Pilot Clinical Trial of Indocyanine Green Fluorescence-Augmented Colonoscopy in High Risk Patients

White light colonoscopy is the current gold standard for early detection and treatment of colorectal cancer, but emerging data suggest that this approach is inherently limited. Even the most experienced colonoscopists, under optimal conditions, miss at least 15–25% of adenomas. There is an unmet clinical need for an adjunctive modality to white light colonoscopy with improved lesion detection and characterization. Optical molecular imaging with exogenously administered organic fluorochromes is a burgeoning imaging modality poised to advance the capabilities of colonoscopy. In this proof-of-principle clinical trial, we investigated the ability of a custom-designed fluorescent colonoscope and indocyanine green, a clinically approved fluorescent blood pool imaging agent, to visualize polyps in high risk patients with polyposis syndromes or known distal colonic masses. We demonstrate (1) the successful performance of real-time, wide-field fluorescence endoscopy using off-the-shelf equipment, (2) the ability of this system to identify polyps as small as 1 mm, and (3) the potential for fluorescence imaging signal intensity to differentiate between neoplastic and benign polyps

The 12 Fundamentals of Highly Effective Communicators: Teaching Theory-Based Professional Communication to Pharmacy Students

Pharmacists are increasingly expected to communicate skillfully, yet few Doctor of Pharmacy (PharmD) curricula include theoretically-derived or evidence-based communication training. The 12 Fundamentals of Highly Effective Communicators is a pedagogical tool that we developed to teach principles of communication to two consecutive cohorts of PharmD students in their second year (P2). Students were asked to reflect on which of the 12 Fundamentals they found most helpful in their pharmacy training and practice. The most frequently selected Fundamental was “There is no ‘one size fits all’ message that will work in EVERY situation.” Students provided specific examples of how they perceived that these Fundamentals could help them have effective and appropriate interactions with patients and colleagues

Optical Imaging with a Cathepsin B Activated Probe for the Enhanced Detection of Esophageal Adenocarcinoma by Dual Channel Fluorescent Upper GI Endoscopy

Despite significant advances in diagnosis and treatment, the prognosis of esophageal adenocarcinoma remains poor highlighting the importance of early detection. Although white light (WL) upper endoscopy can be used for screening of the esophagus, it has limited sensitivity for early stage disease. Thus, development of new imaging technology to improve the diagnostic capabilities of upper GI endoscopy for early detection of esophageal adenocarcinoma is an important unmet need. The goal of this study was to develop a method for the detection of malignant lesions in the esophagus using WL upper endoscopy combined with near infrared (NIR) imaging with a protease activatable probe (Prosense750) selective for cathepsin B (CTSB). An orthotopic murine model for distal esophageal adenocarcinoma was generated through the implantation of OE-33 and OE-19 human esophageal adenocarcinoma lines in immunocompromised mice. The mice were imaged simultaneously for WL and NIR signal using a custom-built dual channel upper GI endoscope. The presence of tumor was confirmed by histology and target to background ratios (TBR) were compared for both WL and NIR imaging. NIR imaging with ProSense750 significantly improved upon the TBRs of esophageal tumor foci, with a TBR of 3.64$\pm$0.14 and 4.50$\pm$0.11 for the OE-33 and OE-19 tumors respectively, compared to 0.88$\pm$0.04 and 0.81$\pm$0.02 TBR for WL imaging. The combination of protease probes with novel imaging devices has the potential to improve esophageal tumor detection by fluorescently highlighting neoplastic regions

Piezoelectric energy harvesting for self-powered wearable upper limb applications

Wearable devices can be used for monitoring vital physical and physiological signs remotely, as well as for interacting with computers. Widespread adoption of wearables is somewhat hindered by the duration time they can be used without re‐recharging. To ensure uninterrupted operation, these devices need a constant and battery‐less energy supply. Scavenging energy from the wearable's surroundings is, therefore, an essential step towards achieving genuinely autonomous and self‐powered devices. While energy harvesting technologies may not completely eliminate the battery storage unit, they can ensure a maximum duration of use. Piezoelectric energy harvesting is a promising and efficient technique to generate electricity for powering wearable devices in response to body movements. Consequently, we systematically survey the range of technologies used for scavenging energy from the human body, with a particular focus on the upper‐limb area. According to our review and in comparison to other upper limb locations, highest power densities can be achieved from piezoelectric transducers located on the wrist. For short and fast battery charging needs, we therefore review the range of materials, architectures and devices used to scavenge energy from these upper‐limb areas. We provide comparisons as well as recommendations and possible future directions for harvesting energy using this promising technique

