Design of a Novel Low Cost Point of Care Tampon (POCkeT) Colposcope for Use in Resource Limited Settings

Introduction: Current guidelines by WHO for cervical cancer screening in low- and middle-income countries involves visual inspection with acetic acid (VIA) of the cervix, followed by treatment during the same visit or a subsequent visit with cryotherapy if a suspicious lesion is found. Implementation of these guidelines is hampered by a lack of: trained health workers, reliable technology, and access to screening facilities. A low cost ultra-portable Point of Care Tampon based digital colposcope (POCkeT Colposcope) for use at the community level setting, which has the unique form factor of a tampon, can be inserted into the vagina to capture images of the cervix, which are on par with that of a state of the art colposcope, at a fraction of the cost. A repository of images to be compiled that can be used to empower front line workers to become more effective through virtual dynamic training. By task shifting to the community setting, this technology could potentially provide significantly greater cervical screening access to where the most vulnerable women live. The POCkeT Colposcope’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes. Evaluation with standard optical imaging targets to assess the POCkeT Colposcope against the state of the art digital colposcope and other VIAM technologies. Results: Our POCkeT Colposcope has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our POCkeT Colposcope capturing comparable quality images to commercial systems. Methods: Rapid 3D printing, consumer grade light sources, and cameras were used to construct the TVDC. The TVDC’s concentric LED ring provides comparable white and green field illumination at a fraction of the electrical power required in commercial colposcopes, and crossed polarizers provide a reduction in glare. Evaluation was performed using standard optical imaging targets to assess the TVDC against the state of the art digital colposcope and other VIA technologies. Results: Our TVDC has comparable resolving power, color reproduction accuracy, minimal lens distortion, and illumination when compared to commercially available colposcopes. In vitro and pilot in vivo imaging results are promising with our TVDC capturing images of comparable quality to commercial systems. Conclusion: The TVDC is capable of capturing images suitable for cervical lesion analysis. Our portable low cost system will be useful for increasing access to cervical cancer screening and diagnostics in resource-limited settings by providing a more readily portable and easy to use device for medical personnel.The image data and support information that is published in the article "Design of a Novel Low Cost Trans-Vaginal Digital Colposcope for use in Resource Limited Settings" are available at: http://dukespace.lib.duke.edu/dspace/handle/10161/8357.National Institutes of Health (US) 5R21CA162747-0

Equivalence Principle Implications of Modified Gravity Models

Theories that attempt to explain the observed cosmic acceleration by modifying general relativity all introduce a new scalar degree of freedom that is active on large scales, but is screened on small scales to match experiments. We show that if such screening occurrs via the chameleon mechanism such as in f(R), it is possible to have order one violation of the equivalence principle, despite the absence of explicit violation in the microscopic action. Namely, extended objects such as galaxies or constituents thereof do not all fall at the same rate. The chameleon mechanism can screen the scalar charge for large objects but not for small ones (large/small is defined by the gravitational potential and controlled by the scalar coupling). This leads to order one fluctuations in the inertial to gravitational mass ratio. In Jordan frame, it is no longer true that all objects move on geodesics. In contrast, if the scalar screening occurrs via strong coupling, such as in the DGP braneworld model, equivalence principle violation occurrs at a much reduced level. We propose several observational tests of the chameleon mechanism: 1. small galaxies should fall faster than large galaxies, even when dynamical friction is negligible; 2. voids defined by small galaxies would be larger compared to standard expectations; 3. stars and diffuse gas in small galaxies should have different velocities, even on the same orbits; 4. lensing and dynamical mass estimates should agree for large galaxies but disagree for small ones. We discuss possible pitfalls in some of these tests. The cleanest is the third one where mass estimate from HI rotational velocity could exceed that from stars by 30 % or more. To avoid blanket screening of all objects, the most promising place to look is in voids.Comment: 27 pages, 4 figures, minor revisions, references added. Accepted for publication in Phys. Rev.

Dual Action Additives for Jet A-1: Fuel Dehydrating Icing Inhibitors

© 2016 American Chemical Society. A novel approach for protecting jet fuel against the effects of water contamination based upon Fuel Dehydrating Icing Inhibitors (FDII) is presented. This dual-action strategy is predicated on the addition of a fuel-soluble water scavenger that undergoes a kinetically fast hydrolysis reaction with free water to produce a hydrophilic ice inhibitor, thereby further militating against the effects of water crystallization. Criteria for an optimum FDII were identified and then used to screen a range of potential water-scavenging agents, which led to a closer examination of systems based upon exo/endo-cyclic ketals and both endo- and exo-cyclic ortho esters. The ice inhibition properties of the subsequent products of the hydrolysis reaction in Jet A-1 were screened by differential scanning calorimetry. The hydrolysis products of 2-methoxy-2-methyl-1,3-dioxolane demonstrate similar ice inhibition performance to DiEGME over a range of blend levels. The calorific values for the products of hydrolysis were also investigated, and it is clear that there would be a significant fuel saving on use of the additive over current fuel system icing inhibitors. Finally, three promising candidates, 2-methoxy-2-methyl-1,3-dioxolane, 2-methoxy-2-methyl-1,3-dioxane, and 2-methoxy-2,4,5-trimethyl-1,3-dioxolane, were shown to effectively dehydrate Jet A-1 at room temperature over a 2 h period

Development and validation of a risk score for hospitalization for heart failure in patients with Type 2 Diabetes Mellitus

