A Plasma Survey Using 38 PfEMP1 Domains Reveals Frequent Recognition of the Plasmodium falciparum Antigen VAR2CSA among Young Tanzanian Children

PfEMP1 proteins comprise a family of variant antigens that appear on the surface of P. falciparum-infected erythrocytes and bind to multiple host receptors. Using a mammalian expression system and BioPlex technology, we developed an array of 24 protein constructs representing 38 PfEMP1 domains for high throughput analyses of receptor binding as well as total and functional antibody responses. We analyzed the reactivity of 561 plasma samples from 378 young Tanzanian children followed up to maximum 192 weeks of life in a longitudinal birth cohort. Surprisingly, reactivity to the DBL5 domain of VAR2CSA, a pregnancy malaria vaccine candidate, was most common, and the prevalence of reactivity was stable throughout early childhood. Reactivity to all other PfEMP1 constructs increased with age. Antibodies to the DBL2βC2PF11_0521 domain, measured as plasma reactivity or plasma inhibition of ICAM1 binding, predicted reduced risk of hospitalization for severe or moderately severe malaria. These data suggest a role for VAR2CSA in childhood malaria and implicate DBL2βC2PF11_0521 in protective immunity

The Regge Limit for Green Functions in Conformal Field Theory

We define a Regge limit for off-shell Green functions in quantum field theory, and study it in the particular case of conformal field theories (CFT). Our limit differs from that defined in arXiv:0801.3002, the latter being only a particular corner of the Regge regime. By studying the limit for free CFTs, we are able to reproduce the Low-Nussinov, BFKL approach to the pomeron at weak coupling. The dominance of Feynman graphs where only two high momentum lines are exchanged in the t-channel, follows simply from the free field analysis. We can then define the BFKL kernel in terms of the two point function of a simple light-like bilocal operator. We also include a brief discussion of the gravity dual predictions for the Regge limit at strong coupling.Comment: 23 pages 2 figures, v2: Clarification of relation of the Regge limit defined here and previous work in CFT. Clarification of causal orderings in the limit. References adde

Plasmodium falciparum Transcriptome Analysis Reveals Pregnancy Malaria Associated Gene Expression

gene.-exposed women than from men.These findings suggest that other parasite proteins, such as PFI1785w, may contribute beside VAR2CSA to the pathogenesis of PAM. These data may be very valuable for future vaccine development

Frailty and Its Impact on Health-Related Quality of Life: A Cross-Sectional Study on Elder Community-Dwelling Preventive Health Service Users

BACKGROUND: The purpose of this study was to identify the incidence of frailty and to investigate the relationship between frailty status and health-related quality of life (HRQoL) in the community-dwelling elderly population who utilize preventive health services. METHODS: People aged 65 years and older who visited a medical center in Taipei City from March to August in 2011 for an annual routine check-up provided by the National Health Insurance were eligible. A total of 374 eligible elderly adults without cognitive impairment had a mean age of 74.6±6.3 years. Frailty status was determined according to the Fried frailty criteria. HRQoL was measured with Short Form-36 (SF-36). Multiple regression analyses examined the relationship between frailty status and the two summary scales of SF-36. Models were adjusted for the participants' sociodemographic and health status. RESULTS: After adjusting for sociodemographic and health-related covariables, frailty was found to be more significantly associated (p<0.001) with lower scores on both physical and mental health-related quality of life summary scales compared with robustness. For the frailty phenotypes, slowness represented the major contributing factor in the physical component scale of SF-36, and exhaustion was the primary contributing factor in the mental component scale. CONCLUSION: The status of frailty is closely associated with HRQoL in elderly Taiwanese preventive health service users. The impacts of frailty phenotypes on physical and mental aspects of HRQoL differ

Discussing prognosis with older people with musculoskeletal pain: a cross-sectional study in general practice

<p>Abstract</p> <p>Background</p> <p>Prognosis has been described as an important but neglected branch of clinical science. While patients' views have been sought in the context of life-threatening illness, similar research is lacking for patients presenting with common, non-life-threatening musculoskeletal complaints. The aim of this study was to gauge whether and why older patients with musculoskeletal pain think prognostic information is important, and how often they felt prognosis was discussed in the general practice consultation.</p> <p>Methods</p> <p>A cross-sectional survey of consecutive patients aged 50 years of over presenting with non-inflammatory musculoskeletal pain to 5 Central Cheshire general practices. The frequency of responses to the prognostic questions were described and the association with sociodemographic, presenting pain complaint, and psychosocial variables explored using logistic regression.</p> <p>Results</p> <p>502 participants (77%) responded to the postal questionnaire. 165 (33%) participants reported discussing prognosis in the consultation with their GP. Discussions about prognosis were more often reported by male patients (OR 1.72, 95% CI 1.09, 2.71) and those for whom this was their first consultation (OR 1.81, 95% CI 1.16, 2.80). 402 (82%) participants thought that prognostic information was important. This was highest among those currently in paid employment (OR 2.95, 95% CI 1.33, 6.57). The reasons patients gave for believing prognostic information was important included 'knowing for the sake of knowing' and planning future activity. Reasons for not believing prognostic information to be important included the belief that progression of pain was inevitable and that nothing could be done to help.</p> <p>Conclusion</p> <p>Prognostic information is thought to be important amongst older people with musculoskeletal pain yet discussions occur infrequently in primary care. Barriers to effective prognostic communication and the exact information needs of patients are still unknown and warrant further research.</p

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Multiple Chronic Conditions: Prevalence, Health Consequences, and Implications for Quality, Care Management, and Costs

Persons with multiple chronic conditions are a large and growing segment of the US population. However, little is known about how chronic conditions cluster, and the ramifications of having specific combinations of chronic conditions. Clinical guidelines and disease management programs focus on single conditions, and clinical research often excludes persons with multiple chronic conditions. Understanding how conditions in combination impact the burden of disease and the costs and quality of care received is critical to improving care for the 1 in 5 Americans with multiple chronic conditions. This Medline review of publications examining somatic chronic conditions co-occurring with 1 or more additional specific chronic illness between January 2000 and March 2007 summarizes the state of our understanding of the prevalence and health challenges of multiple chronic conditions and the implications for quality, care management, and costs

Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets

Abstract Variant surface antigens (VSAs) play a critical role in severe malaria pathogenesis. Defining gaps, or “lacunae”, in immunity to these Plasmodium falciparum antigens in children with severe malaria would improve our understanding of vulnerability to severe malaria and how protective immunity develops. Using a protein microarray with 179 antigen variants from three VSA families as well as more than 300 variants of three other blood stage P. falciparum antigens, reactivity was measured in sera from Malian children with cerebral malaria or severe malarial anaemia and age-matched controls. Sera from children with severe malaria recognized fewer extracellular PfEMP1 fragments and were less reactive to specific fragments compared to controls. Following recovery from severe malaria, convalescent sera had increased reactivity to certain non-CD36 binding PfEMP1s, but not other malaria antigens. Sera from children with severe malarial anaemia reacted to fewer VSAs than did sera from children with cerebral malaria, and both of these groups had lacunae in their seroreactivity profiles in common with children who had both cerebral malaria and severe malarial anaemia. This microarray-based approach may identify a subset of VSAs that could inform the development of a vaccine to prevent severe disease or a diagnostic test to predict at-risk children