Harnessing Science to Solve Global Poverty and Hunger

Text of the Sir John Crawford Memorial Lecture delivered by Peter Doherty, Nobel Laureate, Chairman of the Immunology Department at St. Jude Children's Research Hospital, during CGIAR International Centers Week 1998. Doherty describes the long term nature of research on scientifically complex subjects like AIDS and East Coast Fever, and the challenges of managing this research in a way that permits scientists to pursue long term solutions rather than less consequential, shorter term results. He encourages donors to provide the kind of sustained, unrestricted support that enables CGIAR Centers to pursue long-term objectives that are intrinsically uncertain but that are fundamental to substantive scientific progress

Studies in the experimental pathology of louping-ill encephalitis

Aspects of the pathogenesis and neuropathology of louping-ill encephalitis have been investigated in rodents and sheep. In animals inoculated intraperitoneally virus was detected in the circulation before being isolated from nervous tissue. There was, however, no indication as to the means by which virus particles passed from blood to brain. Replication of virus within the central nervous system appeared to be confined to the cytoplasm of nerve cells. In infant hamster cerebellum virions were found within abnormal cytoplasmic membranes in both Purkinje cells and granule cells. Neurons containing these membranes were depleted of granular endoplasmic reticulum and showed loss of Nissl substance. Chromatolysis was seen also in ventral horn cells of moribund sheep but, although viral antigen was demonstrated in the majority of such cells by immunofluorescence, virus particles were not found on ultrastructural examination. Necrosis of ventral horn cells in sheep was accompanied by diminution in acid phosphatase activity and fragmentation of the Golgi apparatus. Onset of symptoms preceded obvious neuronal loss in 75 per cent, of C57 black mice inoculated intraperitoneally. However in most other experiments nerve cell necrosis could be correlated with neurological dysfunction. In infant hamsters and moribund sheep the distribution patterns of neuronal damage and cells containing virus particles and viral antigen were similar. It is concluded that the basic cause of louping-ill is damage of nerve cells by the virus. Neuronal damage in moribund sheep was most apparent in the vestibular nuclei, the motor nuclei, the Purkinje cells of the cerebellum and the ventral horns of the spinal cord. The telencephalon was relativelyunaffected. This distribution of lesions was seen in animals that were inoculated intracerebrally or subcutaneuosly, and in natural cases. Neuropathological changes were more generalized in mice inoculated intra¬ cerebrally, and were not obviously affected either by the strain of host or the presence of concurrent lesions of scrapie. Severe neuron necrosis was seen in infant hamsters and rats, but not in those more than 14 days old at inoculation. In sheep, however, the severity of lesions was similar in all age groups. No general principle can be formulated to explain the distribution of virus infected nerve cells in animals with louping-ill. Virus was detected in nervous tissue before inflammatory changes were apparent. Severe neuron necrosis was seen in all moribund sheep, and inflammatory changes were most marked in those with the longest incubation times. There were slight generalized inflammatory lesions, which were either perivascular or associated with effete neurons, in all surviving sheep and in subclinically affected hamsters and rats. Inflammation is essentially a secondary phenomenon, which occurs after nerve cells are infected with virus. The perivascular cuff was studied intensively in moribund sheep. Histologically most constituents of the cuff appeared to be of the lymphoid type, with a few classical plasma cells and monocytes. The majority were shown to contain globulin in their cytoplasm, when stained with a fluorescent conjugate prepared against sheep IgG. Electron microscopy showed that most of the perivascular inflammatory cells were plasmacytes. Infiltrating cells were also seen to be of the plasma cell type and were observed to enter nervous tissue without causing any obvious damage to either endothelial cells or their basement membranes. Thus perivascular cuffing in sheep with louping-ill results mainly from migration of circulating plasma cells, or plasma cell precursors, into the central nervous system and is a specific response to the presence of viral antigen in the tissues. The inflammatory reaction is a protective mechanism, and is not responsible for the development of symptoms. In this respect it is unlike the histologically similar delayed allergic reaction

Semiclassical theory of cavity-assisted atom cooling

We present a systematic semiclassical model for the simulation of the dynamics of a single two-level atom strongly coupled to a driven high-finesse optical cavity. From the Fokker-Planck equation of the combined atom-field Wigner function we derive stochastic differential equations for the atomic motion and the cavity field. The corresponding noise sources exhibit strong correlations between the atomic momentum fluctuations and the noise in the phase quadrature of the cavity field. The model provides an effective tool to investigate localisation effects as well as cooling and trapping times. In addition, we can continuously study the transition from a few photon quantum field to the classical limit of a large coherent field amplitude.Comment: 10 pages, 8 figure

