Search

The National Aeronautics and Space Administration (NASA)’s Operation IceBridge (OIB) was a 13-year (2009–2021) airborne mission to survey land and sea ice across the Arctic, Antarctic, and Alaska. Here, we review OIB’s goals, instruments, campaigns, key scientific results, and implications for future investigations of the cryosphere. OIB’s primary goal was to use airborne laser altimetry to bridge the gap in fine-resolution elevation measurements of ice from space between the conclusion of NASA’s Ice, Cloud, and land Elevation Satellite (ICESat; 2003–2009) and its follow-on, ICESat-2 (launched 2018). Additional scientific requirements were intended to contextualize observed elevation changes using a multisensor suite of radar sounders, gravimeters, magnetometers, and cameras. Using 15 different aircraft, OIB conducted 968 science flights, of which 42% were repeat surveys of land ice, 42% were surveys of previously unmapped terrain across the Greenland and Antarctic ice sheets, Arctic ice caps, and Alaskan glaciers, and 16% were surveys of sea ice. The combination of an expansive instrument suite and breadth of surveys enabled numerous fundamental advances in our understanding of the Earth’s cryosphere. For land ice, OIB dramatically improved knowledge of interannual outlet-glacier variability, ice-sheet, and outlet-glacier thicknesses, snowfall rates on ice sheets, fjord and sub-ice-shelf bathymetry, and ice-sheet hydrology. Unanticipated discoveries included a reliable method for constraining the thickness within difficult-to-sound incised troughs beneath ice sheets, the extent of the firn aquifer within the Greenland Ice Sheet, the vulnerability of many Greenland and Antarctic outlet glaciers to ocean-driven melting at their grounding zones, and the dominance of surface-melt-driven mass loss of Alaskan glaciers. For sea ice, OIB significantly advanced our understanding of spatiotemporal variability in sea ice freeboard and its snow cover, especially through combined analysis of fine-resolution altimetry, visible imagery, and snow radar measurements of the overlying snow thickness. Such analyses led to the unanticipated discovery of an interdecadal decrease in snow thickness on Arctic sea ice and numerous opportunities to validate sea ice freeboards from satellite radar altimetry. While many of its data sets have yet to be fully explored, OIB’s scientific legacy has already demonstrated the value of sustained investment in reliable airborne platforms, airborne instrument development, interagency and international collaboration, and open and rapid data access to advance our understanding of Earth’s remote polar regions and their role in the Earth system.

The focus of this article is on the potential land use change impacts associated with the oilseed-based biodiesel consumption. The three main crops used for biodiesel production to date are oilseed rape (OSR), soybeans and oil palm. Therefore, the objective of this paper is to provide a technical assessment of potential land use change arising from the growth of these three major crops at global level, obtained through a broad country-level analysis for their respective major producing countries. The article presents an historical data analysis, evaluating the interaction between the expansion and contraction of these three crops over the last three decades (with a closer look from 2008) together with the carbon stock changes to the land. We categorise the land use by its carbon stock and resulting carbon stock changes from land use change. Crops aimed at the production of ethanol, such as maize (corn), sugarcane, wheat, cassava and sugar beet, although extremely relevant for biofuel policies, are not the subject of this present study. While we did not know at the time of writing this report how the term “significant” would be defined in the EU delegated act we concluded from the analysis of the historical data and using the high ILUC-risk definition as it stands, that the emissions associated with palm and soy are significant. For oil palm, we take Indonesia and Malaysia as proxy for the global position. We calculate an average expansion of 29% on high carbon stock land. For soy, we calculate a global average of 19% expansion. We calculate the global average greenhouse gas emissions intensities based on the ILUC-risks as 56 gCO2eq/MJ for soy oil and 108 gCO2eq/MJ for palm oil. Future projections (OECD-FAO, 2017) suggest these numbers could drop significantly. We do not find evidence for high ILUC-risk expansion of oilseed rape.

Wireless communication technologies for bioelectronic implants enable remote monitoring for diagnosis and adaptive therapeutic intervention without the constraints of wired connections. However, wireless data uplink from millimeter-scale devices deep in the body struggles to achieve low power consumption while maintaining large misalignment tolerances. Here, we report a passive wireless backscatter communication system based on magnetoelectric transducers that consumes less than 0.3 pJ/bit and achieves less than 1E-6 bit error rate at a distance of 55 mm while tolerating a misalignment of 10 mm. Using this robust data uplink, we designed a wireless cardiac sensing node that can transmit electrocardiogram signals from the beating heart surface of a porcine model to a custom external transceiver using the magnetoelectric backscatter uplink. This reliable, near-zero-power communication method provides opportunities for next-generation bioelectronics to feature real-time physiological monitoring and closed-loop therapies while maintaining a small form factor and low power consumption., Competing Interests: Conflict of interest F.A., J.E.W., K.Y., and J.T.R. receive monetary and/or equity compensation from Motif Neurotech. The terms of these arrangements have been reviewed and approved by Rice University in accordance with their policies on conflict of interest in research.

Miniature bioelectronic implants promise revolutionary therapies for cardiovascular and neurological disorders. Wireless power transfer (WPT) is a significant method for miniaturization, eliminating the need for bulky batteries in devices. Despite successful demonstrations of millimetric battery free implants in animal models, the robustness and efficiency of WPT are known to degrade significantly under misalignment incurred by body movements, respiration, heart beating, and limited control of implant orientation during surgery. This article presents an omnidirectional WPT platform for millimetric bioelectronic implants, employing the emerging magnetoelectric (ME) WPT modality, and magnetic field steering technique based on multiple transmitter (TX) coils. To accurately sense the weak coupling in a miniature implant and adaptively control the multicoil TX array in a closed loop, we develop an active echo (AE) scheme using a tiny coil on the implant. Our prototype comprises a fully integrated 14.2 mm3 implantable stimulator embedding a custom low power system on chip (SoC) powered by an ME film, a TX with a custom three channel AE RX chip, and a multicoil TX array with mutual inductance cancellation. The AE RX achieves negative 161 dBm per Hz input referred noise with 64 dB gain tuning range to reliably sense the AE signal, and offers fast polarity detection for driver control. AE simultaneously enhances the robustness, efficiency, and charging range of ME WPT. Under 90 degree rotation from the ideal position, our omnidirectional WPT system achieves 6.8x higher power transfer efficiency (PTE) than a single coil baseline. The tracking error of AE negligibly degrades the PTE by less than 2 percent from using ideal control.

