Validation of a Multivariate Serum Profile for Epithelial Ovarian Cancer Using a Prospective Multi-Site Collection

In previous studies we described the use of a retrospective collection of ovarian cancer and benign disease samples, in combination with a large set of multiplexed immunoassays and a multivariate pattern recognition algorithm, to develop an 11-biomarker classification profile that is predictive for the presence of epithelial ovarian cancer. In this study, customized, Luminex-based multiplexed immunoassay kits were GMP-manufactured and the classification profile was refined from 11 to 8 biomarkers (CA-125, epidermal growth factor receptor, CA 19-9, C-reactive protein, tenascin C, apolipoprotein AI, apolipoprotein CIII, and myoglobin). The customized kits and the 8-biomarker profile were then validated in a double-blinded manner using prospective samples collected from women scheduled for surgery, with a gynecologic oncologist, for suspicion of having ovarian cancer. The performance observed in model development held in validation, demonstrating 81.1% sensitivity (95% CI 72.6 – 87.9%) for invasive epithelial ovarian cancer and 85.4% specificity (95% CI 81.1 – 88.9%) for benign ovarian conditions. The specificity for normal healthy women was 95.6% (95% CI 83.6 – 99.2%). These results have encouraged us to undertake a second validation study arm, currently in progress, to examine the performance of the 8-biomarker profile on the population of women not under the surgical care of a gynecologic oncologist

Mapping the physiography of Michigan with GIS

Abstract: We present a new physiographic map of Michigan, that is also available interactively, online. Only four, small-scale physiographic maps of Michigan had been previously published. Our mapping project made use of a wide variety of spatial data, in a GIS environment, to visualize and delineate the physical landscape in more detail than has been done previously. We also examined many of the unit boundaries in the field, using a GIS running on a GPS-enabled laptop. Unlike previous physiographic maps, the online version of the map enables users to query the criteria used to define each of the 224 boundaries of its 10 major and 91 minor physiographic units. The interactive nature of the online version of the map is a unique enhancement to physiographic maps and mapping. Our study also provides data on the number and types of criteria used to define each of the 224 unit boundaries within the map. Most of our unit boundaries are based on data derived from 10-m raster elevation data and NRCS soils data, e.g., relief, soil wetness, escarpments, landscape fabric, and parent material characteristics. Data gleaned from NRCS SSURGO county-scale soil maps were a strength of the project

The medium term outcome of the Omnifit constrained acetabular cup

Recurrent dislocation requiring revision surgery occurs in approximately 4% of primary total hip arthroplasties (THAs). To reduce this risk, or to treat those patients who recurrently dislocate, a constrained acetabular component may be used, however there are concerns over the success of such components due to increased mechanical stresses. The purpose of this study was to analyse the survivorship and radiological results for the Omnifit constrained acetabular component, providing a longer patient reported outcome follow-up than previous studies.117 patients (median age 82 years) underwent a THA with an Omnifit constrained acetabular component. Of these, 45 were primary replacements and 72 were revisions. Survivorship analysis was performed and patients were assessed both radiologically and functionally.At follow-up, 53 patients (45.3%) had died at a median time of 33 months from operation. The median overall follow-up was 7.0 (5.5–8.2) years. Survivors (median age 83 years) reported a median Oxford Hip Score (OHS) of 16.6 (0–48), 87.8% were satisfied with their surgery. 45 (91.8%) of the acetabular components were stable radiologically, 48 (96%) of the femoral components were stable (5 uncemented, 43 cemented) and two possibly unstable. Four of the 117 patients underwent further surgery. Only one required revision of the prosthesis and this was for a periprosthetic fracture.In the medium term the Omnifit constrained acetabular component prevents dislocation and does not cause excessive loosening of either the acetabular or femoral components in our patient population. Our results support the use of the Omnifit constrained acetabular component in elderly patients at risk of dislocation with low functional demand.</jats:p

Altered Hematopoiesis, Behavior, and Sexual Function in μ Opioid Receptor–deficient Mice

The μ opioid receptor is thought to be the cellular target of opioid narcotics such as morphine and heroin, mediating their effects in both pain relief and euphoria. Its involvement is also implicated in a range of diverse biological processes. Using a mouse model in which the receptor gene was disrupted by targeted homologous recombination, we explored the involvement of this receptor in a number of physiological functions. Mice homozygous for the disrupted gene developed normally, but their motor function was altered. Drug-naive homozygotes displayed reduced locomotor activity, and morphine did not induce changes in locomotor activity observed in wild-type mice. Unexpectedly, lack of a functional receptor resulted in changes in both the host defense system and the reproductive system. We observed increased proliferation of granulocyte-macrophage, erythroid, and multipotential progenitor cells in both bone marrow and spleen, indicating a link between hematopoiesis and the opioid system, both of which are stress-responsive systems. Unexpected changes in sexual function in male homozygotes were also observed, as shown by reduced mating activity, a decrease in sperm count and motility, and smaller litter size. Taken together, these results suggest a novel role of the μ opioid receptor in hematopoiesis and reproductive physiology, in addition to its known involvement in pain relief