Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.biomedical implants | flexible electronics | transfer printing | wearable electronics | heterogeneous integration N early all classes of active wearable and implantable biomedical devices rely on some form of battery power for operation. Heart rate monitors, pacemakers, implantable cardioverterdefibrillators, and neural stimulators together represent a broad subset of bioelectronic devices that provide continuous diagnostics and therapy in this mode. Although advances in battery technology have led to substantial reductions in overall sizes and increases in storage capacities, operational lifetimes remain limited, rarely exceeding a few days for wearable devices and a few years for implants. Surgical procedures to replace the depleted batteries of implantable devices are thus essential, exposing patients to health risks, heightened morbidity, and even potential mortality. The health burden and costs are substantial, and thus motivate efforts to eliminate batteries altogether, or to extend their lifetimes in a significant way.Investigations into energy-harvesting strategies to replace batteries demonstrate several unusual ways to extract power from chemical, mechanical, electrical, and thermal processes in the human body (1, 2). Examples include use of glucose oxidation (3), electric potentials of the inner ear (4), mechanical movements of limbs, and natural vibrations of internal organs (5-7). Such phenomena provide promising opportunities for power supply to wearable and implantable devices (6-8). A recent example involves a hybrid kinetic device integrated with the heart for applications with pacemakers (7). More speculative approaches, based on analytical models of harvesting from pressure-driven deformations of an artery by magneto-hydrodynamics, also exist (9).Cardiac and lung motions, in particular, serve as inexhaustible sources of energy during the lifespan of a patient. Mechanicalto-electrical transduction mechanisms in piezoelectric materials offer viable routes to energy harvesting in such cases, as demonstrated and analyzed by several groups recently (10-17). For example, proposals exist for devices that convert heartbeat vibrations into electrical energy using resonantly coupled motions of thick (1-2 mm) pi...

Thin, soft, and elastic electronics with physical properties well matched to the epidermis can be conformally and robustly integrated with the skin. Materials and optimized designs for such devices are presented for surface electromyography (sEMG). The findings enable sEMG from wide ranging areas of the body. The measurements have quality sufficient for advanced forms of human-machine interface.

The ability to measure subtle changes in arterial pressure using devices mounted on the skin can be valuable for monitoring vital signs in emergency care, detecting the early onset of cardiovascular disease and continuously assessing health status. Conventional technologies are well suited for use in traditional clinical settings, but cannot be easily adapted for sustained use during daily activities. Here we introduce a conformal device that avoids these limitations. Ultrathin inorganic piezoelectric and semiconductor materials on elastomer substrates enable amplified, low hysteresis measurements of pressure on the skin, with high levels of sensitivity (B0.005 Pa) and fast response times (B0.1 ms). Experimental and theoretical studies reveal enhanced piezoelectric responses in lead zirconate titanate that follow from integration on soft supports as well as engineering behaviours of the associated devices. Calibrated measurements of pressure variations of blood flow in near-surface arteries demonstrate capabilities for measuring radial artery augmentation index and pulse pressure velocity.

Non-invasive, biomedical devices have the potential to provide important, quantitative data for the assessment of skin diseases and wound healing. Traditional methods either rely on qualitative visual and tactile judgments of a professional and/or data obtained using instrumentation with forms that do not readily allow intimate integration with sensitive skin near a wound site. Here we report a skin-like electronics platform that can softly and reversibly laminate perilesionally at wounds to provide highly accurate, quantitative data of relevance to the management of surgical wound healing. Clinical studies on patients using thermal sensors and actuators in fractal layouts provide precise time-dependent mapping of temperature and thermal conductivity of the skin near the wounds. Analytical and simulation results establish the fundamentals of the sensing modalities, the mechanics of the system, and strategies for optimized design. The use of this type of ‘epidermal’ electronics system in a realistic, clinical setting with human subjects establishes a set of practical procedures in disinfection, reuse, and protocols for quantitative measurement. The results have the potential to address important unmet needs in chronic wound management.

