Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum

Background Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood. Methods We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42). Results Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied. Conclusions Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria

Small bowel adenocarcinoma in a patient with Coeliac disease: A case report

Coeliac disease is a chronic inflammatory disease of the gut with increased risk of gastrointestinal malignancy. Although enteropathy T-lymphoma is the most common neoplasm in patient affected by coeliac disease, an increased frequency of small bowel carcinoma has been described. We present a case of jejunal carcinoma in a patient suffering for coeliac disease in which gastrointestinal and extraintestinal symptoms of disease developed although he was treated with a gluten-free diet

Torosaurus Is Not Triceratops: Ontogeny in Chasmosaurine Ceratopsids as a Case Study in Dinosaur Taxonomy

Background: In horned dinosaurs, taxonomy is complicated by the fact that the cranial ornament that distinguishes species changes with age. Based on this observation, it has been proposed that the genera Triceratops and Torosaurus are in fact synonymous, with specimens identified as Torosaurus representing the adult form of Triceratops. The hypothesis of synonymy makes three testable predictions: 1) the species in question should have similar geographic and stratigraphic distributions, 2) specimens assigned to Torosaurus should be more mature than those assigned to Triceratops, and 3) intermediates should exist that combine features of Triceratops and Torosaurus. The first condition appears to be met, but it remains unclear whether the other predictions are borne out by the fossil evidence. Methodology/Principal Findings: We assessed the relative maturity of Torosaurus and Triceratops specimens by coding skulls for characters that vary with maturity, and then using a clustering analysis to arrange them into a growth series. We found that a well-defined sequence of changes exists in horned dinosaurs: development of cranial ornament occurs in juveniles, followed by fusion of the skull roof in subadults, and finally, the epoccipitals, epijugals, and rostral fuse to the skull in adults. Using this scheme, we identified mature and immature individuals of both Torosaurus and Triceratops. Furthermore, we describe the ventral depressions on the frill of Triceratops, and show that they differ in shape and position from the parietal fenestrae of Torosaurus. Thus, we conclude that these structures are not intermediates between the soli

Targeted case finding for chronic obstructive pulmonary disease versus routine practice in primary care (TargetCOPD): a cluster-randomised controlled trial.

BACKGROUND: Many individuals with chronic obstructive pulmonary disease (COPD) remain undiagnosed worldwide. Health-care organisations are implementing case-finding programmes without good evidence of which are the most effective and cost-effective approaches. We assessed the effectiveness and cost-effectiveness of two alternative approaches to targeted case finding for COPD compared with routine practice. METHODS: In this cluster-randomised controlled trial, participating general practices in the West Midlands, UK, were randomly assigned (1:1), via a computer-generated block randomisation sequence, to either a targeted case-finding group or a routine care group. Eligible patients were ever-smokers aged 40-79 years without a previously recorded diagnosis of COPD. Patients in the targeted case-finding group were further randomly assigned (1:1) via their household to receive either a screening questionnaire at the general practitioner (GP) consultation (opportunistic) or a screening questionnaire at the GP consultation plus a mailed questionnaire (active). Respondents reporting relevant respiratory symptoms were invited for post-bronchodilator spirometry. Patients, clinicians, and investigators were not masked to allocation, but group allocation was concealed from the researchers who performed the spirometry assessments. Primary outcomes were the percentage of the eligible population diagnosed with COPD within 1 year (defined as post-bronchodilator forced expiratory volume in 1 s [FEV1] to forced vital capacity [FVC] ratio <0·7 in patients with symptoms or a new diagnosis on their GP record) and cost per new COPD diagnosis. Multiple logistic and Poisson regression were used to estimate effect sizes. Costs were obtained from the trial. This trial is registered with ISRCTN, number ISRCTN14930255. FINDINGS: From Aug 10, 2012, to June 22, 2014, 74 818 eligible patients from 54 diverse general practices were randomly assigned and completed the trial. At 1 year, 1278 (4%) cases of COPD were newly detected in 32 789 eligible patients in the targeted case-finding group compared with 337 (1%) cases in 42 029 patients in the routine care group (adjusted odds ratio [OR] 7·45 [95% CI 4·80-11·55], p<0·0001). The percentage of newly detected COPD cases was higher in the active case-finding group (822 [5%] of 15 378) than in the opportunistic case-finding group (370 [2%] of 15 387; adjusted OR 2·34 [2·06-2·66], p<0·0001; adjusted risk difference 2·9 per 100 patients [95% CI 2·3-3·6], p<0·0001). Active case finding was more cost-effective than opportunistic case finding (£333 vs £376 per case detected, respectively). INTERPRETATION: In this well established primary care system, routine practice identified few new cases of COPD. An active targeted approach to case finding including mailed screening questionnaires before spirometry is a cost-effective way to identify undiagnosed patients and has the potential to improve their health. FUNDING: National Institute for Health Research

