Walter Cunto

Protection against severe rotavirus diarrhoea by rhesus rotavirus vaccine in Venezuelan infants

The efficacy of the rhesus rotavirus vaccine candidate MMU-18006 was evaluated in a longitudinal double-blind field trial in Caracas, Venezuela. 247 infants aged 1-10 months were studied and followed for up to 1 year (201 completed the 1-year surveillance): 123 received a dose of 10(4) plaque-forming units of the vaccine orally and 124 received placebo. 21 episodes of rotavirus diarrhoea were detected, 16 in the controls and 5 in the vaccines: vaccine efficacy against any rotavirus diarrhoea was thus 68%. In the 1-5-month-old group the vaccine efficacy was 93%; only 1 episode of rotavirus diarrhoea was detected in 68 vaccinees and 15 such illnesses were observed in 65 controls (p less than 0.0001). For the entire study group vaccine efficacy was 100% against the most severe rotavirus diarrhoeal episodes.

Efficacy of the rhesus rotavirus-based quadrivalent vaccine in infants and young children in Venezuela.

BACKGROUND Rotaviruses are the principal known etiologic agents of severe diarrhea among infants and young children worldwide. Although a rhesus rotavirus-based quadrivalent vaccine is highly effective in preventing severe diarrhea in developed countries, in developing countries its efficacy has been less impressive. We thus conducted a catchment study in Venezuela to assess the efficacy of the vaccine against dehydrating diarrhea. METHODS In this randomized, double-blind, placebo-controlled trial, 2207 infants received three oral doses of the quadrivalent rotavirus vaccine (4x10(5) plaque-forming units per dose) or placebo at about two, three, and four months of age. During approximately 19 to 20 months of passive surveillance, episodes of gastroenteritis were evaluated at the hospital. RESULTS The vaccine was safe, although 15 percent of the vaccinated infants had febrile episodes (rectal temperature, > or =38.1 degrees C) during the six days after the first dose, as compared with 7 percent of the controls (P<0.001). However, the vaccine gave 88 percent protection against severe diarrhea caused by rotavirus and 75 percent protection against dehydration, and produced a 70 percent reduction in hospital admissions. Overall, the efficacy of the vaccine against a first episode of rotavirus diarrhea was 48 percent. Horizontal transmission of vaccine virus was demonstrated in 15 percent of the vaccine recipients and 13 percent of the placebo recipients with rotavirus-positive diarrhea. CONCLUSIONS In this study in a developing country, the quadrivalent rhesus rotavirus-based vaccine induced a high level of protection against severe diarrheal illness caused by rotavirus.

Proximity Matching Using Fixed-Queries Trees

We present a new data structure, called the fixed-queries tree, for the problem of finding all elements of a fixed set that are close, under some distance function, to a query element. Fixed-queries trees can be used for any distance function, not necessarily even a metric, as long as it satisfies the triangle inequality. We give an analysis of several performance parameters of fixed-queries trees and experimental results that support the analysis. Fixed-queries trees are particularly efficient for applications in which comparing two elements is expensive.

Comparison of reactogenicity and antigenicity of M37 rotavirus vaccine and rhesus-rotavirus-based quadrivalent vaccine

90 Venezuelan infants aged 10-20 weeks were randomly allocated to four groups which received one of the following: the M37 vaccine (1 x 10(4) pfu [plaque-forming units]); quadrivalent rotavirus vaccine (1 x 10(4) pfu each of serotype 3 rhesus rotavirus [RRV] and human rotavirus-RRV reassortants of serotypes 1, 2, and 4); balanced quadrivalent vaccine consisting of 1 x 10(4) pfu of serotype 1 and 3 components but 5 x 10(4) pfu of serotype 2 and 4 components; or placebo. The frequencies of transient febrile responses in these four groups were 20%, 27%, 30%, and 9%. 50% of 22 infants tested who received M37 vaccine showed a serum rotavirus IgA antibody response, compared with 74% of the 23 quadrivalent and 86% of the 22 balanced-quadrivalent recipients. 64% of the M37 recipients showed a neutralising antibody response to M37; 27% showed such responses to human serotype 1 Wa strain and 27% to serotype 4 neonatal strain ST3. 17-39% of the quadrivalent recipients and 27-41% of the balanced-quadrivalent recipients showed neutralising antibody responses to serotypes 1-4. 70-73% of the quadrivalent and balanced quadrivalent groups also showed neutralising antibody responses to RRV.

Analysis of KDT-Trees: KD-Trees Improved by Local Reogranisations

This paper deals with kd-tree like structures that implement the multidimensional dictionary. It presents the first efficient online reorganisation method that improves the performance of kd-trees. We propose a new variation of kd-trees, to be called kdt-trees, whereby the updating procedures guarantee that any subtree of size greater than 2t, t≥0, has at least t nodes on each side. Thus, kd-trees are a special case of kdt-trees with t=0. The analysis developed provides, for the first time, an asymptotic expression for the variance of the performance of partial match queries in kd-tree like structures. The relevance of kdt-trees is supported by the fact that they approach the performance of fully balanced kd-trees for small values of t.

