Emerging Challenges and Opportunities in Infectious Disease Epidemiology.

Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners

Outbreak investigations--a perspective.

Outbreak investigations, an important and challenging component of epidemiology and public health, can help identify the source of ongoing outbreaks and prevent additional cases. Even when an outbreak is over, a thorough epidemiologic and environmental investigation often can increase our knowledge of a given disease and prevent future outbreaks. Finally, outbreak investigations provide epidemiologic training and foster cooperation between the clinical and public health communities

Entangled networks, synchronization, and optimal network topology

A new family of graphs, {\it entangled networks}, with optimal properties in many respects, is introduced. By definition, their topology is such that optimizes synchronizability for many dynamical processes. These networks are shown to have an extremely homogeneous structure: degree, node-distance, betweenness, and loop distributions are all very narrow. Also, they are characterized by a very interwoven (entangled) structure with short average distances, large loops, and no well-defined community-structure. This family of nets exhibits an excellent performance with respect to other flow properties such as robustness against errors and attacks, minimal first-passage time of random walks, efficient communication, etc. These remarkable features convert entangled networks in a useful concept, optimal or almost-optimal in many senses, and with plenty of potential applications computer science or neuroscience.Comment: Slightly modified version, as accepted in Phys. Rev. Let

Constraint Satisfaction with Counting Quantifiers

We initiate the study of constraint satisfaction problems (CSPs) in the presence of counting quantifiers, which may be seen as variants of CSPs in the mould of quantified CSPs (QCSPs). We show that a single counting quantifier strictly between exists^1:=exists and exists^n:=forall (the domain being of size n) already affords the maximal possible complexity of QCSPs (which have both exists and forall), being Pspace-complete for a suitably chosen template. Next, we focus on the complexity of subsets of counting quantifiers on clique and cycle templates. For cycles we give a full trichotomy -- all such problems are in L, NP-complete or Pspace-complete. For cliques we come close to a similar trichotomy, but one case remains outstanding. Afterwards, we consider the generalisation of CSPs in which we augment the extant quantifier exists^1:=exists with the quantifier exists^j (j not 1). Such a CSP is already NP-hard on non-bipartite graph templates. We explore the situation of this generalised CSP on bipartite templates, giving various conditions for both tractability and hardness -- culminating in a classification theorem for general graphs. Finally, we use counting quantifiers to solve the complexity of a concrete QCSP whose complexity was previously open

Active bacterial core surveillance of the emerging infections program network.

Active Bacterial Core surveillance (ABCs) is a collaboration between the Centers for Disease Control and Prevention and several state health departments and universities participating in the Emerging Infections Program Network. ABCs conducts population-based active surveillance, collects isolates, and performs studies of invasive disease caused by Streptococcus pneumoniae, group A and group B Streptococcus, Neisseria meningitidis, and Haemophilus influenzae for a population of 17 to 30 million. These pathogens caused an estimated 97,000 invasive cases, resulting in 10,000 deaths in the United States in 1998. Incidence rates of these pathogens are described. During 1998, 25% of invasive pneumococcal infections in ABCs areas were not susceptible to penicillin, and 13.3% were not susceptible to three classes of antibiotics. In 1998, early-onset group B streptococcal disease had declined by 65% over the previous 6 years. More information on ABCs is available at www.cdc.gov/ncidod/dbmd/abcs. ABCs specimens will soon be available to researchers through an archive

Effectiveness of the polysaccharide pneumococcal vaccine among HIV-infected persons in Brazil: a case control study

