Empirical Evidence for Synchrony in the Evolution of TB Cases and HIV plus Contacts among the San Francisco Homeless

The re-emergence of tuberculosis (TB) in the mid-1980s in many parts of the world, including the United States, is often attributed to the emergence and rapid spread of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). Although it is well established that TB transmission is particularly amplified in populations with high HIV prevalence, the epidemiology of interaction between TB and HIV is not well understood. This is partly due to the scarcity of HIV-related data, a consequence of the voluntary nature of HIV status reporting and testing, and partly due to current practices of screening high risk populations through separate surveillance programs for HIV and TB. The San Francisco Department of Public Health, TB Control Program, has been conducting active surveillance among the San Francisco high-risk populations since the early 1990s. We present extensive TB surveillance data on HIV and TB infection among the San Francisco homeless to investigate the association between the TB cases and their HIV+ contacts. We applied wavelet coherence and phase analyses to the TB surveillance data from January 1993 through December 2005, to establish and quantify statistical association and synchrony in the highly non-stationary and ostensibly non-periodic waves of TB cases and their HIV+ contacts in San Francisco. When stratified by homelessness, we found that the evolution of TB cases and their HIV+ contacts is highly coherent over time and locked in phase at a specific periodic scale among the San Francisco homeless, but no significant association was observed for the non-homeless. This study confirms the hypothesis that the dynamics of HIV and TB are significantly intertwined and that HIV is likely a key factor in the sustenance of TB transmission among the San Francisco homeless. The findings of this study underscore the importance of contact tracing in detection of HIV+ individuals that may otherwise remain undetected, and thus highlights the ever-increasing need for HIV-related data and an integrative approach to monitoring high-risk populations with respect to HIV and TB transmission.Mitre Corporatio

An exploration of psychiatrists' understanding and use of psychological formulation

This doctoral thesis explores paradigms currently used in mental health services. The thesis comprises a literature review, a research paper and a critical appraisal. A final section is dedicated to the ethical procedures undertaken prior to undertaking the research. The literature review is a systematic review which synthesises 14 qualitative papers studying the experiences of accessing mental health services for individuals who have received a diagnosis of borderline personality disorder. The overarching theme ‘bpd is a double-edged sword’ is labelled along with four sub-themes: ‘undeserving of care’, ‘disempowerment’, ‘safety and containment’ and ‘approaching recovery’. Findings suggest the need for further inclusion of service users in the development of service provision and an approach that is formulation-based and grounded in attachment theory. The research paper explores psychiatrists’ understanding and use of psychological formulation. A constructivist grounded theory framework led to an initial conceptualisation and model. Four conceptual categories were named as ‘conceptualising formulation’, ‘singing off the same hymn sheet’, ‘barriers to formulation’ and ‘making a Frankenstein’s monster’. In particular the findings suggest that psychiatrists view and use psychological formulation in a different way from that outlined by clinical psychologists and that there are multiple barriers to its use. Finally, the critical review presents challenges encountered during the research project and personal reflections on the process. Overall the thesis highlights the need for mental health services to embrace multiple paradigms and remain open to alternative discourses around mental illness in order to provide a holistic and integrated service provision. A formulation-based approach may provide such an arena, while allowing space for individualised care. Clinical psychologists are well placed to promote such an approach via service development and consultation with multidisciplinary staff

Open-target sparse sensing of biological agents using DNA microarray

Background Current biosensors are designed to target and react to specific nucleic acid sequences or structural epitopes. These 'target-specific' platforms require creation of new physical capture reagents when new organisms are targeted. An 'open-target' approach to DNA microarray biosensing is proposed and substantiated using laboratory generated data. The microarray consisted of 12,900 25 bp oligonucleotide capture probes derived from a statistical model trained on randomly selected genomic segments of pathogenic prokaryotic organisms. Open-target detection of organisms was accomplished using a reference library of hybridization patterns for three test organisms whose DNA sequences were not included in the design of the microarray probes. Results A multivariate mathematical model based on the partial least squares regression (PLSR) was developed to detect the presence of three test organisms in mixed samples. When all 12,900 probes were used, the model correctly detected the signature of three test organisms in all mixed samples (mean(R2)) = 0.76, CI = 0.95), with a 6% false positive rate. A sampling algorithm was then developed to sparsely sample the probe space for a minimal number of probes required to capture the hybridization imprints of the test organisms. The PLSR detection model was capable of correctly identifying the presence of the three test organisms in all mixed samples using only 47 probes (mean(R2)) = 0.77, CI = 0.95) with nearly 100% specificity. Conclusions We conceived an 'open-target' approach to biosensing, and hypothesized that a relatively small, non-specifically designed, DNA microarray is capable of identifying the presence of multiple organisms in mixed samples. Coupled with a mathematical model applied to laboratory generated data, and sparse sampling of capture probes, the prototype microarray platform was able to capture the signature of each organism in all mixed samples with high sensitivity and specificity. It was demonstrated that this new approach to biosensing closely follows the principles of sparse sensing.Mitre Corporatio

Early Detection of Tuberculosis Outbreaks among the San Francisco Homeless: Trade-Offs Between Spatial Resolution and Temporal Scale

