Cosmic ray isotope measurements with a new Cerenkov X total energy telescope

Measurements of the isotopic composition of cosmic nuclei with Z = 7-20 are reported. These measurements were made with a new version of a Cerenkov x total E telescope. Path length and uniformity corrections are made to all counters to a RMS level 1%. Since the Cerenkov counter is crucial to mass measurements using the C x E technique - special care was taken to optimize the resolution of the 2.4 cm thick Pilot 425 Cerenkov counter. This counter exhibited a beta = 1 muon equivalent LED resolution of 24%, corresponding to a total of 90 p.e. collected at the 1st dynodes of the photomultiplier tubes

Cosmic ray charge and energy spectrum measurements using a new large area Cerenkov x dE/dx telescope

In September, 1981, a new 0.5 square meter ster cosmic ray telescope was flown to study the charge composition and energy spectrum of cosmic ray nuclei between 0.3 and 4 GeV/nuc. A high resolution Cerenkov counter, and three dE/dx measuring scintillation counters, including two position scintillators were contained in the telescope used for the charge and energy spectrum measurements. The analysis procedures did not require any large charge or energy dependent corrections, and absolute fluxes could be obtained to an accuracy approximately 5%. The spectral measurements made in 1981, at a time of extreme solar modulation, could be compared with measurements with a similar telescope made by our group in 1977, at a time of minimum modulation and can be used to derive absolute intensity values for the HEAO measurements made in 1979 to 80. Using both data sets precise energy spectra and abundance ratios can be derived over the entire energy range from 0.3 to greater than 15 GeV/nuc

Paging Doctor Google! Heuristics vs. technology

The most dramatic development in medical decision-making technology has been the advent of the Internet. This has had an impact not only on clinicians, but has also become an important resource for patients who often approach their doctors with medical information they have obtained from the Internet.  Increasingly, medical students, residents and attending physicians have been using the Internet as a tool for diagnosing and treating disease. Internet-based resources that are available take various forms, including informational websites, online journals and textbooks, and social media.  Search engines such as Google have been increasingly used to help in making diagnoses of disease entities. Do these search methods fare better than experienced heuristic methods? In a small study, we examined the comparative role of heuristics versus the 'Google' mode of thinking. Internal medicine residents were asked to “google” key words to come up with a diagnosis. Their results were compared to experienced nephrology faculty and fellows in training using heuristics and no additional help of internet. Overall, with the aid of Google, the novices (internal medicine residents) correctly diagnosed renal diseases less often than the experts (the attendings) but with the same frequency as the intermediates (nephrology fellows).  However, in a subgroup analysis of both common diseases and rare diseases, the novices correctly diagnosed renal diseases less often than the experts but more often than the intermediates in each analysis.  The novices correctly diagnosed renal diseases with the same frequency as nephrology fellows in training

A new method for studying human polycystic kidney disease epithelia in culture

A new method for studying human polycystic kidney disease epithelia in culture. Human polycystic kidney disease (PKD) epithelia were successfully grown in culture and expressed abnormal characteristics. Cysts lining epithelia of superficial and deep cysts were microdissected and compared to individual normal human proximal straight tubules (PST) and cortical collecting tubules (CCT) grown in defined media. PKD cyst epithelia differed from normal renal tubular epithelia in growth patterns and structural and functional properties. PKD epithelia grew more rapidly and showed cyst–like areas in otherwise confluent monolayers. Polygonal and elongate cells contained an epithelial–specific cytokeratin antigen and had polarized morphology. An extremely abnormal basement membrane morphology was seen and consisted of some banded collagen and numerous unique blebs or spheroids. These blebs were apparently extruded from intracellular vacuoles and stained with ruthenium red, suggesting a proteoglycan component. Cytochemistry of marker enzymes demonstrated the presence of NaK-ATPase and alkaline phosphatase, but a lack of γ-glutamyl transpeptidase. The response of adenylate cyclase activity to vasopressin, parathyroid hormone, and forskolin was significantly diminished in PKD cells as compared to PST and CCT. These studies suggest a defect in cell growth and basement membrane synthesis in human PKD. Cultured PKD epithelia provide a new tool for the study of the pathogenesis of this disease

Factors determining renal response to water immersion in non-excretor cirrhotic patients