<p>Abstract</p> <p>Background</p> <p>There are no risk scores available for predicting heart failure in Type 2 diabetes mellitus (T2DM). Based on the Hong Kong Diabetes Registry, this study aimed to develop and validate a risk score for predicting heart failure that needs hospitalisation in T2DM.</p> <p>Methods</p> <p>7067 Hong Kong Chinese diabetes patients without history of heart failure, and without history and clinical evidence of coronary heart disease at baseline were analyzed. The subjects have been followed up for a median period of 5.5 years. Data were randomly and evenly assigned to a training dataset and a test dataset. Sex-stratified Cox proportional hazard regression was used to obtain predictors of HF-related hospitalization in the training dataset. Calibration was assessed using Hosmer-Lemeshow test and discrimination was examined using the area under receiver's operating characteristic curve (aROC) in the test dataset.</p> <p>Results</p> <p>During the follow-up, 274 patients developed heart failure event/s that needed hospitalisation. Age, body mass index (BMI), spot urinary albumin to creatinine ratio (ACR), HbA_1c, blood haemoglobin (Hb) at baseline and coronary heart disease during follow-up were predictors of HF-related hospitalization in the training dataset. HF-related hospitalization risk score = 0.0709 × age (year) + 0.0627 × BMI (kg/m²) + 0.1363 × HbA_1c(%) + 0.9915 × Log₁₀(1+ACR) (mg/mmol) - 0.3606 × Blood Hb(g/dL) + 0.8161 × CHD during follow-up (1 if yes). The 5-year probability of heart failure = 1-S₀(5)^{EXP{0.9744 × (Risk Score - 2.3961)}}. Where S₀(5) = 0.9888 if male and 0.9809 if female. The predicted and observed 5-year probabilities of HF-related hospitalization were similar (p > 0.20) and the adjusted aROC was 0.920 for 5 years of follow-up.</p> <p>Conclusion</p> <p>The risk score had adequate performance. Further validations in other cohorts of patients with T2DM are needed before clinical use.</p

Ejection Fraction, Biomarkers, and Outcomes and Impact of Vericiguat on Outcomes Across EF in VICTORIA

Background: Vericiguat reduced the risk of cardiovascular death (CVD) or hospitalization for heart failure (HF) in patients with worsening HF and reduced left ventricular ejection fraction (LVEF).Objectives: The authors assessed the association of LVEF with biomarker levels, risk of outcome, and whether the effect of vericiguat was homogeneous across LVEF in the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure With Reduced Ejection Fraction) trial.Methods: Patients were grouped by LVEF tertiles (≤24%, 25%-33%, and &gt;33%). Patient characteristics, clinical outcomes, and efficacy and safety of vericiguat were examined by tertile. Prespecified biomarkers including N-terminal pro–B-type natriuretic peptide, cardiac troponin T, growth differentiation factor 15, interleukin 6, high-sensitivity C-reactive protein, and cystatin C were examined.Results: The mean LVEF was 29% ± 8% (range: 5%-45%). A pattern of higher N-terminal pro–B-type natriuretic peptide, high-sensitivity C-reactive protein, and interleukin 6 was evident in patients in the lowest LVEF tertile vs the other tertiles. Patients with lower LVEF experienced higher rates of the composite outcome (41.7%, 36.3%, and 33.4% for LVEF ≤24, 25-33, and &gt;33; P &lt; 0.001). There was no significant treatment effect heterogeneity of vericiguat across LVEF groups (adjusted HR from lowest to highest tertiles: 0.79 [95% CI: 0.68-0.94]; 0.95 [95% CI: 0.82-1.11]; 0.94 [95% CI: 0.79-1.11]; P for interaction = 0.222), although the HR was numerically lower in the lowest tertile. There was also no heterogeneity of effect for CVD and HF hospitalization individually (P interaction for CVD = 0.964; HF hospitalization = 0.438). Discontinuation of treatment because of adverse events, symptomatic hypotension, or syncope was consistent across the range of LVEF.Conclusions: Patients with lower LVEF had a distinctive biomarker profile and a higher risk for adverse clinical outcomes vs those with a higher LVEF. There was no significant interaction for the benefit of vericiguat across LVEF tertiles, although the largest signal for benefit in both the primary outcome and HF hospitalizations was noted in tertile 1 (LVEF ≤24%).</p

Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction:The VICTORIA Biomarker Substudy

Background: Circulating biomarkers may be useful in understanding prognosis and treatment efficacy in heart failure with reduced ejection fraction. In the VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction) trial, vericiguat, a soluble guanylate cyclase stimulator, decreased the primary outcome of cardiovascular death or heart failure hospitalization in heart failure with reduced ejection fraction. We evaluated biomarkers of cardiac injury, inflammation, and renal function for associations with outcomes and vericiguat treatment effect. Methods and Results: High-sensitivity cardiac troponin T (hs-cTnT), growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), and cystatin C were measured at baseline and 16 weeks. Associations of biomarkers with the primary outcome and its components were estimated. Interaction with study treatment was tested. Changes in biomarkers over time were examined by study treatment. One or more biomarkers were measured in 4652 (92%) of 5050 participants at baseline and 4063 (81%) at 16 weeks. After adjustment, higher values of hs-cTnT, growth differentiation factor-15, and interleukin-6 were associated with the primary outcome, independent of N-terminal pro-B-type natriuretic peptide. Higher hs-cTnT values were associated with a hazard ratio per log standard deviation of 1.21 (95% confidence interval 1.14–1.27). A treatment interaction with vericiguat was evident with hs-cTnT and cardiovascular death (P = .04), but not HF hospitalization (P = .38). All biomarkers except cystatin C decreased over 16 weeks and no relationship between treatment assignment and changes in biomarker levels was observed. Conclusions: hs-cTnT, growth differentiation factor-15, and interleukin-6 levels were associated with risk of the primary outcome in VICTORIA (Vericiguat Global Study in Subjects with Heart Failure with Reduced Ejection Fraction). Uniquely, lower hs-cTnT was associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with vericiguat.</p