Hubble Space Telescope observations of Mars

Hubble Space Telescope (HST) afforded the possibility of resolving features as small as 100 km on the Martian surface even when it is at the far point of its orbit. Therefore it is ideally suited for monitoring seasonal changes on the red planet. The objectives research include: the study of Martian dust storms; use of images obtained through different filters to study the spectral reflectance of regions on the Martian surface; use of ultraviolet images and spectra to measure the amount of ozone in the planet's atmosphere as a function of location of the planet; use of images to study changes in the albedo of the Mars surface; and use of Planetary Camera images to study Martian clouds and to measure the opacity of the atmosphere

Durable Goods Inventories and the Great Moderation

This paper revisits the hypothesis that changes in inventory management were an important contributor to volatility reductions during the Great Moderation. It documents how changes in inventory behavior contributed to the stabilization of the U.S. economy within the durable goods sector, in particular, and develops a model of inventory behavior that is consistent with the key facts about volatility decline in that sector. The model is calibrated to evidence from survey data showing that lead times for materials orders in manufacturing shrank after the early 1980s. Simulations of the model show large reductions in the volatility of output growth and more modest reductions in the volatility of sales growth. In addition, the model addresses concerns raised by a number of researchers who criticize the inventory literature's focus on finished goods inventories, given that stocks of works-in-process and materials are actually larger and more volatile that those of finished goods. The model adapts the stockout-avoidance concept to a production-to-order setting and shows that much of the intuition and results regarding production volatility still apply

The Medical Informatics Group: Ongoing Research

Two current research projects within the Medical Informatics Group are described. The first, the Diabetes Data Management Project, has as its major goal the effective analysis, display, and summarization of information relevant to the care of insulin-dependent diabetics. These goals are achieved through the use of quantitative and qualitative modeling techniques, object-oriented graphical display methods, and natural language generation programs. The second research activity, the Hypertext Medical Handbook Project, emphasizes many aspects of electronic publishing and biomedical communication. In particular, the project explores machine-assisted information retrieval by combining user feedback with Bayesian inference networks

Outlook for tuberculosis elimination in California: An individual-based stochastic model.

RationaleAs part of the End TB Strategy, the World Health Organization calls for low-tuberculosis (TB) incidence settings to achieve pre-elimination (<10 cases per million) and elimination (<1 case per million) by 2035 and 2050, respectively. These targets require testing and treatment for latent tuberculosis infection (LTBI).ObjectivesTo estimate the ability and costs of testing and treatment for LTBI to reach pre-elimination and elimination targets in California.MethodsWe created an individual-based epidemic model of TB, calibrated to historical cases. We evaluated the effects of increased testing (QuantiFERON-TB Gold) and treatment (three months of isoniazid and rifapentine). We analyzed four test and treat targeting strategies: (1) individuals with medical risk factors (MRF), (2) non-USB, (3) both non-USB and MRF, and (4) all Californians. For each strategy, we estimated the effects of increasing test and treat by a factor of 2, 4, or 10 from the base case. We estimated the number of TB cases occurring and prevented, and net and incremental costs from 2017 to 2065 in 2015 U.S. dollars. Efficacy, costs, adverse events, and treatment dropout were estimated from published data. We estimated the cost per case averted and per quality-adjusted life year (QALY) gained.Measurements and main resultsIn the base case, 106,000 TB cases are predicted to 2065. Pre-elimination was achieved by 2065 in three scenarios: a 10-fold increase in the non-USB and persons with MRF (by 2052), and 4- or 10-fold increase in all Californians (by 2058 and 2035, respectively). TB elimination was not achieved by any intervention scenario. The most aggressive strategy, 10-fold in all Californians, achieved a case rate of 8 (95% UI 4-16) per million by 2050. Of scenarios that reached pre-elimination, the incremental net cost was $20 billion (non-USB and MRF) to$48 billion. These had an incremental cost per QALY of $657,000 to$3.1 million. A more efficient but somewhat less effective single-lifetime test strategy reached as low as $80,000 per QALY.ConclusionsSubstantial gains can be made in TB control in coming years by scaling-up current testing and treatment in non-USB and those with medical risks

Hypertension testing and treatment in Uganda and Kenya through the SEARCH study: An implementation fidelity and outcome evaluation.

BackgroundHypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]-although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions.MethodsWe sought to evaluate the consistency of HTN program delivery within the SEARCH study (NCT01864603) among 95,000 adults in 32 rural communities in Uganda and Kenya from 2013-2016. To achieve this objective, we designed and performed a fidelity evaluation of the step-by-step process (cascade) of HTN care within SEARCH, calculating rates of HTN screening, linkage to care, and follow-up care. We evaluated SEARCH's assessment of each participant's HTN status against measured blood pressure and HTN history.FindingsSEARCH completed blood pressure screens on 91% of participants. SEARCH HTN screening was 91% sensitive and over 99% specific for HTN relative to measured blood pressure and patient history. 92% of participants screened HTN+ received clinic appointments, and 42% of persons with HTN linked to subsequent care. At follow-up, 82% of SEARCH clinic participants received blood pressure checks; 75% received medication appropriate for their blood pressure; 66% remained in care; and 46% had normal blood pressure at their most recent visit.ConclusionThe SEARCH study's consistency in delivering screening and treatment services for HTN was generally high, but SEARCH could improve effectiveness in linking patients to care and achieving HTN control. Its model for implementing population-scale HTN testing and care through an existing HIV test-and-treat program-and protocol for evaluating the intervention's stepwise fidelity and care outcomes-may be adapted, strengthened, and scaled up for use across multiple resource-limited settings