Factors determining renal response to water immersion in non-excretor cirrhotic patients. Non-excretor cirrhotic patients, defined by their inability to normally excrete a standard water load, display variable responses to head–out water immersion. The hemodynamic, hormonal, and renal functional status of fifteen such patients were analyzed relative to water excretion during head-out water immersion. Group 1 patients (N = 7) all excreted less than 40% of the water load during immersion, whereas excretion was greater than 40% in all eight patients in Group 2. Group 1 patients, when compared with Group 2, had more ascites, more diuretic resistance, lower serum sodium concentration (125 ± 2 vs. 130 ± 1 mEq/liter, P < 0.05), and more impaired baseline water excretion (12.9 ± 1.2 vs. 35.9 ± 5.9% of water load in 5 hr, P < 0.005). Systemic hemodynamic responses to water immersion were similar in both groups. Glomerular filtration rate and renal plasma flow were significantly more impaired in Group 1 patients (inulin clearance 28 ± 6 vs. 62 ± 9 ml/min/1.73m2, P < 0.05; para-aminohippurate clearance 212 ± 35 vs. 357 ± 37 ml/min, P < 0.05). Concentrations of plasma vasopressin (1.7 ± 0.5 vs. 0.8 ± 0.1 pg/ml, P < 0.05), renin (8.6 ± 1.7 vs. 3.8 ± 0.9 ng/ml/hr, P < 0.05), aldosterone (82 ± 14 vs. 39 ± 10 ng/dl, P < 0.05) and norepinephrine (1155 ± 183 vs. 603 ± 126 pg/ml, P < 0.05) were all significantly higher in Group 1 than Group 2 patients during water immersion. Thus, non-excretor cirrhotic patients are not homogenous and appear to comprise a spectrum with those patients in whom water excretion is most impaired, having tense ascites, diuretic resistance, lower serum sodium concentrations, more impaired renal function, and more marked abnormalities in the hormonal markers of decreased effective blood volume

Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls

Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cellâ mediated monoarticular arthritis in female Lewis rats. Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukinâ 1 (ILâ 1) and tumor necrosis factor α (TNFâ α) and that the early phase of swelling is neutrophilâ dependent. Neutrophil depletion or passive immunization with antibodies to Pâ selectin or macrophage inflammatory proteinâ 2 reduced the intensity of ankle edema and the influx of neutrophils. After the first few days, however, the arthritic response is mediated primarily by mononuclear cells. Joint tissues showed upâ regulation of mRNA for monocyte chemotactic proteinâ 1 (MCPâ 1), which could be inhibited in part by antiâ ILâ 4; treatment of rats with antibodies to ILâ 4 or MCPâ 1 significantly suppressed development of ankle edema and histopathological evidence of inflammation. Antibodies to interferonâ γ or ILâ 10 had no effect. Treatment with antiâ MCPâ 1 also suppressed influx of 111Inâ labeled T cells into the ankle joint. These data suggest that the late, mononuclearâ dependent phase of SCWâ induced arthritis in female Lewis rats requires cytokines that upâ regulate MCPâ 1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint. J. Leukoc. Biol. 63: 359â 363; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142294/1/jlb0359.pd

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Patients First:Toward a Patient-Centered Instrument to Measure Impact of Chronic Pain

Background. Numerous instruments are available to measure the impact of chronic pain, yet most have been developed with little or no patient involvement. This study seeks to start bridging that gap by determining which health aspects or attributes (to be included in a future instrument) are considered most important by people with chronic pain. Objective. The goal of this study was to reveal which attributes reflecting impact of chronic pain are considered most important by people with chronic pain and to analyze differences in importance according to gender, age categories, diagnostic subgroups, and pain intensity categories. Design. This study used a sequential explanatory mixed-methods design: literature search, focus group meetings, and online survey. Methods. First, a literature search was performed to identify the attributes in existing instruments. In 68 instruments meeting inclusion criteria, 155 unique attributes were identified, 85 of which remained after applying the exclusion criteria. Second, 2 focus group meetings, with 6 and 4 patients, respectively, were held to verify that no attributes had been missed. Three attributes were subsequently added. Third, individuals with chronic pain were then sent an online survey through several patient organizations. Results. A total of 939 patients were asked to select the 8 attributes they deemed most important, which resulted in the following list: fatigue, social life, cramped muscles, sleeping, housekeeping, concentration, not being understood, and control over pain. The importance assigned to these 8 attributes varied slightly according to age, gender, and diagnostic subgroup. Limitations. Participation rate could not be established because of the online survey. Conclusions. Attributes reflecting impact of chronic pain deemed most important by patients are revealed. Importance of impact differs according to subgroups. The "patients-first" methodology used here revealed attributes that were not comprehensively covered in currently available instruments for measuring the impact of chronic pain

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9 ± 1.4 and 1.8 ± 0.3, resp., versus 1.8 ± 0.5, P > 0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08 ± 0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline 0.49 ± 0.92, 95% confidence interval −0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice

ECTACI: European Climatology and Trend Atlas of Climate Indices (1979–2017)

A fundamental key to understanding climate change and its implications is the availability of databases with wide spatial coverage, over a long period of time, with constant updates and high spatial resolution. This study describes a newly gridded data set and its map viewer “European Climatology and Trend Atlas of Climate Indices” (ECTACI), which contains four statistical parameters (climatology, coefficient of variation, slope, and significant trend) from 125 standard climate indices for the whole Europe at 0.25° grid intervals from 1979 to 2017 at various temporal scales (monthly, seasonal, and annual). In addition, this study shows, for the first time, the general trends of a wide variety of updated standard climate indices at seasonal and annual scales for the whole of Europe, which could be a useful tool for climate analysis and its impact on different sectors and socioeconomic activities. The data set and ECTACI map viewer are available for free (http://ECTACI.csic.es/)