Differential Responsivity of the Hypothalamic-Pituitary-Adrenal Axis to Glucocorticoid Negative-Feedback and Corticotropin Releasing Hormone in Rats Undergoing Morphine Withdrawal: Possible Mechanisms Involved in Facilitated and Attenuated Stress Responses

Chronic morphine treatment produces profound and long-lasting changes in the pituitary-adrenal responses to stressful stimuli. The purpose of the present study was to explore the mechanisms involved in these altered stress responses. Chronic morphine administration increased basal plasma concentrations of corticosterone and adrenocorticotropic hormone (ACTH), which peaked at 36 h after the final morphine injection and returned to normal levels within 84-h. Whole brain glucocorticoid receptor protein expression was reduced (approximately 70%) in morphine-treated rats 4-h after the final morphine injection and these levels recovered within 16-h. Twelve hours following morphine withdrawal, rats displayed normal ACTH, but potentiated and prolonged corticosterone responses to restraint stress. Both the ACTH and corticosterone responses to restraint in acutely withdrawn rats were insensitive to dexamethasone. Furthermore, acutely withdrawn rats displayed reduced ACTH but prolonged corticosterone responses to peripheral corticotropin releasing hormone (CRH) administration. These findings suggest that the normal ACTH and enhanced corticosterone responses to stress in acutely withdrawn rats involved decreased sensitivity of negative-feedback systems to glucocorticoids, reduced pituitary responsivity to CRH, and enhanced sensitivity of the adrenals to ACTH. Eight days following morphine withdrawal, rats displayed dramatically reduced ACTH, but normal corticosterone responses to restraint stress. These rats displayed enhanced sensitivity to dexamethasone and normal pituitary-adrenal responses to CRH. These data suggest that the reduced ACTH responses to stress in 8-day withdrawal rats involved increased sensitivity of negative-feedback systems to glucocorticoids as well as reduced CRH and/or AVP function in response to stress. Taken together, the results of this study illustrate some of the mechanisms mediating altered stress responsivity in rats that have received chronic morphine treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73727/1/j.1365-2826.2001.00714.x.pd

Is the Faroe Bank Channel overflow hydraulically controlled?

Author Posting. © American Meteorological Society, 2006. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 36 (2006): 2340-2349, doi:10.1175/JPO2969.1.The overflow of dense water from the Nordic Seas through the Faroe Bank Channel (FBC) has attributes suggesting hydraulic control—primarily an asymmetry across the sill reminiscent of flow over a dam. However, this aspect has never been confirmed by any quantitative measure, nor is the position of the control section known. This paper presents a comparison of several different techniques for assessing the hydraulic criticality of oceanic overflows applied to data from a set of velocity and hydrographic sections across the FBC. These include 1) the cross-stream variation in the local Froude number, including a modified form that accounts for stratification and vertical shear, 2) rotating hydraulic solutions using a constant potential vorticity layer in a channel of parabolic cross section, and 3) direct computation of shallow water wave speeds from the observed overflow structure. Though differences exist, the three methods give similar answers, suggesting that the FBC is indeed controlled, with a critical section located 20–90 km downstream of the sill crest. Evidence of an upstream control with respect to a potential vorticity wave is also presented. The implications of these results for hydraulic predictions of overflow transport and variability are discussed.The Faroe Bank Channel experiment was supported by NSF Grant OCE-9906736. JBG gratefully acknowledges the support of the NOAA/ UCAR Climate and Global Change Postdoctoral Program and NSF Grant OCE-9985840. Author Price was supported in part by the U.S. Office of Naval Research through Grant N00014-04-1-0109

Relations between heart failure, ejection fraction, arrhythmia suppression and mortality: Analysis of the Cardiac Arrhythmia Suppression Trial