Abstract\ud \ud \ud \ud Background\ud \ud Polysaccharide pneumococcal vaccine is recommended for use in HIV-infected adults in Brazil but there is uncertainty about its effectiveness in this patient population.\ud The main objective of this study was to assess the effectiveness of the 23-valent polysaccharide pneumococcal vaccine against invasive pneumococcal infection among HIV-infected adult patients in São Paulo, Brazil.\ud \ud \ud \ud Methods\ud \ud A case-control study of 79 cases and 242 controls matched on CD4+ cell count and health care setting was conducted. Among HIV-infected adults in São Paulo, Brazil, with and without S. pneumoniae recovered from a normally sterile site; prior receipt of 23 valent polysaccharide pneumococcal vaccine was determined by review of medical records and patient interview.\ud \ud \ud \ud Results\ud \ud After adjustment for confounding factors, the point estimate for the effectiveness of 23 valent polysaccharide vaccine among HIV-infected adults against all invasive pneumococcal infection was 18% (95% CI: <0 to 62%).\ud \ud \ud \ud Conclusion\ud \ud We were unable to demonstrate a statistically significant protective effect of 23 valent polysaccharide against invasive pneumococcal infection vaccine among HIV-infected adults in Brazil.\ud While the vaccine is relatively inexpensive and safe, its effectiveness among HIV-infected adults in Brazil is uncertain.Investigators by institution:Investigators by institution:Regina Rocha Gomes de Lemos, Marileide Januaria de Vasconcelos, Luis Carlos Pereira, Jr., Francisco Bonasser Filho, Roberta Schiavon Nogueira, Lucas Alberto Medeiros, Simone and Erica (Emilio Ribas Infectious Diseases Institute); Ana Teresa Rodrigues Viso and Graça Maria A. Vasconcelos (CRT DST/AIDS); Sigrid Sousa Santos (HC FMUSP and Casa da AIDS) and Marise Oliveria Fonseca (Casa da AIDS); Augusto Penalva (HC UNICAMP); Joao Mendonça and Esper Kallas (HSPE); Maria Cristina Brandileone, Silvana Tadeu Casagrande and Maria Luisa L.S. Guerra (Aldolfo Lutz Insitute); João Renato Pinho and Monica Simone (Bioquemistry Laboratory Jardins) and Ana Lucia Schmidt and Gilberto Torquato (Federal University of São Paulo).Regina Rocha Gomes de Lemos, Marileide Januaria de Vasconcelos, Luis Carlos Pereira, Jr., Francisco Bonasser Filho, Roberta Schiavon Nogueira, Lucas Alberto Medeiros, Simone and Erica (Emilio Ribas Infectious Diseases Institute); Ana Teresa Rodrigues Viso and Graça Maria A. Vasconcelos (CRT DST/AIDS); Sigrid Sousa Santos (HC FMUSP and Casa da AIDS) and Marise Oliveria Fonseca (Casa da AIDS); Augusto Penalva (HC UNICAMP); Joao Mendonça and Esper Kallas (HSPE); Maria Cristina Brandileone, Silvana Tadeu Casagrande and Maria Luisa L.S. Guerra (Aldolfo Lutz Insitute); João Renato Pinho and Monica Simone (Bioquemistry Laboratory Jardins) and Ana Lucia Schmidt and Gilberto Torquato (Federal University of São Paulo).We also thank the following individuals for their assistance: Guido Levi, Vasco Pedroso de Lima, Andre de Felice (Emilio Ribas Institute); Arthur Kalichman and Maria Clara Gianna (CRT DST/AIDS); Reinaldo Salomão (Federal University of São Paulo); Rogério de Jesus Pedro (UNICAMP); Olavo Munhoz, Eliana Gutierrez and Aloísio Segurado (Casa da AIDS) and the Emilio Ribas Center for Studies (CEER).We also thank the following individuals for their assistance: Guido Levi, Vasco Pedroso de Lima, Andre de Felice (Emilio Ribas Institute); Arthur Kalichman and Maria Clara Gianna (CRT DST/AIDS); Reinaldo Salomão (Federal University of São Paulo); Rogério de Jesus Pedro (UNICAMP); Olavo Munhoz, Eliana Gutierrez and Aloísio Segurado (Casa da AIDS) and the Emilio Ribas Center for Studies (CEER).Financial Support:Financial Support:This study was funded by the Fogarty AIDS International Training and Research Program (AITRP) through the Division of Epidemiology, School of Public Health of the University of California, Berkeley (D43 TW00003). Logistical support from the Emilio Ribas Infectious Diseases Institute, the Adolfo Lutz Institute, São Paulo State STD/AIDS Reference and Training Center, the Clinical Hospital of São Paulo State University (UNICAMP), and the Casa da AIDS. The Foundation for the Coordination of Higher Education and Graduate Training (CAPES) of the Brazilian Ministry of Education supported the main author during doutoradosanduiche.This study was funded by the Fogarty AIDS International Training and Research Program (AITRP) through the Division of Epidemiology, School of Public Health of the University of California, Berkeley (D43 TW00003). Logistical support from the Emilio Ribas Infectious Diseases Institute, the Adolfo Lutz Institute, São Paulo State STD/AIDS Reference and Training Center, the Clinical Hospital of São Paulo State University (UNICAMP), and the Casa da AIDS. The Foundation for the Coordination of Higher Education and Graduate Training (CAPES) of the Brazilian Ministry of Education supported the main author during "doutorado-sanduiche.

