Assessing the inter- and intra-animal variability of in vivo OsteoProbe skeletal measures in untreated dogs

AbstractThe OsteoProbe is a second-generation reference point indentation (RPI) device without a reference probe that is designed to simplify RPI testing for clinical use. Successful clinical implementation of the OsteoProbe would benefit from a better understanding of how its output, bone material strength index (BMSi), relates to the material properties of bone and under what conditions it reliably correlates with fracture risk. Large animal models have the potential to help fill this knowledge gap, as cadaveric studies are retrospective and limited by incomplete patient histories (including the potential use of bone matrix altering drugs such as bisphosphonates). The goal of this study was to assess the intra and inter-animal variability of OsteoProbe measures in untreated beagle dogs (n=12), and to evaluate this variability in comparison to traditional mechanical testing. OsteoProbe measurements were performed in vivo on the left tibia of each dog and repeated 6months later on the day of sacrifice. Within-animal variation of BMSi (CV of 5–10 indents) averaged 8.9 and 9.0% at the first and second timepoints, respectively. In contrast, inter-animal variation of BMSi increased from 5.3% to 9.1%. The group variation of BMSi was on par with that of traditional 3-point mechanical testing; inter-animal variation was 10% for ultimate force, 13% for stiffness, and 12% for total work as measured on the femur. There was no significant change in mean BMSi after 6months, but the individual change with time across the 12 dogs was highly variable, ranging from −12.4% to +21.7% (mean 1.6%, SD 10.6%). No significant correlations were found between in vivo tibia BMSi and femur mechanical properties measured by ex vivo 3-pt bending, but this may be a limitation of sample size or the tests being performed on different bones. No relationship was found between BMSi and tissue mineral density, but a strong positive correlation was found between BMSi and tibia cortical thickness (ρ=0.706, p=0.010). This report shows that while the OsteoProbe device has inter-individual variability quite similar to that of traditional mechanical testing, the longitudinal changes show high levels of heterogeneity across subjects. We further highlight the need for standardization in post-testing data processing and further study of the relationships between OsteoProbe and traditional mechanical testing

Artificial intelligence for the management of pancreatic diseases

Novel artificial intelligence techniques are emerging in all fields of healthcare, including gastroenterology. The aim of this review is to give an overview of artificial intelligence applications in the management of pancreatic diseases. We performed a systematic literature search in PubMed and Medline up to May 2020 to identify relevant articles. Our results showed that the development of machine-learning based applications is rapidly evolving in the management of pancreatic diseases, guiding precision medicine in clinical, endoscopic and radiologic settings. Before implementation into clinical practice, further research should focus on the external validation of novel techniques, clarifying the accuracy and robustness of these models.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Raloxifene improves bone mechanical properties in mice previously treated with zoledronate

Bisphosphonates represent the gold-standard pharmaceutical agent for reducing fracture risk. Long-term treatment with bisphosphonates can result in tissue brittleness which in rare clinical cases manifests as atypical femoral fracture. Although this has led to an increasing call for bisphosphonate cessation, few studies have investigated therapeutic options for follow-up treatment. The goal of this study was to test the hypothesis that treatment with raloxifene, a drug that has cell-independent effects on bone mechanical material properties, could reverse the compromised mechanical properties that occur following zoledronate treatment. Skeletally mature male C57Bl/6J mice were treated with vehicle (VEH), zoledronate (ZOL), or ZOL followed by raloxifene (RAL; 2 different doses). At the conclusion of 8 weeks of treatment, femora were collected and assessed with microCT and mechanical testing. Trabecular BV/TV was significantly higher in all treated animals compared to VEH with both RAL groups having significantly higher BV/TV compared to ZOL (+21%). All three drug-treated groups had significantly more cortical bone area, higher cortical thickness, and greater moment of inertia at the femoral mid-diaphysis compared to VEH with no difference among the three treated groups. All three drug-treated groups had significantly higher ultimate load compared to VEH-treated animals (+14 to 18%). Both doses of RAL resulted in significantly higher displacement values compared to ZOL-treated animals (+25 to +50%). In conclusion, the current work shows beneficial effects of raloxifene in animals previously treated with zoledronate. The higher mechanical properties of raloxifene-treated animals, combined with similar cortical bone geometry compared to animals treated with zoledronate, suggest that the raloxifene treatment is enhancing mechanical material properties of the tissue

