Current State of Reporting Pain Outcomes in Cochrane Reviews of Chronic Musculoskeletal Pain Conditions and Considerations for an OMERACT Research Agenda.

OBJECTIVE To assess the current state of reporting of pain outcomes in Cochrane reviews on chronic musculoskeletal painful conditions and to elicit opinions of patients, healthcare practitioners, and methodologists on presenting pain outcomes to patients, clinicians, and policymakers. METHODS We identified all reviews in the Cochrane Library of chronic musculoskeletal pain conditions from Cochrane review groups (Back, Musculoskeletal, and Pain, Palliative, and Supportive Care) that contained a summary of findings (SoF) table. We extracted data on reported pain domains and instruments and conducted a survey and interviews on considerations for SoF tables (e.g., pain domains, presentation of results). RESULTS Fifty-seven SoF tables in 133 Cochrane reviews were eligible. SoF tables reported pain in 56/57, with all presenting results for pain intensity (20 different outcome instruments), pain interference in 8 SoF tables (5 different outcome instruments), and pain frequency in 1 multiple domain instrument. Other domains like pain quality or pain affect were not reported. From the survey and interviews [response rate 80% (36/45)], we derived 4 themes for a future research agenda: pain domains, considerations for assessing truth, discrimination, and feasibility; clinically important thresholds for responder analyses and presenting results; and establishing hierarchies of outcome instruments. CONCLUSION There is a lack of standardization in the domains of pain selected and the manner that pain outcomes are reported in SoF tables, hampering efforts to synthesize evidence. Future research should focus on the themes identified, building partnerships to achieve consensus and develop guidance on best practices for reporting pain outcomes.

Interannual Variability in Timing of Bloom Initiation in the California Current System

In the California Current System the spring transition from poleward to equatorward alongshore wind stress heralds the beginning of upwelling-favorable conditions. The phytoplankton response to this transition is investigated using 8 years ( 1998-2005) of daily, 4-km resolution, Sea-viewing Wide Field of view Sensor ( SeaWiFS) chlorophyll a concentration data. Cluster analysis of the chlorophyll a time series at each location is used to separate the inshore upwelling region from offshore and oligotrophic areas. An objective method for estimating the timing of bloom initiation is used to construct a map of the mean bloom start date. Interannual variability in bloom timing and magnitude is investigated in four regions: 45 degrees N - 50 degrees N, 40 degrees N - 45 degrees N, 35 degrees N - 40 degrees N and 20 degrees N - 35 degrees N. Daily satellite derived wind data ( QuikSCAT) allow the timing of the first episode of persistently upwelling favorable winds to be estimated. Bloom initiation generally coincides with the onset of upwelling winds ( +/- 15 days). South of similar to 35 degrees N, where winds are southward year-round, the timing of increased chlorophyll concentration corresponds closely to timing of the seasonal increase in upwelling intensity. A 1-D model and satellite derived photosynthetically available radiation data are used to estimate time series of depth- averaged irradiance. In the far north of the region (> 46 degrees N) light is shown to limit phytoplankton growth in early spring. In 2005 the spring bloom in the northern regions (> 35 degrees N) had a "false start''. A sharp increase in chl a in February quickly receded, and a sustained increase in biomass was delayed until July. We hypothesize that this resulted in a mismatch in timing of food availability to higher trophic levels.

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity. ^

Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. ^ The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. ^ The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only weakly on uncertainties in the risk model and inter-patient variations. Second cancer risks were sensitive to changes in the RBE of neutrons. However, the findings of the study were qualitatively consistent for all patient sizes and risk models considered, and for all neutron RBE values less than 100. ^

