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The objectives of NSTX-U research are to reinforce the advantages of STs while addressing the challenges. To extend confinement physics of low- A , high beta plasmas to lower collisionality levels, understanding of the transport mechanisms that set confinement performance and pedestal profiles is being advanced through gyrokinetic simulations, reduced model development, and comparison to NSTX experiment, as well as improved simulation of RF heating. To develop stable non-inductive scenarios needed for steady-state operation, various performance-limiting modes of instability were studied, including MHD, tearing modes, and energetic particle instabilities. Predictive tools were developed, covering disruptions, runaway electrons, equilibrium reconstruction, and control tools. To develop power and particle handling techniques to optimize plasma exhaust in high performance scenarios, innovative lithium-based solutions are being developed to handle the very high heat flux levels that the increased heating power and compact geometry of NSTX-U will produce, and will be seen in future STs. Predictive capabilities accounting for plasma phenomena, like edge harmonic oscillations, ELMs, and blobs, are being tested and improved. In these ways, NSTX-U researchers are advancing the physics understanding of ST plasmas to maximize the benefit that will be gained from further NSTX-U experiments and to increase confidence in projections to future devices.

A theoretical model is presented that for the first time matches experimental measurements of the pedestal width-height Diallo scaling in the low-aspect-ratio high- β tokamak NSTX. Combining linear gyrokinetics with self-consistent pedestal equilibrium variation, kinetic-ballooning, rather than ideal-ballooning plasma instability, is shown to limit achievable confinement in spherical tokamak pedestals. Simulations are used to find the novel Gyrokinetic Critical Pedestal constraint, which determines the steepest pressure profile a pedestal can sustain subject to gyrokinetic instability. Gyrokinetic width-height scaling expressions for NSTX pedestals with varying density and temperature profiles are obtained. These scalings for STs depart significantly from that of conventional aspect ratio tokamaks.

A gyrokinetic threshold model for pedestal width–height scaling prediction is applied to multiple devices. A shaping and aspect ratio scan is performed on National Spherical Torus Experiment (NSTX) equilibria, finding $\Delta_{\mathrm{ped}} = 0.92 A^{1.04} \kappa^{-1.24} 0.38^{\delta} \beta_{\theta,\mathrm{ped}}^{1.05}$ for the wide-pedestal branch with pedestal width $\Delta_{\mathrm{ped}}$ , aspect ratio A , elongation κ , triangularity δ , and normalized pedestal height $\beta_{\theta,\mathrm{ped}}$ . The width–transport scaling is found to vary significantly if the pedestal height is varied either with a fixed density or fixed temperature, showing how fueling and heating sources affect the pedestal density and temperature profiles for the kinetic-ballooning-mode (KBM) limited profiles. For an NSTX equilibrium, at fixed density, the wide branch is $\Delta_{\mathrm{ped} } = 0.028 \left(q_\textrm e/\Gamma_\textrm e - 1.7 \right)^{1.5} \sim \eta_\textrm e ^{1.5}$ and at fixed temperature $\Delta_{\mathrm{ped} } = 0.31 \left(q_\textrm e/\Gamma_\textrm e - 4.7 \right)^{0.85}$ $ \sim \eta_\textrm e ^{0.85}$ , where $q_\textrm e$ and $\Gamma_\textrm e$ are turbulent electron heat and particle fluxes and $\eta_\textrm e = \nabla \ln T_\textrm e / \nabla \ln n_\textrm e$ for an electron temperature $T_\textrm e$ and density $n_\textrm e$ . Pedestals close to the KBM limit are shown to have modified turbulent transport coefficients compared to the strongly driven KBMs. The role of flow shear is studied as a width–height scaling constraint and pedestal saturation mechanism for a standard and lithiated wide pedestal discharge. Finally, the stability, transport, and flow shear constraints are combined and examined for an NSTX experiment.

We investigate the nonlinear absorption of laser energy in the bulk of transparent dielectrics for femtosecond and picosecond laser pulses focused by a conical lens. We highlight the influence of the pulse duration, laser pulse energy, and cone angle on laser energy absorption in transparent dielectrics. We provide a semi-analytical model allowing the calculation of maps for the density of nonlinear absorption of energy in BK7 and in SiO2 as a function of the pulse duration and peak fluence in the focal region. The comparison of the density of nonlinear absorption of energy with the available energy density determines optimal pulse durations and Bessel beam cone angles compatible with uniform laser energy deposition in the Bessel zone. The results reproduce quantitatively the transmission measurements for experiments in BK7 with picosecond pulses and suggest that the loss of propagation invariance and uniform laser energy deposition is responsible for a previously reported transition between different types of damage morphology in SiO2 [M. K. Bhuyan et al., Appl. Phys. Lett. 104, 021107 (2014)].

