Non-pharmacological interventions for the treatment and prevention of cardio-metabolic disease

In recent years there has been a surge in interest concerning high intensity intermittent exercise training (HIT) due to its ability to confer rapid notable cardio-metabolic health benefits. Specifically, HIT has been shown to improve insulin sensitivity and glycaemic control as well as other cardiovascular health factors after just 2 weeks of training (typically 6 training sessions). This thesis investigated the potential therapeutic role of HIT training within obese cohorts specifically addressing metabolic health, inclusive of inflammatory profiles and glycaemic control. [Continues.

Quantifying the Tibiofemoral Joint Space Using X-ray Tomosynthesis

Purpose: Digital x-ray tomosynthesis (DTS) has the potential to provide 3D information about the knee joint in a load-bearing posture, which may improve diagnosis and monitoring of knee osteoarthritis compared with projection radiography, the current standard of care. Manually quantifying and visualizing the joint space width (JSW) from 3D tomosynthesis datasets may be challenging. This work developed a semiautomated algorithm for quantifying the 3D tibiofemoral JSW from reconstructed DTS images. The algorithm was validated through anthropomorphic phantom experiments and applied to three clinical datasets. Methods: A user-selected volume of interest within the reconstructed DTS volume was enhanced with 1D multiscale gradient kernels. The edge-enhanced volumes were divided by polarity into tibial and femoral edge maps and combined across kernel scales. A 2D connected components algorithm was performed to determine candidate tibial and femoral edges. A 2D joint space width map (JSW) was constructed to represent the 3D tibiofemoral joint space. To quantify the algorithm accuracy, an adjustable knee phantom was constructed, and eleven posterior–anterior (PA) and lateral DTS scans were acquired with the medial minimum JSW of the phantom set to 0–5 mm in 0.5 mm increments (VolumeRadTM, GE Healthcare, Chalfont St. Giles, United Kingdom). The accuracy of the algorithm was quantified by comparing the minimum JSW in a region of interest in the medial compartment of the JSW map to the measured phantom setting for each trial. In addition, the algorithm was applied to DTS scans of a static knee phantom and the JSW map compared to values estimated from a manually segmented computed tomography (CT) dataset. The algorithm was also applied to three clinical DTS datasets of osteoarthritic patients. Results: The algorithm segmented the JSW and generated a JSW map for all phantom and clinical datasets. For the adjustable phantom, the estimated minimum JSW values were plotted against the measured values for all trials. A linear fit estimated a slope of 0.887 (R2¼0.962) and a mean error across all trials of 0.34 mm for the PA phantom data. The estimated minimum JSW values for the lateral adjustable phantom acquisitions were found to have low correlation to the measured values (R2¼0.377), with a mean error of 2.13 mm. The error in the lateral adjustable-phantom datasets appeared to be caused by artifacts due to unrealistic features in the phantom bones. JSW maps generated by DTS and CT varied by a mean of 0.6 mm and 0.8 mm across the knee joint, for PA and lateral scans. The tibial and femoral edges were successfully segmented and JSW maps determined for PA and lateral clinical DTS datasets. Conclusions: A semiautomated method is presented for quantifying the 3D joint space in a 2D JSW map using tomosynthesis images. The proposed algorithm quantified the JSW across the knee joint to sub-millimeter accuracy for PA tomosynthesis acquisitions. Overall, the results suggest that x-ray tomosynthesis may be beneficial for diagnosing and monitoring disease progression or treatment of osteoarthritis by providing quantitative images of JSW in the load-bearing knee

Fostering Socio-Ecological Resilience to Wildfire by Interconnecting Knowledge Systems at Cal Poly Humboldt

The wildfire-related challenges of Northern California and many other regions in the western United States are daunting in scope and magnitude. Ecologically and culturally salient solutions that limit the negative impacts of wildfire and promote resilience of human and ecological systems will require newer approaches. Through Cal Poly Humboldt and the Fire Resilience Institute, there is greater emphasis on the interconnection of knowledge systems across education, training, research, and management. Here we highlight several on-going efforts that seek to enhance the fire resilience workforce, promote socio-ecological resilience through interdisciplinary projects, and inform management through monitoring and research projects that intentionally incorporate multiple knowledge systems. Shifting to a more inclusive process has many potential benefits but will also pose challenges and require modification of approaches. Here we emphasize some on-going efforts at Cal Poly Humboldt to intentionally bridge knowledge systems to make advances on wildfire-related challenges. Socio-ecological resilience and coexistence with fire can be fostered but the long-term effectiveness will greatly benefit from approaches that are inclusive, equitable, and interconnected across the many stakeholders affected and disciplines involved

NOX1 and NOX4 are required for the differentiation of mouse F9 cells into extraembryonic endoderm

