Doing Good in American Communities: Congregations and Service Organizations Working Together

A Research Report from the "Organizing Religious Work Project," Hartford Institute for Religion Research Hartford Seminary

The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports

BACKGROUND:The Framingham Heart Study (FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms (SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies.METHODS:Adult participants (n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests.RESULTS:The participants were white of European descent and from the FHS Original and Offspring Cohorts (examination 1 Offspring mean age 32 +/- 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency [greater than or equal to] 10%, genotype call rate [greater than or equal to] 80%, Hardy-Weinberg equilibrium p-value [greater than or equal to] 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007.CONCLUSION:We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication.

The Retail Market for Bednets in Kenya: How Well Is It Working?

Background Achieving the goals set by Roll Back Malaria and the Government of Kenya for use of insecticide treated bednets (ITNs) will require that the private retail market for nets and insecticide treatments grow substantially. This paper applies some basic concepts of market structure and pricing to a set of recently-collected retail price data from Kenya in order to answer the question, “How well are Kenyan retail markets for ITNs working?” Methods Data on the availability and prices of ITNs at a wide range of retail outlets throughout Kenya were collected in January 2002, and vendors and manufacturers were interviewed regarding market structure. Findings Untreated nets are manufactured in Kenya by a number of companies and are widely available in large and medium-sized towns. Availability in smaller villages is limited. There is relatively little geographic price variation, and nets can be found at competitive prices in towns and cities. Marketing margins on prices appear to be within normal ranges. No finished nets are imported. Few pre-treated nets or net+treatment combinations are available, with the exception of the subsidized Supanet/Power Tab combination marketed by a donor-funded social marketing project. Conclusions Retail markets for untreated nets in Kenya are well established and appear to be competitive. Markets for treated nets and insecticide treatment kits are not well established. The role of subsidized ITN marketing projects should be monitored to ensure that these projects support, rather than hinder, the development of retail markets.

Rationing Antiretroviral Therapy for HIV/AIDS in Africa: Efficiency, Equity, and Reality

Background: Rationing of access to antiretroviral therapy already exists in sub-Saharan Africa and will intensify as national treatment programs develop. The number of people who are medically eligible for therapy will far exceed the human, infrastructural, and financial resources available, making rationing of public treatment services inevitable. Methods: We identified 15 criteria by which antiretroviral therapy could be rationed in African countries and analyzed the resulting rationing systems across 5 domains: clinical effectiveness, implementation feasibility, cost, economic efficiency, and social equity. Findings: Rationing can be explicit or implicit. Access to treatment can be explicitly targeted to priority subpopulations such as mothers of newborns, skilled workers, students, or poor people. Explicit conditions can also be set that cause differential access, such as residence in a designated geographic area, co-payment, access to testing, or a demonstrated commitment to adhere to therapy. Implicit rationing on the basis of first-come, first-served or queuing will arise when no explicit system is enforced; implicit systems almost always allow a high degree of queue-jumping by the elite. There is a direct tradeoff between economic efficiency and social equity. Interpretation: Rationing is inevitable in most countries for some period of time. Without deliberate social policy decisions, implicit rationing systems that are neither efficient nor equitable will prevail. Governments that make deliberate choices, and then explain and defend those choices to their constituencies, are more likely to achieve a socially desirable outcome from the large investments now being made than are those that allow queuing and queue-jumping to dominate.

Geometric Generalizations of the Power of Two Choices

A well-known paradigm for load balancing in distributed systems is the``power of two choices,''whereby an item is stored at the less loaded of two (or more) random alternative servers. We investigate the power of two choices in natural settings for distributed computing where items and servers reside in a geometric space and each item is associated with the server that is its nearest neighbor. This is in fact the backdrop for distributed hash tables such as Chord, where the geometric space is determined by clockwise distance on a one-dimensional ring. Theoretically, we consider the following load balancing problem. Suppose that servers are initially hashed uniformly at random to points in the space. Sequentially, each item then considers d candidate insertion points also chosen uniformly at random from the space,and selects the insertion point whose associated server has the least load. For the one-dimensional ring, and for Euclidean distance on the two-dimensional torus, we demonstrate that when n data items are hashed to n servers,the maximum load at any server is log log n / log d + O(1) with high probability. While our results match the well-known bounds in the standard setting in which each server is selected equiprobably, our applications do not have this feature, since the sizes of the nearest-neighbor regions around servers are non-uniform. Therefore, the novelty in our methods lies in developing appropriate tail bounds on the distribution of nearest-neighbor region sizes and in adapting previous arguments to this more general setting. In addition, we provide simulation results demonstrating the load balance that results as the system size scales into the millions.

From Working Memory to Long-term Memory and Back: Linked but Distinct

Neural models have proposed how short-term memory (STM) storage in working memory and long-term memory (LTM) storage and recall are linked and interact, but are realized by different mechanisms that obey different laws. The authors' data can be understood in the light of these models, which suggest that the authors may have gone too far in obscuring the differences between these processes.