BACKGROUND: San Francisco has the highest rate of tuberculosis (TB) in the U.S. with recurrent outbreaks among the homeless and marginally housed. It has been shown for syndromic data that when exact geographic coordinates of individual patients are used as the spatial base for outbreak detection, higher detection rates and accuracy are achieved compared to when data are aggregated into administrative regions such as zip codes and census tracts. We examine the effect of varying the spatial resolution in the TB data within the San Francisco homeless population on detection sensitivity, timeliness, and the amount of historical data needed to achieve better performance measures. METHODS AND FINDINGS: We apply a variation of space-time permutation scan statistic to the TB data in which a patient's location is either represented by its exact coordinates or by the centroid of its census tract. We show that the detection sensitivity and timeliness of the method generally improve when exact locations are used to identify real TB outbreaks. When outbreaks are simulated, while the detection timeliness is consistently improved when exact coordinates are used, the detection sensitivity varies depending on the size of the spatial scanning window and the number of tracts in which cases are simulated. Finally, we show that when exact locations are used, smaller amount of historical data is required for training the model. CONCLUSION: Systematic characterization of the spatio-temporal distribution of TB cases can widely benefit real time surveillance and guide public health investigations of TB outbreaks as to what level of spatial resolution results in improved detection sensitivity and timeliness. Trading higher spatial resolution for better performance is ultimately a tradeoff between maintaining patient confidentiality and improving public health when sharing data. Understanding such tradeoffs is critical to managing the complex interplay between public policy and public health. This study is a step forward in this direction

Optimizing Use of Multistream Influenza Sentinel Surveillance Data

We applied time-series methods to multivariate sentinel surveillance data recorded in Hong Kong during 1998–2007. Our study demonstrates that simultaneous monitoring of multiple streams of influenza surveillance data can improve the accuracy and timeliness of alerts compared with monitoring of aggregate data or of any single stream alone

Lo-Fi Matchmaking: A Study of Social Pairing for Backpackers

There is a new world emerging around mobile social networks and the technologies used to facilitate and mediate them. It is technically feasible for mobile social software such as pairing or matchmaking systems to introduce people to others and assist information exchange. However, little is known about the social structure of many mobile communities or why they would want pairing systems. When these systems are built, it is not clear what the social response by those communities will be or what the systems will be like to use in practice. While engaged in other work determining requirements for a mobile travel assistant we saw a potentially useful application for a pairing system to facilitate the exchange of travel information between backpackers. To explore this area, we designed two studies involving usage of a low-fidelity role prototype of a social pairing system for backpackers. Graphs of the resulting social pairings showed backpackers who were hubs in the network of travel information. It also demonstrated the effect of travel direction on information utility. Backpackers rated the utility of different pairing types, and provided feedback on the social implications of being paired based on travel histories. Practical usage of the social network pairing activity and the implications of broader societal usage are discussed

Maximum-Likelihood Parameter Estimation in Terahertz Time-Domain Spectroscopy

We present a maximum-likelihood method for parameter estimation in terahertz time-domain spectroscopy. We derive the likelihood function for a parameterized frequency response function, given a pair of time-domain waveforms with known time-dependent noise amplitudes. The method provides parameter estimates that are superior to other commonly used methods and provides a reliable measure of the goodness of fit. We also develop a simple noise model that is parameterized by three dominant sources and derive the likelihood function for their amplitudes in terms of a set of repeated waveform measurements. We demonstrate the method with applications to material characterization

VX Hydrolysis by Human Serum Paraoxonase 1: A Comparison of Experimental and Computational Results

Human Serum paraoxonase 1 (HuPON1) is an enzyme that has been shown to hydrolyze a variety of chemicals including the nerve agent VX. While wildtype HuPON1 does not exhibit sufficient activity against VX to be used as an in vivo countermeasure, it has been suggested that increasing HuPON1's organophosphorous hydrolase activity by one or two orders of magnitude would make the enzyme suitable for this purpose. The binding interaction between HuPON1 and VX has recently been modeled, but the mechanism for VX hydrolysis is still unknown. In this study, we created a transition state model for VX hydrolysis (VXts) in water using quantum mechanical/molecular mechanical simulations, and docked the transition state model to 22 experimentally characterized HuPON1 variants using AutoDock Vina. The HuPON1-VXts complexes were grouped by reaction mechanism using a novel clustering procedure. The average Vina interaction energies for different clusters were compared to the experimentally determined activities of HuPON1 variants to determine which computational procedures best predict how well HuPON1 variants will hydrolyze VX. The analysis showed that only conformations which have the attacking hydroxyl group of VXts coordinated by the sidechain oxygen of D269 have a significant correlation with experimental results. The results from this study can be used for further characterization of how HuPON1 hydrolyzes VX and design of HuPON1 variants with increased activity against VX.United States. Defense Threat Reduction Agenc

Indirect Reciprocity under Incomplete Observation

Indirect reciprocity, in which individuals help others with a good reputation but not those with a bad reputation, is a mechanism for cooperation in social dilemma situations when individuals do not repeatedly interact with the same partners. In a relatively large society where indirect reciprocity is relevant, individuals may not know each other's reputation even indirectly. Previous studies investigated the situations where individuals playing the game have to determine the action possibly without knowing others' reputations. Nevertheless, the possibility that observers of the game, who generate the reputation of the interacting players, assign reputations without complete information about them has been neglected. Because an individual acts as an interacting player and as an observer on different occasions if indirect reciprocity is endogenously sustained in a society, the incompleteness of information may affect either role. We examine the game of indirect reciprocity when the reputations of players are not necessarily known to observers and to interacting players. We find that the trustful discriminator, which cooperates with good and unknown players and defects against bad players, realizes cooperative societies under seven social norms. Among the seven social norms, three of the four suspicious norms under which cooperation (defection) to unknown players leads to a good (bad) reputation enable cooperation down to a relatively small observation probability. In contrast, the three trustful norms under which both cooperation and defection to unknown players lead to a good reputation are relatively efficient