Global Analysis of a Stochastic Two-Scale Network Human Epidemic Dynamic Model with Varying Immunity Period

A stochastic SIR epidemic dynamic model with distributed-time-delay, for a two-scale dynamic population is derived. The distributed time delay is the varying naturally acquired immunity period of the removal class of individuals who have recovered from the infection, and have acquired natural immunity to the disease. We investigate the stochastic asymptotic stability of the disease free equilibrium of the epidemic dynamic model, and verify the impact on the eradication of the disease

Clinical Inertia in Type 2 Diabetes: A Retrospective Analysis of Pharmacist-Managed Diabetes Care vs. Usual Medical Care

Background: Evidence suggests that patients with type 2 diabetes (T2DM) suffer from a high rate of “clinical inertia” or “recognition of the problem but failure to act.” Objective: The aim of this study is to quantify the rate of clinical inertia between two models of care: Pharmacist-Managed Diabetes Clinic (PMDC) vs. Usual Medical Care (UMC). Methods: Patients in a university based medical clinic with type 2 diabetes (T2DM) were analyzed in this retrospective cohort study. Patients were exposed to either PMDC or UMC. The difference in days to intervention in response to suboptimal laboratory values and time to achieve goal hemoglobin A1c (A1c), systolic blood pressure (SBP) and low-density lipoprotein (LDL) was compared in the two models of care. Results: A total of 113 patients were included in the analysis of this study, 54 patients were in the PMDC and 59 patients were in the UMC group. Median time (days) to intervention for A1c values \u3e7% was 8 days and 9 days in the PMDC and UMC groups, respectively (p\u3e0.05). In patients with baseline A1c values \u3e8%, median time to achieving A1c Conclusions: Rates of clinical inertia, defined as time to intervention of suboptimal clinical values, did not differ significantly between patients enrolled in a PMDC compared to patients with UMC with respect to A1c, SBP and LDL. Participation in PMDC, however, was associated with achieving goal A1c, SBP, and LDL levels sooner compared to UMC

Bone Nanomechanical Properties and Relationship to Bone Turnover and Architecture in Patients With Atypical Femur Fractures: A Prospective Nested Case-Control Study

Atypical femur fractures (AFFs) are well-established serious complication of long-term bisphosphonate and denosumab therapy in patients with osteopenia or osteoporosis. To elucidate underlying mechanism(s) for the development of AFF, we performed a nested case-control study to investigate bone tissue nanomechanical properties and prevailing bone microstructure and tissue-level remodeling status as assessed by bone histomorphometry. We hypothesized that there would be differences in nanomechanical properties between patients with and without AFF and that bone microstructure and remodeling would be related to nanomechanical properties. Thirty-two full-thickness transiliac bone biopsies were obtained from age- and sex-matched patients on long-term bisphosphonate therapy with (n = 16) and without an AFF (n = 16). Standard histomorphometric measurements were made in each sample on three different bone envelopes (cancellous, intracortical, and endosteal). Iliac bone wall thickness was significantly lower on all three bone surfaces in patients with AFF than in those without AFF. Surface-based bone formation rate was suppressed similarly in both groups in comparison to healthy premenopausal and postmenopausal women, with no significant difference between the two groups. Nanoindentation was used to assess material properties of cortical and cancellous bone separately. Elastic modulus was higher in cortical than in cancellous bone in patients with AFF as well as compared to the elastic modulus of cortical bone from non-AFF patients. However, the elastic modulus of the cancellous bone was not different between AFF and non-AFF groups or between cortical and cancellous bone of non-AFF patients. Resistance to plastic deformation was decreased in cortical bone in both AFF and non-AFF groups compared to cancellous bone, but to a greater extent in AFF patients. We conclude that long-term bisphosphonate therapy is associated with prolonged suppression of bone turnover resulting in altered cortical remodeling and tissue nanomechanical properties leading to AFF

AXL modulates extracellular matrix protein expression and is essential for invasion and metastasis in endometrial cancer

The receptor tyrosine kinase AXL promotes migration, invasion, and metastasis. Here, we evaluated the role of AXL in endometrial cancer. High immunohistochemical expression of AXL was found in 76% (63/83) of advanced-stage, and 77% (82/107) of high-grade specimens and correlated with worse survival in uterine serous cancer patients. In vitro, genetic silencing of AXL inhibited migration and invasion but had no effect on proliferation of ARK1 endometrial cancer cells. AXL-deficient cells showed significantly decreased expression of phospho-AKT as well as uPA, MMP-1, MMP-2, MMP-3, and MMP-9. In a xenograft model of human uterine serous carcinoma with AXL-deficient ARK1 cells, there was significantly less tumor burden than xenografts with control ARK1 cells. Together, these findings underscore the therapeutic potentials of AXL as a candidate target for treatment of metastatic endometrial cancer

Dynamic contrast enhanced (DCE) MRI estimation of vascular parameters using knowledge-based adaptive models

