Retinal Degeneration Progression Changes Lentiviral Vector Cell Targeting in the Retina

In normal mice, the lentiviral vector (LV) is very efficient to target the RPE cells, but transduces retinal neurons well only during development. In the present study, the tropism of LV has been investigated in the degenerating retina of mice, knowing that the retina structure changes during degeneration. We postulated that the viral transduction would be increased by the alteration of the outer limiting membrane (OLM). Two different LV pseudotypes were tested using the VSVG and the Mokola envelopes, as well as two animal models of retinal degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After light damage, the OLM is altered and no significant increase of the number of transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the Rho-/- mice, an alteration of the OLM was also observed, but the possibility of transducing photoreceptors was decreased, probably by ongoing gliosis. The use of a ubiquitous promoter allows better photoreceptor transduction, suggesting that photoreceptor-specific promoter activity changes during late stages of photoreceptor degeneration. However, the number of targeted photoreceptors remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide dispersion of the vector into the retina (corresponding to the injection bleb) with preferential targeting of Müller cells, a situation which does not occur in the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer these glial cells to deliver secreted therapeutic factors to a diseased area of the retina

Chinese multinationals: host country factors and foreign direct investment location

The study of Chinese multinationals (MNEs) is becoming one of the most promising research topics in the international business literature. After outlining the distinctive characteristics of the internationalization process of Chinese MNEs, this chapter analyzes the influence of various host country factors on the location of Chinese outward foreign direct investment (FDI). From a sample of 189 outward FDI decisions made by 35 mainland Chinese firms in 63 countries, our results show that host market size and the existence of overseas Chinese in the host country are positively associated with the number of Chinese FDIs. However, greater difficulty in doing business and host country political risk have no effect

The use of discrete choice experiments to inform health workforce policy: a systematic review.

BACKGROUND: Discrete choice experiments have become a popular study design to study the labour market preferences of health workers. Discrete choice experiments in health, however, have been criticised for lagging behind best practice and there are specific methodological considerations for those focused on job choices. We performed a systematic review of the application of discrete choice experiments to inform health workforce policy. METHODS: We searched for discrete choice experiments that examined the labour market preferences of health workers, including doctors, nurses, allied health professionals, mid-level and community health workers. We searched Medline, Embase, Global Health, other databases and grey literature repositories with no limits on date or language and contacted 44 experts. Features of choice task and experimental design, conduct and analysis of included studies were assessed against best practice. An assessment of validity was undertaken for all studies, with a comparison of results from those with low risk of bias and a similar objective and context. RESULTS: Twenty-seven studies were included, with over half set in low- and middle-income countries. There were more studies published in the last four years than the previous ten years. Doctors or medical students were the most studied cadre. Studies frequently pooled results from heterogeneous subgroups or extrapolated these results to the general population. Only one third of studies included an opt-out option, despite all health workers having the option to exit the labour market. Just five studies combined results with cost data to assess the cost effectiveness of various policy options. Comparison of results from similar studies broadly showed the importance of bonus payments and postgraduate training opportunities and the unpopularity of time commitments for the uptake of rural posts. CONCLUSIONS: This is the first systematic review of discrete choice experiments in human resources for health. We identified specific issues relating to this application of which practitioners should be aware to ensure robust results. In particular, there is a need for more defined target populations and increased synthesis with cost data. Research on a wider range of health workers and the generalisability of results would be welcome to better inform policy

Synthesising Corporate Responsibility on Organisational and Societal Levels of Analysis: An Integrative Perspective

This article develops an integrative perspective on corporate responsibility by synthesising competing perspectives on the responsibility of the corporation at the organisational and societal levels of analysis. We review three major corporate responsibility perspectives, which we refer to as economic, critical, and politico-ethical. We analyse the major potential uses and pitfalls of the perspectives, and integrate the debate on these two levels. Our synthesis concludes that when a society has a robust division of moral labour in place, the responsibility of a corporation may be economic (as suggested under the economic perspective) without jeopardising democracy and sustainability (as reported under the critical perspective). Moreover, the economic role of corporations neither signifies the absence of deliberative democratic mechanisms nor business practices extending beyond compliance (as called for under the politico-ethical perspective). The study underscores the value of integrating different perspectives and multiple levels of analysis to present comprehensive descriptions and prescriptions of the responsibility phenomenon

An investigation into the optimal number of distractors in single-best answer exams

In UK medical schools, five-option single-best answer (SBA) questions are the most widely accepted format of summative knowledge assessment. However, writing SBA questions with four effective incorrect options is difficult and time consuming, and consequently, many SBAs contain a high frequency of implausible distractors. Previous research has suggested that fewer than five-options could hence be used for assessment, without deterioration in quality. Despite an existing body of empirical research in this area however, evidence from undergraduate medical education is sparse. The study investigated the frequency of non-functioning distractors in a sample of 480 summative SBA questions at Cardiff University. Distractor functionality was analysed, and then various question models were tested to investigate the impact of reducing the number of distractors per question on examination difficulty, reliability, discrimination and pass rates. A survey questionnaire was additionally administered to 108 students (33 % response rate) to gain insight into their perceptions of these models. The simulation of various exam models revealed that, for four and three-option SBA models, pass rates, reliability, and mean item discrimination remained relatively constant. The average percentage mark however consistently increased by 1–3 % with the four and three-option models, respectively. The questionnaire survey revealed that the student body had mixed views towards the proposed format change. This study is one of the first to comprehensively investigate distractor performance in SBA examinations in undergraduate medical education. It provides evidence to suggest that using three-option SBA questions would maximise efficiency whilst maintaining, or possibly improving, psychometric quality, through allowing a greater number of questions per exam paper