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A wide variety of speech processing strategies for multichannel auditory prostheses were compared in studies of two patients implanted with the UCSF electrode array. Each strategy was evaluated using tests of vowel and consonant confusions, with and without lipreading. Included among the strategies were the compressed analog processor of the present UCSF/Storz prosthesis and a group of interleaved pulses processors in which the amplitudes of nonsimultaneous pulses code the spectral variations of speech. For these patients, each with indications of poor nerve survival, test scores were significantly higher with the interleaved pulses processors. We believe this superior performance was a result of 1. the substantial release from channel interactions provided by nonsimultaneous stimuli and 2. a fast enough rotation among the channels to support adequate temporal and spectral resolution of perceived speech sounds. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in the April 7, 1989 issue of the 'Journal of the American Medical Association,' noting the adequacy of continuous hyperchlorination of plumbing systems in the prevention of colonization and replication of Legionella in potable water.

Introduction: Acute inflammatory demyelinating polyneuropathy (AIDP) is characterized by progressive, mild sensory symptoms and progressive areflexic weakness. It typically follows a gastrointestinal or respiratory infection but has rarely been described after acute viral hepatitis., Case Report: This is the case of a 59-year-old male who presented to the emergency department after acutely developing progressive neurologic symptoms following a hospitalization for acute hepatitis A. Cerebrospinal fluid analysis revealed albuminocytologic dissociation, and cervical spine magnetic resonance imaging revealed nerve root enhancement., Discussion: The patient was diagnosed with AIDP, which is the most common subtype of Guillain-Barré syndrome in the United States and Europe. There have been few previously reported cases of AIDP following acute hepatitis A infection.

Introduction: Patient safety (PS) is one of the most important priorities in modern healthcare systems. Unfortunately, PS education is limited in many medical school curricula. Our objective was to implement an innovative curriculum to introduce third-year medical students on their pediatric clerkship to PS concepts and domains, and to provide a safe environment to discuss lapses in PS that they identified while caring for patients., Methods: At the start of the pediatric clerkship, students were introduced to the curriculum, instructed to identify a lapse of PS, and to submit a description and analysis of the lapse using the SAFE framework (S = Safety concern, A = Action taken, F = Failure, linked to safety domains, E = Effects on patient outcome). Two sessions, 90-mins each, were conducted every clerkship during which there was a brief didactic presentation, each student presented their case, and the case discussed by students and faculty., Results: Over 19 months, 75 students participated. The most common PS themes identified were Communication (57% of cases), Human factors (39%), and System issues (37%). Anonymous written feedback was obtained; learners reported improved knowledge and ability to identify lapses in PS and to propose potential solutions to prevent similar future events. They expressed a desire for additional PS and quality improvement education., Discussion: Our results show that third-year medical students are able to identify lapses in PS and able to propose solutions. This aligns with the Association of American Medical Colleges (AAMC) goals of entrustable professional activities (EPA) 13. We intend to expand the curriculum to other third-year core clerkships., Competing Interests: Declaration of conflicting interests:MA declares that she is a shareholder in CGN Global. There are no other potential conflicts of interest to disclose.

Progesterone receptor (PR), a member of the nuclear receptor superfamily, is a key regulator of several processes in reproductive function. We have studied the dynamics of the interaction of PR with a natural target promoter in living cells through the use of fluorescence recovery after photobleaching (FRAP) analysis and also have characterized the dynamics of the interaction of PR with the mouse mammary tumor virus (MMTV) promoter reconstituted into chromatin in vitro. In photobleaching experiments, PR in the presence of the agonist R5020 exhibits rapid exchange with the MMTV promoter in living cells. Two PR antagonists, RU486 and ZK98299, have opposite effects on receptor dynamics in vivo. In the presence of RU486, PR binds to the promoter and is exchanged more slowly than the agonist-activated receptor. In contrast, PR bound to ZK98299 is not localized to the promoter and exhibits higher mobility in the nucleoplasm than the agonist-bound receptor. Significantly, PR bound to R5020 or RU486 can recruit the SWI/SNF chromatin remodeling complex to the promoter, but PR activated with ZK98299 cannot. Furthermore, we found ligand-specific active displacement of PR from the MMTV promoter during chromatin remodeling in vitro and conclude that the interaction of PR with chromatin is highly dynamic both in vivo and in vitro. We propose that factor displacement during chromatin remodeling is an important component of receptor mobility and that ligand-specific interactions with remodeling complexes can strongly influence receptor nuclear dynamics and rates of exchange with chromatin in living cells.