Improving time and space efficiency in generalized binary search trees

SummaryThis paper deals with main memory data structures for which time and space performance are simultaneously considered. The main contribution is a new data structure called Generalised Binary Search Tree (GBS-tree) together with searching and updating algorithms on this structure. GBS-trees generalise different data structures based on binary trees that have appeared in the literature. A k-t GBS-tree allows up to t keys per node and subtrees in the trees fringe of exactly 2k-1 full nodes are kept balanced. Their time and space performances are analysed in depth. The time performance is expressed in terms of the average and the variance of the number of binary comparisons between a given key and keys already in the structure. The space performance measures both the space used to space generated ratio (space utilization factor) and the pointers to keys ratio of these trees. The analysis shows that the time performance always improves when GBS-trees of higher order are considered. In the absence of balancing techniques, larger values of t, which produces smaller pointers to key ratios, induce unacceptably poor space utilizations factors. We show that both pointers to keys ratio and space utilization factor improve when larger values of k are used. Thus, local balancing techniques are adequate, not only for time performance improvement, but also, for space performance improvement.

Binary Searching with Nonuniform Costs and Its Application to Text Retrieval

Abstract. We study the problem of minimizing the expected cost of binary searching for data where the access cost is not fixed and depends on the last accessed element, such as data stored in magnetic or optical disk. We present an optimal algorithm for this problem that finds the optimal search strategy in O(n3) time, which is the same time complexity of the simpler classical problem of fixed costs. Next, we present two practical linear expected time algorithms, under the assumption that the access cost of an element is independent of its physical position. Both practical algorithms are online, that is, they find the next element to access as the search proceeds. The first one is an approximate algorithm which minimizes the access cost disregarding the goodness of the problem partitioning. The second one is a heuristic algorithm, whose quality depends on its ability to estimate the final search cost, and therefore it can be tuned by recording statistics of previous runs. We present an application for our algorithms related to text retrieval. When a text collection is large it demands specialized indexing techniques for efficient access. One important type of index is the suffix array, where data access is provided through an indirect binary search on the text stored in magnetic disk or optical disk. Under this cost model we prove that the optimal algorithm cannot perform better than Ω(1/ log n) times the standard binary search. We also prove that the approximate strategy cannot, on average, perform worse than 39% over the optimal one. We confirm the analytical results with simulations, showing improvements between 34% (optimal) and 60% (online) over standard binary search for both magnetic and optical disks.

Optimal binary search trees with costs depending on the access paths

We describe algorithms for constructing optimal binary search trees, in which the access cost of a key depends on the k preceding keys which were reached in the path to it. This problem has applications to searching on secondary memory and robotics. Two kinds of optimal trees are considered, namely optimal worst case trees and weighted average case trees. The time and space complexities of both algorithms are O(nk+2) and O(nk+1), respectively. The algorithms are based on a convenient decomposition and characterizations of sequences of keys which are paths of special kinds in binary search trees. Finally, using generating functions, we present an exact analysis of the number of steps performed by the algorithms.

Average case selection

We consider problems such as selecting the <italic>k</italic>-th smallest of <italic>n</italic> numbers in as few comparisons as possible on average. <italic>n</italic> + <italic>k</italic> - 0(1) comparisons are proved to be necessary for this particular problem when <italic>k</italic> ≤ <italic>n</italic>/2. This shows a technique of Floyd and Rivest is essentially optimal. 7<italic>n</italic>/4 &equil; <italic>o(n)</italic> comparisons, on average, are shown to be necessary and sufficient to find the maximum and median of a set. An upper bound of 9<italic>n</italic>/4 + <italic>o(n)</italic> and a lower bound of 2<italic>n</italic> − <italic>o(n)</italic> are shown for the max-min-median problem.

Transforming unbalanced multiway trees into a practical external data structure

SummaryUnbalanced Multiway Trees (UM-trees) of degree m are external data structures wherein each node may be linked to at most m subtrees. Although they allow fast searches and updates UM-trees show poor space efficiency. In order to improve their time and space performance an overflow technique similar to that used previously for B*-trees is adapted to UM-trees. Analytical results show that when compared with UM-trees the new data structure improves average searching time and substantially increases space efficiency. Asymptotic space efficiency, measured as the ratio of space used to space generated, is 50% in the worst case and in the average case it is upper bounded by at least 85.7% for any m. Simulations suggest that this upper bound is tight. Compared with a homologous variant of B*-trees, simulation results indicate that the data structure proposed is highly balanced with comparable average space efficiency and lower average searching time. We conclude that overflow techniques can be applied not only to bottom-up type trees (e.g., B-trees) but also to top-down type trees such as UM-trees, in cases when the performance of an external data structure needs to be improved with little overhead.