Existing vital sign monitoring systems in the neonatal intensive care unit (NICU) require multiple wires connected to rigid sensors with strongly adherent interfaces to the skin. We introduce a pair of ultrathin, soft, skin-like electronic devices whose coordinated, wireless operation reproduces the functionality of these traditional technologies but bypasses their intrinsic limitations. The enabling advances in engineering science include designs that support wireless, battery-free operation; real-time, in-sensor data analytics; time-synchronized, continuous data streaming; soft mechanics and gentle adhesive interfaces to the skin; and compatibility with visual inspection and with medical imaging techniques used in the NICU. Preliminary studies on neonates admitted to operating NICUs demonstrate performance comparable to the most advanced clinical-standard monitoring systems.

Recently developed classes of ultrasmall, fully implantable devices for optogenetic neuromodulation eliminate physical tethers associated with conventional setups and avoid bulky head-stages and batteries in alternative wireless technologies. The resulting systems enable completely untethered, battery-free operation for high fidelity behavioral studies that eliminate motion constraints and enable experiments in a range of environments and contexts (e.g. social interactions) that would be otherwise difficult or impossible to explore. These devices are, however, purely passive in their electronics design, thereby precluding any form of active control or programmability; independent operation of multiple devices or of multiple active components in a single device is impossible. This paper introduces a series of important concepts in integrated circuit and antenna design which, taken together, enable low power operation, energy efficient and position and angle independent wireless power harvesting with full user-programmability over individual devices or collections of them, in integrated platforms that have sizes and weights not significantly larger than those of previous, passive systems. The results qualitatively expand options in output stabilization, intensity control and multimodal operation, with broad potential applications in neuroscience research, with specific advances in precise dissection of neural circuit function during unconstrained behavioral studies.

Standard of care management in neonatal and pediatric intensive care units (NICUs and PICUs) involve continuous monitoring of vital signs with hard-wired devices that adhere to the skin and, in certain instances, include catheter-loaded pressure sensors that insert into the arteries. These protocols involve risks for complications and impediments to clinical care and skin-to-skin contact between parent and child. Here we present a wireless, non-invasive technology that not only offers measurement equivalency to these management standards but also supports a range of important additional features (without limitations or shortcomings of existing approaches), supported by data from pilot clinical studies in the neonatal intensive care unit (NICU) and pediatric ICU (PICU). The combined capabilities of these platforms extend beyond clinical quality measurements of vital signs (heart rate, respiration rate, temperature and blood oxygenation) to include novel modalities for (1) tracking movements and changes in body orientation, (2) quantifying the physiological benefits of skin-to-skin care (e.g. Kangaroo care) for neonates, (3) capturing acoustic signatures of cardiac activity by directly measuring mechanical vibrations generated through the skin on the chest, (4) recording vocal biomarkers associated with tonality and temporal characteristics of crying impervious to confounding ambient noise, and (5) monitoring a reliable surrogate for systolic blood pressure. The results have potential to significantly enhance the quality of neonatal and pediatric critical care.In the United States, over 480,000 critically-ill infants and children enter intensive care units (ICUs) each year. Those less than one year of age suffer from the highest morbidity and mortality rates and therefore require the most intensive care 1,2 . These fragile patients include

The phenomenon of acute desensitization of G-protein-coupled receptors has been associated with several events, including receptor phosphorylation, loss of high affinity agonist binding, receptor:G-protein uncoupling, and receptor internalization. However, the biochemical events underlying these processes are not fully understood, and their contributions to the loss of signaling remain correlative. In addition, the nature of the kinases and the receptor domains which are involved in modulation of activity have only begun to be investigated. In order to directly measure the role of G-proteincoupled receptor kinases (GRKs) in the desensitization of the m2 muscarinic acetylcholine receptor (m2 mAChR), a dominant-negative allele of GRK2 was used to inhibit receptor phosphorylation by endogenous GRK activity in a human embryonic kidney cell line. The dominant-negative GRK2 K220R reduced agonist-dependent phosphorylation of the m2 mAChR by ϳ50% and prevented acute desensitization of the receptor as measured by the ability of the m2 mAChR to attenuate adenylyl cyclase activity. In contrast, the agonist-induced internalization of the m2 mAChR was unaffected by the GRK2 K220R construct. Further evidence linking receptor phosphorylation to acute receptor desensitization was obtained when two deletions of the third intracellular loop were made which created m2 mAChRs that did not become phosphorylated in an agonist-dependent manner and did not desensitize. However, the mutant mAChRs retained the ability to internalize. These data provide the first direct evidence that GRK-mediated receptor phosphorylation is necessary for m2 mAChR desensitization; the likely sites of in vivo phosphorylation are in the central portion of the third intracellular loop (amino acids 282-323). These results also indicate that internalization of the m2 receptor is not a key event in desensitization and is mediated by mechanisms distinct from GRK phosphorylation of the receptor.