An ultrafast UV laser crosslinking assay has provided novel insights into the progression of the SWI/SNF-mediated chromatin-remodeling reaction and transcription factor binding in real time. We demonstrate site-specific crosslinking between the glucocorticoid receptor (GR), the hSWI/SNF chromatin-remodeling complex, and the mouse mammary tumor virus (MMTV) promoter assembled in an array of correctly positioned nucleosomes. GR first demonstrates rapid binding to the promoter and then is actively displaced from the template during the remodeling reaction. This displacement reaction requires the hSWI/SNF complex and ATP, is specific to the nucleoprotein template, and is accompanied by a core histone rearrangement. The hSWI/SNF complex associates with random positions on the chromatin template in the absence of GR but is recruited specifically to the B/C region when GR is included. These results indicate that enhancement of hSWI/SNF-mediated factor accessibility, a hallmark of chromatin remodeling, is in some cases transient, reversible, and periodic.

Chromatin remodeling by the glucocorticoid receptor (GR) is associated with activation of transcription at the mouse mammary tumor virus (MMTV) promoter. We reconstituted this nucleoprotein transition with chromatin assembled on MMTV DNA. The remodeling event was ATP dependent and required either a nuclear extract from HeLa cells or purified human Swi/Snf. Through the use of a direct interaction assay (magnetic bead pull-down), we demonstrated recruitment of human Swi/Snf to MMTV chromatin by GR. Unexpectedly, we found that GR is actively displaced from the chromatin template during the remodeling process. ATP-dependent GR displacement was reversed by the addition of apyrase and was specific to chromatin templates. The disengagement reaction could also be induced with purified human Swi/Snf. Although GR apparently dissociated during chromatin remodeling by Swi/Snf, it participated in binding of the secondary transcription factor, nuclear factor 1. These results are paralleled by a recent discovery that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment in living cells. Both the in vitro and in vivo results are consistent with a dynamic model (hit and run) in which GR first binds to chromatin after ligand activation, recruits a remodeling activity, facilitates transcription factor binding, and is simultaneously lost from the template.

Introduction: Recent changes by the Health Care Financing Administration (HCFA) have resulted in decreased Medicare support for emergency medicine (EM) residencies., Objective: To determine the effects of reduced graduate medical education (GME) funding support on residency size, resident rotations, and support for a fourth postgraduate year (PGY) of training and for residents with previous training., Methods: A 36-question survey was developed by the Council of Emergency Medicine Residency Directors (CORD) committee on GME funding and sent to all 122 EM program directors (PDs). Responses were collected by the Society for Academic Emergency Medicine (SAEM) office and blinded with respect to the institution., Results: Of 122 programs, 109 (89%) responded, of which 78 were PGY 1-3 programs, 19 were PGY 2-4, and 12 were PGY 1-4. The PDs were asked specifically whether there were changes in program size due to changes in Medicare reimbursement. Although few programs (12%) decreased their size or planned to decrease their size, 39% had discussions regarding decreasing their size. Thirty percent of the PDs responded that other programs at their institution had already decreased their size; 26% of the PDs had problems with financing outside rotations; and 24% had a decrease in off-service residents in their emergency departments (EDs). Only seven (6%) of programs paid residents from practice plan dollars, while most (82%) were fully supported by federal GME funding. Nearly all four-year programs (97%) received full resident salary support from their institutions and 77% of programs accept residents with previous training., Conclusions: Nearly all EM programs are fully supported by their institutions, including the fourth postgraduate year. Most programs take residents with previous training. Although few programs have reduced their size, many are discussing this. Many programs have had difficulty with funding off-service rotations and many have had decreased numbers of off-service residents in their EDs. Recent GME funding changes have had adverse effects on EM residency programs.