We introduce and validate four adaptive models (AMs) to perform a physiologically based Nested-Model-Selection (NMS) estimation of such microvascular parameters as forward volumetric transfer constant, K(trans), plasma volume fraction, v(p), and extravascular, extracellular space, v(e), directly from Dynamic Contrast-Enhanced (DCE) MRI raw information without the need for an Arterial-Input Function (AIF). In sixty-six immune-compromised-RNU rats implanted with human U-251 cancer cells, DCE-MRI studies estimated pharmacokinetic (PK) parameters using a group-averaged radiological AIF and an extended Patlak-based NMS paradigm. One-hundred-ninety features extracted from raw DCE-MRI information were used to construct and validate (nested-cross-validation, NCV) four AMs for estimation of model-based regions and their three PK parameters. An NMS-based a priori knowledge was used to fine-tune the AMs to improve their performance. Compared to the conventional analysis, AMs produced stable maps of vascular parameters and nested-model regions less impacted by AIF-dispersion. The performance (Correlation coefficient and Adjusted R-squared for NCV test cohorts) of the AMs were: 0.914/0.834, 0.825/0.720, 0.938/0.880, and 0.890/0.792 for predictions of nested model regions, v(p), K(trans), and v(e), respectively. This study demonstrates an application of AMs that quickens and improves DCE-MRI based quantification of microvasculature properties of tumors and normal tissues relative to conventional approaches

An Objective Method to Assess and Recommend Exertion and Exercise Targets for Return to Play Post concussion

Introduction. Concussions are of significant concern for athletic trainers, and there is a critical need to objectively and safely allow an athlete to return to play. In sports the objective is return as safely and soon as possible. Exertion is a consideration regarding progressing an athlete back to play. The ability to exert in cardiovascular and strength and conditioning contexts are two critical steps in most return to play protocols. Being able to make objective recommendations is urgently needed, as trial and error leads to unnecessary risk of eliciting symptoms and/or causing setbacks. Objective. The object of this paper is to present the athletic trainer with data associated with a methodology that can be used to aid in designing a cardiovascular and strength training program post concussion. This objective measure does not rely on subjective patient reports of symptoms and utilizes a reflex based assessment method. Description. The transient exertion related carotid (TERC) murmur is a murmur that is heard at the carotid arteries during exercise. It normally is heard at around a heart rate of 150, but is heard at lower heart rates in patients who have sustained a concussion. Listening for the TERC murmur during a cardiovascular and strength training assessment can be used to provide information to the athletic trainer about safer target heart rates or safer lifting strategies post-concussion. We present data concerning 71 athletes (mean age 20.8 years) who were assessed for cardiovascular conditioning and body weight assessment. With 73% of the cardio assessment subjects, a TERC murmur was detected at a heart rate of 127.2 bpm (± 16 SD). For the strength assessment 42.1% had a TERC murmur. Clinical advantages. The clinical advantage of the TERC murmur is that it can be utilized by any athletic trainer trained to take a blood pressure. It provides objective information concerning safe target heart rates that will allow an athletic trainer to recommend appropriate exercise prescriptions. The TERC murmur assessment can also be used to help guide strength training protocols to facilitate safe return. Being able to safely recommend a means by which an athlete can recommence their training (cardiovascular and/or strength training) may accelerate return to play as well as aid in keeping the athlete happy, healthy and engaged

Implications of surface flooding on airborne estimates of snow depth on sea ice

Snow depth observations from airborne snow radars, such as the NASA's Operation IceBridge (OIB) mission, have recently been used in altimeter-derived sea ice thickness estimates, as well as for model parameterization. A number of validation studies comparing airborne and in situ snow depth measurements have been conducted in the western Arctic Ocean, demonstrating the utility of the airborne data. However, there have been no validation studies in the Atlantic sector of the Arctic. Recent observations in this region suggest a significant and predominant shift towards a snow-ice regime caused by deep snow on thin sea ice. During the Norwegian young sea Ice, Climate and Ecosystems (ICE) expedition (N-ICE2015) in the area north of Svalbard, a validation study was conducted on 19 March 2015. This study collected ground truth data during an OIB overflight. Snow and ice thickness measurements were obtained across a two-dimensional (2-D) 400 m × 60 m grid. Additional snow and ice thickness measurements collected in situ from adjacent ice floes helped to place the measurements obtained at the gridded survey field site into a more regional context. Widespread negative freeboards and flooding of the snowpack were observed during the N-ICE2015 expedition due to the general situation of thick snow on relatively thin sea ice. These conditions caused brine wicking into and saturation of the basal snow layers. This causes the airborne radar signal to undergo more diffuse scattering, resulting in the location of the radar main scattering horizon being detected well above the snow–ice interface. This leads to a subsequent underestimation of snow depth; if only radar-based information is used, the average airborne snow depth was 0.16 m thinner than that measured in situ at the 2-D survey field. Regional data within 10 km of the 2-D survey field suggested however a smaller deviation between average airborne and in situ snow depth, a 0.06 m underestimate in snow depth by the airborne radar, which is close to the resolution limit of the OIB snow radar system. Our results also show a broad snow depth distribution, indicating a large spatial variability in snow across the region. Differences between the airborne snow radar and in situ measurements fell within the standard deviation of the in situ data (0.15–0.18 m). Our results suggest that seawater flooding of the snow–ice interface leads to underestimations of snow depth or overestimations of sea ice freeboard measured from radar altimetry, in turn impacting the accuracy of sea ice thickness estimates.</p