Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery.

Development of a hardened THz energy meter for use on the kilojoule-scale, short-pulse OMEGA EP laser.

A highly adaptable and robust terahertz (THz) energy meter is designed and implemented to detect energetic THz pulses from high-intensity (>1018 W/cm2) laser-plasma interactions on the OMEGA EP. THz radiation from the laser driven target is detected by a shielded pyrometer. A second identical pyrometer is used for background subtraction. The detector can be configured to detect THz pulses in the 1 mm to 30 µm (0.3- to 10-THz) range and pulse energies from joules to microjoules via changes in filtration, aperture size, and position. Additional polarization selective filtration can also be used to determine the THz pulse polarization. The design incorporates significant radiation and electromagnetic pulse shielding to survive and operate within the OMEGA EP radiation environment. We describe the design, operational principle, calibration, and testing of the THz energy meter. The pyrometers were calibrated using a benchtop laser and show linear sensitivity to up to 1000 nJ of absorbed energy. The initial results from four OMEGA EP THz experiments detected up to ∼15µJ at the detector, which can correspond to hundreds of mJ depending on THz emission and reflection models.

A knock-on deuteron imager for measurements of fuel and hotspot asymmetry in direct-drive inertial confinement fusion implosions (invited).

A knock-on deuteron imager (KoDI) has been implemented to measure the fuel and hotspot asymmetry of cryogenic inertial confinement fusion implosions on OMEGA. Energetic neutrons produced by D-T fusion elastically scatter ("knock on") deuterons from the fuel layer with a probability that depends on ρR. Deuterons above 10 MeV are produced by near-forward scattering, and imaging them is equivalent to time-integrated neutron imaging of the hotspot. Deuterons below 6 MeV are produced by a combination of side scattering and ranging in the fuel, and encode information about the spatial distribution of the dense fuel. The KoDI instrument consists of a multi-penumbral aperture positioned 10-20 cm from the implosion using a ten-inch manipulator and a detector pack at 350 cm from the implosion to record penumbral images with magnification of up to 35×. Range filters and the intrinsic properties of CR-39 are used to distinguish different charged-particle images by energy along the same line of sight. Image plates fielded behind the CR-39 record a 10 keV x-ray image using the same aperture. A maximum-likelihood reconstruction algorithm has been implemented to infer the source from the projected penumbral images. The effects of scattering and aperture charging on the instrument point-spread function are assessed. Synthetic data are used to validate the reconstruction algorithm and assess an appropriate termination criterion. Significant aperture charging has been observed in the initial experimental dataset, and increases with aperture distance from the implosion, consistent with a simple model of charging by laser-driven EMP.

Ten Best Practices for Improving Emergency Medicine Provider-Nurse Communication.

BACKGROUND: The current state of scientific knowledge regarding communication between emergency medicine (EM) providers indicates that communication is critical to safe and effective patient care. OBJECTIVES: In this study, we identified communication needs of EM nurses and physicians; in particular, what information should be conveyed, when, how, and to whom. METHODS: Five semi-structured focus groups and one interview were conducted with nine nurses, eight attending physicians, and four residents. Questions addressed how EM personnel use and share information about patients and clinical work, what information tends to be exchanged, and what additional information would be helpful to share. Sessions were audio recorded. Transcripts were generated and analyzed using a concept mapping approach (a visual qualitative analysis technique to represent and convey synthesized knowledge). RESULTS: Eleven concept maps were produced summarizing: information physicians needed from nurses and vice versa; methods of communication that could be utilized; barriers or obstacles to effective communication; strategies to enhance or ensure effective communication; and environmental or situational factors that impact communication. CONCLUSIONS: Our main finding of this research is that communication ensures shared awareness of patient health status, the care plan, status of plan steps and orders, and, especially, any critical changes or "surprises" regarding the health of a patient. Additionally, the research identified shared information needs; communication methods, strategies and barriers; and factors affecting successful communication, and has implications for both system and training design. Key implications for emergency nursing practice from this research are distilled in 10 'best practice' strategies for improving EM nurse-physician communication.