Regulatory agencies increasingly require hospitals to provide evidence of employee compliance with mandated competencies. This article provides information on the innovative use of Intranet-delivered computer-based training as an effective and efficient method of providing and documenting training to meet regulatory requirements. The authors discuss the advantages and disadvantages of Intranet-based instructional modules, instruction on developing Intranet-based modules, and an example of a healthcare system that is effectively using intranet-based modules for competency training.

The glucocorticoid receptor interacting protein-1 (GRIP1) is a member of the steroid receptor coactivator (SRC) family of transcriptional regulators. Green fluorescent protein (GFP) fusions were made to full-length GRIP1, and a series of GRIP1 mutants lacking the defined regulatory regions and the intracellular distribution of these proteins was studied in HeLa cells. The distribution of GRIP1 was complex, ranging from diffuse nucleoplasmic to discrete intranuclear foci. Formation of these foci was dependent on the C-terminal region of GRIP1, which contains the two characterized transcriptional activation domains, AD1 and AD2. A subpopulation of GRIP1 foci associate with ND10s, small nuclear bodies that contain several proteins including PML, SP100, DAXX, and CREB-binding protein (CBP). Association with the ND10s is dependent on the AD1 of GRIP1, a region of the protein previously described as a CBP-interacting domain. The GRIP1 foci are enriched in components of the 26S proteasome, including the core 20S proteasome, PA28alpha, and ubiquitin. In addition, the irreversible proteasome inhibitor lactacystin induced an increase in the total fluorescence intensity of the GFP-GRIP1 expressing cells, demonstrating that GRIP1 is degraded by the proteasome. These findings suggest the intriguing possibility that degradation of GRIP1 by the 26S proteasome may be a key component of its regulation.

Activated steroid receptors induce chromatin remodeling events in the promoters of some target genes. We previously reported that transiently expressed progesterone receptor (PR) cannot activate mouse mammary tumor virus (MMTV) promoter when it adopts the form of ordered chromatin. However, when expressed continuously, the PR acquires this ability. In this study we explored whether this gain of function occurs through alterations in nucleoprotein structure at the MMTV promoter or through changes in receptor status. We observed no major structural differences at the MMTV promoter in the presence of constitutively expressed PR and found its mechanism of activation to be very similar to that of the glucocorticoid receptor (GR). However, a systematic comparison of the functional behavior of the transiently and constitutively expressed PR elucidated significant differences. The transiently expressed PR is activated in the absence of ligand by cAMP and by components in FBS and has significantly increased sensitivity to progestins. In contrast, the constitutively expressed PR is refractory to activation by cAMP and serum and has normal sensitivity to its ligand. In addition, while the PR is localized to the nucleus in both cases, a significant fraction of the transiently expressed PR is tightly bound to the nucleus even in the absence of ligand, while the majority of constitutively expressed PR is not. These results strongly suggest that the PR undergoes processing in the cell subsequent to its initial expression and that this processing is important for various aspects of its function, including its ability to productively interact with target genes that require chromatin remodeling for activation.

The majority of skin trauma incidents cause minor injury that can be treated effectively in the outpatient setting. A new approach to the closure of skin lacerations using tissue adhesive is presented and the current management of abrasions, blisters, burns, skin tears, and subungual hematomas are reviewed. An overview of wound dressings is provided to assist in obtaining the optimal wound-healing environment.

Steroid receptors bind to site-specific response elements in chromatin and modulate gene expression in a hormone-dependent fashion. With the use of a tandem array of mouse mammary tumor virus reporter elements and a form of glucocorticoid receptor labeled with green fluorescent protein, targeting of the receptor to response elements in live mouse cells was observed. Photobleaching experiments provide direct evidence that the hormone-occupied receptor undergoes rapid exchange between chromatin and the nucleoplasmic compartment. Thus, the interaction of regulatory proteins with target sites in chromatin is a more dynamic process than previously believed.

