Left atrial appendage occlusion: What is its role today?

In many patients with paroxysmal or permanent nonvalvular atrial fibrillation and a CHA2DS2-VASc score of 2 or more, warfarin or other newer oral anti-coagulant therapies are contra-indicated, or are not prescribed, for a variety of reasons. These patients are therefore at risk of serious life threatening thrombo-embolic events particularly large stroke. Percutaneous occlusion of the left atrial appendage, the source of the majority of these emboli, is a therapy which should be considered in these patients. There is growing evidence that this procedure is as good as, if not superior in the long term, to chronic warfarin therapy

Pentagastric infusions in patients with panic disorder I. Symptoms and cardiovascular responses

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142733/1/Abelson-Nesse-Penta_Infusions-BioPsych-1994.pd

Impaired contextual modulation of memories in PTSD: an fMRI and psychophysiological study of extinction retention and fear renewal

Post-traumatic stress disorder (PTSD) patients display pervasive fear memories, expressed indiscriminately. Proposed mechanisms include enhanced fear learning and impaired extinction or extinction recall. Documented extinction recall deficits and failure to use safety signals could result from general failure to use contextual information, a hippocampus-dependent process. This can be probed by adding a renewal phase to standard conditioning and extinction paradigms. Human subjects with PTSD and combat controls were conditioned (skin conductance response), extinguished, and tested for extinction retention and renewal in a scanner (fMRI). Fear conditioning (light paired with shock) occurred in one context, followed by extinction in another, to create danger and safety contexts. The next day, the extinguished conditioned stimulus (CS+E) was re-presented to assess extinction recall (safety context) and fear renewal (danger context). PTSD patients showed impaired extinction recall, with increased skin conductance and heightened amygdala activity to the extinguished CS+ in the safety context. However, they also showed impaired fear renewal; in the danger context, they had less skin conductance response to CS+E and lower activity in amygdala and ventral-medial prefrontal cortex compared with combat controls. Control subjects displayed appropriate contextual modulation of memory recall, with extinction (safety) memory prevailing in the safety context, and fear memory prevailing in the danger context. PTSD patients could not use safety context to sustain suppression of extinguished fear memory, but they also less effectively used danger context to enhance fear. They did not display globally enhanced fear expression, but rather showed a globally diminished capacity to use contextual information to modulate fear expression

Natural Resistance to Methotrexate in Human Melanomas

Human melanomas are naturally resistant to methotrexate (MTX). The mechanism of intrinsic drug resistance has been explored in 3 melanoma cell lines not previously exposed to tins agent. All 3 lines exhibited relative MTX resistance with ID50 values of greater than 1 μm. Drug uptake studies were performed over an extracellular concentration range of 0.1 to 10 μm MTX. The uptake was linear over the initial 10min at all concentrations and subsequently reached plateau level only at the 10 μm Concentration. Lineweaver-Burke transformations yielded apparent Km (uptake) values of 1.4 to 5 μm, similar to data obtained from other human cell lines. The level of dihydrofolate reductase (DHFR) in the human melanoma cells ranged between 8.42 to 11.98 pmoles/mg protein. The melanoma DHFR levels are several fold higher than in MTX-sensitive human tumor lines and up to a hundred-fold higher than that measured in human brain tumor cells by our assay. The intrinsic resistance of these melanoma lines has therefore been attributed to elevated intracellular levels of DHFR

Major Depressive Disorder Among Older African Americans, Caribbean Blacks, And Non‐Hispanic Whites: Secondary Analysis Of The National Survey Of American Life

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98298/1/da22041.pd

Shock Temperature of Stainless Steel and a High Pressure - High Temperature Constraint on Thermal Diffusivity of Al_2O_3

Time dependent shock temperatures were measured for stainless steel (SS) films in contact with transparent anvils. The anvil/window material was the same as the driver material so that there would be symmetric heat flow from the sample. Inferred Hugoniot temperatures, T_h , of 5800–7500 K at 232–321 GPa are consistent with previous measurements in SS. Temperatures at the film‐anvil interface (T_i ), which are more directly measured than T_h , indicate that T_i did not decrease measurably during the approximately 250 ns that the shock wave was in Al_2O_3 or LiF anvils. Thus an upper bound is obtained for the thermal diffusivity of Al_2O_3 at the metal/anvil interface at 230 GPa and 6000K of κ≤0.00096 cm_2/s. This is a factor of 17 lower than previously calculated values, resulting in a decrease of the inferred T_h by 730 k. The observed shock temperatures are combined with temperatures calculated from measured Hugoniots and are used to calculate thermal conductivities of Al_2O_3. Also we note that since there was no measurable intensity decrease during the time when the shock wave propagated through the window, we infer from this that Al_2O_3 remained transparent while in the shocked state. Thus sapphire is a good window material to at least 250 GPa for shock temperature measurements for metals

Protocol for a randomized controlled trial examining multilevel prediction of response to behavioral activation and exposure-based therapy for generalized anxiety disorder.