Evidence for solar cycles in a late Holocene speleothem record from Dongge Cave, China

The association between solar activity and Asian monsoon (AM) remains unclear. Here we evaluate the possible connection between them based on a precisely-dated, high-resolution speleothem oxygen isotope record from Dongge Cave, southwest China during the past 4.2 thousand years (ka). Without being adjusted chronologically to the solar signal, our record shows a distinct peak-to-peak correlation with cosmogenic nuclide 14C, total solar irradiance (TSI) and sunspot number (SN) at multi-decadal to centennial timescales. Further cross-wavelet analyses between our calcite δ18O and atmospheric 14C show statistically strong coherence at three typical periodicities of ~80, 200 and 340 years, suggesting important roles of solar activities in modulating AM changes at those timescales. Our result has further indicated a better correlation between our calcite δ18O record and atmospheric 14C than between our record and TSI. This better correlation may imply that the Sun–monsoon connection is dominated most likely by cosmic rays and oceanic circulation (both associated to atmospheric 14C), instead of the direct solar heating (TSI)

Susceptibility of hamsters to clostridium difficile isolates of differing toxinotype

Clostridium difficile is the most commonly associated cause of antibiotic associated disease (AAD), which caused ~21,000 cases of AAD in 2011 in the U.K. alone. The golden Syrian hamster model of CDI is an acute model displaying many of the clinical features of C. difficile disease. Using this model we characterised three clinical strains of C. difficile, all differing in toxinotype; CD1342 (PaLoc negative), M68 (toxinotype VIII) and BI-7 (toxinotype III). The naturally occurring non-toxic strain colonised all hamsters within 1-day post challenge (d.p.c.) with high-levels of spores being shed in the faeces of animals that appeared well throughout the entire experiment. However, some changes including increased neutrophil influx and unclotted red blood cells were observed at early time points despite the fact that the known C. difficile toxins (TcdA, TcdB and CDT) are absent from the genome. In contrast, hamsters challenged with strain M68 resulted in a 45% mortality rate, with those that survived challenge remaining highly colonised. It is currently unclear why some hamsters survive infection, as bacterial and toxin levels and histology scores were similar to those culled at a similar time-point. Hamsters challenged with strain BI-7 resulted in a rapid fatal infection in 100% of the hamsters approximately 26 hr post challenge. Severe caecal pathology, including transmural neutrophil infiltrates and extensive submucosal damage correlated with high levels of toxin measured in gut filtrates ex vivo. These data describes the infection kinetics and disease outcomes of 3 clinical C. difficile isolates differing in toxin carriage and provides additional insights to the role of each toxin in disease progression

Mean platelet volume could be a promising biomarker to monitor dietary compliance in celiac disease

