Combining Surveillance Systems: Effective Merging of U.S. Veteran and Military Health Data

Background

The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) had more than 18 million healthcare beneficiaries in 2011. Both Departments conduct individual surveillance for disease events and health threats.

Methods

We performed joint and separate analyses of VA and DoD outpatient visit data from October 2006 through September 2010 to demonstrate geographic and demographic coverage, timeliness of influenza epidemic awareness, and impact on spatial cluster detection achieved from a joint VA and DoD biosurveillance platform.

Results

Although VA coverage is greater, DoD visit volume is comparable or greater. Detection of outbreaks was better in DoD data for 58% and 75% of geographic areas surveyed for seasonal and pandemic influenza, respectively, and better in VA data for 34% and 15%. The VA system tended to alert earlier with a typical H3N2 seasonal influenza affecting older patients, and the DoD performed better during the H1N1 pandemic which affected younger patients more than normal influenza seasons. Retrospective analysis of known outbreaks demonstrated clustering evidence found in separate DoD and VA runs, which persisted with combined data sets.

Conclusion

The analyses demonstrate two complementary surveillance systems with evident benefits for the national health picture. Relative timeliness of reporting could be improved in 92% of geographic areas with access to both systems, and more information provided in areas where only one type of facility exists. Combining DoD and VA data enhances geographic cluster detection capability without loss of sensitivity to events isolated in either population and has a manageable effect on customary alert rates.     

Multimodal Imaging of Orthotopic Mouse Model of Endometrial Carcinoma

Background

Orthotopic endometrial cancer models provide a unique tool for studies of tumour growth and metastatic spread. Novel preclinical imaging methods also have the potential to quantify functional tumour characteristics in vivo, with potential relevance for monitoring response to therapy.

Methods

After orthotopic injection with luc-expressing endometrial cancer cells, eleven mice developed disease detected by weekly bioluminescence imaging (BLI). In parallel the same mice underwent positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI) employing ¹⁸F-fluorodeoxyglocose (¹⁸F-FDG) or ¹⁸F- fluorothymidine (¹⁸F-FLT) and contrast reagent, respectively. The mice were sacrificed when moribund, and post-mortem examination included macroscopic and microscopic examination for validation of growth of primary uterine tumours and metastases. PET-CT was also performed on a patient derived model (PDX) generated from a patient with grade 3 endometrioid endometrial cancer.

Results

Increased BLI signal during tumour growth was accompanied by increasing metabolic tumour volume (MTV) and increasing MTV x mean standard uptake value of the tumour (SUV_mean) in ¹⁸F-FDG and ¹⁸F-FLT PET-CT, and MRI conspicuously depicted the uterine tumour. At necropsy 82% (9/11) of the mice developed metastases detected by the applied imaging methods. ¹⁸F-FDG PET proved to be a good imaging method for detection of patient derived tumour tissue.

Conclusions

We demonstrate that all imaging modalities enable monitoring of tumour growth and metastatic spread in an orthotopic mouse model of endometrial carcinoma. Both PET tracers, ¹⁸F-FDG and ¹⁸F-FLT, appear to be equally feasible for detecting tumour development and represent, together with MRI, promising imaging tools for monitoring of patient-derived xenograft (PDX) cancer models.     

The N-glycosylation pattern of Caenorhabditis elegans

Determining the exact nature of N-glycosylation in Caenorhabditis elegans, a nematode worm and genetic model organism, has proved to have been an unexpected challenge in recent years; a wide range of modifications of its N-linked oligosaccharides have been proposed on the basis of structural and genomic analysis. Particularly mass spectrometric studies by a number of groups, as well as the characterisation of recombinant enzymes, have highlighted those aspects of N-glycosylation that are conserved in animals, those which are seemingly unique to this species and those which are shared with parasitic nematodes. These data, of importance for therapeutic developments, are reviewed.     

Cenomanian carbonate facies and rudists along shallow intraplatform basin margin-the island of Cres (Adriatic Sea, Croatia)

Summary The island of Cres is located in the northern part of the Adriatic Sea. The island is built up of predominantly Cretaceous carbonates deposited in north-western part of extensive and long-lasting Adriatic Carbonate Platform. Owing to the influence of synsedimentary tectonics supported by eustatic changes during the latest Albian/Early Cenomanian, different sedimentary environments were established: from shallow intraplatform basin and related slope, across basin margin to protected shallow-platform. During the Early to Middle Cenomanian rudist communities (ichthyosarcolitid/caprinid/radiolitid)flourished along a relatively high-energy intraplatform basin margin. Fair amounts of coarse-grained bioclasts, derived almost exclusively from broken rudist shells, were deposited over a marginal depocenter. Contemporaneously, pithonellid wackestone-packstones containing microbioclasts and planktonic foraminifera were deposited basinward while marginal bioclastic sediments and limestone blocks of the basin margin origin were sporadically deposited within the basin. The opening of the Cres intraplatform basin was aborted and the basin was finally filled up during the Late Cenomanian. Since the Cres intraplatform basin was established at the beginning of the Cenomanian it probably represented the initiation phase in the north-western extension of the later Adriatic Trough development.     

