The editors have tried to ensure the accuracy of this report but cannot accept responsibility for any errors or omissions. They would like to thank the referees for their constructive comments on the draft document.

In the past decade, neuroscientists and clinicians have begun to use implantable MEMS multielectrode arrays (e.g., [1]) to observe the simultaneous activity of many neurons in the brain. By observing the action potentials, or "spikes," of many neurons in a localized region of the brain it is possible to gather enough information to predict hand trajectories in real time during reaching tasks [2]. Recent experiments have shown that it is possible to develop neuroprosthetic devices -machines controlled directly by thoughts -if the activity of multiple neurons can be observed.Currently, data is recorded from implanted multielectrode arrays using bundles of fine wires and head-mounted connectors; all electronics for amplification and recording is external to the body. This presents three major barriers to the development of practical neuroprosthetic devices: (1) the transcutaneous connector provides a path for infection, (2) external noise and interfering signals easily couple to the wires conveying weak neural signals (<500µV) from high-impedance electrodes (>100kΩ), and (3) the connector and external electronics are typically large and bulky compared to the ~5mm electrode arrays. To eliminate these problems, data from the implanted electrodes should be transmitted out of the body wirelessly. This requires electronics at the recording site to amplify, condition, and digitize the neural signals from each electrode. These circuits must be powered wirelessly since rechargeable batteries are relatively large and have limited lifetimes. Low power operation (<100mW) is essential for any implanted electronics as elevated temperatures can easily kill neurons.A wireless, fully-implantable neural recording system is being developed to facilitate neuroscience research and neuroprosthetic applications (see Fig. 30.2.

Mucous membrane pemphigoid (MMP) is an autoimmune blistering disease frequently associated with scarring of involved clinical sites. At present, therapeutic intervention in the form of immunomodulating or immunosuppressive agents is often reserved until the onset of significant inflammation and/or early cicatrization. We have therefore studied the clinical and immunopathological findings in 67 patients with MMP in order to try to establish a reliable prognostic indicator by which patients at high risk may be identified early in the disease. Inclusion criteria were a predominantly mucosal disease and the detection of IgG and/or C3 anti-basement membrane zone (BMZ) immunoreactants using immunofluorescence techniques. Patients were allocated to three disease subgroups on the basis of the modality and duration of therapeutic intervention required to achieve effective control of disease. In addition, at presentation and at each follow-up visit, a clinical score for severity of involved clinical sites was awarded and serum collected for indirect immunofluorescence (IIF). A dual circulating anti-basement membrane zone (anti-BMZ) antibody response with IgG and IgA was significantly associated with a more severe and persistent disease profile (P < 0.001). The odds ratios for requiring systemic therapy were: 11.6 among patients in whom there was a clinical score > or = 5 compared with a score < 5, and 31.3 and 66.9 among patients with IgG alone and both IgG and IgA, respectively, compared with negative IIF. The findings suggest that an assessment based upon a combination of site severity score and the presence of circulating IgG and IgA by IIF using 1 mol/L salt-split human skin substrate may be considered a useful prognostic indicator.

Previous studies suggested the involvement of the neuronal nitric oxide synthase (nNOS) in the development of sensitization to psychostimulants. In the present study we investigated the role of nNOS in the rewarding properties of cocaine. Swiss Webster mice treated with cocaine (20 mg/kg) and saline every other day for 8 days (four drug and four saline sessions) developed conditioned place preference (CPP) for the drug-paired compartment of the cage. Pretreatment with the nNOS inhibitor, 7-nitroindazole (7-NI; 25 mg/kg), completely blocked cocaine-induced CPP. Mice deficient for the nNOS gene (homozygote nNOS(-/-) mice) were resistant to cocaine-induced CPP, while wild-type nNOS(+/+) mice developed a marked CPP following cocaine administration. Both, the pharmacological and genetic manipulations of nNOS suggest that nitric oxide (NO) is involved in the rewarding properties of cocaine.

Bandwidth Selection and the Estimation of Treatment Effects with Unbalanced Data *This paper addresses the selection of smoothing parameters for estimating the average treatment effect on the treated using matching methods. Because precise estimation of the expected counterfactual is particularly important in regions containing the mass of the treated units, we define and implement weighted cross-validation approaches that improve over conventional methods by considering the location of the treated units in the selection of the smoothing parameters. We also implement a locally varying bandwidth method that uses larger bandwidths in areas where the mass of the treated units is located. A Monte Carlo study compares our proposed methods to the conventional unweighted method and to a related method inspired by Bergemann et al. (2005). The Monte Carlo analysis indicates efficiency gains from all methods that take account of the location of the treated units. We also apply all five methods to bandwidth selection in the context of the data from LaLonde's (1986) study of the performance of non-experimental estimators using the experimental data from the National Supported Work (NSW) Demonstration program as a benchmark. Overall, both the Monte Carlo analysis and the empirical application show feasible precision gains for the weighted cross-validation and the locally varying bandwidth approaches. JEL Classification:C13, C14