In the last years, Microsoft has driven innovation in the aerial photogrammetry community. Besides the market leading camera technology, UltraMap has grown to an outstanding photogrammetric workflow system which enables users to effectively work with large digital aerial image blocks in a highly automated way. Best example is the project-based color balancing approach which automatically balances images to a homogeneous block. UltraMap V3 continues innovation, and offers a revolution in terms of ortho processing. A fully automated dense matching module strives for high precision digital surface models (DSMs) which are calculated either on CPUs or on GPUs using a distributed processing framework. By applying constrained filtering algorithms, a digital terrain model can be derived which in turn can be used for fully automated traditional ortho texturing. By having the knowledge about the underlying geometry, seamlines can be generated automatically by applying cost functions in order to minimize visual disturbing artifacts. By exploiting the generated DSM information, a DSMOrtho is created using the balanced input images. Again, seamlines are detected automatically resulting in an automatically balanced ortho mosaic. Interactive block-based radiometric adjustments lead to a high quality ortho product based on UltraCam imagery. UltraMap v3 is the first fully integrated and interactive solution for supporting UltraCam images at best in order to deliver DSM and ortho imagery.

A statistical method for the estimation of the spatial correlation lengths of Gaussian-shaped fluctuating signals with two measurement points is examined to quantitatively evaluate its reliability (variance) and accuracy (bias error). The standard deviation of the correlation value is analytically derived for randomly distributed Gaussian shaped fluctuations satisfying stationarity and homogeneity, allowing us to evaluate, as a function of fluctuation-to-noise ratios, the sizes of averaging time windows and the ratios of the distance between the two measurement points to the true correlation length, and the goodness of the two-point measurement for estimating the spatial correlation length. Analytic results are confirmed with numerically generated synthetic data and real experimental data obtained with the KSTAR beam emission spectroscopy diagnostic. Our results can be applied to Gaussian-shaped fluctuating signals where a correlation length must be measured with only two measurement points. [ABSTRACT FROM AUTHOR]

Understanding fast pedestal dynamics and turbulent transport in the edge and scrape-off layer (SOL) plasma of spherical tokamaks is crucial for the design and operation of future fusion reactors. The alkali beam emission spectroscopy diagnostic technique offers a means to measure the absolute electron density radial profile and fluctuation amplitude in these regions. In this study, we demonstrate that injecting a sodium neutral beam radially into the plasma and analyzing the light emission from its 3p-3s atomic transition using near-orthogonal viewing angles allows for accurate measurement of the electron density profile and fluctuations in the National Spherical Torus Experiment (NSTX) Upgrade spherical tokamak. Our findings indicate a peak signal-to-noise ratio of 118 in the pedestal and 12 in the SOL under typical NSTX plasma conditions. The spatial resolution for the electron density profile is estimated to be between 2 and 8 mm, while for fluctuation measurements, it ranges from 12 to 15 mm., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Scrape-off layer (SOL) and edge plasma turbulence significantly contribute to the radial particle and heat transport, lowering the plasma confinement and increasing the heat load on the plasma facing components. SOL turbulence is predominantly intermittent, which manifests in the occurrence of isolated density filaments or blobs. Filaments propagate radially outward toward plasma facing components, limiting their lifetime by erosion and sputtering. To characterize this phenomenon in detail, few diagnostic techniques are available. Beam emission spectroscopy is a diagnostic capable of measuring plasma turbulence in both SOL and edge plasmas. Due to the finite lifetime of the excitation states during the beam-plasma interaction and the misalignment between the optics and the magnetic field, spatial smearing is introduced in the measurement. In this paper, a novel method is introduced to overcome this hindering effect by inverting the fluctuation response matrix on an optimally smoothed signal. We show that this method is fast and provides significantly more accurate absolute density fluctuation reconstruction than the direct inversion technique. The presented method is usable for all types of beam emission diagnostics where the spatial resolution is higher than the combined smearing of the atomic physics and the observation., (© 2023 Author(s). Published under an exclusive license by AIP Publishing.)