Minimally invasive neural interfaces can be used to diagnose, manage and treat many disorders, with reduced risks of surgical complications. However, endovascular probes lack access to key cortical, subcortical and spinal targets, and are not typically explantable after endothelialization. Here we report the development and testing, in sheep, of endocisternal neural interfaces that approach brain and spinal cord targets through inner and outer spaces filled with cerebrospinal fluid. Thus, the interfaces gain access to the entire brain convexity, to deep brain structures within the ventricles and to the spinal cord from the spinal subarachnoid space. We combined an endocisternal neural interface with wireless miniature magnetoelectrically powered bioelectronics so that it can be freely navigated percutaneously from the spinal space to the cranial subarachnoid space, and from the cranial subarachnoid space to the ventricles. In sheep, we show recording and stimulation functions, as well as repositioning of the flexible electrodes and explantation of the interface after chronic implantation. Minimally invasive endocisternal bioelectronics may enable chronic and transient therapies, particularly for stroke rehabilitation and epilepsy monitoring., Competing Interests: Competing interests: J.T.R., Sunil A. Sheth, Sameer A. Sheth and J.E.W. receive monetary or equity compensation from Motif Neurotech. Sameer A. Sheth has consulting agreements with Boston Scientific, Zimmer Biomet, Koh Young, Neuropace, Sensoria Therapeutics and Varian Medical. Sunil A. Sheth has consulting agreements with Viz.ai, Penumbra, Medtronic and Imperative Care, as well as grant funding from the McNair Foundation and the NIH. The terms of these agreements have been reviewed and approved by Rice University, UTHealth and Baylor College of Medicine in accordance with their policies on conflicts of interest in research. A.K.W. is a cofounder of Deinde and P.K. is an investor in Deinde. The other authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Wireless minimally invasive bioelectronic implants enable a wide range of applications in healthcare, medicine, and scientific research. Magnetoelectric (ME) wireless power transfer (WPT) has emerged as a promising approach for powering miniature bio-implants because of its remarkable efficiency, safety limit, and misalignment tolerance. However, achieving low-power and high-quality uplink communication using ME remains a challenge. This paper presents a pulse-width modulated (PWM) ME backscatter uplink communication enabled by a switched-capacitor energy extraction (SCEE) technique. The SCEE rapidly extracts and dissipates the kinetic energy within the ME transducer during its ringdown period, enabling time-domain PWM in ME backscatter. Various circuit techniques are presented to realize SCEE with low power consumption. This paper also describes the high-order modeling of ME transducers to facilitate the design and analysis, which shows good matching with measurement. Our prototyping system includes a millimeter-scale ME implant with a fully integrated system-on-chip (SoC) and a portable transceiver for power transfer and bidirectional communication. SCEE is proven to induce >50% amplitude reduction within 2 ME cycles, leading to a PWM ME backscatter uplink with 17.73 kbps data rate and 0.9 pJ/bit efficiency. It also achieves 8.5 × 10 -5 bit-error-rate (BER) at a 5 cm distance, using a lightweight multi-layer-perception (MLP) decoding algorithm. Finally, the system demonstrates continuous wireless neural local-field potential (LFP) recording in an in vitro setup.

Networks of miniature bioelectronic implants would enable precise measurement and manipulation of the complex and distributed physiological systems in the body. For example, sensing and stimulation nodes throughout the heart, brain, or peripheral nervous system would more accurately track and treat disease or support prosthetic technologies with many degrees of freedom. A main challenge to creating this type of in-body bioelectronic network is the fact that wireless power and data transfer are often inefficient when communicating through biological tissues. This challenge is typically compounded as one increases the number of implants within the network. Here, we show that magnetoelectric wireless data and power transfer enable a network of millimeter-sized bioelectronic implants where the power transfer efficiency of the system improves as the number of implanted devices increases. Using this property, we demonstrate networks of wireless battery-free bioelectronics ranging from 1 to 6 implants where the wireless power transfer efficiency for the system increases from 0.2% to 1.3%, with each node in the network receiving 2.2 mW at a distance of 1 cm. We use this system for efficient and robust wireless data and power transfer to demonstrate proof-of-concept networks of miniature spinal cord stimulators and cardiac pacing devices in large animals. The scalability of this network architecture enabled by magnetoelectric wireless power transfer provides a platform for building wireless closed-loop networks of bioelectronic implants for next-generation electronic medicine., Competing Interests: Competing interests J.T.R., F.A., and J.E.W. receive monetary and/or equity compensation from Motif Neurotech. A.F. is a consultant for Medtronic, Inc. and Abbott, Inc. M.R. receives monetary and/or equity compensation from Maxwell Biomedical, Rhythio, XNHealth, consults for Ziopatch, and is the medical director for IRhythm. The terms of these arrangements have been reviewed and approved by Rice University, the Houston Methodist Research Institute, Baylor College of Medicine, and The Texas Heart Institute in accordance with their policies on conflict of interest in research. The other authors declare no competing interests.

Background: Very low calorie diets (VLCDs) are an obesity treatment option in the general population, but their efficacy and safety in patients on haemodialysis (HD) is unknown., Methods: Prospective single arm study of VLCD in haemodialysis patients. All participants received 2.5-3.3 MJ/day for 12 weeks. Weekly assessment of VLCD, pre- and post-dialysis weight, inter-dialytic weight gain, and blood electrolytes occurred for the first 4 weeks, then fortnightly for another 8 weeks. Linear mixed models compared the change in weight over time as well as biochemical outcomes including potassium., Results: Twenty-two participants [nine home HD (HHD) and 13 satellite HD (SHD)] enrolled with 19 completing the 12-week intervention. Mean post-dialysis weight declined from 121.1 kg at baseline to 109.9 at week 12 resulting in average decline of 0.88 kg per week (95% C.I. 0.71, 1.05, P  < .001) with 12-week mean percentage weight loss9.3% (SD 3.5). Mean post-dialysis body mass index declined from 40.9 kg/m 2 at baseline to 37.1 kg/m 2 at week 12 (95% C.I. 0.25, 0.35, P  < .001). Serum potassium rose from week 1 to 3, stabilized during weeks 4 to 6, and fell from week 8, returning near baseline by week 12. Six of the nine (66.6%) HHD participants and seven of the 13 (70%) SHD participants had at least one episode of hyperkalaemia ( K  > 6 mmol/l). There were no clinical changes in serum sodium, corrected calcium, or phosphate levels during the study., Conclusion: VLCD with dietitian supervision was effective in producing significant weight reduction, with an acceptable safety profile in patients treated with haemodialysis., Competing Interests: The authors have no conflict of interest to declare in relation to this study. The results presented in this paper have not been published previously in whole or part, except in abstract format., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Miniaturized neuromodulation systems could improve the safety and reduce the invasiveness of bioelectronic neuromodulation. However, as implantable bioelectronic devices are made smaller, it becomes difficult to store enough power for long-term operation in batteries. Here, we present a battery-free epidural cortical stimulator that is only 9 millimeters in width yet can safely receive enough wireless power using magnetoelectric antennas to deliver 14.5-volt stimulation bursts, which enables it to stimulate cortical activity on-demand through the dura. The device has digitally programmable stimulation output and centimeter-scale alignment tolerances when powered by an external transmitter. We demonstrate that this device has enough power and reliability for real-world operation by showing acute motor cortex activation in human patients and reliable chronic motor cortex activation for 30 days in a porcine model. This platform opens the possibility of simple surgical procedures for precise neuromodulation.