Paleoanthropologists and vertebrate paleontologists have for decades debated the etiology of tooth wear and its implications for understanding the diets of human ancestors and other extinct mammals. The debate has recently taken a twist, calling into question the efficacy of dental microwear to reveal diet. Some argue that endogenous abrasives in plants (opal phytoliths) are too soft to abrade enamel, and that tooth wear is caused principally by exogenous quartz grit on food. If so, variation in microwear among fossil species may relate more to habitat than diet. This has important implications for paleobiologists because microwear is a common proxy for diets of fossil species. Here we reexamine the notion that particles softer than enamel (e.g., silica phytoliths) do not wear teeth. We scored human enamel using a microfabrication instrument fitted with soft particles (aluminum and brass spheres) and an atomic force microscope (AFM) fitted with silica particles under fixed normal loads, sliding speeds, and spans. Resulting damage was measured by AFM, and morphology and composition of debris were determined by scanning electron microscopy with energy-dispersive X-ray spectroscopy. Enamel chips removed from the surface demonstrate that softer particles produce wear under conditions mimicking chewing. Previous models posited that such particles rub enamel and create ridges alongside indentations without tissue removal. We propose that although these models hold for deformable metal surfaces, enamel works differently. Hydroxyapatite crystallites are "glued" together by proteins, and tissue removal requires only that contact pressure be sufficient to break the bonds holding enamel together. dental microwear | diet reconstruction | tooth wear

Cancer dormancy refers to the prolonged clinical disease-free time between removal of the primary tumor and recurrence, which is common in prostate cancer (PCa), breast cancer, esophageal cancer, and other cancers. PCa disseminated tumor cells (DTC) are detected in both patients with no evidence of disease (NED) and advanced disease (ADV). However, the molecular and cellular nature of DTC is unknown. We performed a first-in-field study of single DTC transcriptomic analyses in cancer patients to identify a molecular signature associated with cancer dormancy. We profiled eighty-five individual EpCAM+/CD45− cells from the bone marrow of PCa patients with NED or ADV. We analyzed 44 DTC with high prostate-epithelial signatures, and eliminated 41 cells with high erythroid signatures and low prostate epithelial signatures. DTC were clustered into 3 groups: NED, ADV_1, and ADV_2, in which the ADV_1 group presented a distinct gene expression pattern associated with the p38 stress activated kinase pathway. Additionally, DTC from the NED group were enriched for a tumor dormancy signature associated with head and neck squamous carcinoma and breast cancer. This study provides the first clinical evidence of the p38 pathway as a potential biomarker for early recurrence and an attractive target for therapeutic intervention.

945 Gastrointestinal: Enema nozzle injury to the rectum, a vague presentation with significant morbidity 946 Gastrointestinal: Gastric perforation during esophageal endoscopic submucosal dissection: A serious adverse event in a patient with esophageal stricture 947 Gastrointestinal: Idiopathic granulomatous gastritis observed by magnifying narrow-band imaging endoscopy 948 Hepatobiliary and Pancreatic: Unusual cause of acute pancreatitis 949 Gastrointestinal: Severe congestive heart failure and acute gastric mucosal necrosis Meta Analysis and Systematic Reviews 950 Systematic review: Current evidence in non-alcoholic fatty liver disease lacks relevance to patients with advanced fibrosis R Parker, J Hodson and IAC Rowe 957 Metformin use and the risk of colorectal adenoma: A systematic review and meta-analysis YS Jung, Reviews 966 Urgency to treat patients with chronic hepatitis C Clinical Gastroenterology 992 Inflammatory bowel disease detection and monitoring by measuring biomarkers in non-invasively collected colorectal mucus A Loktionov, V Chhaya, T Bandaletova and A Poullis 1003 Identifying the optimal strategy for screening of advanced colorectal neoplasia YS Jung, 1026 Do surveillance intervals in patients with more than five adenomas at index colonoscopy be shorter than those in patients with three to four adenomas? A Korean Association for the Study of Intestinal Experimental Gastroenterology 1040 Effects of argon plasma coagulation on human stomach tissue: An ex vivo study EJ Gong, Endoscopy 1046 Probe-based confocal laser endomicroscopy in the margin delineation of early gastric cancer for endoscopic submucosal dissection JC

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