Molecular understanding of the serum antibody repertoires after seasonal influenza vaccination among different age cohorts

Numerous influenza vaccination studies based on bulk serology have indicated that the antibody responses to the vaccine markedly decrease in the elderly. However, whether such decline results from the changes in the overall quantity or the quality of the circulating antibodies in serum remains unknown. Utilizing novel antibody repertoire profiling technologies, combining tandem mass spectrometry (LC-MS/MS) and high-throughput sequencing, we investigated the influenza-specific serological repertoires of 10 donors ranging from 26 to 70 years old vaccinated with Fluzone® 2013-2014 and/or 2014-2015. In particular, we determined the serum antibodies that are specific to the H1 or H3 component of the vaccine or cross-reactive between the two (H1+H3) and examined their relative quantitative distributions. Our data indicate that the proportion of H1+H3 antibodies significantly increases in the elderly and that the somatic hypermutation rates of the influenza-specific antibodies are higher in the elderly. These results suggest that the repeated exposure to the different virus subtypes could have led to the prolonged selection of H1+H3 antibodies targeting highly conserved epitopes. To evaluate the potency of the antibodies circulating in different age groups, we recombinantly expressed a number of representative monoclonal antibodies isolated from the donors in different age groups for further characterizations. Overall, our analysis suggests that the influenza-specific repertoire in the elderly may converge toward shared epitopes but the quality of the antibodies can be superior in terms of cross-reactivity. However, because the antibody repertoire “shrinks” as we age while targeting more conserved epitopes across different influenza subtypes, it is possible that the elderly is particularly susceptible to significantly altered strains. Collectively, profiling vaccine induced serological repertoires among different age cohorts can provide unprecedented insights regarding humoral immunity associated with age and a potential explanation for the vulnerability of the elderly

Broadband, site selective and time resolved photoluminescence spectroscopic studies of finely size-modulated Y2O3:Eu3+ phosphors synthesized by a complex based precursor solution method

Undoped and Eu3+-doped cubic yttria (Y2O3) nanophosphors of good crystallinity, with selective particle sizes ranging between 6 and 37 nm and showing narrow size distributions, have been synthesized by a complex-based precursor solution method. The systematic size tuning has been evidenced by transmission electron microscopy, X-ray diffraction, and Raman scattering measurements. Furthermore, size-modulated properties of Eu3+ ions have been correlated with the local structure of Eu3+ ion in different sized Y2O3:Eu3+ nanophosphors by means of steady-state and time-resolved site-selective laser spectroscopies. Time-resolved site-selective excitation measurements performed in the 7F0 ¿ 5D0 peaks of the Eu3+ ions at C2 sites have allowed us to conclude that Eu3+ ions close to the nanocrystal surface experience a larger crystal field than those in the nanocrystal core. Under the site-selective excitation in the 7F0 ¿ 5D0 peaks, energy transfer between the sites has also been observed.Authors are grateful to Ministerio de Ciencia e Innovacion of Spain (MICINN) under The National Program of Materials (MAT2010-21270-C04-02/03/04), the Consolider-Ingenio 2010 Program (MALTA CSD2007-0045), Generalitat Valenciana (GVA-ACOMP-2013-012), and to the EU-FEDER Funds for their financial support. F.J.M. and O.G. are grateful to the Vicerrectorado de Investigacion y Desarrollo of the Universitat Politecnica de Valencia (UPV2011-0914 PAID-05-11 and UPV2011-0966 PAID-06-11). S.F.L-L. wishes to thank MICCIN for an FPI grant (BES-2008-003353). Finally, S. R. wishes to thank Universitat Politecnica de Valencia and Universidad de La Laguna for the financial support during her research stays.Ray, S.; León-Luis, SF.; Manjón Herrera, FJ.; Mollar García, MA.; Gomis Hilario, O.; Rodríguez-Mendoza, UR.; Agouram, S.... (2014). Broadband, site selective and time resolved photoluminescence spectroscopic studies of finely size-modulated Y2O3:Eu3+ phosphors synthesized by a complex based precursor solution method. Current Applied Physics. 14(1):72-81. https://doi.org/10.1016/j.cap.2013.07.027S728114