Opportunities in IT Support of Workflow & Information Flow in the Emergency Department Digital Imaging Process.

The goal of this study is to examine workflow and information flow in the emergency department (ED) digital imaging process to identify features of an optimized system. Radiological imaging (x-rays, CT scans, etc) is unique in the ED setting, as the need for fast turn-around time and interactive communication between radiologists and emergency physicians is different than that of most other healthcare settings. The information technology systems which are used by both radiologists and emergency physicians to support these processes have been designed with a focus on the routine workflow of radiologists. We report the results of 14 hours of naturalistic observations of the use of digital imaging systems by a total of 22 ED and radiology staff. A hierarchical task analysis and an information process diagram are presented, and disparate theories that groups in the system have about other groups were discovered, particularly in the communication of clinical information.

Ambulance stretcher adverse events.

INTRODUCTION: Ambulance personnel use wheeled stretchers for moving patients in the out-of-hospital setting. The nature of adverse events and associated injuries occurring during ambulance stretcher operation was characterised. METHODS: Data from the United States Food and Drug Administration's Manufacturer and User Facility Device Experience Database (MAUDE) were used. All adverse events involving ambulance stretchers during the years 1996-2005 were identified. The nature of the event, the method of stretcher handling, the individuals injured and the nature of the resulting injuries were identified. RESULTS: There were 671 reported adverse events. The most common adverse events were stretcher collapse (54%; 95% CI 50 to 57%), broken, missing or malfunctioning part (28%; 95% CI 25 to 32%) and dropped stretcher (7%; 95% CI 5 to 9%). Adverse events most commonly occurred during unloading of the stretcher from the ambulance (16%; 13 to 19%). Injuries occurred in 121 events (18%; 95% CI 15 to 21%), most often involving sprains/strains (29%), fractures (16%) and lacerations/avulsions (13%). There were three traumatic brain injuries and three deaths. Patients sustained injuries in 52 events (43%), and ambulance personnel sustained injuries in 64 events (53%). More than one individual sustained injuries in 12 events. CONCLUSION: Adverse events may occur during ambulance stretcher operation and can result in significant injury to patients and ambulance personnel.

How residents spend their nights on call.

PURPOSE: Night call is a significant part of residents' education, but little information about their night-call activities is available. This study recorded residents' activities during night-call rotations on internal medicine and pediatrics wards. METHOD: In June and July 1997, on-call pediatrics and internal medicine residents at an urban academic medical center were accompanied by trained observers on the general wards between the hours of 7 PM and 7 AM. The types and duration of activities were recorded. RESULTS: Residents were observed for 106 nights. Internal medicine and pediatrics residents spent their time similarly. They spent 5.3 hours and 5.7 hours per night, respectively, on "basic" activities such as eating, resting, chatting, and sleeping, and an average of 2.6 hours and 2.2 hours, respectively, on chart review and documentation. In both programs, discussing the case with team members averaged 1.5 hours per night and use of the computer averaged slightly more than half an hour. Internal medicine residents spent approximately 1.5 hours on patients' history and physical examinations while pediatrics residents spent 1.3 hours. With each new patient, internal medicine residents spent an average of 19.7 minutes and pediatrics residents spent 16.5 minutes. The only significant difference between the two groups of residents was that the pediatrics residents spent more time per night on procedures than did the internal medicine residents (37 minutes versus 14 minutes, p < 0.01). CONCLUSIONS: Residents from both programs spent a surprising amount of time each night on chart review and documentation. In fact, they spent more time with charts than with patients. Whether this activity truly contributes to residents' education or improved patients' outcomes is not clear.

Tropical temperature variations since 20,000 years ago: modulating interhemispheric climate change.

Tropical sea surface temperatures (SSTs), as thermodynamically recorded in Barbados corals, were 5 degrees C colder than present values 19,000 years ago. Variable tropical SSTs may explain the interhemispheric synchroneity of global climate change as recorded in ice cores, snowline reconstructions, and vegetation records. Radiative changes due to cloud type and cloud cover are plausible mechanisms for maintaining cooler tropical SSTs in the past.