Public access to the countryside: An exploration of the costs and benefits of farmland walking trails

To date, estimates of individuals’ willingness to pay (WTP) for access to the countryside have typically been on sites of special interest such as developed walking routes, public rights of way in specific areas, national parks and forests (see Lockwood and Tracy, 1995; Bennett and Tranter, 1997; Crabtree and MacDonald, 1997; Liston-Heyes and Heyes, 1999; Garrod et al., 1998; Bennett et al., 2003; Buckley et al., 2009; Morris et al., 2009). There has been little if any attempt to derive estimates of individuals’ WTP for the provision of walking trails in the wider countryside at a national level. The present study aims to build on previous work by examining the demand for particular types of walking trails through a nationally representative survey of the Irish population. One further advantage of this research is that apart from valuing walking activities in a generic sense this paper investigates what types of investment in facilities associated with walking trails generate the greatest welfare gains. Furthermore, using a nationally representative survey of the farming population this paper examines farmers’ willingness to participate in a hypothetical walking scheme whereby the general public will be allowed access to specific trails. First by way of background this paper will discuss the situation in relation to access rights to the countryside across a number of countries. Second this paper will outline the research approach which is followed with a discussion of the empirical results. Finally this paper will conclude with a discussion of the papers main findings and their implications for the provision of public access to the countryside.This work was funded by the Department of Agriculture, Fisheries and Food under the Stimulus Funding

Optimized strategy for real-time qPCR detection of Onchocerca volvulus DNA in pooled Simulium sp. blackfly vectors

BACKGROUND: Onchocerca volvulus is a filarial parasite that is a major cause of dermatitis and blindness in endemic regions primarily in sub-Saharan Africa. Widespread efforts to control the disease caused by O. volvulus infection (onchocerciasis) began in 1974 and in recent years, following successful elimination of transmission in much of the Americas, the focus of efforts in Africa has moved from control to the more challenging goal of elimination of transmission in all endemic countries. Mass drug administration (MDA) with ivermectin has reached more than 150 million people and elimination of transmission has been confirmed in four South American countries, with at least two African countries having now stopped MDA as they approach verification of elimination. It is essential that accurate data for active transmission are used to assist in making the critical decision to stop MDA, since missing low levels of transmission and infection can lead to continued spread or recrudescence of the disease. METHODOLOGY/PRINCIPAL FINDINGS: Current World Health Organization guidelines for MDA stopping decisions and post-treatment surveillance include screening pools of the Simulium blackfly vector for the presence of O. volvulus larvae using a PCR-ELISA-based molecular technique. In this study, we address the potential of an updated, practical, standardized molecular diagnostic tool with increased sensitivity and species-specificity by comparing several candidate qPCR assays. When paired with heat-stable reagents, a qPCR assay with a mitochondrial DNA target (OvND5) was found to be more sensitive and species-specific than an O150 qPCR, which targets a non-protein coding repetitive DNA sequence. The OvND5 assay detected 19/20 pools of 100 blackfly heads spiked with a single L3, compared to 16/20 for the O150 qPCR assay. CONCLUSIONS/SIGNIFICANCE: Given the improved sensitivity, species-specificity and resistance to PCR inhibitors, we identified OvND5 as the optimal target for field sample detection. All reagents for this assay can be shipped at room temperature with no loss of activity. The qPCR protocol we propose is also simpler, faster, and more cost-effective than the current end-point molecular assays

Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease

Women’s experiences of coping with the sexual side effects of antidepressant medication

A growing body of evidence has highlighted the sexual side effects of selective serotonin reuptake inhibitor (SSRI) medication. Whilst most of the research has focused on the prevalence and treatment of sexual difficulties, little is known about how patients cope with the SSRI-related sexual side effects. The objective of this study was to explore women’s experiences of coping with the sexual side effects of SSRI medication and interpretative phenomenological analysis was employed for an in-depth exploratory study of a sample of 10 women. Four broad themes emerged which are discussed under the following headings: searching, suffering in silence, trying to resolve and accepting what is. The themes provide an insight into the different strategies used by women to cope with the sexual side effects of SSRI medication and highlight the importance of contextualising these difficulties as part of an overall approach to improve the management and treatment of SSRI-related sexual side effects