Goal: Readmissions are a significant financial burden for payers. Cardiovascular-related discharges are particularly prone to readmission. Posthospital discharge support can impact patient recovery and probably reduce patient readmissions. This study aimed to address the underlying behavioral and psychosocial factors that can negatively affect patients after discharge., Methods: The study population was adult patients admitted to the hospital with a cardiovascular diagnosis who had a plan to discharge home. Those who consented to participate were randomized to intervention or control groups on a 1:1 basis. The intervention group received behavioral and emotional support, whereas the control group received usual care. Interventions included motivational interviewing, patient activation, empathetic communication, addressing mental health and substance use, and mindfulness., Principal Findings: Observed total readmission costs were significantly lower in the intervention group than in the control group ($1.1 million vs. $2.0 million) as was the observed mean cost per readmitted patient ($44,052 vs. $91,278). The mean expected cost of readmission after adjustment for confounding variables was lower in the intervention group than in the control group ($8,094 vs. $9,882, p = .011)., Practical Applications: Readmissions are a costly spend category. In this study, posthospital discharge support addressing the psychosocial factors contributing to patients' readmissions resulted in a lower total cost of care for those with a cardiovascular diagnosis. We describe an intervention that is reproducible and can be scaled broadly through technology to reduce readmission costs., Competing Interests: Drs. Minga, Balasubramanian, Salazar Adum, Kwak, and Marcrinici declare no conflicts of interest. See note for additional disclosures., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the Foundation of the American College of Healthcare Executives.)

Magnetic field aligned filaments such as blobs and edge localized mode filaments carry significant amounts of heat and particles to the plasma facing components and they decrease their lifetime. The dynamics of these filaments determine at least a part of the heat and particle loads. These dynamics can be characterized by their translation and rotation. In this paper, we present an analysis method novel for fusion plasmas, which can estimate the angular velocity of the filaments on frame-by-frame time resolution. After pre-processing, the frames are two-dimensional (2D) Fourier-transformed, then the resulting 2D Fourier magnitude spectra are transformed to log-polar coordinates, and finally the 2D cross-correlation coefficient function (CCCF) is calculated between the consecutive frames. The displacement of the CCCF's peak along the angular coordinate estimates the angle of rotation of the most intense structure in the frame. The proposed angular velocity estimation method is tested and validated for its accuracy and robustness by applying it to rotating Gaussian-structures. The method is also applied to gas-puff imaging measurements of filaments in National Spherical Torus Experiment plasmas.

Dynamics of fast transient events are challenging to be analyzed with high time resolution. Such events can occur in fusion plasmas such as the filaments during edge-localized modes (ELMs). In this paper, we present a robust method-the spatial displacement estimation-for estimating the displacements of structures with fast dynamics from high spatial and time resolution imaging diagnostics [e.g., gas-puff imaging (GPI)] with sampling time temporal resolution. First, a background suppression method is shown, which suppresses the slowly time-evolving and spatially non-uniform background in the signal. In the second step, a two-dimensional polynomial trend subtraction method is presented to tackle the remaining polynomial order trend in the signal. After performing these pre-processing steps, the spatial displacement of the propagating structure is estimated from the two-dimensional spatial cross-correlation coefficient function calculated between consecutive frames. The method is tested for its robustness and accuracy by simulated Gaussian events and spatially displaced random noise. An example application of the method is presented on propagating ELM filaments measured by the GPI system on the National Spherical Torus Experiment spherical tokamak.

Transcatheter mitral valve replacement has been successfully performed with the use of aortic transcatheter heart valves in hundreds of patients worldwide with severe dysfunction of a degenerated mitral bioprosthesis and high surgical risk for repeat operation. The delivery approach in the vast majority of the mitral valve-in-valve procedures has been transapical. Although the transseptal approach may be more technically challenging, it is less invasive and may be preferred by patients. Data from case series and a large international registry suggest that patients treated with transseptal mitral valve-in-valve have faster recovery, more improvement in left ventricular ejection fraction and possibly lower mortality compared with patients treated with transapical approach. A prospective clinical trial, the MITRAL trial (Mitral Implantation of TRAnscatheter vaLves) is evaluating the safety and feasibility of transvenous transseptal mitral valve-in-valve. The experience from this trial has allowed us to improve our procedural approach. In anticipation of a wider adoption of the transseptal approach for mitral valve-in-valve, we describe our current method step-by-step from planning the procedure through postprocedural management. This is an evolving technique that has changed with experience and the transition to newer generation transcatheter heart valve devices. We discuss the use of cardiac computed tomography for planning the procedure including transseptal puncture and valve size selection, provide procedural and technical tips, and discuss postprocedural care., (© 2017 Wiley Periodicals, Inc.)

