Probing the role of the cation–π interaction in the binding sites of GPCRs using unnatural amino acids

We describe a general application of the nonsense suppression methodology for unnatural amino acid incorporation to probe drug–receptor interactions in functional G protein-coupled receptors (GPCRs), evaluating the binding sites of both the M2 muscarinic acetylcholine receptor and the D2 dopamine receptor. Receptors were expressed in Xenopus oocytes, and activation of a G protein-coupled, inward-rectifying K^+ channel (GIRK) provided, after optimization of conditions, a quantitative readout of receptor function. A number of aromatic amino acids thought to be near the agonist-binding site were evaluated. Incorporation of a series of fluorinated tryptophan derivatives at W6.48 of the D2 receptor establishes a cation–π interaction between the agonist dopamine and W6.48, suggesting a reorientation of W6.48 on agonist binding, consistent with proposed “rotamer switch” models. Interestingly, no comparable cation–π interaction was found at the aligning residue in the M2 receptor

Use of Death Certificates to Identify Tuberculosis-related Deaths in Washington State

Thesis (Master's)--University of Washington, 2012OBJECTIVE: To compare the accuracy of ICD-10 coded and text cause of death data in identifying tuberculosis (TB)-related deaths in Washington State. DESIGN: A cross-sectional study was performed comparing TB-related deaths identified through death certificates using either text fields or ICD-10 codes to TB-related deaths identified in the TB registry. RESULTS: All methods using death certificate data overestimated the number of TB-related deaths and had low to moderate agreement with the tuberculosis registry. Several subjects assigned a TB ICD-10 code had no evidence of TB on the death certificate. CONCLUSION: Death certificates are not highly predictive of TB-related deaths. If death certificates are utilized, then TB-related deaths should be identified using direct cause of death text fields

Restructuring routine elective services to reduce overall capacity requirements within a local health economy

The U.K. Government has introduced a new class of health service providers called Treatment Centres that provide routine elective services but that do not deal with emergency cases or non-routine elective patients. The introduction of these centres provides a possible mechanism for improving the efficiency of service delivery in terms of overall capacity requirements. In this paper we discuss a mathematical modelling approach that has been used to examine circumstances under which such benefits might be realised. As an illustration of the analysis, we present results obtained using data concerning urological services, for which there would seem to be benefits associated with the introduction of a TC in only a limited range of circumstances

A stochastic model to evaluate options for antenatal genetic screening

Haemoglobinopathies are a group of genetic disorders which are particularly prevalent among certain risk groups such as ethnic groups. Antenatal screening of potential haemoglobinopathy carriers allows early diagnosis for affected fetuses, leading to therapeutic intervention or termination. However, it has drawbacks such as screening costs and possible miscarriage as a result of fetal testing. This paper describes a model that allows the outcomes of a screening programme to be estimated for different risk groups. The model has been implemented as a computer package that can be used to inform decisions made by health care planners. Copyright Springer Science + Business Media, Inc. 2006Haemoglobinopathies, Genetic screening, Antenatal screening, Mathematical modelling, Stochastic models, Computer models,

Epidemiology of Human Mycobacterium bovis Disease, California, USA, 2003–2011

We conducted a retrospective review of California tuberculosis (TB) registry and genotyping data to evaluate trends, analyze epidemiologic differences between adult and child case-patients with Mycobacterium bovis disease, and identify risk factors for M. bovis disease. The percentage of TB cases attributable to M. bovis increased from 3.4% (80/2,384) in 2003 to 5.4% (98/1,808) in 2011 (p = 0.002). All (6/6) child case-patients with M. bovis disease during 2010–2011 had >1 parent/guardian who was born in Mexico, compared with 38% (22/58) of child case-patients with M. tuberculosis disease (p = 0.005). Multivariate analysis of TB case-patients showed Hispanic ethnicity, extrapulmonary disease, diabetes, and immunosuppressive conditions, excluding HIV co-infection, were independently associated with M. bovis disease. Prevention efforts should focus on Hispanic binational families and adults with immunosuppressive conditions. Collection of additional risk factors in the national TB surveillance system and expansion of whole-genome sequencing should be considered

Using social media to estimate Zika's impact on tourism: #babymoon, 2014-2017.

Zika virus infection during pregnancy can cause microcephaly and other birth defects. We hypothesized that the Latin America Zika epidemic resulted in pregnant women and their partners adopting behavioral changes to limit risk, leading them to forego travel to Zika-affected locations. We evaluated this hypothesis by studying travelers' intent and behavior through Twitter data related to babymoon: a holiday taken by parents-to-be before their baby is born. We found the odds of mentioning representative Zika-affected locations in #babymoon tweets dropped significantly (Odds ratio: 0.29, 95% CI: 0.20-0.40) after the Zika-microcephaly association became well-known. This result was further corroborated through a content analysis of #babymoon tweets mentioning Zika-affected locations, which identified if the Twitter user was physically present in the Zika-affected locations. Conversely, we found a small but statistically insignificant increase in the odds of mentioning Zika-free locations from #babymoon tweets (Odds Ratio: 1.11, 95% CI: 0.97-1.27) after the Zika-microcephaly association became well-known