Glacial-interglacial changes in moisture sources for greenland: influences on the ice core record of climate.

Large, abrupt shifts in the (l8)O/(16)O ratio found in Greenland ice must reflect real features of the climate system variability. These isotopic shifts can be viewed as a result of air temperature fluctuations, but determination of the cause of the changes-the most crucial issue for future climate concerns-requires a detailed understanding of the controls on isotopes in precipitation. Results from general circulation model experiments suggest that the sources of Greenland precipitation varied with different climate states, allowing dynamic atmospheric mechanisms for influencing the ice core isotope shifts.

Treatment of stage IE primary lymphoma of bone.

PURPOSE: A retrospective analysis was performed to assess the efficacy of various treatments of Stage IE primary non-Hodgkins lymphoma of bone. METHODS AND MATERIALS: Sixty-three patients with Stage IE primary non-Hodgkins lymphoma of bone (single osseous focus) were seen at our institution between the years 1970 and 1989. Information was obtained regarding each patients' presentation and clinical course. The histology was reviewed in all patients. Modern immunohistochemical stains were performed on each case with available paraffin-embedded tissue. RESULTS: The histologic classification of the tumors was as follows: 43 diffuse large cell, 13 diffuse mixed cell, 3 small noncleaved, and 4 unclassified. The most common presenting symptom was pain (97%) and the following bony sites were involved: 36 long bone, 9 flat bone, 13 spine, and 5 pelvis. Of the 63 cases, 50 were treated with radiation alone, 10 with chemotherapy and radiation, 2 with chemotherapy alone, and 1 with surgery alone. Univariate analysis revealed a suggestion of an improved 5-year disease-free survival for patients treated with chemotherapy and radiation vs. radiation alone (90% vs. 57% respectively, p = .08). Multivariate analysis (controlling for extent of initial evaluation, extent of pathological evaluation and other potential prognostic factors) showed that neither treatment resulted in superior outcome with respect to disease-free survival, disease specific survival, or overall survival, however, doses of radiation greater than 4000 cGy resulted in improved overall survival compared to lower doses (p = 0.01). CONCLUSION: This study supports the use of primary RT (> 4000 cGy) for Stage IE PLB, however, the addition of chemotherapy to the radiotherapeutic management may decrease the initial relapse rate of some patients. Future studies should address this question.

Recent variability in the southern oscillation: isotopic results from a tarawa atoll coral.

In the western tropical Pacific, the interannual migration of the Indonesian Low convective system causes changes in rainfall that dominate the regional signature of the El Niño-Southern Oscillation (ENSO) system. A 96-year oxygen isotope record from a Tarawa Atoll coral (1 degrees N, 172 degrees E) reflects regional convective activity through rainfall-induced salinity changes. This monthly resolution record spans twice the length of the local climatological record and provides a history of ENSO variability comparable in quality with those derived from instrumental climate data. Comparison of this coral record with a historical chronology of EI Niño events indicates that climate anomalies in coastal South America are occasionally decoupled from Pacific-wide ENSO extremes. Spectral analysis suggests that the distribution of variance in this record has shifted among annual to interannual periods during the present century, concurrent with observed changes in the strength of the Southern Oscillation.

Using audit in a district-wide management system.

As a consequence of the NHS reforms, the budgeting and competitive tendering of clinical services between districts requires accurate accumulation of data. John Mosley and Roger Fairbanks describe how data obtained by clinicians from their own audit has been used to construct a casemix solution that provides the necessary financial information for a district.

Oxygen isotopes in biogenic silica: global changes in ocean temperature and isotopic composition.