BACKGROUND:Only 40-60% of patients with generalized anxiety disorder experience long-lasting improvement with gold standard psychosocial interventions. Identifying neurobehavioral factors that predict treatment success might provide specific targets for more individualized interventions, fostering more optimal outcomes and bringing us closer to the goal of "personalized medicine." Research suggests that reward and threat processing (approach/avoidance behavior) and cognitive control may be important for understanding anxiety and comorbid depressive disorders and may have relevance to treatment outcomes. This study was designed to determine whether approach-avoidance behaviors and associated neural responses moderate treatment response to exposure-based versus behavioral activation therapy for generalized anxiety disorder. METHODS/DESIGN:We are conducting a randomized controlled trial involving two 10-week group-based interventions: exposure-based therapy or behavioral activation therapy. These interventions focus on specific and unique aspects of threat and reward processing, respectively. Prior to and after treatment, participants are interviewed and undergo behavioral, biomarker, and neuroimaging assessments, with a focus on approach and avoidance processing and decision-making. Primary analyses will use mixed models to examine whether hypothesized approach, avoidance, and conflict arbitration behaviors and associated neural responses at baseline moderate symptom change with treatment, as assessed using the Generalized Anxiety Disorder-7 item scale. Exploratory analyses will examine additional potential treatment moderators and use data reduction and machine learning methods. DISCUSSION:This protocol provides a framework for how studies may be designed to move the field toward neuroscience-informed and personalized psychosocial treatments. The results of this trial will have implications for approach-avoidance processing in generalized anxiety disorder, relationships between levels of analysis (i.e., behavioral, neural), and predictors of behavioral therapy outcome. TRIAL REGISTRATION:The study was retrospectively registered within 21 days of first participant enrollment in accordance with FDAAA 801 with ClinicalTrials.gov, NCT02807480. Registered on June 21, 2016, before results

Automated grading system for evaluation of ocular redness associated with dry eye

Background: We have observed that dry eye redness is characterized by a prominence of fine horizontal conjunctival vessels in the exposed ocular surface of the interpalpebral fissure, and have incorporated this feature into the grading of redness in clinical studies of dry eye. Aim To develop an automated method of grading dry eye-associated ocular redness in order to expand on the clinical grading system currently used. Methods: Ninety nine images from 26 dry eye subjects were evaluated by five graders using a 0–4 (in 0.5 increments) dry eye redness (Ora Calibra™ Dry Eye Redness Scale [OCDER]) scale. For the automated method, the Opencv computer vision library was used to develop software for calculating redness and horizontal conjunctival vessels (noted as “horizontality”). From original photograph, the region of interest (ROI) was selected manually using the open source ImageJ software. Total average redness intensity (Com-Red) was calculated as a single channel 8-bit image as R – 0.83G – 0.17B, where R, G and B were the respective intensities of the red, green and blue channels. The location of vessels was detected by normalizing the blue channel and selecting pixels with an intensity of less than 97% of the mean. The horizontal component (Com-Hor) was calculated by the first order Sobel derivative in the vertical direction and the score was calculated as the average blue channel image intensity of this vertical derivative. Pearson correlation coefficients, accuracy and concordance correlation coefficients (CCC) were calculated after regression and standardized regression of the dataset. Results: The agreement (both Pearson’s and CCC) among investigators using the OCDER scale was 0.67, while the agreement of investigator to computer was 0.76. A multiple regression using both redness and horizontality improved the agreement CCC from 0.66 and 0.69 to 0.76, demonstrating the contribution of vessel geometry to the overall grade. Computer analysis of a given image has 100% repeatability and zero variability from session to session. Conclusion: This objective means of grading ocular redness in a unified fashion has potential significance as a new clinical endpoint. In comparisons between computer and investigator, computer grading proved to be more reliable than another investigator using the OCDER scale. The best fitting model based on the present sample, and usable for future studies, was C4=−12.24+2.12C2HOR+0.88C2RED:C4 is the predicted investigator grade, and C2HOR and C2RED are logarithmic transformations of the computer calculated parameters COM-Hor and COM-Red. Considering the superior repeatability, computer automated grading might be preferable to investigator grading in multicentered dry eye studies in which the subtle differences in redness incurred by treatment have been historically difficult to define

The effects of central cholecystokinin receptor blockade on hypothalamic-pituitary-adrenal and symptomatic responses to overnight withdrawal from alprazolam

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142739/1/Abelson-Nesse-alprazolam-BioPsych-1995.pd

Comparing women's financial costs of induced abortion at a facility vs. seeking treatment for complications from unsafe abortion in Zambia.

Although abortion is legal in Zambia under a variety of broad conditions, unsafe abortion remains common. The purpose of this project was to compare the financial costs for women when they have an induced abortion at a facility, with costs for an induced abortion outside a facility, followed by care for abortion-related complications. We gathered household wealth data at one point in time (T1) and longitudinal qualitative data at two points in time (T1 and T2, three-four months later), in Lusaka and Kafue districts, between 2014 and 2015. The data were collected from women (n = 38) obtaining a legal termination of pregnancy (TOP), or care for unsafe abortions (CUA). The women were recruited from four health facilities (two hospitals and two private clinics, one of each per district). At T2, CUA cost women, on average, 520 ZMW (USD 81), while TOP cost women, on average, 396 ZMW (USD 62). About two-thirds of the costs had been incurred by T1, while an additional one-third of the total costs was incurred between T1 and T2. Women in all three wealth tertiles sought a TOP in a health facility or an unsafe abortion outside a facility. Women who obtained CUA tended to be further removed from the money that was used to pay for their abortion care. Women's financial dependence leaves them unequipped to manage a financial shock such as an abortion. Improved TOP and post-abortion care are needed to reduce the health sequelae women experience after both types of abortion-related care