Identification of individuals at high-risk for pancreatic cancer using a digital patient-input tool combining family cancer history screening and new-onset diabetes

Capturing family history might be a valuable tool for identification of individuals at increased risk of pancreatic cancer, which would allow enrollment into pancreatic surveillance programs. In addition, weight loss and concurrent new-onset diabetes may be utilized as an early marker for pancreatic cancer. This study evaluates the yield of combining family history and the Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) model to identify individuals who could benefit from pancreatic surveillance. A novel questionnaire and digital input tool was created that combined questions on family cancer history and criteria of the ENDPAC model. Individuals meeting ENDPAC criteria were enrolled directly in the high-risk pancreatic clinic. Individuals who met the criteria for a significant family history of cancer were offered referral to a genetic counselor. The questionnaire was completed by 453 patients. Of those, 25.8% (117/453) had significant familial risk factors. Eighteen individuals (15.4%) completed genetic testing previously, of whom five had a pathogenic variant. Thirty-four (29.9%) out of 117 individuals with a strong family history – flagged by the questionnaire – underwent genetic testing. Four (11.8%) of these patients harbored a pathogenic variant. Additionally, through cascade family testing, two siblings were found to carry pathogenic variants. Four (0.9%) of the 453 patients matched ENDPAC criteria. Two were diagnosed with pancreatic cancer and the others were enrolled in the surveillance program. In conclusion, identification of high-risk individuals for pancreatic cancer can be achieved by combining family history screening and the ENDPAC model to facilitate referral to genetic counseling and high-risk clinics.Gastroenterology and Hepatolog

Prevalence, features, and explanations of missed and misinterpreted pancreatic cancer on imaging: a matched case-control study

Purpose To characterize the prevalence of missed pancreatic masses and pancreatic ductal adenocarcinoma (PDAC)-related findings on CT and MRI between pre-diagnostic patients and healthy individuals.Materials and methods Patients diagnosed with PDAC (2010-2016) were retrospectively reviewed for abdominal CT- or MRI-examinations 1 month-3 years prior to their diagnosis, and subsequently matched to controls in a 1:4 ratio. Two blinded radiologists scored each imaging exam on the presence of a pancreatic mass and secondary features of PDAC. Additionally, original radiology reports were graded based on the revised RADPEER criteria.Results The cohort of 595 PDAC patients contained 60 patients with a pre-diagnostic CT and 27 with an MRI. A pancreatic mass was suspected in hindsight on CT in 51.7% and 50% of cases and in 1.3% and 0.9% of controls by reviewer 1 (p < .001) and reviewer 2 (p < .001), respectively. On MRI, a mass was suspected in 70.4% and 55.6% of cases and 2.9% and 0% of the controls by reviewer 1 (p < .001) and reviewer 2 (p < .001), respectively. Pancreatic duct dilation, duct interruption, focal atrophy, and features of acute pancreatitis is strongly associated with PDAC (p < .001). In cases, a RADPEER-score of 2 or 3 was assigned to 56.3% of the CT-reports and 71.4% of MRI-reports.Conclusion Radiological features as pancreatic duct dilation and interruption, and focal atrophy are common first signs of PDAC and are often missed or unrecognized. Further investigation with dedicated pancreas imaging is warranted in patients with PDAC-related radiological findings.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Temperature and Photoperiod Effects on Sterility in a Cytoplasmic Male-Sterile Soybean

Manual cross-pollination to produce large quantities of hybrid soybean seed is difficult and time consuming. An environmentally stable sterility system is one of the necessary components to produce large quantities of hybrid seed. The objective of this study was to subject cytoplasmic male-sterile (CMS) BC5F1 plants, from a cross of a Chinese Glycine max wild-type soybean with a Chinese wild annual soybean G. soja (male parent) and controls, to a variety of different temperature and photoperiod treatments to test whether CMS is stable under various environmental conditions. Plants were grown in growth chambers under controlled temperature, photoperiod, and irradiance regimes until pod set, and then they were transferred to a glasshouse until they matured. Plants were evaluated for time of anthesis after photoperiod induction (13 h light/11 h dark) and fertility or sterility. Anther squash and pod set data showed that sterility of the CMS line was stable under all environmental conditions tested, whereas fertility-restored control plants remained fertile. Extreme environmental conditions led to delayed floral induction and/or stunted growth