Methemoglobinemia is a rare cause of cyanosis in pediatric patients. A 16-month-old male presented to the Emergency Department cyanotic and short of breath after ingestion of a hair-care-equipment cleaning solution. After calling the salon and consulting Poisindex, the substance was found to be Mar-V-cide, containing 20% Hyamine 3500, 50% cationic detergents, 20% isopropyl alcohol, and 1% sodium nitrite, which caused the methemoglobinemia in this case. Initial pulse oximetry on room air was 72% and improved minimally with supplemented oxygen. The patient's methemoglobin level was 63%. Methylene blue was administered (2 mg/kg intravenously), and the patient rapidly improved. Nitrates occur in high concentrations in some food and water. Infants are particularly susceptible to chronic nitrate-induced methemoglobinemia because of their low stomach acid production, large numbers of nitrite-reducing bacteria, and the relatively easy oxidation of fetal hemoglobin. Acute nitrite toxicity results from industrial exposure, accidental ingestion (e.g., abuse of organic nitrites as an aphrodisiac, especially in the male homosexual population), and suicidal ingestion. Methemoglobinemia may occur in a number of drug or chemical ingestions, but a comprehensive review of the literature failed to identify a similar reported case.

This paper presents a theory on which to base intervention research in the construction industry, along with a hypothetical case study involving construction painters. The hypothetical case is based on data from research in a three-state study of construction painters currently under way. Difficulties facing researchers who conduct research in construction are described. Advantages of the intervention research design for construction are discussed.

New strategies for representing acoustic information with multichannel cochlear implants have produced substantial improvements in speech recognition for implant users. This report reviews within-subject comparison of a new continuous interleaved sampling (CIS) strategy with a compressed analog (CA) strategy used in a standard clinical device. In general, the comparison show higher levels of open-set speech recognition with CIS for each of the 11 subjects studied. Data on the importance of the patients variable in determining outcomes with cochlear implants are presented. A brief description of another new strategy, the spectral maxima sound processor (SMSP) strategy is given as well as information on the availability of CIS in various implant systems.

Removal of an acoustic neuroma using the translabyrinthine approach has previously been considered "incompatible" with hearing preservation. By modifying the approach and preventing the loss of endolymph, we have successfully removed two intracanalicular acoustic neuromas that originated from the inferior vestibular nerves, and preserved serviceable hearing in the ears operated on. This report represents the preliminary findings using this particular technique in the management of intracanalicular acoustic neuromas.

Within-subjects comparisons of processing strategies for cochlear implants are reviewed. Compressed analog strategies were compared to interleaved pulses strategies in tests with one group of 8 subjects, and to continuous interleaved sampling strategies in tests with another group of 11 subjects. The tests included open-set recognition of words and sentences. The results show that, while different strategies may produce quite different outcomes across subjects, individual performances with one processing strategy are significantly correlated with those of alternative strategies. These findings emphasize the importance of patient variables in determining outcomes across a variety of prosthesis designs.

Two approaches for representing speech information with multichannel cochlear prostheses are being compared in tests with implant patients. Included in these studies are the compressed analog (CA) approach of a standard clinical device and research processors utilizing continuous interleaved sampling (CIS). Initial studies have been completed with nine subjects, seven of whom were selected on the basis of excellent performance with the Ineraid clinical processor, and the remaining two for their relatively poor performance with the same device. The tests include open-set recognition of words and sentences. Every subject has obtained a higher score--or repeated a score of 100% correct--on every test when using a CIS processor. These results are discussed in terms of their implications for processor design.

