Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation-assay based diagnostic kit

Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses.

Multivariate Moments Expansion Density: Application of the Dynamic Equicorrelation Model

In this study, we propose a new semi-nonparametric (SNP) density model for describing the density of portfolio returns. This distribution, which we refer to as the multivariate moments expansion (MME), admits any non-Gaussian (multivariate) distribution as its basis because it is specified directly in terms of the basis density’s moments. To obtain the expansion of the Gaussian density, the MME is a reformulation of the multivariate Gram-Charlier (MGC), but the MME is much simpler and tractable than the MGC when positive transformations are used to produce well-defined densities. As an empirical application, we extend the dynamic conditional equicorrelation (DECO) model to an SNP framework using the MME. The resulting model is parameterized in a feasible manner to admit two-stage consistent estimation and it represents the DECO as well as the salient non-Gaussian features of portfolio return distributions. The in- and out-of-sample performance of a MME-DECO model of a portfolio of 10 assets demonstrate that it can be a useful tool for risk management purposes.

Task Competency in the Rights Analytic: Mental Health and the Justification for Rights and Duties

The paper concerns the moral status of persons for the purposes of rights-holding and duty-bearing. Developing from Gewirth’s argument to the Principle of Generic Consistency (PGC) and Beyleveld et al.’s Principle of Precautionary Reasoning, I argue in favour of a capacity-based assessment of the task competencies required for choice-rights and certain duties (within the Hohfeldian analytic). Unlike other, traditional, theories of rights, I claim that precautionary reasoning as to agentic status holds the base justification for rights-holding. If this is the basis for generic legal rights, then the contingent argument must be used to explain communities of rights. Much in the same way as two ‘normal’ adult agents may not have equal rights to be an aeroplane pilot, not all adults hold the same task competencies in relation to the exercise of the generic rights to freedom derived from the PGC. In this paper, I set out to consider the rights held by children, persons suffering from mental illness and generic ‘full’ agents. In mapping the developing ‘portfolio’ of rights and duties that a person carries during their life we might better understand the legal relations of those who do not ostensibly fulfil the criteria of ‘full’ agent.

Liver fat in adults with GH deficiency: comparison to matched controls and the effect of GH replacement

CONTEXT: Existing data regarding the association between growth hormone deficiency (GHD) and liver fat content are conflicting. OBJECTIVE: We aimed i) to assess intrahepatocellular lipid (IHCL) content in hypopituitary adults with GHD compared to matched controls and ii) to evaluate the effect of growth hormone (GH) replacement on IHCL content. DESIGN: Cross-sectional comparison and controlled intervention study. PATIENTS, PARTICIPANTS: Cross-sectional comparison: 22 hypopituitary adults with GHD and 44 healthy controls matched for age, BMI, gender and ethnicity. Intervention study: 9 GHD patients starting GH replacement (GH Rx group), 9 GHD patients not starting replacement therapy (non-GH Rx group). INTERVENTION: Intervention study:GH replacement for 6 months in the GH Rx group, dosage was titrated to achieve normal IGF-1 levels. MAIN OUTCOME MEASURES: IHCL content determined by proton magnetic resonance spectroscopy (1 H MRS). RESULTS: Cross-sectional comparison: There was no difference in IHCL content between GHD patients and healthy controls (1.89% (0.30, 4.03) vs. 1.14% (0.22, 2.32); p=0.2), the prevalence of patients with hepatic steatosis (IHCL of ≥ 5.56%) was similar in the two groups (22.7% vs. 15.9%; chi square probability = 0.4). Intervention study: The change in IHCL content over 6 months did not differ between the GH Rx group and the non-GH Rx group (-0.63 ± 4.53% vs. +0.11 ± 1.46%; p=0.6). CONCLUSIONS: In our study liver fat content and the prevalence of hepatic steatosis did not differ between hypopituitary adults with GHD and matched controls. In GHD patients GH replacement had no effect on liver fat content.

Who controls whom? Interaction dynamics and success of university-industry initiatives

This chapter looks into the importance of having a clear identity of a boundary spanner in determining the role of the partners in a university-industry knowledge transfer programme. It highlights issues around the relationship between the business and the graduate as the boundary spanner, where the university's level of control differs between two programmes: Knowledge Transfer Partnership (KTP) and Knowledge Exchange and Enterprise Network (KEEN) programme. The four case studies illustrate interesting points since the university is the employer for the KTPs associate and the business is the employer for the KEEN associate, whilst successful KTP and KEEN projects rely on a full understanding of the role of the graduate within the business.

Higher-order moments in the theory of diversifying and portfolio composition

This paper examines the role of higher-order moments in portfolio choice within an expected-utility framework. We consider two-, three-, four- and five-parameter density functions for portfolio returns and derive exact conditions under which investors would all be optimally plungers rather than diversifiers. Through comparative statics we show the importance of higher-order risk preference properties, such as riskiness, prudence and temperance, in determining plunging behaviour. Empirical estimates for the S&P500 provide evidence for the optimality of diversification.