Use of light intensity, temperature, and humidity to verify exposure location

Research studies on the association between exposures to air contaminants and disease frequently use worn dosimeters to measure the concentration of the contaminant of interest. But investigation of exposure determinants requires additional knowledge beyond concentration, i.e., knowledge about personal activity such as whether the exposure occurred in a building or outdoors. Current studies frequently depend upon manual activity logging to record location. This study's purpose was to evaluate the use of a worn data logger recording three environmental parameters—temperature, humidity, and light intensity—as well as time of day, to determine indoor or outdoor location, with an ultimate aim of eliminating the need to manually log location or at least providing a method to verify such logs. For this study, data collection was limited to a single geographical area (Houston, Texas metropolitan area) during a single season (winter) using a HOBO H8 four-channel data logger. Data for development of a Location Model were collected using the logger for deliberate sampling of programmed activities in outdoor, building, and vehicle locations at various times of day. The Model was developed by analyzing the distributions of environmental parameters by location and time to establish a prioritized set of cut points for assessing locations. The final Model consisted of four "processors" that varied these priorities and cut points. Data to evaluate the Model were collected by wearing the logger during "typical days" while maintaining a location log. The Model was tested by feeding the typical day data into each processor and generating assessed locations for each record. These assessed locations were then compared with true locations recorded in the manual log to determine accurate versus erroneous assessments. The utility of each processor was evaluated by calculating overall error rates across all times of day, and calculating individual error rates by time of day. Unfortunately, the error rates were large, such that there would be no benefit in using the Model. Another analysis in which assessed locations were classified as either indoor (including both building and vehicle) or outdoor yielded slightly lower error rates that still precluded any benefit of the Model's use.^

Pleistocene sedimentation in the Benguela Current, southeastern Atlantic

We infer variations in paleoproductivity and eolian input at ODP Site 1082 in the Walvis Basin from stable oxygen isotope compositions of the planktonic foraminifera Globorotalia inflata, total organic carbon mass accumulation rates (TOC MAR), and X-ray fluorescence analyses of Fe content. The most pronounced paleoclimatic changes correspond to the time at about 0.9 Ma, when glacial conditions in the northern hemisphere (NH) led to the onset of pronounced 100-kyr glacial-interglacial cycles. We used Fe intensity as a proxy for eolian terrigenous input, and TOC MAR as a paleoproductivity indicator. Paleoproductivity and eolian input show generally higher-amplitude variations of glacial-interglacial cyclicity from 1.5 to 0.58 Ma, indicating pronounced variations in upwellingfavorable winds in this area. At 0.58 Ma, paleoproductivity and eolian input shifted abruptly to lower-amplitude variations with a periodicity of 100 kyr while delta18O values show a trend toward more negative isotope values for the past 0.65 Myr. Especially during glacial periods, oxygen isotope values indicate increasingly warmer sea-surface temperatures toward the end of the Pleistocene. To evaluate the relative influences of NH glaciation and southern hemisphere (SH) insolation as potential forcing mechanisms for variations of eolian input and productivity in the northern Benguela system, we filtered our proxy records at orbital frequencies. The filtered records of Fe intensity and TOC MAR indicate a strong influence of the 100-kyr and 41-kyr frequency bands, supporting our assumption that strong ice buildup in the NH is the dominant trigger for climate changes on the continent and probably in trade-wind intensity. SH insolation and low-latitude precession-related insolation changes were important for paleoproductivity variations in the northern Benguela system, modifying the nutrient supply by southern ocean intermediate waters and the zonal direction of upwelling-inducing trades by the African monsoon system, respectively.

Age determination of sediment cores of the California Current System

Alkenone sea surface temperature (SST) records were generated from the Ocean Drilling Program's (ODP) Sites 1014 and 1016 to examine the response of the California Current System to global climate change during the last 136 ka. The temperature differences between these sites (Delta SST(NEP)=SST(ODP1014)-SST(ODP1016)) reflected the intensity of the California Current and varied between 0.4 and 6.1 °C. A high Delta SST(NEP) (weaker California Current) was found for late marine isotope stage (MIS) 2 and early MIS 5e, while a low Delta SST(NEP) (stronger California Current) was detected for mid-MIS 5e and MIS 1. Spectral analysis indicated that this variation pattern dominated 23- (precession) and 30-ka periods. Comparison of the Delta SST(NEP) and SST based on data from core MD01-2421 at the Japan margin revealed anti-phase variation; the high Delta SST(NEP) (weakening of the California Current) corresponded to the low SST at the Japan margin (the southward displacement of the NW Pacific subarctic boundary), and vice versa. This variation was synchronous with a model prediction of the tropical El Niño-Southern Oscillation behavior. These findings suggest that the intensity of the North Pacific High varied in response to precessional forcing, and also that the response has been linked with the changes of tropical ocean-atmosphere interactions.

