In this paper, we describe the design and performance of the first integrated-circuit microsensor developed for daily ingestion by patients. The ingestible sensor is a device that allows patients, families, and physicians to measure medication ingestion and adherence patterns in real time, relate pharmaceutical compliance to important physiologic metrics, and take appropriate action in response to a patient's adherence pattern and specific health metrics. The design and theory of operation of the device are presented, along with key in-vitro and in-vivo performance results. The chemical, toxicological, mechanical, and electrical safety tests performed to establish the device's safety profile are described in detail. Finally, aggregate results from multiple clinical trials involving 412 patients and 5656 days of system usage are presented to demonstrate the device's reliability and performance as part of an overall digital health feedback system.

Background. The impact of the surgical margin status on long term local control rates for breast cancer in women treated with lumpectomy and radiation therapy is unclear. Methods. The records of 289 women with 303 invasive breast cancers who were treated with lumpectomy and radiation therapy from 1972 to 1992 were reviewed. The surgical margin was classified as positive (transecting the inked margin), close (less than or equal to 2 mm from the margin), negative, or indeterminate, based on the initial biopsy findings and reexcision specimens, as appropriate. Various clinical and pathologic factors were analyzed as potential prognostic factors for local recurrence in addition to the margin status, including T classification, N classification, age, histologic features, and use of adjuvant therapy. The mean follow‐up was 6.25 years. Results. The actuarial probability of freedom from local recurrence for the entire group of patients at 5 and 10 years was 94% and 87%, respectively. The actuarial probability of local control at 10 years was 98% for those patients with negative surgical margins versus 82% for all others (P = 0.007). The local control rate at 10 years was 97% for patients who underwent reexcision and 84% for those who did not. Reexcision appears to convey a local control benefit for those patients with close, indeterminate, or positive initial margins, when negative final margins are attained (P = 0.0001). Final margin status was the most significant determinant of local recurrence rates in univariate analysis. By multivariate analysis, the final margin status and use of adjuvant chemotherapy were significant prognostic factors. Conclusions. The attainment of negative surgical margins, initially or at the time of reexcision, is the most significant predictor of local control after breast‐conserving treatment with lumpectomy and radiation therapy. Cancer 1995; 76:259–67.

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Taking oral medication on a prescribed schedule can be a nuisance, especially for elderly individuals and busy people with lots of things on their minds. Nonetheless, taking medication as prescribed is important for maintaining health and well-being. In cases where medication use is part of a clinical trial, taking prescribed medication is important to the entire investigation and outcome of the study, including the determination of whether a drug is effective and safe.

Abstincf-A scanning tunneling microscope (STM) with dimensions lo00 x 200 x 8 pm has been constructed by planar microfabrication techniques. The device incorporates a novel piezoelectric actuator capable of three-dimensional motion for scanning and control of the tunneling gap spacing. Operation of the device has been successfully demonstrated by imaging the surface of a graphite sample with atomic resolution.HE SCANNING tunneling microscope (STM) is a rel-T atively new instrument which is capable of probing the surface topography and electronic structure of electrically conducting samples with angstrom-scale lateral and vertical resolution [l], [2]. In addition to imaging applications, a number of techniques have been demonstrated for nanometer-scale surface modification with the STM (see, for example, [3]), with future applications aimed at high-density data storage and nanolithography. Conventional instrumentation for the STM includes bulk piezoelectric transducers for scanning over the sample surface with a tunneling tip prepared from wire by chemical or mechanical sharpening [4]. We present a planar process for microfabricating an integrated STM scanner and tip to replace these bulk components with microstructures. Planar processing allows batch fabrication of arrays of STM's with circuitry for parallel operation, making technological applications of the STM more practical. Reducing the size of the STM scanner and tip also enhances STM performance by reducing thermal drift, raising mechanical resonant frequencies, and reducing sensitivity to external vibrations.The design of the microfabricated STM is shown in Fig. 1. The substrate is a "chip" from a Si wafer. The heart of the device is the piezoelectric actuator, which is a single cantilever piezoelectric bimorph (lo00 x 200 x 8 pm) capable of three-dimensional motion. The cantilever is constructed from alternating layers of metal electrodes, dielectric films, and piezoelectric ZnO films. The cantilever cross section shown in Fig. l(b) reveals that the top and bottom electrodes are each split into two large left-and right-side electrodes plus a narrow center conductor for the tunneling tip. This combination of electrodes provides four independently addressable piezoelectric sections. The polycrystalline ZnO films exhibit strong c-axis orientation (and piezoelectric poling) in the vertical (2) direction. Lateral (in-plane) expansion and contraction of the four ZnO sections can be used to produce four indeManuscript received July 13, 1989. This work was supported by the Defense Advanced Research Projects Agency and the Joint Services Electronics Program. The authors are with the Edward L. Ginzton Laboratory, Stanford University, Stanford, CA 94305. IEEE Log Number 893151 1. cantilever / a width t (b) (a) Design of the microfabricated STM. The actuator is a piezoelectric bimorph cantilever capable of three-dimensional motion. (b) Cross section of the cantilever.Fig. 1.pendent motions, as shown in Fig. 2. Any linear combination of these motions can be achieved...