The impacts of re-introducing Mississippi River water on the hydrologic budget and nutrient inputs of a deltaic estuary

Most wetlands of the Mississippi deltaic plain are isolated from riverine input due to flood control levees along the Mississippi River. These levees have altered hydrology and ecology and are a primary cause of massive wetland loss in the delta. River water is being re-introduced into coastal basins as part of a large-scale ecological engineering effort to restore the delta. We quantified freshwater, nitrogen, and phosphorus inputs to the Breton Sound Estuary for three climatically different years (2000, 2001, and 2002). Water budgets included precipitation, potential evapotranspiration, the diversion, stormwater pumps, and groundwater. Precipitation contributed 48–57% of freshwater input, while the diversion accounted for 33–48%. Net groundwater input accounted for less than 0.05% of freshwater inputs. Inputs of ammonium (NH₄-N), nitrate (NO₃-N), total nitrogen (TN), and total phosphorus (TP) were determined for each of the water sources. Atmospheric deposition was the most important input of NH₄-N (57–62% or 1.44 × 10⁵–2.32 × 10⁵ kg yr⁻¹) followed by the diversion. The diversion was the greatest source of NO₃-N (67–83%, 7.78 × 10⁵–1.64 × 10⁶ kg yr⁻¹) and TN (60–71%). The diversion contributed 41–60% of TP input (1.17 × 10⁵–2.32 × 10⁵ kg yr⁻¹). Annual loading rates of NH₄-N and NO₃-N were 0.17–0.27 and 1.2–2.3 g N m⁻² yr⁻¹, respectively, for the total basin indicating strong retention of nitrogen in the basin. Nitrogen retention through denitrification and burial was estimated for the upper basin.     

Loss or Mislocalization of Aquaporin-4 Affects Diffusion Properties and Intermediary Metabolism in Gray Matter of Mice

The first aim of this study was to determine how complete or perivascular loss of aquaporin-4 (AQP4) water channels affects membrane permeability for water in the mouse brain grey matter in the steady state. Time-dependent diffusion magnetic resonance imaging was performed on global Aqp4 knock out (KO) and α-syntrophin (α-syn) KO mice, in the latter perivascular AQP4 are mislocalized, but still functioning. Control animals were corresponding wild type (WT) mice. By combining in vivo diffusion measurements with the effective medium theory and previously measured extra-cellular volume fractions, the effects of membrane permeability and extracellular volume fraction were uncoupled for Aqp4 and α-syn KO. The second aim was to assess the effect of α-syn KO on cortical intermediary metabolism combining in vivo [1-¹³C]glucose and [1,2-¹³C]acetate injection with ex vivo ¹³C MR spectroscopy. Aqp4 KO increased the effective diffusion coefficient at long diffusion times by 5%, and a 14% decrease in membrane water permeability was estimated for Aqp4 KO compared with WT mice. α-syn KO did not affect the measured diffusion parameters. In the metabolic analyses, significantly lower amounts of [4-¹³C]glutamate and [4-¹³C]glutamine, and percent enrichment in [4-¹³C]glutamate were detected in the α-syn KO mice. [1,2-¹³C]acetate metabolism was unaffected in α-syn KO, but the contribution of astrocyte derived metabolites to GABA synthesis was significantly increased. Taken together, α-syn KO mice appeared to have decreased neuronal glucose metabolism, partly compensated for by utilization of astrocyte derived metabolites.     

Thrombus size is associated with etiology of deep venous thrombosis--a cross-sectional study

The aim of this study was to evaluate the impact of risk factors for deep vein thrombosis (DVT) on thrombus sizes in lower extremities. The size and extent of thrombus was scored according to International Consensus Committee for venous disease classification. After the diagnosis of DVT was established and its size scored, predominant risk factors for DVT in each patient were identified (malignant disease, thrombophilia, postoperative state, hormonal therapy, heredity, limb trauma, immobilization, others and unknown risk factors). The average thrombus score was 6 (95% CI 5.47-6.53). The analysis of thrombus size indicated that the largest thrombi were found in patients with malignancy. Their average score was 8.5 (95% CI 7-10) and was significantly higher than in patients with other risk factors for deep vein thrombosis. There was no significant correlation between numbers of days from the onset of symptoms to the moment of DVT diagnosis and thrombus score (r = -0.08, p = 0.38). Age was very slightly correlated to thrombus size (r = 0.19; p = 0.046), while the gender did not have significant impact on thrombus score (p = 0.074). The conclusion of our study was that etiology of thrombosis and particularly malignant diseases has the largest impact on venous thrombus size.     

Maternal and fetal cadmium and selenium status in normotensive and hypertensive pregnancy

Cadmium and selenium concentrations in maternal and umbilical cord blood and amniotic fluid were determined in 37 normotensive and 23 hypertensive women during the last trimester of pregnancy in relation to their smoking status. Thiocyanate concentration in plasma was used as the index of smoking status. Cadmium and selenium were determined with atomic absorption spectrometry (graphite furnace and mercury hydride system). In the group of normotensive and hypertensive women, significantly higher cadmium and lower selenium concentrations in blood in smokers were observed than in nonsmokers. Umbilical cord blood selenium concentrations in both normotensive and hypertensive smokers were significantly lower than in nonsmokers as well. In the group of normotensive women, significant differences in selenium concentrations in amniotic fluid were observed between smokers and nonsmokers. In conclusion, the results of this study show that hypertension in pregnant women smokers is related to significantly higher blood cadmium concentrations, which indicates that cadmium may be considered as an independent factor involved in hypertension.