A 60 keV neutral lithium beam system was designed and built up for beam emission spectroscopy measurement of edge plasma on the KSTAR and EAST tokamaks. The electron density profile and its fluctuation can be measured using the accelerated lithium beam-based emission spectroscopy system. A thermionic ion source was developed with a SiC heater to emit around 4-5 mA ion current from a 14 mm diameter surface. The ion optic is following the 2 step design used on other devices with small modifications to reach about 2-3 cm beam diameter in the plasma at about 4 m from the ion source. A newly developed recirculating sodium vapour neutralizer neutralizes the accelerated ion beam at around 260-280 °C even during long (<20 s) discharges. A set of new beam diagnostic and manipulation techniques are applied to allow optimization, aiming, cleaning, and beam modulation. The maximum 60 keV beam energy with 4 mA ion current was successfully reached at KSTAR and at EAST. Combined with an efficient observation system, the Li-beam diagnostic enables the measurement of the density profile and fluctuations on the plasma turbulence time scale.

A novel beam emission spectroscopy observation system was designed, built, and installed onto the Korea Superconducting Tokamak Advanced Research tokamak. The system is designed in a way to be capable of measuring beam emission either from a heating deuterium or from a diagnostic lithium beam. The two beams have somewhat complementary capabilities: edge density profile and turbulence measurement with the lithium beam and two dimensional turbulence measurement with the heating beam. Two detectors can be used in parallel: a CMOS camera provides overview of the scene and lithium beam light intensity distribution at maximum few hundred Hz frame rate, while a 4 × 16 pixel avalanche photo-diode (APD) camera gives 500 kHz bandwidth data from a 4 cm × 16 cm region. The optics use direct imaging through lenses and mirrors from the observation window to the detectors, thus avoid the use of costly and inflexible fiber guides. Remotely controlled mechanisms allow adjustment of the APD camera's measurement location on a shot-to-shot basis, while temperature stabilized filter holders provide selection of either the Doppler shifted deuterium alpha or lithium resonance line. The capabilities of the system are illustrated by measurements of basic plasma turbulence properties.

Background: Cav1.3 voltage-gated L-type calcium channels (LTCCs) are part of postsynaptic neuronal signaling networks. They play a key role in brain function, including fear memory and emotional and drug-taking behaviors. A whole-exome sequencing study identified a de novo mutation, p.A749G, in Cav1.3 α1-subunits (CACNA1D), the second main LTCC in the brain, as 1 of 62 high risk-conferring mutations in a cohort of patients with autism and intellectual disability. We screened all published genetic information available from whole-exome sequencing studies and identified a second de novo CACNA1D mutation, p.G407R. Both mutations are present only in the probands and not in their unaffected parents or siblings., Methods: We functionally expressed both mutations in tsA-201 cells to study their functional consequences using whole-cell patch-clamp., Results: The mutations p.A749G and p.G407R caused dramatic changes in channel gating by shifting (~15 mV) the voltage dependence for steady-state activation and inactivation to more negative voltages (p.A749G) or by pronounced slowing of current inactivation during depolarizing stimuli (p.G407R). In both cases, these changes are compatible with a gain-of-function phenotype., Conclusions: Our data, together with the discovery that Cav1.3 gain-of-function causes primary aldosteronism with seizures, neurologic abnormalities, and intellectual disability, suggest that Cav1.3 gain-of-function mutations confer a major part of the risk for autism in the two probands and may even cause the disease. Our findings have immediate clinical relevance because blockers of LTCCs are available for therapeutic attempts in affected individuals. Patients should also be explored for other symptoms likely resulting from Cav1.3 hyperactivity, in particular, primary aldosteronism., (Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Beam emission spectroscopy (BES) system in Korea Superconducting Tokamak Advanced Research (KSTAR) has recently been upgraded. The background intensity was reduced from 30% to 2% by suppressing the stray lights. This allows acquisition of the relative electron density profiles on the plasma edge without background subtraction from the beam power modulation signals. The KSTAR BES system has its spatial resolution of 1 cm, the temporal resolution of 2 MHz, and a total 32 channel (8 radial × 4 poloidal) avalanche photo diode array. Most measurements were done on the plasma edge, r/a ∼ 0.9, with 8 cm radial measurement width that covers the pedestal range. High speed density profile measurements reveal temporal behaviors of fast transient events, such as the precursors of edge localized modes and the transitions between confinement modes. Low background level also allows analysis of the edge density fluctuation patterns with reduced background fluctuations. Propagation of the density structures can be investigated by comparing the phase delays between the spatially distributed channels.