Magnetic and electric current morphoiogy in the plasma ejected by a laser-irradiated foil

A quasisteady model for the plasma ablated from a thick foil by a laser pulse, at low $lln $ and R /A i within a low, narrow range, is given (4, is absorbed intensity, /zL wavelength, R focalspot radius). An approximate analytical solution is given for the two-dimensional plasma dynamics. At large magnetic Reynolds number Rm, the morphology of the magnetic field shows features in agreement with recent results for high intensities. Current lines are open: electric current flows toward the spot near its axis, then turns and flows away. The efficiency of converting light energy into electric energy peaks at Rm- 1, both the validity of the model. and accuracy of the solution are discussed, The neighborhood of the spot boundary is analyzed in detail by extending classical Prandtl-Meyer results.

The adaptive response of humans to exercise: Impact of exercise intensity, fibre-type specific responses and molecular patterns of response

In an attempt to improve the current understanding of the adaptive response to exercise in humans, this dissertation performed a series of studies designed to examine the impact of training intensity and mode on aerobic capacity and performance, fibre-type specific adaptations to training, and individual patterns of response across molecular, morphological and genetic factors. Project #1 determined that training intensity, session dose, baseline VO2max and total training volume do not influence the magnitude of change in VO2max by performing a meta-regression, and meta-analysis of 28 different studies. The intensity of training had no effect on the magnitude of increase in maximal oxygen uptake in young healthy participants, but similar adaptations were achieved with lower training doses following high intensity training. Project # 2 determined the acute molecular response, and training-induced adaptations in aerobic performance, aerobic capacity and muscle phenotype following high-intensity interval training (HIT) or endurance exercise (END). The acute molecular response (fibre recruitment and signal activation) and training-induced adaptations in aerobic capacity, aerobic performance, and muscle phenotype were similar following HIT and END. Project # 3 examined the impact of baseline muscle morphology and molecular characteristics on the training response, and if muscle adaptations are coordinated. The muscle phenotype of individuals who experience the largest improvements (high responders) were lower before training for some muscle characteristics and molecular adaptations were coordinated within individual participants. Project # 4 examined the impact of 2 different intensities of HIT on the expression of nuclear and mitochondrial encoded genes targeted by PGC-1α. A systematic upregulation of nuclear and mitochondrial encoded genes was not present in the early recovery period following acute HIT, but the expression of mitochondrial genes were coordinated at an individual level. Collectively, results from the current dissertation contribute to our understanding of the molecular mechanisms influencing skeletal muscle and whole-body adaptive responses to acute exercise and training in humans.

A detector based on silica fibers for ion beam monitoring in a wide current range

A detector based on doped silica and optical fibers was developed to monitor the profile of particle accelerator beams of intensity ranging from 1 pA to tens of µA. Scintillation light produced in a fiber moving across the beam is measured, giving information on its position, shape and intensity. The detector was tested with a continuous proton beam at the 18 MeV Bern medical cyclotron used for radioisotope production and multi-disciplinary research. For currents from 1 pA to 20 µA, Ce3+ and Sb3+ doped silica fibers were used as sensors. Read out systems based on photodiodes, photomultipliers and solid state photomultipliers were employed. Profiles down to the pA range were measured with this method for the first time. For currents ranging from 1 pA to 3 µA, the integral of the profile was found to be linear with respect to the beam current, which can be measured by this detector with an accuracy of ∼1%. The profile was determined with a spatial resolution of 0.25 mm. For currents ranging from 5 µA to 20 µA, thermal effects affect light yield and transmission, causing distortions of the profile and limitations in monitoring capabilities. For currents higher than ∼1 µA, non doped optical fibers for both producing and transporting scintillation light were also successfully employed.