The Dualism of Contemporary Traditional Governance and the State

In many parts of the world, people live in “dual polities”: they are governed by the state and organize collective decision making within their ethnic community according to traditional rules. We examine the substantial body of works on the traditional–state dualism, focusing on the internal organization of traditional polities, their interaction with the state, and the political consequences of the dualism. We find the descriptions of the internal organization of traditional polities scattered and lacking comparative perspective. The literature on the interaction provides a good starting point for theorizing the strategic role of traditional leaders as intermediaries, but large potentials for inference remain underexploited. Studies on the consequences of “dual polities” for democracy, conflict, and development are promising in their explanatory endeavor, but they do not yet allow for robust conclusions. We therefore propose an institutionalist research agenda addressing the need for theory and for systematic data collection and explanatory approaches

Towards Customary Legal Empowerment

Rule of Law and Development: Formation, Implementation and Improvement of Law and Governance in Developing Countrie

Brucellosis in Sub-Saharan Africa:Current challenges for management, diagnosis and control

Brucellosis is a highly contagious zoonosis caused by bacteria of the genus Brucella and affecting domestic and wild mammals. In this paper, the bacteriological and serological evidence of brucellosis in Sub-Saharan Africa (SSA) and its epidemiological characteristics are discussed. The tools available for the diagnosis and treatment of human brucellosis and for the diagnosis and control of animal brucellosis and their applicability in the context of SSA are presented and gaps identified. These gaps concern mostly the need for simpler and more affordable antimicrobial treatments against human brucellosis, the development of a B. melitensis vaccine that could circumvent the drawbacks of the currently available Rev 1 vaccine, and the investigation of serological diagnostic tests for camel brucellosis and wildlife. Strategies for the implementation of animal vaccination are also discussed.Publishe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

The IDENTIFY study: the investigation and detection of urological neoplasia in patients referred with suspected urinary tract cancer - a multicentre observational study

Objective To evaluate the contemporary prevalence of urinary tract cancer (bladder cancer, upper tract urothelial cancer [UTUC] and renal cancer) in patients referred to secondary care with haematuria, adjusted for established patient risk markers and geographical variation. Patients and Methods This was an international multicentre prospective observational study. We included patients aged ≥16 years, referred to secondary care with suspected urinary tract cancer. Patients with a known or previous urological malignancy were excluded. We estimated the prevalence of bladder cancer, UTUC, renal cancer and prostate cancer; stratified by age, type of haematuria, sex, and smoking. We used a multivariable mixed-effects logistic regression to adjust cancer prevalence for age, type of haematuria, sex, smoking, hospitals, and countries. Results Of the 11 059 patients assessed for eligibility, 10 896 were included from 110 hospitals across 26 countries. The overall adjusted cancer prevalence (n = 2257) was 28.2% (95% confidence interval [CI] 22.3–34.1), bladder cancer (n = 1951) 24.7% (95% CI 19.1–30.2), UTUC (n = 128) 1.14% (95% CI 0.77–1.52), renal cancer (n = 107) 1.05% (95% CI 0.80–1.29), and prostate cancer (n = 124) 1.75% (95% CI 1.32–2.18). The odds ratios for patient risk markers in the model for all cancers were: age 1.04 (95% CI 1.03–1.05; P < 0.001), visible haematuria 3.47 (95% CI 2.90–4.15; P < 0.001), male sex 1.30 (95% CI 1.14–1.50; P < 0.001), and smoking 2.70 (95% CI 2.30–3.18; P < 0.001). Conclusions A better understanding of cancer prevalence across an international population is required to inform clinical guidelines. We are the first to report urinary tract cancer prevalence across an international population in patients referred to secondary care, adjusted for patient risk markers and geographical variation. Bladder cancer was the most prevalent disease. Visible haematuria was the strongest predictor for urinary tract cancer

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

A Multidisciplinary Approach to Unlocking Television Broadcast Archives

Audiovisual material is a vital component of the world's heritage but it remains difficult to access. With the Netherlands Institute for Sound and Vision as one of its partners, the MuNCH project aims to investigate new methods for improving access to a wide range of audiovisual documents. MuNCH brings together three research fields: multimedia analysis, language technology and semantic technologies. Within the MuNCH project, we have investigated several combinations of these fields. We have compared text matching, ontology querying, and semantic visual querying as methods to translate a multimedia query to the vocabulary of the retrieval system. In addition, we have investigated how users make such a translation, and have used this as a benchmark to create automatic methods. We have used multimedia technology to automatically detect objects and scenes as they occur in video, and made use of language technology to exploit automatic transcriptions of speech. We have enriched the Sound and Vision thesaurus that is used to annotate the TV programmes in order to provide a user with a wider range of search results. In order to verify the results of the project against real user needs, MuNCH has participated in the creation of a logging system which monitors the usage of the Sound and Vision catalogue system. Insights in the needs of real users will be used as input for all three of MuNCH's research strands