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The development of highly effective and durable vaccines against the human malaria parasites Plasmodium falciparum and P. vivax remains a key priority. Decades of endeavor have taught that achieving this goal will be challenging; however, recent innovation in malaria vaccine research and a diverse pipeline of novel vaccine candidates for clinical assessment provides optimism. With first-generation pre-erythrocytic vaccines aiming for licensure in the coming years, it is important to reflect on how next-generation approaches can improve on their success. Here we review the latest vaccine approaches that seek to prevent malaria infection, disease, and transmission and highlight some of the major underlying immunological and molecular mechanisms of protection. The synthesis of rational antigen selection, immunogen design, and immunization strategies to induce quantitatively and qualitatively improved immune effector mechanisms offers promise for achieving sustained high-level protection., Development of highly effective vaccines against human malaria remains a public health priority. In this Review, Draper et al. describe the latest vaccine approaches to prevent malaria alongside immunological and molecular mechanisms of protection. Rational antigen selection, immunogen design, and novel immunization strategies offer promise for achieving high-level protection.

Length of travel appears to be associated with health risks. GeoSentinel Surveillance Network data for 4,039 long-term travelers (trip duration >6 months) seen after travel during June 1, 1996, through December 31, 2008, were compared with data for 24,807 short-term travelers (trip duration 1 month, eosinophilia, cutaneous leishmaniasis, schistosomiasis, and Entamoeba histolytica diarrhea. Areas of concern for long-term travelers were vector-borne diseases, contact-transmitted diseases, and psychological problems. Our results can help prioritize screening for and diagnosis of illness in long-term travelers and provide evidence-based pretravel advice.

Homocysteine has been implicated in multiple diseases that involve changes in structural tissue. In vitro studies have found that it alters the structure of collagen cross-linking thus affecting stability and mineralization such as that occurring in bone tissue. In the present study we considered the possible relationship between plasma homocysteine levels and the development and progression of knee osteoarthritis (OA).The study question was posed in 691 men and 966 women from the original and offspring cohorts of the Framingham Osteoarthritis Study. We divided individuals into three groups according to plasma homocysteine levels and compared their risk for the development of new and progression of existing OA. We adjusted for potential confounders including age, body mass index, weight change, and physical activity.In the crude analysis, men in the middle homocysteine tertile were found to be at a greater risk than men in the lowest tertile for incident OA [odds ratios of 1.9 (1.1-3.5)]. This result persisted after adjusting for covariates [odds: 2.0, (1.1-3.8)]. No significant correlation was seen in women for the development of OA. In the evaluation of progression no significant trends were seen for both men and women.Although cellular and molecular studies of homocysteine-related pathophysiology suggest a possible correlation between plasma homocysteine levels and OA, the present clinical study did not conclusively demonstrate such an association. However, further research is needed to explore the role of homocysteine in specific aspects of OA etiopathogenesis.

Atypical patterns may indicate onset of epidemic activity., We examined seasonality and annual trends for dengue cases among 522 returned travelers reported to the international GeoSentinel Surveillance Network. Dengue cases showed region-specific peaks for Southeast Asia (June, September), South Central Asia (October), South America (March), and the Caribbean (August, October). Travel-related dengue exhibited annual oscillations with several epidemics occurring during the study period. In Southeast Asia, annual proportionate morbidity increased from 50 dengue cases per 1,000 ill returned travelers in nonepidemic years to an average of 159 cases per 1,000 travelers during epidemic years. Dengue can thus be added to the list of diseases for which pretravel advice should include information on relative risk according to season. Also, dengue cases detected at atypical times in sentinel travelers may inform the international community of the onset of epidemic activity in specific areas.

Background Data on relative rates of acquisition of gastrointestinal infections by travelers are incomplete. The objective of this study was to analyze infections associated with oral ingestion of pathogens in international travelers in relation to place of exposure. Methods We performed a multicenter, retrospective observational analysis of 6,086 travelers ill enough with any gastrointestinal infection to seek medical care at a GeoSentinel clinic after completion of travel during 2000 to 2005. We determined regional and country-specific reporting rate ratios (RRRs) in comparison to risk in northern and western Europe. Results Travel to sub-Saharan Africa (RRR = 282), South America (RRR = 203), and South Asia (RRR = 890) was associated with the greatest rate of gastrointestinal infections. RRRs were moderate (25–142) for travel to Oceania, the Middle East, North Africa, Central America, the Caribbean, and Southeast Asia. RRRs were least (

We have measured the total normalized cross section R for the process e+e− → hadrons at centre-of-mass energies between 14.0 and 46.8 GeV based on an integrated luminosity of 60.3 pb−1. The data are well described by the standard SU(3)c⊗SU(2)L⊗U(1) model with the production of the five known quarks. No open production of a sixth quark with charge 2/3 or 1/3 occurs below a centre-of-mass energy of 46.6 or 46.3 GeV, respectively. A fitting procedure which takes the correlations between measurements into account was used to determine the electroweak mixing angle sin2θw and the strong coupling constant αs(S) in second-order QCD. We applied this procedure to the CELLO data and in addition included the data from other experiments at PETRA and PEP. Both fits give consistent results. The fit to the combined data yields αs(342 GeV2) = 0.165±0.030, and sin2θw = 0.236±0.020. Fixing sin2θw at the world average value of 0.23 yields αs(342GeV2) = 0.169±0.025.