Artificial intelligence in gastroenterology: a state-of-the-art review

The development of artificial intelligence (AI) has increased dramatically in the last 20 years, with clinical applications progressively being explored for most of the medical specialties. The field of gastroenterology and hepatology, substantially reliant on vast amounts of imaging studies, is not an exception. The clinical applications of AI systems in this field include the identification of premalignant or malignant lesions (e.g., identification of dysplasia or esophageal adenocarcinoma in Barrett's esophagus, pancreatic malignancies), detection of lesions (e.g., polyp identification and classification, small-bowel bleeding lesion on capsule endoscopy, pancreatic cystic lesions), development of objective scoring systems for risk stratification, predicting disease prognosis or treatment response [e.g., determining survival in patients post-resection of hepatocellular carcinoma), determining which patients with inflammatory bowel disease (IBD) will benefit from biologic therapy], or evaluation of metrics such as bowel preparation score or quality of endoscopic examination. The objective of this comprehensive review is to analyze the available AI-related studies pertaining to the entirety of the gastrointestinal tract, including the upper, middle and lower tracts; IBD; the hepatobiliary system; and the pancreas, discussing the findings and clinical applications, as well as outlining the current limitations and future directions in this field.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Modeling the actinides with disordered local moments

A first-principles disordered local moment (DLM) picture within the local-spin-density and coherent potential approximations (LSDA+CPA) of the actinides is presented. The parameter free theory gives an accurate description of bond lengths and bulk modulus. The case of $\delta$-Pu is studied in particular and the calculated density of states is compared to data from photo-electron spectroscopy. The relation between the DLM description, the dynamical mean field approach and spin-polarized magnetically ordered modeling is discussed.Comment: 6 pages, 4 figure

Discriminant Analysis and Secondary-Beam Charge Recognition

The discriminant-analysis method has been applied to optimize the exotic-beam charge recognition in a projectile fragmentation experiment. The experiment was carried out at the GSI using the fragment separator (FRS) to produce and select the relativistic secondary beams, and the ALADIN setup to measure their fragmentation products following collisions with Sn target nuclei. The beams of neutron poor isotopes around 124La and 107Sn were selected to study the isospin dependence of the limiting temperature of heavy nuclei by comparing with results for stable 124Sn projectiles. A dedicated detector to measure the projectile charge upstream of the reaction target was not used, and alternative methods had to be developed. The presented method, based on the multivariate discriminant analysis, allowed to increase the efficacy of charge recognition up to about 90%, which was about 20% more than achieved with the simple scalar methods.Comment: 6 pages, 7 eps figures, elsart, submitted to Nucl. Instr. and Meth.

Mass and Isospin Effects in Multifragmentation

A systematic study of isospin effects in the breakup of projectile spectators at relativistic energies has been performed with the ALADiN spectrometer at the GSI laboratory (Darmstadt). Four different projectiles 197Au, 124La, 124Sn and 107Sn, all with an incident energy of 600 AMeV, have been used, thus allowing a study of various combinations of masses and N/Z ratios in the entrance channel. The measurement of the momentum vector and of the charge of all projectile fragments with Z>1 entering the acceptance of the ALADiN magnet has been performed with the high efficiency and resolution achieved with the TP-MUSIC IV detector. The Rise and Fall behavior of the mean multiplicity of IMFs as a function of Zbound and its dependence on the isotopic composition has been determined for the studied systems. Other observables investigated so far include mean N/Z values of the emitted light fragments and neutron multiplicities. Qualitative agreement has been obtained between the observed gross properties and the predictions of the Statistical Multifragmentation Model.Comment: 10 pages,7 figure, 18th Nuclear Physics Division Conference of the EPS, Prague, submitted to Nucl. Phys.