Mouse F9 cells differentiate to primitive endoderm (PrE) when treated with retinoic acid (RA). Differentiation is accompanied by increased reactive oxygen species (ROS) levels, and while treating F9 cells with antioxidants attenuates differentiation, H2O2 treatment alone is sufficient to induce PrE. We identified the NADPH oxidase (NOX) complexes as candidates for the source of this endogenous ROS, and within this gene family, and over the course of differentiation, Nox1 and Nox 4 show the greatest upregulation induced by RA. Gata6, encoding a master regulator of extraembryonic endoderm is also up-regulated by RA and we provide evidence that NOX1 and NOX4 protein levels increase in F9 cells overexpressing Gata6. Pan-NOX and NOX1-specific inhibitors significantly reduced the ability of RA to induce PrE, and this was recapitulated using a genetic approach to knockdown Nox1 and/or Nox4 transcripts. Interestingly, overexpressing either gene in untreated F9 cells did not induce differentiation, even though each elevated ROS levels. Thus, the data suggests that ROS produced during PrE differentiation is dependent in part on increased NOX1 and NOX4 levels, which is under the control of GATA6. Furthermore, these results suggest that the combined activity of multiple NOX proteins is necessary for the differentiation of F9 cells to primitive endoderm

Raw and Count Data Comparability of Hip-Worn ActiGraph GT3X+ and Link Accelerometers

To enable inter- and intrastudy comparisons it is important to ascertain comparability among accelerometer models. Purpose: The purpose of this study was to compare raw and count data between hip-worn ActiGraph GT3X+ and GT9X Link accelerometers. Methods: Adults (n = 26 (n = 15 women); age, 49.1 T 20.0 yr) wore GT3X+ and Link accelerometers over the right hip for an 80-min protocol involving 12–21 sedentary, household, and ambulatory/exercise activities lasting 2–15 min each. For each accelerometer, mean and variance of the raw (60 Hz) data for each axis and vector magnitude (VM) were extracted in 30-s epochs. A machine learning model (Montoye 2015) was used to predict energy expenditure in METs from the raw data. Raw data were also processed into activity counts in 30-s epochs for each axis and VM, with Freedson 1998 and 2011 count-based regression models used to predictMETs. Time spent in sedentary, light, moderate, and vigorous intensities was derived from predicted METs from each model. Correlations were calculated to compare raw and count data between accelerometers, and percent agreement was used to compare epoch-by-epoch activity intensity. Results: For raw data, correlations for mean acceleration were 0.96 T 0.05, 0.89 T 0.16, 0.71 T 0.33, and 0.80 T 0.28, and those for variance were 0.98 T 0.02, 0.98 T 0.03, 0.91 T 0.06, and 1.00 T 0.00 in the X, Y, and Z axes and VM, respectively. For count data, corresponding correlations were 1.00 T 0.01, 0.98 T 0.02, 0.96 T 0.04, and 1.00 T 0.00, respectively. Freedson 1998 and 2011 count-based models had significantly higher percent agreement for activity intensity (95.1% T 5.6% and 95.5% T 4.0%) compared with theMontoye 2015 raw data model (61.5% T 27.6%; P G 0.001). Conclusions: Count data were more highly comparable than raw data between accelerometers. Data filtering and/or more robust raw data models are needed to improve raw data comparability between ActiGraph GT3X+ and Link accelerometers

Evaluation of uncomplicated acute respiratory tract infection management in veterans: A national utilization review.

BackgroundAntibiotics are overprescribed for acute respiratory tract infections (ARIs). Guidelines provide criteria to determine which patients should receive antibiotics. We assessed congruence between documentation of ARI diagnostic and treatment practices with guideline recommendations, treatment appropriateness, and outcomes.MethodsA multicenter quality improvement evaluation was conducted in 28 Veterans Affairs facilities. We included visits for pharyngitis, rhinosinusitis, bronchitis, and upper respiratory tract infections (URI-NOS) that occurred during the 2015-2016 winter season. A manual record review identified complicated cases, which were excluded. Data were extracted for visits meeting criteria, followed by analysis of practice patterns, guideline congruence, and outcomes.ResultsOf 5,740 visits, 4,305 met our inclusion criteria: pharyngitis (n = 558), rhinosinusitis (n = 715), bronchitis (n = 1,155), URI-NOS (n = 1,475), or mixed diagnoses (>1 ARI diagnosis) (n = 402). Antibiotics were prescribed in 68% of visits: pharyngitis (69%), rhinosinusitis (89%), bronchitis (86%), URI-NOS (37%), and mixed diagnosis (86%). Streptococcal diagnostic testing was performed in 33% of pharyngitis visits; group A Streptococcus was identified in 3% of visits. Streptococcal tests were ordered less frequently for patients who received antibiotics (28%) than those who did not receive antibiotics 44%; P < .01). Although 68% of visits for rhinosinusitis had documentation of symptoms, only 32% met diagnostic criteria for antibiotics. Overall, 39% of patients with uncomplicated ARIs received appropriate antibiotic management. The proportion of 30-day return visits for ARI care was similar for appropriate (11%) or inappropriate (10%) antibiotic management (P = .22).ConclusionsAntibiotics were prescribed in most uncomplicated ARI visits, indicating substantial overuse. Practice was frequently discordant with guideline diagnostic and treatment recommendations