Surgical left atrial appendage (LAA) exclusion has a failure rate as high as 60% due to persistent residual flow in the LAA or large LAA remnants. We describe a novel technique for treatment of incomplete surgical LAA ligation, and define the mechanism that led to persistence of the remnant LAA without any thrombus formation.

Objective: To examine the influence of audiological and non-audiological factors on help-seeking for hearing impairment (HI) in older adults., Design: A retrospective research design was employed. Participants completed 14 measures, after which two multivariate, multinomial logistic regression models were fitted to the data to determine which factors were associated with consultation for HI and hearing aid uptake., Study Sample: Three-hundred-and-seven individuals who were 60 years or older and who presented with a unilateral or bilateral HI participated in the study. Non-hearing aid owners were assigned to a non-consulter group (n=55) or a consulter group (n=92); hearing aid owners were assigned to an unsuccessful hearing aid owner group (n=75) or a successful hearing aid owner group (n=85)., Results: A similar combination of factors was associated with the decisions to consult a health professional about HI and/or to adopt hearing aids. The most important factors related to attitudinal beliefs (e.g. perceived benefits of hearing aids) and external cues to action (e.g. support from significant others). Greater HI also influenced consultation and adoption of hearing aids., Conclusions: Findings highlight the importance of non-audiological factors in hearing rehabilitation to improve consultation for HI and hearing aid adoption.

Objective: To examine associations between audiological and non-audiological factors and successful hearing aid use in older adults., Design: In a retrospective study, audiological factors, attitudinal beliefs (as derived from the health belief model), client demographics, psychological factors, and age-related factors were evaluated., Study Sample: Participants included 160 individuals, 60 years or older, with unilateral or bilateral hearing impairment (HI), fitted with hearing aids for the first time in the previous two years. Participants were assigned to either an unsuccessful hearing aid owner group (n=75) or a successful hearing aid owner group (n=85) based on their self-reported hearing aid use and benefit., Results: A multivariate, binomial logistic regression model indicated five factors associated with group membership: participants who had greater support from significant others; more difficulties with hearing and communication in everyday life before getting hearing aids; more positive attitudes to hearing aids; coupled with greater perceived self-efficacy for advanced handling of hearing aids; or who were receiving more gain from their devices; were more likely to be successful hearing aid owners., Conclusions: These findings highlight the importance of addressing non-audiological factors in order to assist older adults achieve success with hearing aids.

One of the main diagnostic tools for measuring electron density profiles and the characteristics of long wavelength turbulent wave structures in fusion plasmas is beam emission spectroscopy (BES). The increasing number of BES systems necessitated an accurate and comprehensive simulation of BES diagnostics, which in turn motivated the development of the Rate Equations for Neutral Alkali-beam TEchnique (RENATE) simulation code that is the topic of this paper. RENATE is a modular, fully three-dimensional code incorporating all key features of BES systems from the atomic physics to the observation, including an advanced modeling of the optics. Thus RENATE can be used both in the interpretation of measured signals and the development of new BES systems. The most important components of the code have been successfully benchmarked against other simulation codes. The primary results have been validated against experimental data from the KSTAR tokamak.

A beam emission spectroscopy (BES) system based on direct imaging avalanche photodiode (APD) camera has been designed for Korea Superconducting Tokamak Advanced Research (KSTAR) and a trial system has been constructed and installed for evaluating feasibility of the design. The system contains two cameras, one is an APD camera for BES measurement and another is a fast visible camera for position calibration. Two pneumatically actuated mirrors were positioned at front and rear of lens optics. The front mirror can switch the measurement between edge and core region of plasma and the rear mirror can switch between the APD and the visible camera. All systems worked properly and the measured photon flux was reasonable as expected from the simulation. While the measurement data from the trial system were limited, it revealed some interesting characteristics of KSTAR plasma suggesting future research works with fully installed BES system. The analysis result and the development plan will be presented in this paper.