In this paper, acoustic, dynamic and static strain variations along a steel I-beam generated by an impact load are reconstructed simultaneously within a single measurement. Based on the chirped pulse φ-OTDR system with the single-shot measurement technique, both a higher strain-sensing resolution and a higher measurable vibration frequency are achieved. In addition, a weak fiber Bragg gratings array (WFBGA) with enhanced Rayleigh reflection is employed as a sensor, providing high signal-to-noise ratio Rayleigh traces, resulting in lower measurement uncertainty. In the experiments, the damping constant and fundamental frequency of the damped harmonic oscillator could then be measured based on the recovered strain variation profile for further structural health analysis. Compared with commercial strain gauges, linear potentiometers, and OFDR systems, the proposed sensing system ensures a distributed, quantitative, and high-frequency sensing ability, with an extensive range of potential applications.

Shrinkage is an important component of the behaviour of reinforced concrete (RC) structures, however, the number of variables that affect shrinkage make it a complex time-dependent phenomenon. Additionally, as new concrete materials with lower embodied carbon gain popularity, there is a need for an in-depth understanding into their shrinkage behaviour before they can be widely adopted by industry. Currently, the shrinkage behaviour of concrete is studied using discrete measurements on small-scale unrestrained prisms. Distributed fibre optic sensing (DFOS) potentially provides a method of measuring both restrained (with reinforcement) and unrestrained (without reinforcement) shrinkage in both small-scale specimens and structural elements. In the current study, methods of measuring distributed unrestrained shrinkage strains were developed and evaluated, and the restrained shrinkage strains in different types of structural members were studied. Unrestrained shrinkage strains were measured using fibres optic cables embedded in small concrete prisms, while restrained shrinkage strains were measured with fibres bonded to the longitudinal reinforcement. Unrestrained shrinkage strains were found to be highly variable (as large as 3800 microstrain range) depending on location, but further research needs to be undertaken to account for end effects, early-stage shrinkage, and bond between the fibre optic cable and the concrete. Restrained shrinkage strains from structural members revealed non-uniform shrinkage strain distributions along member length due to functional grading as well as high supplementary cementitious material concretes, suggesting that shrinkage models will need to account for this variability.

While salarin C (SalaC) is a potent marine cytotoxin, Kashman demonstrated that congeners which had undergone Wasserman rearrangement exhibit little to no cytotoxicity. Given that thiazoles are known to undergo Wasserman rearrangement at a significantly reduced rate, we hypothesized that a thiazole-containing SalaC would exhibit greater stability without significantly altering the macrocyclic conformation. Herein, we describe the synthesis of a simplified, thiazole-containing macrocycle which demonstrates significantly improved stability under identical aerobic conditions.

Bioelectric medicine treatments target disorders of the nervous system unresponsive to pharmacological methods. While current stimulation paradigms effectively treat many disorders, the underlying mechanisms are relatively unknown, and current neuroscience recording electrodes are often limited in their specificity to gross averages across many neurons or axons. Here, we develop a novel, durable carbon fiber electrode array adaptable to many neural structures for precise neural recording. Carbon fibers ( [Formula: see text] diameter) were sharpened using a reproducible blowtorchmethod that uses the reflection of fibers against the surface of a water bath. The arrays were developed by partially embedding carbon fibers in medical-grade silicone to improve durability. We recorded acute spontaneous electrophysiology from the rat cervical vagus nerve (CVN), feline dorsal root ganglia (DRG), and rat brain. Blowtorching resulted in fibers of 72.3 ± 33.5-degree tip angle with [Formula: see text] exposed carbon. Observable neural clusters were recorded using sharpened carbon fiber electrodes fromrat CVN ( [Formula: see text]), feline DRG ( [Formula: see text]), and rat brain ( [Formula: see text]). Recordings from the feline DRG included physiologically relevant signals from increased bladder pressure and cutaneous brushing. These results suggest that this carbon fiber array is a uniquely durable and adaptable neural recordingdevice. In the future, this device may be useful as a bioelectric medicine tool for diagnosis and closed-loop neural control of therapeutic treatments and monitoring systems.

Objective: Carbon fiber electrodes may enable better long-term brain implants, minimizing the tissue response commonly seen with silicon-based electrodes. The small diameter fiber may enable high-channel count brain-machine interfaces capable of reproducing dexterous movements. Past carbon fiber electrodes exhibited both high fidelity single unit recordings and a healthy neuronal population immediately adjacent to the recording site. However, the recording yield of our carbon fiber arrays chronically implanted in the brain typically hovered around 30%, for previously unknown reasons. In this paper we investigated fabrication process modifications aimed at increasing recording yield and longevity., Approach: We tested a new cutting method using a 532nm laser against traditional scissor methods for the creation of the electrode recording site. We verified the efficacy of improved recording sites with impedance measurements and in vivo array recording yield. Additionally, we tested potentially longer-lasting coating alternatives to PEDOT:pTS, including PtIr and oxygen plasma etching. New coatings were evaluated with accelerated soak testing and acute recording., Main Results: We found that the laser created a consistent, sustainable 257 ± 13.8 µm 2 electrode with low 1 kHz impedance (19 ± 4 kΩ with PEDOT:pTS) and low fiber-to-fiber variability. The PEDOT:pTS coated laser cut fibers were found to have high recording yield in acute (97% > 100 µV pp , N = 34 fibers) and chronic (84% > 100 µV pp , day 7; 71% > 100 µV pp , day 63, N = 45 fibers) settings. The laser cut recording sites were good platforms for the PtIr coating and oxygen plasma etching, slowing the increase in 1 kHz impedance compared to PEDOT:pTS in an accelerated soak test., Significance: We have found that laser cut carbon fibers have a high recording yield that can be maintained for over two months in vivo and that alternative coatings perform better than PEDOT:pTS in accelerated aging tests. This work provides evidence to support carbon fiber arrays as a viable approach to high-density, clinically-feasible brain-machine interfaces.