Objectives.We studied the relations between heart failure, ejection fraction, arrhythmia suppression and mortality.Background.Both left ventricular ejection fraction and functional class of heart failure are strongly associated with mortality after acute myocardial infarction. Both are also related to the presence of ventricular arrhythmias and have been identified as factors related to the ability to suppress ventricular arrhythmias. Little has been reported about the relations between these two factors and arrhythmia suppression or mortality.Methods.Baseline data from the Cardiac Arrhythmia Suppression Trial were used to define several categories of heart failure and to relate both the resulting categories and ejection fraction to arrhythmia suppression and mortality using logistic and survival regression analytic methodologies.Results.Regardless of the prospective baseline definition of heart failure used, the data consistently showed that heart failure was a more powerful predictor of subsequent congestive heart failure events and arrhythmia suppression and was equally powerful in predicting death. However, each variable provided incremental information when included in the prediction model. Heart failure and ejection fraction appeared to be independent predictors of death. Interactions were observed: A low ejection fraction was more predictive of failure of arrhythmia suppression in patients with than without evidence of heart failure before or at baseline; a low ejection fraction was more predictive of subsequent congestive heart failure events in patients without than with evidence of heart failure before or at baseline.Conclusions.Although heart failure as a prognostic feature appears to be somewhat superior to ejection fraction, both are powerful predictors of arrhythmia suppression and cardiac events in patients with ventricular arrhythmia after myocardial infarction. Each provides incremental prediction

Pacific abyssal transport and mixing: Through the Samoan Passage versus around the Manihiki Plateau

Author Posting. © American Meteorological Society, 2019. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 49(6), (2019): 1577-1592, doi:10.1175/JPO-D-18-0124.1.The main source feeding the abyssal circulation of the North Pacific is the deep, northward flow of 5–6 Sverdrups (Sv; 1 Sv ≡ 106 m3 s−1) through the Samoan Passage. A recent field campaign has shown that this flow is hydraulically controlled and that it experiences hydraulic jumps accompanied by strong mixing and dissipation concentrated near several deep sills. By our estimates, the diapycnal density flux associated with this mixing is considerably larger than the diapycnal flux across a typical isopycnal surface extending over the abyssal North Pacific. According to historical hydrographic observations, a second source of abyssal water for the North Pacific is 2.3–2.8 Sv of the dense flow that is diverted around the Manihiki Plateau to the east, bypassing the Samoan Passage. This bypass flow is not confined to a channel and is therefore less likely to experience the strong mixing that is associated with hydraulic transitions. The partitioning of flux between the two branches of the deep flow could therefore be relevant to the distribution of Pacific abyssal mixing. To gain insight into the factors that control the partitioning between these two branches, we develop an abyssal and equator-proximal extension of the “island rule.” Novel features include provisions for the presence of hydraulic jumps as well as identification of an appropriate integration circuit for an abyssal layer to the east of the island. Evaluation of the corresponding circulation integral leads to a prediction of 0.4–2.4 Sv of bypass flow. The circulation integral clearly identifies dissipation and frictional drag effects within the Samoan Passage as crucial elements in partitioning the flow.This work was supported by the National Science Foundation under Grants OCE-1029268, OCE-1029483, OCE-1657264, OCE-1657870, OCE-1658027, and OCE-1657795. We thank the captain, crew, and engineers at APL/UW for their hard work and skill.2020-06-1

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs

Fluorescence characterization of clinically-important bacteria

Healthcare-associated infections (HCAI/HAI) represent a substantial threat to patient health during hospitalization and incur billions of dollars additional cost for subsequent treatment. One promising method for the detection of bacterial contamination in a clinical setting before an HAI outbreak occurs is to exploit native fluorescence of cellular molecules for a hand-held, rapid-sweep surveillance instrument. Previous studies have shown fluorescence-based detection to be sensitive and effective for food-borne and environmental microorganisms, and even to be able to distinguish between cell types, but this powerful technique has not yet been deployed on the macroscale for the primary surveillance of contamination in healthcare facilities to prevent HAI. Here we report experimental data for the specification and design of such a fluorescence-based detection instrument. We have characterized the complete fluorescence response of eleven clinically-relevant bacteria by generating excitation-emission matrices (EEMs) over broad wavelength ranges. Furthermore, a number of surfaces and items of equipment commonly present on a ward, and potentially responsible for pathogen transfer, have been analyzed for potential issues of background fluorescence masking the signal from contaminant bacteria. These include bedside handrails, nurse call button, blood pressure cuff and ward computer keyboard, as well as disinfectant cleaning products and microfiber cloth. All examined bacterial strains exhibited a distinctive double-peak fluorescence feature associated with tryptophan with no other cellular fluorophore detected. Thus, this fluorescence survey found that an emission peak of 340nm, from an excitation source at 280nm, was the cellular fluorescence signal to target for detection of bacterial contamination. The majority of materials analysed offer a spectral window through which bacterial contamination could indeed be detected. A few instances were found of potential problems of background fluorescence masking that of bacteria, but in the case of the microfiber cleaning cloth, imaging techniques could morphologically distinguish between stray strands and bacterial contamination

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far