Optimal network topologies: Expanders, Cages, Ramanujan graphs, Entangled networks and all that

We report on some recent developments in the search for optimal network topologies. First we review some basic concepts on spectral graph theory, including adjacency and Laplacian matrices, and paying special attention to the topological implications of having large spectral gaps. We also introduce related concepts as ``expanders'', Ramanujan, and Cage graphs. Afterwards, we discuss two different dynamical feautures of networks: synchronizability and flow of random walkers and so that they are optimized if the corresponding Laplacian matrix have a large spectral gap. From this, we show, by developing a numerical optimization algorithm that maximum synchronizability and fast random walk spreading are obtained for a particular type of extremely homogeneous regular networks, with long loops and poor modular structure, that we call entangled networks. These turn out to be related to Ramanujan and Cage graphs. We argue also that these graphs are very good finite-size approximations to Bethe lattices, and provide almost or almost optimal solutions to many other problems as, for instance, searchability in the presence of congestion or performance of neural networks. Finally, we study how these results are modified when studying dynamical processes controlled by a normalized (weighted and directed) dynamics; much more heterogeneous graphs are optimal in this case. Finally, a critical discussion of the limitations and possible extensions of this work is presented.Comment: 17 pages. 11 figures. Small corrections and a new reference. Accepted for pub. in JSTA

Association of BCG, DTP, and measles containing vaccines with childhood mortality:systematic review

Objectives To evaluate the effects on non-specific and all cause mortality, in children under 5, of Bacillus Calmette-Guérin (BCG), diphtheria-tetanus-pertussis (DTP), and standard titre measles containing vaccines (MCV); to examine internal validity of the studies; and to examine any modifying effects of sex, age, vaccine sequence, and co-administration of vitamin A. Design Systematic review, including assessment of risk of bias, and meta-analyses of similar studies. Study eligibility criteria Clinical trials, cohort studies, and case-control studies of the effects on mortality of BCG, whole cell DTP, and standard titre MCV in children under 5. Data sources Searches of Medline, Embase, Global Index Medicus, and the WHO International Clinical Trials Registry Platform, supplemented by contact with experts in the field. To avoid overlap in children studied across the included articles, findings from non-overlapping birth cohorts were identified. Results Results from 34 birth cohorts were identified. Most evidence was from observational studies, with some from short term clinical trials. Most studies reported on all cause (rather than non-specific) mortality. Receipt of BCG vaccine was associated with a reduction in all cause mortality: the average relative risks were 0.70 (95% confidence interval 0.49 to 1.01) from five clinical trials and 0.47 (0.32 to 0.69) from nine observational studies at high risk of bias. Receipt of DTP (almost always with oral polio vaccine) was associated with a possible increase in all cause mortality on average (relative risk 1.38, 0.92 to 2.08) from 10 studies at high risk of bias; this effect seemed stronger in girls than in boys. Receipt of standard titre MCV was associated with a reduction in all cause mortality (relative risks 0.74 (0.51 to 1.07) from four clinical trials and 0.51 (0.42 to 0.63) from 18 observational studies at high risk of bias); this effect seemed stronger in girls than in boys. Seven observational studies, assessed as being at high risk of bias, have compared sequences of vaccines; results of a subset of these suggest that administering DTP with or after MCV may be associated with higher mortality than administering it before MCV. Conclusions Evidence suggests that receipt of BCG and MCV reduce overall mortality by more than would be expected through their effects on the diseases they prevent, and receipt of DTP may be associated with an increase in all cause mortality. Although efforts should be made to ensure that all children are immunised on schedule with BCG, DTP, and MCV, randomised trials are needed to compare the effects of different sequences

Development of the (d,n) proton-transfer reaction in inverse kinematics for structure studies

Transfer reactions have provided exciting opportunities to study the structure of exotic nuclei and are often used to inform studies relating to nucleosynthesis and applications. In order to benefit from these reactions and their application to rare ion beams (RIBs) it is necessary to develop the tools and techniques to perform and analyze the data from reactions performed in inverse kinematics, that is with targets of light nuclei and heavier beams. We are continuing to expand the transfer reaction toolbox in preparation for the next generation of facilities, such as the Facility for Rare Ion Beams (FRIB), which is scheduled for completion in 2022. An important step in this process is to perform the (d,n) reaction in inverse kinematics, with analyses that include Q-value spectra and differential cross sections. In this way, proton-transfer reactions can be placed on the same level as the more commonly used neutron-transfer reactions, such as (d,p), (9Be,8Be), and (13C,12C). Here we present an overview of the techniques used in (d,p) and (d,n), and some recent data from (d,n) reactions in inverse kinematics using stable beams of 12C and 16O.Comment: 9 pages, 4 figures, presented at the XXXV Mazurian Lakes Conference on Physics, Piaski, Polan