A record of oxygen isotopes in biogenic silica from a deep-sea sediment core from the Southern Ocean reveals that marine diatoms retain their primary isotopic composition after burial. As a result, the marine diatom record can be combined with data on coexisting planktonic foraminifera to monitor past surface temperature and isotopic composition of seawater. The coupling of these two records allows the solution of two paleotemperature equations for each core interval. Data from a South Atlantic core show that the average delta(18)O during the glacial period at this site was higher by about 1.3 per mil than average Holocene values, and that average glacial-age temperatures were not significantly different from average Holocene values.

Arginine vasopressin stimulates human mesangial cell production of endothelin.

Endothelin (ET) is a vasoactive peptide produced by both endothelial epithelial cells with documented mitogenic action on mesangial cells. The present studies were designed to test the hypothesis that ET is also produced by human mesangial cells (HMC) and that other mitogens such as arginine vasopressin (AVP) and insulin stimulate cellular proliferation, in part, through modulation of endogenous production of this peptide. Studies were conducted on cultured normal HMC between the third and seventh passages. All mitogenesis experiments were carried out in 96-well plates and assessed by tritiated thymidine incorporation into DNA under various concentrations of AVP in the presence and absence of insulin, antiendothelin antisera (ETAS), a MAb against ET-1 (AbET), and a vasopressin-1 receptor antagonist. ET concentrations were measured daily from conditioned medium by a sensitive and specific RIA. ET was present in all concentrations of FCS as well as conditioned medium compared with medium alone. AVP (10(-6) M) in the presence of insulin increased ET production by quiescent HMC by 261% as well as cellular proliferation by 440% after 48 h incubation. In addition, cells cultured with ETAS or AbET demonstrated a blunted mitogenic response to AVP, a response not observed in cells cultured with ETAS where ET was added. Insulin significantly potentiated the mitogenic effects of AVP as well as media levels of ET, an effect significantly blunted by AbET. We conclude that ET is produced by HMC and its production is affected, in part, by both AVP and insulin. ET may thus serve to modulate the mitogenic effects of AVP on human mesangial cells.

Carbon-14 in methane sources and in atmospheric methane: the contribution from fossil carbon.

Measurements of carbon-14 in small samples of methane from major biogenic sources, from biomass burning, and in "clean air" samples from both the Northern and Southern hemispheres reveal that methane from ruminants contains contemporary carbon, whereas that from wetlands, pat bogs, rice fields, and tundra is somewhat, depleted in carbon-14. Atmospheric (14)GH(4) seems to have increased from 1986 to 1987, and levels at the end of 1987 were 123.3 +/- 0.8 percent modern carbon (pMC) in the Northern Hemisphere and 120.0 +/- 0.7 pMC in the Southern Hemisphere. Model calculations of source partitioning based on the carbon-14 data, CH(4) concentrations, and delta(13)C in CH(4) indicate that 21 +/- 3% of atmospheric CH(4) was derived from fossil carbon at the end of 1987. The data also indicate that pressurized water reactors are an increasingly important source of (14)CH(4).

Pleistocene sea levels from raised coral reefs of haiti.

The elevations and ages of a sequence of three uplifted Pleistocene coral reefs on the Northwest Peninsula of Haiti have been determined. With the assignment of a sea level of +6 meters (relative to the present day) at 130,000 years before present and constant uplift of the reefs, the data indicate that sea level stood -10 and -13 meters at 108,000 and 81,000 years before present, respectively. These results are in substantial agreement with those reported for Barbados and New Guinea and support the hypothesis of constant uplift for each area. Sea level data from raised reefs indicate that the interglacial marine oxygen isotope oscillations during oxygen isotope stage 5 are a result of 30 percent ice volume effects and 70 percent temperature effects.

Foraminifera and chlorophyll maximum: vertical distribution, seasonal succession, and paleoceanographic significance.

Many planktonic foraminiferal species deposit their shells at the chlorophyll maximum zone, and it is the temperature range here that is relevant to oceanographic models which use ratios of oxygen-18 to oxygen-16 in fossil foraminifera and foraminiferal fossil assemblages to ascertain past climates. During periods of stratification of the upper water column, the temperature at the chlorophyll maximum may differ from the sea surface temperature by 10 degrees C in the western North Atlantic.