The mouse mammary tumor virus (MMTV) promoter attains a phased array of six nucleosomes when introduced into rodent cells. This architecture excludes nuclear factor 1/CCAAT transcription factor (NF1/CTF) from the promoter before glucocorticoid treatment and hormone-dependent access of nucleolytic agents to promoter DNA. In contrast, when the promoter was transiently introduced into cells, NF1/CTF was bound constitutively and nucleolytic attack was hormone-independent. Thus, induction at this promoter was a bimodal process involving receptor-dependent remodeling of chromatin that allows NF1/CTF loading and direct receptor-mediated recruitment of additional transcription factors.

The POMC gene is expressed predominantly in the anterior pituitary. The high level of POMC transcription in this tissue is modulated by peptide hormones and repressed by glucocorticoids. In this present study we have investigated promoter elements required for the high basal transcription and glucocorticoid repression using transient transfection and in vitro transcription assays. We first determined that the region between -77 to -51 of the promoter, which has previously been shown to harbor a glucocorticoid receptor-binding site, is required for high basal expression both in vivo and in vitro. This promoter domain is also required for glucocorticoid repression of transcription in vivo. Two site-directed mutants within this area both decreased basal transcription, but were fully repressed by glucocorticoids, implying that the -77 to -51 region is a complex regulatory region harboring separable basal and glucocorticoid-repressible elements. Electrophoretic mobility shift and exonuclease III footprinting analysis revealed the existence of two factors that bind in this region. We also examined the effect of broad promoter deletions on basal expression and glucocorticoid repression. These experiments revealed that the region between -480 and -320 is also required for glucocorticoid repression. Taken together, the data suggest a model in which high basal transcription is generated by direct interaction of factors binding between -480 to -320 and -77 to -51. Glucocorticoid repression could occur by direct receptor disruption of these interactions.

HIGH levels of speech recognition have been achieved with a new sound processing strategy for multielectrode cochlear implants. A cochlear implant system consists of one or more implanted electrodes for direct electrical activation of the auditory nerve, an external speech processor that transforms a microphone input into stimuli for each electrode, and a transcutaneous (rf-link) or percutaneous (direct) connection between the processor and the electrodes. We report here the comparison of the new strategy and a standard clinical processor. The standard compressed analogue (CA) processor presented analogue waveforms simultaneously to all electrodes, whereas the new continuous interleaved sampling (CIS) strategy presented brief pulses to each electrode in a nonoverlapping sequence. Seven experienced implant users, selected for their excellent performance with the CA processor, participated as subjects. The new strategy produced large improvements in the scores of speech reception tests for all subjects. These results have important implications for the treatment of deafness and for minimal representations of speech at the auditory periphery.

Comparisons of analog and pulsatile coding strategies for multichannel cochlear prostheses are reviewed. The results are related to design considerations for pediatric implants, including efficacy, safety, ease of fitting, and access to future improvements.

This study evaluated risk factors for injurious and noninjurious slips, trips, and falls among painters and investigated the hypothesis that exposure to solvents influenced the risk of such accidents. The data were collected longitudinally over an 11 month period. Weekly self-administered questionnaires detailed paint solvent exposure; work-related slips, trips, and falls (STFs); and potentially hazardous job tasks and environmental conditions. An initial questionnaire ascertained personal data, such as age, solvent exposure history, and alcohol consumption. During the study, 2,088 person-weeks of data were collected. Some participants provided many weeks of data, while others responded sporadically. Exposure to potentially hazardous environmental conditions was significantly related to the occurrence of STFs during a week. Several measures of solvent exposure were evaluated for their effect on STFs. Low solvent exposure during a week significantly increased the occurrence of slips, trips, and falls compared to no exposure. Moderate and high weekly exposure were not associated with increased risk, however. Week-to-week variability in the amount of solvent exposure was a strong positive predictor of STFs. Further analysis showed that both increases and decreases in solvent exposure between the preceding 2 weeks and the week of the STF were positively related to the risk of such events. The strongest effect was observed for exposure increases over the preceding 2 weeks. Overall, the results suggest that solvent exposure variability may increase accident risk, and possible explanations are explored.