SpliceCenter: A suite of web-based bioinformatic applications for evaluating the impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based studies

<p>Abstract</p> <p>Background</p> <p>Over 60% of protein-coding genes in vertebrates express mRNAs that undergo alternative splicing. The resulting collection of transcript isoforms poses significant challenges for contemporary biological assays. For example, RT-PCR validation of gene expression microarray results may be unsuccessful if the two technologies target different splice variants. Effective use of sequence-based technologies requires knowledge of the specific splice variant(s) that are targeted. In addition, the critical roles of alternative splice forms in biological function and in disease suggest that assay results may be more informative if analyzed in the context of the targeted splice variant.</p> <p>Results</p> <p>A number of contemporary technologies are used for analyzing transcripts or proteins. To enable investigation of the impact of splice variation on the interpretation of data derived from those technologies, we have developed SpliceCenter. SpliceCenter is a suite of user-friendly, web-based applications that includes programs for analysis of RT-PCR primer/probe sets, effectors of RNAi, microarrays, and protein-targeting technologies. Both interactive and high-throughput implementations of the tools are provided. The interactive versions of SpliceCenter tools provide visualizations of a gene's alternative transcripts and probe target positions, enabling the user to identify which splice variants are or are not targeted. The high-throughput batch versions accept user query files and provide results in tabular form. When, for example, we used SpliceCenter's batch siRNA-Check to process the Cancer Genome Anatomy Project's large-scale shRNA library, we found that only 59% of the 50,766 shRNAs in the library target all known splice variants of the target gene, 32% target some but not all, and 9% do not target any currently annotated transcript.</p> <p>Conclusion</p> <p>SpliceCenter <url>http://discover.nci.nih.gov/splicecenter</url> provides unique, user-friendly applications for assessing the impact of transcript variation on the design and interpretation of RT-PCR, RNAi, gene expression microarrays, antibody-based detection, and mass spectrometry proteomics. The tools are intended for use by bench biologists as well as bioinformaticists.</p

ARF GTPases and their GEFs and GAPs: concepts and challenges

Detailed structural, biochemical, cell biological, and genetic studies of any gene/protein are required to develop models of its actions in cells. Studying a protein family in the aggregate yields additional information, as one can include analyses of their coevolution, acquisition or loss of functionalities, structural pliability, and the emergence of shared or variations in molecular mechanisms. An even richer understanding of cell biology can be achieved through evaluating functionally linked protein families. In this review, we summarize current knowledge of three protein families: the ARF GTPases, the guanine nucleotide exchange factors (ARF GEFs) that activate them, and the GTPase-activating proteins (ARF GAPs) that have the ability to both propagate and terminate signaling. However, despite decades of scrutiny, our understanding of how these essential proteins function in cells remains fragmentary. We believe that the inherent complexity of ARF signaling and its regulation by GEFs and GAPs will require the concerted effort of many laboratories working together, ideally within a consortium to optimally pool information and resources. The collaborative study of these three functionally connected families ( \u3e /=70 mammalian genes) will yield transformative insights into regulation of cell signaling

Are Voluntary Agreements Better? Evidence from Baseball Arbitration

This paper empirically examines the widespread belief that voluntarily negotiated agreements produce better long-run relationships than third-party imposed settlements, such as arbitrator decisions or court judgments. Two key outcomes are analyzed – subsequent player performance and the durability of club-player relationship. Major League Baseball provides a compelling setting for these analyses because individual performance is well measured, there is the possibility of relationship breakdown, and both voluntary and imposed settlements are routinely used. While the results clearly show that a third-party imposed settlement is not better than a voluntary one, the evidence in support of the widespread belief is mixed

Estimating the Resources Needed and Savings Anticipated from Roll-Out of Adult Male Circumcision in Sub-Saharan Africa

Background: Trials in Africa indicate that medical adult male circumcision (MAMC) reduces the risk of HIV by 60%. MAMC may avert 2 to 8 million HIV infections over 20 years in sub-Saharan Africa and cost less than treating those who would have been infected. This paper estimates the financial and human resources required to roll out MAMC and the net savings due to reduced infections. Methods: We developed a model which included costing, demography and HIV epidemiology. We used it to investigate 14 countries in sub-Saharan Africa where the prevalence of male circumcision was lower than 80% and HIV prevalence among adults was higher than 5%, in addition to Uganda and the Nyanza province in Kenya. We assumed that the roll-out would take 5 years and lead to an MC prevalence among adult males of 85%. We also assumed that surgery would be done as it was in the trials. We calculated public program cost, number of full-time circumcisers and net costs or savings when adjusting for averted HIV treatments. Costs were in USD, discounted to 2007. 95% percentile intervals (95% PI) were estimated by Monte Carlo simulations. Results: In the first 5 years the number of circumcisers needed was 2 282 (95% PI: 2 018 to 2 959), or 0.24 (95% PI: 0.21 to 0.31) per 10 000 adults. In years 6-10, the number of circumcisers needed fell to 513 (95% PI: 452 to 664). The estimated 5-year cost of rolling out MAMC in the public sector was $919 million (95$672 million (95% PI: 437 to 1 021) and over 20 years there were net savings of $2.3 billion (95% PI: 1.4 to 3.4). Conclusion: A rapid roll-out of MAMC in sub-Saharan Africa requires substantial funding and a high number of circumcisers for the first five years. These investments are justified by MAMC's substantial health benefits and the savings accrued by averting future HIV infections. Lower ongoing costs and continued care savings suggest long-term sustainability