select cases

Transcriptional Subtyping and CD8 Immunohistochemistry Identifies Patients With Stage II and III Colorectal Cancer With Poor Prognosis Who Benefit From Adjuvant Chemotherapy

This work was funded by Cancer Research UK: C212/A13721 and C11884/A24387Peer reviewedPublisher PD

Management of Advanced Laryngeal Cancer

Squamous cell carcinoma of the larynx continues to be the commonest head and neck cancer in many Western countries. The larynx plays a key role for many essential functions, including breathing, voice production, airway protection, and swallowing. The goals of laryngeal cancer treatment are thus to provide best possible oncologic control, while optimizing functional outcomes. In recent decades, the treatment paradigm for advanced laryngeal cancer has shifted from one of primary surgery (total laryngectomy) as gold standard, toward non-surgical organ-preserving treatment using radiotherapy or chemoradiotherapy. However, concerns have emerged regarding functional outcomes after chemoradiotherapy, as well as possible decreased overall survival in patients with laryngeal cancer. The purpose of the present review is to review surgical and non-surgical options for treatment of advanced laryngeal cancer, as well as the evidence supporting each of these