Problems associated with pharmacotherapy (in particular, medication errors and adverse drug events) are frequent and are associated with increased costs for treatment. Analysis of original publications published between 1990 and 2005 on the topics of medication errors and/or adverse drug events in hospitalised patients, focusing on the frequency of, risk factors for and avoidance of such problems associated with pharmacotherapy, indicated that medication errors occurred in a mean of 5.7% of all episodes of drug administration, but with a high variability among the 35 studies retrieved. This variability was explained by the methods by which medication errors were detected (systematic screening of patients versus chart review or spontaneous reporting) and by the way drugs were administered (intravenously administered drugs are associated with the highest error frequencies). Errors occurred throughout the whole medication process, with administration errors accounting for more than half of all errors. Important risk factors included insufficient pharmacological knowledge of health professionals, errors in the patient charts or documentation by nurses and inadequate pharmacy services.Adverse events or reactions, on the other hand, affected 6.1 patients per 100 hospitalised and also showed a high variability among the 46 studies retrieved. This variability could also be explained by the different methods of assessment of the frequency of adverse drug events or reactions, as well as by the different wards on which the studies were performed. Important risk factors for adverse drug events or reactions included polypharmacy, female sex, drugs with a narrow therapeutic range, renal elimination of drugs, age >65 years and use of anticoagulants or diuretics. Since medication errors are strong risk factors for preventable adverse drug events or reactions, strategies have to be put in place for their reduction. Such strategies include ensuring that all persons involved in the medication process (nurses, pharmacists and physicians) have good pharmacological knowledge, computerisation of the entire medication process, and the engagement of a sufficient number of clinical pharmacists on the wards.

Human serum albumin labeled with technetium-99m was encapsulated together with magnetite particles into phosphatidylcholine/cholesterol liposomes. In order to investigate the stability of this complex and its ability to be used for magnetic drug targeting, the in-vivo distribution after intravenous administration in rats was estimated. For in-vivo targeting an SmCo permanent magnet with intensity approximately 0.35 T was attached near the right kidney. Difference between the relative radioactivity in the magnetically targeted right kidney (25.92+/-5.84%) and non-targeted left kidney (0.93+/-0.05%) is sufficiently high for relevant clinical applications.

This study demonstrates that gonadal steroids (estradiol, testosterone, dihydrotestosterone) can regulate the expression of glial fibrillary acidic protein in the adult male rat brain. Previously, we showed that castration of adult male rats increased glial fibrillary acidic protein messenger RNA in the hippocampus and that this increase was additive with the increase induced by deafferenting entorhinal cortex lesions [Day et al. (1990) Molec. Endocr. 4, 1995-2002 . We extended these effects of castration and entorhinal cortex lesion to glial fibrillary acidic protein, using immunoassays. Furthermore, we found regional differences in responses to castration and inhibited by sex steroids. In contrast, hypothalamic glial fibrillary acidic protein expression was inhibited by castration. Similar regional differences were also shown for astrocyte glial fibrillary acidic protein distribution by immunocytochemistry. The regional specificity of glial fibrillary acidic protein expression after castration and sex steroid replacement is pertinent to the role of astrocytes in synaptic plasticity in unlesioned adults as well as in responses to lesions where the steroid milieu has been shown to influence sprouting.

This investigation describes the schedule and regional distribution of astrocytic responses in striatum following deafferentation by unilateral frontal cortex ablation. In the ipsilateral deafferented striatum, glial fibrillary acidic protein and clusterin (sulfated glycoprotein-2) messengerRNA showed peak elevations by 10 days postlesioning (Northern blots). Vimentin messengerRNA responded faster, with a transient elevation by three days postlesioning. The messengerRNA for glial fibrillary acidic protein, clusterin and vimentin returned toward control levels by 27 days postlesioning. However, the neuronal marker growth-associated protein messengerRNA, was decreased at all postlesion times. By in situ hybridization, the increased glial fibrillary acidic protein messengerRNA and clusterin messengerRNA signals were localized mainly to the dorsal half of the ipsilateral deafferented striatum and followed the same schedule as found by Northern blots. Glial fibrillary acidic protein messengerRNA was widely diffused in the dorsal striatum and was excluded from fascicles of the internal capsule; a similar distribution was found for glial fibrillary acidic protein-immunopositive astrocytes. While clusterin messengerRNA signal showed a distinct clustering, its immunoreactivity appeared as deposits in the deafferented striatal neuropil; Western blots confirmed the immunocytochemical results. By in situ hybridization, vimentin messengerRNA was mostly localized to the cortical wound cavity dorsal to the deafferented striatum and overlapped the distribution of vimentin-immunopositive cells. These findings suggest a coordination of striatal astrocytic messengerRNA responses with the degeneration of corticostriatal afferents. We also compared these same parameters with those from published reports on the hippocampus after deafferenting lesions. Certain astrocyte molecular responses to deafferentation are detected about five days earlier in the hippocampus than in the striatum. This different schedule in response to decortication may pertain to differences in synaptic remodeling in the hippocampus vs striatum.

