Prostate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70–76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.
This is the first study to simultaneously measure material properties in tension, compression, nanoindentation as well as microstructure (crystallinity and lamellar level properties) across a wide variety of clinically relevant ultra-high molecular weight polyethylene (UHMWPE) formulations. Methodologies for the measurement of UHMWPE mechanical properties-namely elastic modulus, yield stress, yield strain, ultimate strength, energetic toughness, Poisson's ratio, hardness and constitutive variables-are evaluated. Engineering stress-strain behavior is compared to true stress-strain behavior for UHMWPE across a range of cross-linking and antioxidant chemistry. The tensile mechanical properties and constitutive behavior of UHMWPE are affected by resin type, antioxidant source and degree of cross-linking. Poisson's ratio is shown to be affected by resin type, antioxidant addition, and cross-linking dosage. Relationships between bulk mechanical properties from different measurement methodologies as well as microstructure are analyzed across all material formulations using Spearman rank correlation coefficients. Modulus and yield strength correlate in both tension and compression. Similarly, tensile and compressive properties including modulus and yield strength correlate strongly with crystallinity (X) and lamellar thickness (D). This work has broad application and provides a basis for interpreting the mechanical behavior of UHMWPE used in orthopedic implants.
The seventh case of probable cefazolin-induced pseudomembranous colitis is reported. Perforation of the colon necessitated sigmoid resection. The postoperative course was protracted, and illustrates the difficulty of managing advanced pseudomembranous colitis when the oral route of antibiotic administration is not available. Although rare, pseudomembranous colitis related to cefazolin administration is a potentially fatal complication. The routine use of prophylactic antibiotics must be weighed against this possibility.
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