Geographic and Sociodemographic Disparities in Drive Times to Joint Commission–Certified Primary Stroke Centers in North Carolina, South Carolina, and Georgia

Introduction: Timely access to facilities that provide acute stroke care is necessary to reduce disabilities and death from stroke. We examined geographic and sociodemographic disparities in drive times to Joint Commission–certified primary stroke centers (JCPSCs) and other hospitals with stroke care quality improvement initiatives in North Carolina, South Carolina, and Georgia. Methods: We defined boundaries for 30- and 60-minute drive-time areas to JCPSCs and other hospitals by using geographic information systems (GIS) mapping technology and calculated the proportions of the population living in these drive-time areas by sociodemographic characteristics. Age-adjusted county-level stroke death rates were overlaid onto the drive-time areas. Results: Approximately 55% of the population lived within a 30-minute drive time to a JCPSC; 77% lived within a 60-minute drive time. Disparities in percentage of the population within 30-minute drive times were found by race/ethnicity, education, income, and urban/rural status; the disparity was largest between urban areas (70% lived within 30-minute drive time) and rural areas (26%). The rural coastal plains had the largest concentration of counties with high stroke death rates and the fewest JCPSCs. Conclusion: Many areas in this tri-state region lack timely access to JCPSCs. Alternative strategies are needed to expand provision of quality acute stroke care in this region. GIS modeling is valuable for examining and strategically planning the distribution of hospitals providing acute stroke care

Magnetic drug targeting: Preclinical in vivo studies, mathematical modeling, and extrapolation to humans

A sound theoretical rationale for the design of a magnetic nanocarrier capable of magnetic capture in vivo after intravenous administration could help elucidate the parameters necessary for in vivo magnetic tumor targeting. In this work, we utilized our long-circulating polymeric magnetic nanocarriers, encapsulating increasing amounts of superparamagnetic iron oxide nanoparticles (SPIONs) in a biocompatible oil carrier, to study the effects of SPION loading and of applied magnetic field strength on magnetic tumor targeting in CT26 tumor-bearing mice. Under controlled conditions, the in vivo magnetic targeting was quantified and found to be directly proportional to SPION loading and magnetic field strength. Highest SPION loading, however, resulted in a reduced blood circulation time and a plateauing of the magnetic targeting. Mathematical modeling was undertaken to compute the in vivo magnetic, viscoelastic, convective, and diffusive forces acting on the nanocapsules (NCs) in accordance with the Nacev–Shapiro construct, and this was then used to extrapolate to the expected behavior in humans. The model predicted that in the latter case, the NCs and magnetic forces applied here would have been sufficient to achieve successful targeting in humans. Lastly, an in vivo murine tumor growth delay study was performed using docetaxel (DTX)-encapsulated NCs. Magnetic targeting was found to offer enhanced therapeutic efficacy and improve mice survival compared to passive targeting at drug doses of ca. 5–8 mg of DTX/kg. This is, to our knowledge, the first study that truly bridges the gap between preclinical experiments and clinical translation in the field of magnetic drug targeting

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries

BEBOP V. Homogeneous stellar analysis of potential circumbinary planet hosts

Planets orbiting binary systems are relatively unexplored compared to those around single stars. Detections of circumbinary planets and planetary systems offer a first detailed view into our understanding of circumbinary planet formation and dynamical evolution. The BEBOP (binaries escorted by orbiting planets) radial velocity survey plays a special role in this adventure as it focuses on eclipsing single-lined binaries with an FGK dwarf primary and M dwarf secondary allowing for the highest radial velocity precision using the HARPS and SOPHIE spectrographs. We obtained 4512 high-resolution spectra for the 179 targets in the BEBOP survey which we used to derive the stellar atmospheric parameters using both equivalent widths and spectral synthesis. We furthermore derive stellar masses, radii, and ages for all targets. With this work, we present the first homogeneous catalogue of precise stellar parameters for these eclipsing single-lined binaries