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

These data show the presence of mRNAs for two complement components (C) in the adult rat brain and describe their responses to experimental lesions. Cortical deafferentation caused elevations in striatal C1qB and C4 mRNAs that coincided temporally and overlapped anatomically with the course of degeneration of corticostriatal afferent fibers. By in situ hybridization, C1qB mRNA in the lesioned striatum was colocalized to cells immunoreactive for CR3, a complement receptor found on microglia-macrophages. The mRNA for SGP-2, a putative C inhibitor in rat, showed parallel changes. Similarly, in hippocampus and other brain regions, kainic acid lesions increased C1qB mRNA. The data suggest that microglia-macrophages and possibly other cells in rat brain rapidly up-regulate C-mRNAs in response to deafferentation and local neuron injury. These experimental responses provide models to analyze changes in C components during Alzheimer's disease and other chronic neurodegenerative conditions.

Recent data suggest that prognosis is similar for women with primary breast cancer whether they receive modified radical mastectomy (MRM) or local excision and axillary dissection with radiation (XRT). The effects of either of these treatments on arm mobility, pain, or edema have not been compared. To assess the impact of MRM or XRT on mobility, pain, or edema, we evaluated patients treated in a prospective randomized trial designed to assess prognosis following MRM or XRT. All were provided a standardized physical therapy program including arm mobilization, shoulder strengthening, prevention and treatment of upper extremity edema, and education about arm function. Patients were evaluated for chest wall pain, arm motion, muscle strength, and edema as determined by circumferential measurements at the wrist, forearm, and arm. Evaluations were performed preoperatively and at yearly anniversaries of their surgery. Women receiving XRT had more chest wall tenderness at 1 and 2 years after surgery than those receiving MRM (p2 less than 0.0001 and p2 = 0.0007 respectively). Those receiving MRM were slower to reach their preoperative range of motion (ROM) (p2 = 0.043). Incidence of muscle weakness was similar in both groups. The few patients with local recurrence of tumor had more upper extremity edema than those who did not recur (p2 = 0.085) at 1 year and (p2 = 0.02) at 2 years. In patients who did not develop local recurrence, those who had received XRT had greater but nonsignificant increases in upper extremity circumferential measures compared with those receiving MRM at any anniversary evaluation. Patients receiving MRM and XRT are likely to have some differences in functional outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Thios study showed responses of sulfated glycoprotein-2 (SGP-2) in the rat hippocampus after deafferenting lesion. SGP-2 is a plasma protein that also occurs in many peripheral tissues. In some circumstances, elevations of SGP-2 mRNA are associated with cell degeneration and responses to injury. This study used entorhinal cortex lesions (ECL) to partially deafferent the hippocampus by damaging the perforant path and to induce synaptic remodeling. SGP-2 mRNA is increased in hippocampal astrocytes after ECL. Western blot analysis of soluble hippocampal proteins identified 3 major forms of rat SGP-2 protein: a precursor (61 kDa) and 2 reduced subunits at 39.5 and 35 kDa. These forms increased at 4 days post ECL ipsilaterally to the lesion. By immunocytochemistry (ICC), SGP-2 showed an increased immunoreactivity on the lesioned side by 2 days post ECL that continued through 14 days post ECL. Besides immunopositive astrocytes, punctate immunochemical reaction products occurred among the degenerating fibers of the perforant path. We conclude that changes of SGP-2 protein in the hippocampus after ECL occur roughly in parallel with increases of SGP-2 mRNA. The punctate immuno-deposits could represent secreted SGP-2 and may be useful as a marker for degenerating pathways.

A hippocampal poly(A) RNA, pADHC-9, was cloned by differential screening of a human hippocampal cDNA library. By RNA blot analysis, pADHC-9 was elevated 2-fold in Alzheimer's disease hippocampus. In situ analyses identified pADHC-9 expression in pyramidal and non-pyramidal cells of the hippocampus and entorhinal cortex. Nucleotide sequence analysis identified pADHC-9 as a potential human homolog of rat sulfated glycoprotein 2 (SGP-2). SGP-2 expression increased in rat hippocampus following experimental lesions that mimic intrinsic neuronal loss and/or deafferentation. The function of pADHC-9 in brain has not been defined, but in serum, a similar protein inhibits complement-dependent cytolysis. Increased expression of pADHC-9 in Alzheimer's disease hippocampus may be a compensatory response mounted to retard a complement-driven neurodegenerative cascade.