Variable Rate Working Memories for Phonetic Categorization and Invariant Speech Perception

Speech can be understood at widely varying production rates. A working memory is described for short-term storage of temporal lists of input items. The working memory is a cooperative-competitive neural network that automatically adjusts its integration rate, or gain, to generate a short-term memory code for a list that is independent of item presentation rate. Such an invariant working memory model is used to simulate data of Repp (1980) concerning the changes of phonetic category boundaries as a function of their presentation rate. Thus the variability of categorical boundaries can be traced to the temporal in variance of the working memory code.

Neural Models of Temporally Organized Behaviors: Handwriting Production and Working Memory

Advanced Research Projects Agency (ONR N00014-92-J-4015); Office of Naval Research (N00014-91-J-4100, N00014-92-J-1309)

Laminar Cortical Dynamics of Cognitive and Motor Working Memory, Sequence Learning and Performance: Toward a Unified Theory of How the Cerebral Cortex Works

How do the layered circuits of prefrontal and motor cortex carry out working memory storage, sequence learning, and voluntary sequential item selection and performance? A neural model called LIST PARSE is presented to explain and quantitatively simulate cognitive data about both immediate serial recall and free recall, including bowing of the serial position performance curves, error-type distributions, temporal limitations upon recall, and list length effects. The model also qualitatively explains cognitive effects related to attentional modulation, temporal grouping, variable presentation rates, phonemic similarity, presentation of non-words, word frequency/item familiarity and list strength, distracters and modality effects. In addition, the model quantitatively simulates neurophysiological data from the macaque prefrontal cortex obtained during sequential sensory-motor imitation and planned performance. The article further develops a theory concerning how the cerebral cortex works by showing how variations of the laminar circuits that have previously clarified how the visual cortex sees can also support cognitive processing of sequentially organized behaviors.

Working Memory Networks for Learning Multiple Groupings of Temporarily Ordered Events: Applications to 3-D Visual Object Recognition

Working memory neural networks are characterized which encode the invariant temporal order of sequential events that may be presented at widely differing speeds, durations, and interstimulus intervals. This temporal order code is designed to enable all possible groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system. Such a competence is needed in neural architectures which self-organize learned codes for variable-rate speech perception, sensory-motor planning, or 3-D visual object recognition. Using such a working memory, a self-organizing architecture for invariant 3-D visual object recognition is described that is based on the model of Seibert and Waxman [1].

Working Memory Networks for Learning Temporal Order, with Application to 3-D Visual Object Recognition

Working memory neural networks are characterized which encode the invariant temporal order of sequential events. Inputs to the networks, called Sustained Temporal Order REcurrent (STORE) models, may be presented at widely differing speeds, durations, and interstimulus intervals. The STORE temporal order code is designed to enable all emergent groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system. Such a competence is needed in neural architectures which self-organize learned codes for variable-rate speech perception, sensory-motor planning, or 3-D visual object recognition. Using such a working memory, a self-organizing architecture for invariant 3-D visual object recognition is described. The new model is based on the model of Seibert and Waxman (1990a), which builds a 3-D representation of an object from a temporally ordered sequence of its 2-D aspect graphs. The new model, called an ARTSTORE model, consists of the following cascade of processing modules: Invariant Preprocessor --> ART 2 --> STORE Model --> ART 2 --> Outstar Network.

Working Memories for Storage and Recall of Arbitrary Temporal Sequences

A working memory model is described that is capable of storing and recalling arbitrary temporal sequences of events, including repeated items. These memories encode the invariant temporal order of sequential events that may be presented at widely differing speeds, durations, and interstimulus intervals. This temporal order code is designed to enable all possible groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system.

Store Working Memory Networks for Storage and Recall of Arbitrary Temporal Sequences

Neural network models of working memory, called Sustained Temporal Order REcurrent (STORE) models, are described. They encode the invariant temporal order of sequential events in short term memory (STM) in a way that mimics cognitive data about working memory, including primacy, recency, and bowed order and error gradients. As new items are presented, the pattern of previously stored items is invariant in the sense that, relative activations remain constant through time. This invariant temporal order code enables all possible groupings of sequential events to be stably learned and remembered in real time, even as new events perturb the system. Such a competence is needed to design self-organizing temporal recognition and planning systems in which any subsequence of events may need to be categorized in order to to control and predict future behavior or external events. STORE models show how arbitrary event sequences may be invariantly stored, including repeated events. A preprocessor interacts with the working memory to represent event repeats in spatially separate locations. It is shown why at least two processing levels are needed to invariantly store events presented with variable durations and interstimulus intervals. It is also shown how network parameters control the type and shape of primacy, recency, or bowed temporal order gradients that will be stored.