Carbonic anhydrase IX (CAIX) is a membrane-spanning zinc metalloenzyme that catalyzes the reversible consumption of CO 2 and water to form H + + HCO 3 - . Many human cancers upregulate CAIX to help control the pH in their hypoxic microenvironments. The consequent overexpression of CAIX on malignant cells and low expression on normal tissues render CAIX a particularly attractive target for small molecule inhibitors, antibody-drug conjugates, and ligand-targeted drugs. In this study, CAIX-targeted fluorescent reporter molecules were initially exploited to investigate CAIX-specific binding to multiple cancer cell lines, where they were shown to display potent and selective binding to CAIX positive cells. A small molecule CAIX-targeted tubulysin B conjugate was then synthesized and examined for its ability to kill CAIX-expressing tumor cells in vitro. Potent therapeutic conjugates were subsequently tested in vivo and demonstrated to eliminate solid human tumor xenografts in murine tumor models without exhibiting overt signs of toxicity. Because most solid tumors contain hypoxic regions where CAIX is overexpressed, development of a method to selectively deliver drugs to these hypoxic regions could aid in the therapy of otherwise difficult to treat tumors.

An essential goal for individuals with autism spectrum disorder (ASD) is to reach maximal independence on a variety of tasks that facilitate academic and vocational engagement and community integration. One-to-one instructional arrangements do not adequately prepare individuals with autism to function within various group contexts and limit opportunities for positive social interactions with one or more peers. Furthermore, group instructional formats have multiple benefits, including potentially increased instructional time and additional learning opportunities. The purpose of this pilot study was to evaluate the acquisition and maintenance of verbal behavior targets in individual and dyad instruction, as well as to compare levels of engagement across these instructional arrangements. Results suggest that three of the four participants acquired more targets during individual instruction, and three of the four participants maintained more targets within individual instruction. In addition, three of the four participants spent less time in instruction and more time on break during dyad instruction. These findings demonstrate the diversity of outcomes for dyad instruction for people with ASD. Directions for future research and suggestions for clinical implementation are provided., Competing Interests: Compliance with Ethical StandardsAll procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.Informed consent was obtained from all individual participants included in the study.The authors declare that they have no conflict of interest.

The electrochemistry of several p-phenylenediamine derivatives, in which one of the amino groups is part of an urea functional group, has been investigated in methylene chloride and acetonitrile. The ureas are abbreviated U(R)R', where R' indicates the substituent on the N that is part of the phenylenediamine redox couple and R indicates the substituent on the other urea N. Cyclic voltammetry and UV-vis spectroelectrochemical studies indicate that U(Me)H and U(H)H undergo an apparent 1e(-) oxidation that actually corresponds to 2e(-) oxidation of half the ureas to a quinoidal-diimine cation, U(R)(+). This is accompanied by proton transfer to the other half of the ureas to make the electroinactive cation HU(R)H(+). This explains the observed irreversibility of the oxidation of U(Me)H in both solvents and U(H)H in acetonitrile. However, the oxidation of U(H)H in methylene chloride is reversible at higher concentrations and slower scan rates. Several lines of evidence suggest that the most likely reason for this is the accessibility of a H-bond complex between U(H)(+) and HU(H)H(+) in methylene chloride. Reduction of the H-bond complex occurs at a less negative potential than that of U(H)(+), leading to reversible behavior. This conclusion is strongly supported by the appearance of a more negative reduction peak at lower concentrations and faster scan rates, conditions in which the H-bond complex is less favored. The overall reaction mechanism is conveniently described by a "wedge scheme", which is a more general version of the square scheme typically used to describe redox processes in which proton transfer accompanies electron transfer.

Background: In some patients, a satisfactory aesthetic result of reconstruction following a nipple-sparing mastectomy (NSM) is limited by breast ptosis that goes uncorrected in the early phase of reconstruction. Most plastic surgeons remain hesitant to perform a mastopexy at the time of NSM due to concerns with nipple and/or skin flap loss., Methods: From 1990 to 1995, 33 female patients underwent NSM with simultaneous mastopexy and immediate implant-based reconstruction by a single surgeon at our institution. On chart review, the following data were extracted: age, co-morbidity, indication, breast size, initial/final implant volumes, type of implant, mastopexy technique, mastectomy flap/nipple necrosis, other complications, revision surgery and follow-up. An unpaired, two-tailed t-test was performed where indicated. P-value<0.05 was considered significant., Results: Wound complications occurred in 18.2% patients (10.9% breasts) without delaying tissue expansion. As many as 3% patients developed unilateral, isolated partial ischaemia of the mastectomy flap and 8% patients developed unilateral, superficial areolar loss. All resolved with conservative treatment. Only one patient developed bilateral total nipple loss. There was no correlation between preoperative breast size and postoperative complications. None of the patients developed breast cancer. Average follow-up was 11.6 years., Conclusion: With proper technique, simultaneous mastopexy is a safe procedure in highly selected patients undergoing NSM with reconstruction., (Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

The voltammetry of 2,3,5,6-tetramethyl-p-phenylenediamine, H 2 PD, has been studied and compared to that of its isomer N,N,N'N'-tetramethyl-p-phenylenediamine, Me 2 PD. Both undergo two reversible electron transfer processes in acetonitrile that nominally correspond to 1e- oxidation to the radical cations, Me 2 PD + and H 2 PD + , and a second 1e- oxidation at more positive potentials to the quinonediimine dications, Me 2 PD 2+ and H 2 PD 2+ . While the voltammetry of Me 2 PD agrees with this simple mechanism, that of H 2 PD does not. The second voltammetric wave is too small. UV/Vis spectroelectrochemical experiments indicate that the second wave does correspond to oxidation of H 2 PD + to H 2 PD 2+ in solution. The fact that the second wave is not present at all at the lowest concentrations (5 µM), and that it increases at longer times and higher concentrations, indicates that H 2 PD + is not the initial solution product of the first oxidation. A number of lines of evidence suggest instead that the initial product is a mixed valent, H-bonded dimer between one H 2 PD in the the full reduced, fully protonated state, H 4 PD 2+ , and another in the fully oxidized, fully deprotonated state, PD. A mechanism is proposed in which this dimer is formed on the electrode surface through proton transfer and H-bonding. Once desorbed into solution, it breaks apart via reaction with other H 2 PD's, to give 2 H 2 PD + , which is the thermodynamically favored species in solution.

Oxidation of a dimethylaminophenyl-substituted urea leads to a > 2000-fold increase in binding strength between the urea and a diamide guest in 0.1 M NBu4B(C6F5)4/CH2Cl2. The strength of this interaction is obscured when NBu4ClO4 or NBu4PF6 is used as the electrolyte due to competition between the neutral guest and the electrolyte anion for H-bonding to the urea cation.

Objective: To determine whether Mycoplasma haemofelis (Mhf) and Candidatus Mycoplasma haemominutum (Mhm) can be transmitted by ingestion of Mycoplasma-infected Ctenocephalides felis and by-products (feces, larvae, and eggs)., Animals: 10 cats., Procedure: 3 cats were carriers of Mhf, and 1 was a carrier of Mhm. Six cats had negative results of PCR assay for Mhf and Mhm DNA. A chamber containing 100 C felis was bandaged to 2 Mhf carrier cats. Five days later, fleas and by-products were analyzed for Mycoplasma spp DNA. The remaining fleas and a sample of by-products were fed to 2 Mycoplasma-naïve cats. A chamber containing 200 C felis was bandaged to the Mhm carrier cat. Five days later, fleas and by-products were analyzed for Mycoplasma spp DNA. The remaining fleas and a sample of by-products were fed to 2 Mycoplasma-naïve cats. A chamber containing 200 C felis was bandaged to an Mhf carrier cat and Mhm-carrier cat. Three days later, fleas and by-products were analyzed for Mycoplasma spp DNA. The remaining fleas and a random sample of by products were fed to 4 Mycoplasma-naïve cats. All cats were monitored for infection for >or=7 weeks., Results: Uptake of Mhf and Mhm DNA into fleas and by-products was detected. None of the naïve cats became infected., Conclusions and Clinical Relevance: Results suggested that ingestion of Mycoplasma-infected C felis or by-products is not an important means of transmission for Mhf or Mhm.

The prospect of biological attacks is a growing strategic threat. Covert aerosol attacks inside a building are of particular concern. In the summer of 2005, the Center for Biosecurity of the University of Pittsburgh Medical Center convened a Working Group to determine what steps could be taken to reduce the risk of exposure of building occupants after an aerosol release of a biological weapon. The Working Group was composed of subject matter experts in air filtration, building ventilation and pressurization, air conditioning and air distribution, biosecurity, building design and operation, building decontamination and restoration, economics, medicine, public health, and public policy. The group focused on functions of the heating, ventilation, and air conditioning systems in commercial or public buildings that could reduce the risk of exposure to deleterious aerosols following biological attacks. The Working Group's recommendations for building owners are based on the use of currently available, off-the-shelf technologies. These recommendations are modest in expense and could be implemented immediately. It is also the Working Group's judgment that the commitment and stewardship of a lead government agency is essential to secure the necessary financial and human resources and to plan and build a comprehensive, effective program to reduce exposure to aerosolized infectious agents in buildings.

Purpose: Contralateral prophylactic mastectomy (CPM) is one option for reducing the risk of a second breast cancer in women with a personal and family history of breast cancer. Few data are available regarding satisfaction, psychological, and social function after CPM. The purpose of this research is to evaluate women's long-term satisfaction with CPM, factors influencing satisfaction, and psychological and social function after CPM., Patients and Methods: This was a descriptive study of all women with a family history of breast cancer, known to be alive, who elected CPM at Mayo Clinic (Rochester, MN) between 1960 and 1993 (n = 621). Ninety-four percent of the women (n = 583) completed a study-specific questionnaire., Results: A mean of 10.3 years after the procedure, the majority of women (83%) were satisfied with their CPM. A smaller number were neutral (8%) or dissatisfied (9%). Women who had a subcutaneous mastectomy had more problems with reconstruction, and fewer of these women were satisfied than women with simple mastectomy. Decreased satisfaction with CPM was associated with decreased satisfaction with appearance, complications with reconstruction, reconstruction after CPM, and increased level of stress in life. The majority of women experienced no change or favorable effects in self-esteem (83%), level of stress in life (83%), and emotional stability (88%). Satisfaction with body appearance, feelings of femininity, and sexual relationships were the most adversely affected with 33%, 26%, and 23% of the women responding negatively., Conclusion: Although most women are satisfied with CPM, each woman should weigh the benefits alongside the potential adverse effects.

Objective: To determine whether Ctenocephalides felis can transmit Mycoplasma haemofelis (Mhf) and Candidatus Mycoplasma haemominutum (Mhm) through hematophagous activity between cats., Animals: 11 cats., Procedure: 2 cats were carriers of either Mhf or Mhm. Nine cats had negative results via polymerase chain reaction (PCR) assay for Mhf and Mhm DNA; 3 of those cats were infected from the chronic carriers via i.v. inoculation of blood. At the time of maximum organism count for each of the Mycoplasma spp, 1 chamber containing 100 C felis was bandaged to the amplifier cats. Five days later, fleas, feces, larvae, or eggs from each chamber were analyzed for Mycoplasma spp DNA. Viable fleas from the chambers were allocated into new chambers (3 Mhm and 6 Mhf) and attached to naïve cats for 5 days. Cats were monitored daily for clinical signs and weekly via CBC and PCR assay for infection with Mhf or Mhm for a minimum of 8 weeks., Results: Uptake of Mhf and Mhm DNA into fleas, feces, and, potentially, eggs and larvae was detected. Of the naïve cats fed on by Mhf-infected fleas, 1 cat transiently yielded positive PCR assay results for Mhf on 1 sampling date without clinical or hematologic changes consistent with Mhf infection., Conclusions and Clinical Relevance: Results suggest that hematophagous transfer of Mhm and Mhf into fleas occurred and that C felis is a possible vector for Mhf via hematophagous activity.

Reduction of nitrobenzene derivatives in the presence of arylureas in aprotic solvents results in large positive shifts in potential of the nitrobenzene(0/)(-) cyclic voltammetry wave with little change in wave shape. This behavior is indicative of reversible hydrogen bonding between nitrobenzene radical anions and arylureas. Computer fitting of the cyclic voltammetry of 4-nitroaniline, NA, plus 1,3-diphenylurea in DMF shows essentially no binding between urea and NA in the oxidized state (K(ox) < 1 M(-)(1)), but very strong binding in the reduced state (K(red) = 8 x 10(4) M(-)(1)), along with very rapid rates of hydrogen bond formation (k(f)'s approximately 10(8)-10(10) M(-)(1) s(-)(1)), making this system a fast on/off redox switch.

Background: The relation between ethanol (EtOH) preference and sensitivity to brain stimulation reward (BSR) was examined under multiples schedules of reinforcement in the current study. For comparison, the study also examined the relation between EtOH preference and motivation for a sweet, palatable sucrose solution under similar schedules of reinforcement., Methods: To investigate sensitivity to BSR performance, alcohol-preferring and -nonpreferring rats were tested using the curve-shift (rate-frequency) paradigm under several intensity levels during a 20-min session. Animals were first trained under an optimal current intensity, which produced maximal responding (i.e., 100%) across a series of descending frequencies (i.e., 300-20 Hz). BSR was then evaluated at 100%, 75%, and 50% of the optimal current. The sensitivity of the curve-shift method was further evaluated under the animal's optimal current using the FR1, FR6, and FR12 schedules. To examine responding for the sucrose solution, a separate group of alcohol-preferring and -nonpreferring rats was initially stabilized on an FR1 schedule and then subsequently on FR6 and FR12 schedules., Results: The results demonstrated that reducing the reinforcing efficacy of BSR via reduction in current intensity/reinforcement schedule produced marked orderly rightward shifts in the rate-frequency curves relating responding to stimulation frequency in both rat lines. However, no differences were found between the lines with either manipulation. Specifically, both lines demonstrated orderly reductions in response rate and increases in BSR threshold parameters (i.e., half maximal frequency/responding, minimum and maximum frequencies). In contrast to BSR, genetic selection for EtOH preference was highly associated with responding for the sweet, palatable sucrose solution. The association was even more salient as the reinforcement schedule increased (i.e., reward cost)., Conclusion: The results demonstrate that responding for BSR is not associated with EtOH preference, insofar as alcohol-preferring and -nonpreferring rats respond similarly under an array of reinforcement schedules and current intensities. In contrast, genetic selection for EtOH preference is highly associated with responding for a palatable sucrose reward, and the relation increases as the reward cost for the sucrose increases. These findings suggest that similar/overlapping mechanisms of action regulate the reinforcing properties of EtOH and sucrose but that overlapping yet distinct neuronal mechanism may modulate the reward characteristics of BSR and EtOH preference.

This study compares the outcome of Singapore flap, vertical rectus abdominis musculocutaneous flap (VRAM), and gracilis musculocutaneous flap vaginal reconstruction. A retrospective review of 99 consecutive patients with complete vaginal defects was conducted at the Mayo Clinic from January 1988 to October 2001. All possible complications were determined for each of the 3 reconstructive techniques, along with the effects of radiation and smoking on the respective complication rates. Preoperative and postoperative sexual function and adequacy were compared between each group. Ninety-nine patients ranging in age from 19 to 80 years (mean, 51.6 years) were compared, with a mean follow-up of 28.9 months. Forty-one VRAM, 13 gracilis, and 45 modified Singapore flaps were used for vaginal reconstruction. The majority was due to acquired vaginal defects due to recurrent pelvic malignancy. The overall complication rate was lower following VRAM than either gracilis or Singapore flap reconstructions (13/41, 31.7%; 8/13, 61.5%; and 21/45, 46.7%, respectively). The flap specific complication rate was least in the VRAM group (9/41, 22%; 7/13, 53.8%; and 17/45, 37.8%, respectively). The VRAM had a significant protective effect against the development of postoperative small bowel obstruction. Preoperative sexual activity predicted postoperative activity in 75 of 88 patients (85.2%) and was not affected by the type of reconstruction, although more patients with a Singapore flap required vaginal dilatation to maintain patency. In conclusion, the VRAM has a lower overall and flap-related complication rate compared with either gracilis or Singapore flap reconstruction. It has become our vaginal reconstructive flap of choice.

It has been hypothesized that alcohol addiction is mediated, at least in part, by specific gamma-aminobutyric acid(A) (GABA(A)) receptors within the ventral pallidum (VP). Among the potential GABA(A) receptor isoforms regulating alcohol-seeking behaviors within the VP, the GABA(A) alpha1 receptor subtype (GABA(A1)) appears pre-eminent. In the present study, we developed beta-carboline-3-carboxylate-t-butyl ester (betaCCt), a mixed agonist-antagonist benzodiazepine (BDZ) site ligand, with binding selectivity at the A1 receptor to explore the functional role of VP(A1) receptors in the euphoric properties of alcohol. The in vivo actions of betaCCt were then determined following microinfusion into the VP, a novel alcohol reward substrate that primarily expresses the A1 receptor. In two selectively bred rodent models of chronic alcohol drinking (HAD-1, P rats), bilateral microinfusion of betaCCt (0.5-40 microg) produced marked reductions in alcohol-reinforced behaviors. Further, VP infusions of betaCCt exhibited both neuroanatomical and reinforcer specificity. Thus, no effects on alcohol-reinforced behaviors were observed following infusion in the nucleus accumbens (NACC)/caudate putamen (CPu), or on response maintained by saccharin. Parenteral-administered betaCCt (1-40 mg/kg) was equally effective and selective in reducing alcohol-reinforced behaviors in P and HAD-1 rats. Additional tests of locomotor activity revealed that betaCCt reversed the locomotor sedation produced by both chlordiazepoxide (10 mg/kg) and EtOH (1.25 g/kg), but was devoid of intrinsic effects when given alone. Studies in recombinant receptors expressed in Xenopus oocytes revealed that betaCCt acted as a low-efficacy partial agonist at alpha3beta3gamma2 and alpha4beta3gamma2 receptors and as a low-efficacy inverse agonist at alpha1beta3gamma2, alpha2beta3gamma2, and alpha5beta3gamma2 receptors. The present study indicates that betaCCt is capable of antagonizing the reinforcing and the sedative properties of alcohol. These anti-alcohol properties of betaCCt are primarily mediated via the GABA(A1) receptor. betaCCt may represent a prototype of a pharmacotherapeutic agent to effectively reduce alcohol drinking behavior in human alcoholics.

Background: The authors characterized the unanticipated reoperations after prophylactic mastectomy, with or without implant reconstruction., Methods: The surgical cohort was comprised of 1417 women with a family history of breast carcinoma. The women received a prophylactic mastectomy with (bilateral, n = 593; contralateral, n = 506) or without reconstruction (n = 318) at the Mayo Clinic (Rochester, MN) between 1960 and 1993. Reoperations and indications for reoperation were compiled from medical records and a patient survey., Results: Three hundred eighteen women received a bilateral (n = 39) or contralateral (n = 279) prophylactic mastectomy without reconstruction. With a median follow-up of 15 years, 18 women (6%) required reoperation. Most of these reoperations occurred within the first year after prophylactic mastectomy. Five hundred ninety-three women had reconstruction with implants following bilateral prophylactic mastectomy. Approximately one-half of the women (52%) required at least 1 unanticipated reoperation during a median follow-up of 14 years. Approximately 39% of all reoperations occurred within 1 year of breast reconstruction and 69% within 5 years. Implant-related issues were the most common cause for reoperation. Some women with breast carcinoma elected to receive contralateral prophylactic mastectomy with therapeutic mastectomy for the affected breast. Five hundred six women received reconstruction with implants. During a median follow-up of 8.8 years, 189 women (37%) required unanticipated reoperation. The most common indication was implant-related issues. The time course of reoperations was similar to that for women in the bilateral group., Conclusions: Surgical reoperations were fairly common among women who received prophylactic mastectomy with implant reconstruction. Most of the reoperations were implant related. Reoperations were fairly uncommon after prophylactic mastectomy without reconstruction., (Copyright 2003 American Cancer Society.)

Objective: To estimate the number of unowned free-roaming cats in a college community in the southern United States and identify the characteristics of community residents who feed these cats., Design: Cross-sectional, random-digit telephone survey., Sample Population: 587 households in Alachua County, Florida, surveyed between March 1 and May 10, 1999., Procedure: Telephone surveys were conducted, and respondents were asked questions about feeding of unowned free-roaming cats., Results: 70 (12%) households fed free-roaming cats; mean +/- SD number of free-roaming cats fed per household was 3.6 +/- 1.9. Households that fed free-roaming cats were more likely to own pet cats than were households that did not feed free-roaming cats; however, 30 of 70 (43%) households feeding free-roaming cats did not own cats or dogs. Although the percentage of pet cats that were neutered was high (90%), only 8 (11%) households that fed free-roaming cats attempted to have such cats neutered. The free-roaming cat population was estimated to represent approximately 44% of the population of cats in the county., Conclusions and Clinical Relevance: Results suggest that unowned free-roaming cats may represent a substantial portion of the total cat population in a region. Public policies and education programs aimed at reducing cat overpopulation should include provisions for neutering unowned free-roaming cats, and efforts should target the general public, not only pet owners, because not all households that feed unowned free-roaming cats own pets.

Previous studies have demonstrated significant discrepancy rates between clinical and autopsy diagnoses. However, infectious diseases have not received emphasis in these studies. We conducted a study to determine whether the clinical and autopsy diagnoses of infectious diseases are concordant or discrepant and to determine discrepancy rates. Retrospective reviews of the records of 276 patients (adults, 182; fetuses and neonates, 94) who underwent autopsy during the years 1996 through 2001 were performed. Comparison of clinical and autopsy diagnoses was performed using the Goldman classification scheme. Of 182 adult patients, 137 (75.3%) had an infectious disease at autopsy. In 59 (43.1%) of 137 patients, the infectious disease diagnoses were unknown clinically. Of 94 fetuses and neonates, 45 (48%) had an infectious disease at autopsy. In 26 (58%) of 45 patients, the infectious disease diagnoses were unknown before death. There are substantial discrepancies between clinical and autopsy diagnoses of infectious diseases. In adults, acute bronchopneumonia is the infectious disease most often missed clinically; in fetuses and neonates, it is acute chorioamnionitis.

Background: This study examined the associations among selective breeding for alcohol preference, intake of sweet solutions, and responding for brain stimulation reward (BSR), a nonoral reinforcer, in alcohol-preferring high-alcohol-drinking (HAD)-1 and nonpreferring low-alcohol-drinking (LAD)-1 rats., Methods: Adult male HAD-1 and LAD-1 rats were trained to lever press for medial forebrain bundle stimulation. Current intensity was varied in separate sessions to generate a rate/intensity function. To further examine BSR responding, the animals responded for stimulation at 100 Hz and at a fixed current intensity on an FR1 schedule. In subsequent sessions, the schedule was increased to FR6 and then to FR12. To examine responding for the sucrose solution, we trained a separate group of HAD-1/LAD-1 rats to bar press for sucrose on an FR1 schedule. Similar to the BSR experiment, in following sessions, the schedule was increased to an FR6 and then to an FR12 schedule., Results: No significant differences were observed between the two rat lines across a range of current intensities. As the reinforcement schedule increased, HAD-1 rats exhibited a dramatic decrease in BSR responding, whereas the LAD-1 rats displayed a more protracted reduction. In contrast to BSR, marked elevations in responding were observed for sucrose as the schedule increased. However, in HAD-1 rats, response rates were similar on the FR6 and FR12 schedules, whereas LAD-1 rats showed a reduction in response rates from the FR6 to FR12 schedule. Furthermore, HAD-1 rats exhibited significantly more responses compared with LAD-1 rats across the three reinforcement schedules. An analysis of the response profile for the three reinforcement schedules suggested that few if any postreinforcement pauses were exhibited when the reinforcer was BSR compared with sucrose in both lines., Conclusion: Medial forebrain bundle BSR is a powerful reinforcer in both HAD-1 and LAD-1 lines. However, BSR responding was not associated with selective breeding for alcohol preference. In contrast, selective breeding for alcohol preference was associated with sucrose consumption, especially as the amount of work increased. The lack of correspondence between BSR and sweet taste rewards in HAD-1 and LAD-1 lines may suggest important differences yet an overlapping brain reward mechanism in the control of motivated behaviors in these selected lines.

A randomized, double-blind, placebo-controlled phase III clinical trial was performed to assess megestrol acetate (Megace) as a postsurgical adjuvant therapy for patients with locally advanced malignant melanoma. Patients whose tumors were greater than 1.7 mm thick and had no regional lymph node involvement and patients with regional lymph node involvement were randomized to receive either 160 mg twice per day oral suspension of megestrol acetate or placebo. Treatment was administered for a maximum of 2 years or until disease progression. The study accrued 262 eligible patients. All but two patients were followed until death or a minimum of 4.5 years. Disease progression was documented in 156 patients. Neither progression-free survival (PFS) nor overall survival (OS) was found to differ between the treatments. The median PFS was 2.4 years in the megestrol acetate arm and 2.3 years in the placebo arm. Multivariate analysis revealed a significantly decreased PFS for patients with four or more positive regional lymph nodes and metachronous nodal disease. Median OS was 5.3 years in the megestrol acetate arm and 3.9 years in the placebo arm. Multivariate analysis revealed that OS was significantly decreased for patients 70 years of age or older with four or more positive lymph nodes. Adjuvant therapy with megestrol acetate oral suspension administered at a dose of 160 mg twice a day for 2 years was not found to be effective in prolonging PFS or OS in patients with surgically resected, locally advanced melanoma.

We investigated the potential role of the alpha1-containing GABA(A) receptor in regulating the reinforcing properties of alcohol. To accomplish this, we developed 3-propoxy-beta-carboline hydrochloride (3-PBC), a mixed agonist-antagonist benzodiazepine site ligand with binding selectivity at the alpha1 receptor. We then tested the capacity of 3-PBC to block alcohol-maintained responding in the ventral pallidum (VP), a novel alcohol reward substrate, which primarily expresses the alpha1-receptor isoform. Our results demonstrated that bilateral microinfusion of 3-PBC (0.5-40 microg) in the anterior and medial VP produced marked reductions in alcohol-maintained responding in a genetically selected rodent model of alcohol drinking. The VP infusions showed both neuroanatomical and reinforcer specificity because no effects were seen in sites dorsal to the VP (e.g., nucleus accumbens, caudate putamen). The saccharin-maintained responding was reduced only with the highest dose (40 microg). Parenteral injections of 3-PBC (1-20 mg/kg) also showed a similar selectivity on alcohol-maintained responding. Complementary in vitro studies revealed that 3-PBC exhibited a low partial agonist efficacy profile at recombinant diazepam-sensitive receptors (e.g., alpha1beta3gamma2, alpha2beta3gamma, and alpha3beta3gamma2). The selective suppression of 3-PBC on alcohol-maintained responding after central and parenteral administrations, together with its low-efficacy agonist profile, suggest that the reduction in alcohol-maintained behaviors was not attributable to a general suppression on consummatory behaviors. These results demonstrate that the alpha1-containing GABA(A) receptors in both the anterior and medial VP are important in regulating the reinforcing properties of alcohol. These receptors represent novel targets in the design and development of pharmacotherapies for alcohol-dependent subjects.

Malignant hypertension and cardiac tamponade are uncommon but potentially life-threatening medical emergencies. Both conditions may be associated with collagen vascular diseases, such as systemic lupus erythematosus. We report a case of acute cardiac tamponade associated with malignant hypertension secondary to lupus nephritis. Immediately after pericardiocentesis, blood pressure declined substantially. Although malignant hypertension is seen with modest frequency in patients with systemic lupus erythematosus, true cardiac tamponade is a less common complication of lupus serositis. Acute, simultaneous presentation of both life-threatening entities and the hemodynamic course have not been described., (Copyright 2002 by the National Kidney Foundation, Inc.)

Telomerase expression is a potentially important marker of high-grade cervical dysplasia and squamous cell carcinoma (SCC). The routine practice of cervical cytology is limited by problems of false negative diagnoses as well as by poor specificity for clinically significant lesions in patients with low-grade cytologic abnormalities. Telomerase is widely expressed in most SCCs as well as in a high proportion of high-grade squamous intraepithelial lesions. Histochemical studies have confirmed that telomerase is expressed in the lower portions of normal or metaplastic squamous mucosa but that telomerase positive cells extend into the upper epithelial layers in cases of high-grade dysplasia. Since the cervical smear samples the uppermost cell layers of the cervical mucosa, but does not normally include cells derived from the lower layers of the squamous mucosa, the detection of telomerase in exfoliated cells of the cervical smear may have specificity for clinically significant lesions. The analysis of hTR, hTERT, and telomerase activity are complicated by a number of technical factors that may lead to either false negative or false positive test results. Thus, the practical application of telomerase analysis as a diagnostic adjunct for cervical cytopathology may depend on the development of more reliable and sensitive assay systems, possibly formatted for cytochemical applications.

Background: In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes., Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models., Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of follow-up (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%)., Conclusions: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

Purpose: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer., Patients and Methods: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy., Results: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%)., Conclusion: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Background: Research comparing the alcohol-preferring (P) and -nonpreferring (NP) rat lines has detected an apparent association between ethanol preference and lower responsivity to ethanol, as well as the capacity to develop and maintain tolerance to ethanol's effects. However, past studies of tolerance to ethanol's effects generally involved relatively high doses. The present study examined recovery from functional impairment induced by moderate doses of ethanol after a single dose (responsivity) and after multiple doses (development of tolerance) in the P and NP rat lines., Method: Adult female P and NP rats were trained, for 5 consecutive days, to stay on an oscillating bar for 120 sec. Rats were then assigned to one of three groups to receive 1.0, 1.25, or 1.5 g/kg ethanol for 5 consecutive test days. Rats were tested each day at 15-min intervals, following intraperitoneal injection, until recovery to the 120 sec criterion., Results: On the first test day, NP rats took longer to recover to criterion than the P rats following the 1.0 and 1.25 g/kg doses, whereas at the 1.5 g/kg dose no line difference was evident. Trunk blood alcohol concentrations (BACs), associated with time to recovery, indicated higher values for the P than NP rat on day 1 following injection of the two lower doses. Compared to day 1, NP rats demonstrated significantly shorter times to recovery beginning on day 2 following injections of the 1.0 and 1.25 g/kg doses. However, NP rats did not show significantly different recovery times on days 2-5 compared to day 1 following injection of the 1.5 g/kg dose. The shorter recovery times at the 1.0 and 1.25 g/kg doses were associated with BACs at recovery on day 3 being equal to or greater than values obtained on day 1. In contrast, compared to day 1, P rats did not show shorter recovery times until days 3 and 5 following the 1.0 and 1.25 g/kg doses, respectively. However, P rats did demonstrate shorter recovery times on day 2 and higher BACs on day 3 compared to day 1 following the 1.5 g/kg dose., Conclusion: With regard to motor impairment, lower responsivity to moderate doses of ethanol may be a factor associated with high alcohol-seeking behavior. The present results confirm past research supporting an association between ethanol preference and low ethanol responsivity but at doses that are more reflective of those self-administered by P rats.