Mastectomy is frequently performed after intensive chemotherapy for locally advanced breast cancer. The effects of preoperative chemotherapy on the postoperative course and the timing of subsequent adjuvant therapy, however, have not been defined. We therefore reviewed the perioperative course of 54 patients undergoing mastectomy after combination (CAMFPT) chemotherapy for stage IIIA,B (IIIA - 25 pts; IIIB noninflammatory - 5 pts; IIIB inflammatory-24 patients) breast cancer. A median of 7 cycles (6 months) of chemotherapy was administered preoperatively. Mastectomy was performed a median of 20 days after last chemotherapy; white blood cell count (WBC) and platelet counts returned to normal limits preoperatively. Total mastectomy with or without axillary node dissection was performed in 53 patients, and a Halsted radical mastectomy in 1 patient. Negative margins on breast and/or axillary tissue were achieved in 47 patients (87.0%). Postoperative complications included skin flap necrosis in 8 patients (14.8%), seroma formation in 5 patients (9.3%), and wound infection in 1 patient (1.9%). Median operative blood loss (550 cc), hospital stay (8 days), and duration of wound catheter drainage (6 days) were comparable to published reports for modified radical mastectomy without preoperative chemotherapy. Systemic chemotherapy was resumed a median of 16 days after mastectomy, and radiotherapy started a median of 33 days after mastectomy. These findings indicate that intensive preoperative chemotherapy does not increase the hospital course or the postoperative complications of mastectomy for locally advanced breast cancer. In view of the current interest in treatment of stage I and II breast cancer with preoperative chemotherapy, this information may be useful in their management as well.

Twenty-four above-knee amputees (AKA) treated with rigid plaster dressings were randomized to receive ambulation on pylon within 24 hours of surgery or at time of suture removal. Casts were applied by physical therapists in half of each group, and by a prosthesist in the other half. There were no statistically significant differences among the groups with respect to age, sex, stump length, gait characteristics and wound healing. Time to prescription of final prosthetis was similar in all groups. Specifically, there was no delay in the group ambulated immediately. The immediate ambulators did have significantly greater stump pain requiring more analgesia than the group ambulated after suture removal. Patients with case applied by physical therapists used their prostheses more than patients with cases applied by prosthetists. There was no detectable difference among treatment groups with regard to participation in therapy, acceptance of prosthesis, and psychological status. Recommendation for management of AKA's include: use of rigid dressing; ambulation on pylon after suture removal; utilization of physical therapist for application of rigid dressings and alignment of pylon.

We review the evidence for altered gene expression in Alzheimer's disease brain and identify alternative molecular approaches for isolating additional novel markers. One marker, pADHC-9, was isolated from a human hippocampal cDNA library by differential screening with AD and control cDNA probes. This clone hybridizes to a 2 Kb RNA which is increased 2 fold in AD hippocampus. The deduced amino acid sequence of pADHC-9 codes for a 52 kDAL protein similar to a testicular sulfated glycoprotein secreted by rat Sertoli cells. The normal function of this protein in brain and whether that function is altered in Alzheimer's disease is unknown.

Somatic cell hybrids were constructed between the human papovavirus, BKV, transformed BHK-21 cells and human embryonic kidney cells, the permissive host for BKV using the polyethylene glycol-DMSO cell fusion method. Hybrids were selected to preserve the phenotype of transformation as anchorage independence to allow examination of the synthesis of BKV early gene products, the T proteins. Several hybrid clones which survived the selection procedure demonstrated an enhanced production of the small t or approximately 22 K protein while the viral large T or approximatley 94 K protein was not detectable. It was also determined in this study that BHK-21 cells which are thymidine kinase deficient (TK-) can be stably transformed by BKV and appear to remain enzyme deficient after transformation.

Two cellular proteins (molecular weights: 56,000 and 32,000) were specifically co-immunoprecipitated by simian virus 40 and BK virus t-antigens and by polyoma virus non-T early proteins.

The Tikhoff-Linberg resection is a limb-sparing surgical option to be considered for bony and soft-tissue tumors in and around the proximal humerus and shoulder girdle. Careful selection of patients whose tumor does not involve the neurovascular bundle in the axilla is required. The distal clavicle, upper humerus, and part or all of the scapula are resected. The tumor remains covered by the deltoid muscle plus portions of the muscles that arise from or insert into the resected specimen. In patients with tumors of the proximal humerus a custom prosthesis is used to maintain length and stabilize the distal humerus. Elbow flexion plus stability of the shoulder without the need of an orthosis may be achieved with muscle transfers. Function of the hand and forearm after Tikhoff-Linberg resection should be near normal. Review of results in 10 patients shows no local recurrences and excellent function. The major postoperative problem was nerve palsy. The Tikhoff-Linberg procedure should continue to be used for limb salvage in selected patients with tumors in or around the shoulder girdle.