Summary Background Skin disorders are common in travelers. Knowledge of the relative frequency of post - travel-related skin disorders, including their geographic and demographic risk factors, will allow for effective pre-travel counseling, as well as improved post-travel diagnosis and therapeutic intervention. Methods We performed a retrospective study using anonymous patient demographic, clinical, and travel-related data from the GeoSentinel Surveillance Network clinics from January 1997 through February 2006. The characteristics of these travelers and their itineraries were analyzed using SAS 9.0 statistical software. Results A skin-related diagnosis was reported for 4594 patients (18% of all patients seen in a GeoSentinel clinic after travel). The most common skin-related diagnoses were cutaneous larva migrans (CLM), insect bites including superinfected bites, skin abscess, and allergic reaction (38% of all diagnoses). Arthropod-related skin diseases accounted for 31% of all skin diagnoses. Ill travelers who visited countries in the Caribbean experienced the highest proportionate morbidity due to dermatologic conditions. Pediatric travelers had significantly more dog bites and CLM and fewer insect bites compared with their adult counterparts; geriatric travelers had proportionately more spotted fever and cellulitis. Conclusions Clinicians seeing patients post-travel should be alert to classic travel-related skin diseases such as CLM as well as more mundane entities such as pyodermas and allergic reactions. To prevent and manage skin-related morbidity during travel, international travelers should avoid direct contact with sand, soil, and animals and carry a travel kit including insect repellent, topical antifungals, and corticosteroids and, in the case of extended and/or remote travel, an oral antibiotic with ample coverage for pyogenic organisms.

The energy balance of a fusion power station based on the TOKAMAK concept is examined with the aid of a model comprising three distinct elements : the reactor, the energy converter and the reactor operation equipment . The efficiency of each element is expressed in terms of the various energy flows and the product of these efficiencies gives the net station efficiency. The analysis takes account of pulsed operation and has general applicability. Numerical values for the net station efficiency are derived from detailed estimates of the energy flows for a TOKAMAK reactor and its auxiliary equipment operating with advanced energy converters. The derivation of these estimates is given in eleven appendices. The calculated station efficiencies span ranges similar to those quoted for the current generation of fission reactors, though lower than those predicted for HTGR and LMFBR stations. Credible parameter domains for pulsed TOKAMAK operation are firmly delineated and factors inimical to improved performance are indicated. It is concluded that the net thermal efficiency of a TOKAMAK reactor power station based on present designs and using advanced thermal converters will be $\sim$0.3 and is unlikely to exceed 0.33.

5 pp. (1987)., A search for light leptoquarks decaying into a lepton and a quark has been performed using the CELLO detector at the storage ring PETRA. Decay modes have been looked for where the lepton is either a muon or a neutrino, the latter being detected by a high missing transverse momentum. Except for one event previously reported no further two-jet events with two isolated muons were observed. No evidence for pair production of these particles has been found in other final states configurations. Our results are interpreted within a model where leptoquarks appear as a coloured Goldsone multiplet of charges 2/3.A 95% CL upper limit of 0.30 pb is set on the pair production cross section of such leptoquarks, thus excluding masses between 7 and 20.5 GeV.

Progression of knee osteoarthritis (OA) has typically been assessed in the medial tibiofemoral (TF) compartment on the anteroposterior (AP) or posteroanterior (PA) view. We propose a new approach using multiple views and compartments that is likely to be more sensitive to change and reveals progression throughout the knee.We tested our approach in the Multicenter Osteoarthritis Study, a study of persons with OA or at high risk of disease. At baseline and 30 months, subjects provided PA (fixed flexion without fluoro) and lateral weight-bearing knee radiographs. Paired radiographs were read by 2 readers who scored joint space (JS) using a 0-3 atlas-based scale. When JS narrowed but narrowing did not reach a full grade on the scale, readers used half-grades. Change was scored in medial and lateral TF compartments on both PA and lateral views and in the patellofemoral (PF) joint on lateral view. A knee showed progression when there was at least a half-grade worsening in JS width in any compartment at followup. Disagreements were adjudicated by a panel of 3 readers. To validate progression, we tested definitions for TF progression to see if malalignment on long-limb radiographs at baseline (or=3 degrees malaligned in any direction with nonmalaligned knees being reference) increased risk of progression. A valid definition of progression would show that malalignment strongly predicted progression.We studied 842 knees with either Kellgren-Lawrence gradeor=2 or PF OA at baseline in 606 subjects (age range 50-79 yrs, mean 63.9 yrs; 66.6% women). Mean body mass index was 31.9, and 32.8% of knees had frequent knee pain at baseline. Of these, 500 knees (59.4%) showed progression. Of the 500, 75 (15%) had progression only in the PF joint, while the remainder had progression in the TF joint. Malalignment increased the risk of overall progression in TF joint and increased the risk of half-grade progression, suggesting that half-grade progression had validity.PA and lateral views obtained in persons at high risk of OA progression can produce a cumulative incidence of progression above 50% at 30 months. Keys to increasing the yield include imaging PF and lateral compartments, using semiquantitative scales designed to detect change, and examining more than one radiographic view.