Background. Celiac disease (CD) is an autoimmune disease that develops in patients with a genetic predisposition, incurring a susceptibility to gluten-containing foods such as barley, wheat, and rye. The elimination of gluten from the diet is the main therapeutic approach and usually leads to clinical and laboratory improvement. There are no ideal markers that objectively assess dietary compliance in CD patients. Materials and methods. Sixty newly diagnosed CD patients (male/female: 43/17) and 40 healthy subjects (male/female: 23/17) were enrolled in this study. The diagnosis of CD was established by both histological findings of duodenum biopsy (total villous atrophy and lymphocytic infiltration) and positive antibodies against endomysium or gliadin. Results. A significantly higher mean platelet volume (MPV) was observed in the CD group compared with healthy subjects (8.45 +/- 0.96 fL versus 7.93 +/- 0.63 fL; p = 0.004). After introduction of a gluten-free diet, the MPV of CD patients in the dietary adherent group was significantly lower than that of the non-adherent group (8.09 +/- 0.6 fL versus 8.9 +/- 1.08 fL; p = 0.001). Overall dietary adherence rate was 71.6% (43/60 CD patients). In the dietary compliant group, initiation of gluten-free diet was associated with a significant decrease in MPV from base-line values (8.56 fL versus 8.25 fL; p = 0.008). In the non-adherent group, MPV on 3-month follow-up was higher than at base-line (8.05 fL versus 8.91 fL; p = 0.001). Conclusion. MPV could be a promising and easily available biomarker for monitoring of dietary adherence in CD patients at a low cost in comparison with other modalities.WoSScopu

Declining malaria transmission differentially impacts on the maintenance of humoral immunity to Plasmodium falciparum in children

BACKGROUND We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to P. falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity. METHODS In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different merozoite AMA1 and MSP2 alleles, IE surface antigens, and antibody functional activities were quantified. RESULTS Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 and 1-3 years, respectively. However, 69-74% of children maintained their sero-positivity to AMA1 alleles and 42-52% to MSP2 alleles. Levels and prevalence of anti-merozoite antibodies were consistently associated with increasing age and concurrent parasitaemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life 4-10 years). CONCLUSIONS A decline in malaria transmission is associated with reduction in naturally-acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development

Estimating the Impacts of Radiation Belt Electrons on Atmospheric Chemistry Using FIREBIRD II and Van Allen Probes Observations

This study considers the impact of electron precipitation from Earth's radiation belts on atmospheric composition using observations from the NASA Van Allen Probes and NSF Focused Investigations of Relativistic Electron Burst Intensity, Range, and Dynamics (FIREBIRD II) CubeSats. Ratios of electron flux between the Van Allen Probes (in near-equatorial orbit in the radiation belts) and FIREBIRD II (in polar low Earth orbit) during spacecraft conjunctions (2015–2017) allow an estimate of precipitation into the atmosphere. Total Radiation Belt Electron Content, calculated from Van Allen Probes RBSP-ECT MagEIS data, identifies a sustained 10-day electron loss event in March 2013 that serves as an initial case study. Atmospheric ionization profiles, calculated by integrating monoenergetic ionization rates across the precipitating electron flux spectrum, provide input to the NCAR Whole Atmosphere Community Climate Model in order to quantify enhancements of atmospheric HOx and NOx and subsequent destruction of O3 in the middle atmosphere. Results suggest that current APEEP parameterizations of radiation belt electrons used in Coupled Model Intercomparison Project may underestimate the duration of events as well as higher energy electron contributions to atmospheric ionization and modeled NOx concentrations in the mesosphere and upper stratosphere

Measurement of the Relative Branching Fraction of Υ(4S)\Upsilon(4S) to Charged and Neutral B-Meson Pairs

We analyze 9.7 x 10^6 B\bar{B}$ pairs recorded with the CLEO detector to determine the production ratio of charged to neutral B-meson pairs produced at the Y(4S) resonance. We measure the rates for B^0 -> J/psi K^{(*)0} and B^+ -> J/psi K^{(*)+} decays and use the world-average B-meson lifetime ratio to extract the relative widths f+-/f00 = Gamma(Y(4S) -> B+B-)/Gamma(Y(4S) -> B0\bar{B0}) = = 1.04 +/- 0.07(stat) +/- 0.04(syst). With the assumption that f+- + f00 = 1, we obtain f00 = 0.49 +/- 0.02(stat) +/- 0.01(syst) and f+- = 0.51 +/- 0.02(stat) +/- 0.01(syst). This production ratio and its uncertainty apply to all exclusive B-meson branching fractions measured at the Y(4S) resonance.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN