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Abstract Background Typically, researchers and clinicians determine the agenda in sarcoma research. However, patient involvement can have a meaningful impact on research. Therefore, the Patient-Powered Research Network (PPRN) of the Sarcoma Patient Advocacy Global Network (SPAGN) set up a Priority Setting Partnership (PSP). The primary objective of this partnership is to identify priorities for research and patient advocacy topics. Methods In the first phase of this PSP, including 264 sarcoma patients and carers from all over the world, 23 research topics regarding sarcomas and 15 patient advocacy topics were identified using an online survey. In the second phase, participants were asked to fill in a top five and a top three of research and patient advocacy topics, respectively. Additionally, sociodemographic characteristics and sarcoma characteristics were collected. Social media channels, local national patient advocacy groups and the SPAGN website were used to distribute the survey. Results In total, 671 patients (75%) and carers (25%) participated in this survey. The five highest ranked research topics were related to causes of sarcoma (43%), prognosis and risk of recurrence (40%), specific subtypes of sarcoma (33%), the role of immunotherapy, targeted therapy and combined therapy (30%), and hereditary aspects (30%). The three highest ranked patient advocacy topics were improving the diagnostic process of sarcoma (39%), access to tumor DNA analysis (37%) and establishing an international sarcoma registry (37%). Conclusions This sarcoma PSP has identified priorities for research and patient advocacy, offering guidance for researchers, assisting funding agencies with assessing project relevance and empowering patient advocates to represent the needs of patients and carers.

To investigate the potential value of tree ring blue intensity as a robust climate proxy in central and western China, four species from five sites were assessed. As well as latewood inverted blue intensity, we also examined earlywood blue intensity. To explore the sensitivity of using different extraction parameter settings using the software CooRecorder, seven percentile (P) variant settings for earlywood blue intensity and latewood inverted blue intensity were used, namely P50 : 50, P60 : 40, P70 : 30, P80 : 20, P85 : 15, P90 : 10, and P95 : 5. Age-dependent spline was used for all, and the positive trends were not retained. Correlation analysis was applied between the tree ring parameter chronologies and monthly/seasonal mean temperature, precipitation, and self-calibrated Palmer drought severity index variables. Linear regression was also used to further highlight the potential of developing climate reconstructions using these species. Only subtle differences were found between the different percentile extraction variants. As has been shown for many other Northern Hemisphere studies, latewood inverted blue intensity expresses a strong positive relationship with growing-season temperatures (the two southern sites explain almost 56 % of the temperature variance when combined). However, the low latitude of these sites shows an exciting potential for regions south of 30∘ N that are traditionally not targeted for temperature reconstructions. Earlywood blue intensity also shows good potential to reconstruct hydroclimate parameters in some humid areas.

DNA damage is frequently utilized as the basis for cancer therapies; however, resistance to DNA damage remains one of the biggest challenges for successful treatment outcomes. Critically, the molecular drivers behind resistance are poorly understood. To address this question, we created an isogenic model of prostate cancer exhibiting more aggressive characteristics to better understand the molecular signatures associated with resistance and metastasis. 22Rv1 cells were repeatedly exposed to DNA damage daily for 6 weeks, similar to patient treatment regimes. Using Illumina Methylation EPIC arrays and RNA-seq, we compared DNA methylation and transcriptional profiles between the parental 22Rv1 cell line and the lineage exposed to prolonged DNA damage. Here we show that repeated DNA damage drives the molecular evolution of cancer cells to a more aggressive phenotype and identify molecular candidates behind this process. Total DNA methylation was increased while RNA-seq demonstrated these cells had dysregulated expression of genes involved in metabolism and the unfolded protein response (UPR) with Asparagine synthetase (ASNS) identified as central to this process. Despite the limited overlap between RNA-seq and DNA methylation, oxoglutarate dehydrogenase-like (OGDHL) was identified as altered in both data sets. Utilising a second approach we profiled the proteome in 22Rv1 cells following a single dose of radiotherapy. This analysis also highlighted the UPR in response to DNA damage. Together, these analyses identified dysregulation of metabolism and the UPR and identified ASNS and OGDHL as candidates for resistance to DNA damage. This work provides critical insight into molecular changes which underpin treatment resistance and metastasis.

This article deals with the detection of small-scale turbulence from in situ meteorological measurements performed under superpressure balloons (SPBs). These balloons allow long-duration flights (several months) at a prerequisite height level. The data set is gathered from the Strateole-2 probationary campaign during which eights SPBs flew in the tropical tropopause layer at altitudes of around 19 and 20.5 km from November 2019 to March 2020. Turbulence is not directly measured by the instrument set onboard the SPBs. Nonetheless, there is the potential to derive information about the occurrence of turbulence from the temporally well-resolved measurements of pressure, temperature, and position. It constitutes a challenge to extract the aforementioned information from a measurement set that was not designed for quantifying turbulence, and the paper explains the methodology developed to overcome this difficulty. It is observed that SPBs oscillate quasi-periodically around their equilibrium positions. The oscillation periods, which are 220 s on average with a range of 130 to 500 s, are close to but noticeably smaller than the Brunt–Väisälä period (∼300 s). The amplitude of these vertical motions is ∼±15 m, inducing large fluctuations in all quantities, whether measured (e.g., pressure, temperature and position) or inferred (e.g., density and potential temperature). The relationships between the changes in these quantities and the vertical displacements of the balloons are used to infer properties of the flow in which the SPBs drift. In the case of active turbulence, the vertical stratification as well as the wind shear are likely to be reduced by mixing. Hence, the increments of potential temperature, δθ, and of the vertical displacements of the balloon, δzB, are expected to be uncorrelated because ∂θ/∂z→0. Moreover, the local vertical gradients of measured quantities, temperature (T) and horizontal velocities (u and v), are estimated from the covariance of the increments of the considered quantity with δzB. The Richardson number of the flow is deduced. Several binary indexes (true or false) to describe the state of the flow, laminar or turbulent, are evaluated. These turbulence indexes, based either on correlations between δθ and δzB or on estimates of the local Richardson number, are found to be consistent, as they differ in less than 3 % of cases. The flow is observed to be turbulent for about 5 % of the time, with strong inhomogeneities along the longitude.

BACKGROUND: A perioperative acute pain care program integrating standardized assessment and treatment forms into pain care was developed and implemented at an urban hospital in Rwanda through a collaboration between Rwandan and Canadian experts. This study evaluated the perioperative acute pain care program using a quality improvement lens. METHODS: Using the Model for Improvement: Plan, Do, Study, Act (PDSA) cycle, a mixed methods evaluation was performed. Over one year, 519 randomized patient chart audits were conducted and analyzed through control charts. Through purposeful sampling, focus groups comprised of surgeons and nurses (N=34) involved in pain care in surgery, obstetrics, and anesthesiology were performed and analyzed via thematic coding. RESULTS: The average attempted form completion rate across all forms varied monthly between 56-93% (mean=79%; median=81%). Across all forms, both the mean and median total number of errors per form were 12.5. Enablers of form use included improved pain care for patients and feelings of professional satisfaction. Program implementation was challenged by resource constraints, form integration, and health care provider training. CONCLUSION: Future quality improvement collaborations should identify and address improved pain care while working with local experts to ensure PDSA cycles are continuous, and evidence based.

Aquatic insect communities in inland waters of Chile are characterised by the presence of certain species depending on water quality, but there is little information on statistical ecology in the structure of insect communities. The aim of the present study was to apply null models to explain the structure of aquatic insects in the middle zone of the Loa River, in the Atacama Desert (Antofagasta Region, Chile; 23°S). The results of the null models of species co-occurrence showed that species associations are random, while niche sharing showed that species share ecological niches and consequently there is interspecific competition. The reported taxa are similar to communities for other North Patagonian rivers in terms of community structure.

The continuous development of new proxies as well as a refinement of existing tools are key to advances in paleoclimate research and improvements in the accuracy of existing climate reconstructions. Herein, we build on recent methodological progress in dendroanatomy, the analyses of wood anatomical parameters in dated tree rings, and introduce the longest (1585–2014 CE) dendroanatomical dataset currently developed for North America. We explore the potential of dendroanatomy of high-elevation Engelmann spruce (Picea engelmannii) as a proxy of past temperatures by measuring anatomical cell dimensions of 15 living trees from the Columbia Icefield area. X-ray maximum latewood density (MXD) and its blue intensity counterpart (MXBI) have previously been measured, allowing comparison between the different parameters. Our findings highlight anatomical MXD and maximum radial cell wall thickness as the two most promising wood anatomical proxy parameters for past temperatures, each explaining 46 % and 49 %, respectively, of detrended instrumental July–August maximum temperatures over the 1901–1994 period. While both parameters display comparable climatic imprinting at higher frequencies to X-ray derived MXD, the anatomical dataset distinguishes itself from its predecessors by providing the most temporally stable warm season temperature signal. Further studies, including samples from more diverse age cohorts and the adaptation of the regional curve standardization method, are needed to disentangle the ontogenetic and climatic components of long-term signals stored in the wood anatomical traits and to more comprehensively evaluate the potential contribution of this new dataset to paleoclimate research.

Abstract Increasing the intensity to which high power laser pulses are focused has opened up new research possibilities, including promising new approaches to particle acceleration and phenomena such as high field quantum electrodynamics. Whilst the intensity achievable with a laser pulse of a given power can be increased via tighter focusing, the focal spot profile also plays an important role in the interaction physics. Here we show that the spatial-intensity distribution, and specifically the ratio of the intensity in the peak of the laser focal spot to the halo surrounding it, is important in the interaction of ultraintense laser pulses with solid targets. By comparing proton acceleration measurements from foil targets irradiated with by a near-diffraction-limited wavelength scale focal spot and larger F-number focusing, we find that this spatial-intensity contrast parameter strongly influences laser energy coupling to fast electrons. We find that for multi-petawatt pulses, spatial-intensity contrast is potentially as important as temporal-intensity contrast.

The optimum parameters for the generation of synchrotron radiation in ultraintense laser pulse interactions with planar foils are investigated with the application of Bayesian optimization, via Gaussian process regression, to 2D particle-in-cell simulations. Individual properties of the synchrotron emission, such as the yield, are maximized, and simultaneous mitigation of bremsstrahlung emission is achieved with multi-variate objective functions. The angle-of-incidence of the laser pulse onto the target is shown to strongly influence the synchrotron yield and angular profile, with oblique incidence producing the optimal results. This is further explored in 3D simulations, in which additional control of the spatial profile of synchrotron emission is demonstrated by varying the polarization of the laser light. The results demonstrate the utility of applying a machine learning-based optimization approach and provide new insights into the physics of radiation generation in laser–foil interactions, which will inform the design of experiments in the quantum electrodynamics (QED)-plasma regime.

We evaluate a range of blue intensity (BI) tree-ring parameters in eight conifer species (12 sites) from Tasmania and New Zealand for their dendroclimatic potential, and as surrogate wood anatomical proxies. Using a dataset of ca. 10–15 trees per site, we measured earlywood maximum blue intensity (EWB), latewood minimum blue intensity (LWB), and the associated delta blue intensity (DB) parameter for dendrochronological analysis. No resin extraction was performed, impacting low-frequency trends. Therefore, we focused only on the high-frequency signal by detrending all tree-ring and climate data using a 20-year cubic smoothing spline. All BI parameters express low relative variance and weak signal strength compared to ring width. Correlation analysis and principal component regression experiments identified a weak and variable climate response for most ring-width chronologies. However, for most sites, the EWB data, despite weak signal strength, expressed strong coherence with summer temperatures. Significant correlations for LWB were also noted, but the sign of the relationship for most species is opposite to that reported for all conifer species in the Northern Hemisphere. DB results were mixed but performed better for the Tasmanian sites when combined through principal component regression methods than for New Zealand. Using the full multi-species/parameter network, excellent summer temperature calibration was identified for both Tasmania and New Zealand ranging from 52 % to 78 % explained variance for split periods (1901–1950/1951–1995), with equally robust independent validation (coefficient of efficiency = 0.41 to 0.77). Comparison of the Tasmanian BI reconstruction with a quantitative wood anatomical (QWA) reconstruction shows that these parameters record essentially the same strong high-frequency summer temperature signal. Despite these excellent results, a substantial challenge exists with the capture of potential secular-scale climate trends. Although DB, band-pass, and other signal processing methods may help with this issue, substantially more experimentation is needed in conjunction with comparative analysis with ring density and QWA measurements.

The “1809 eruption” is one of the most recent unidentified volcanic eruptions with a global climate impact. Even though the eruption ranks as the third largest since 1500 with a sulfur emission strength estimated to be 2 times that of the 1991 eruption of Pinatubo, not much is known of it from historic sources. Based on a compilation of instrumental and reconstructed temperature time series, we show here that tropical temperatures show a significant drop in response to the ∼ 1809 eruption that is similar to that produced by the Mt. Tambora eruption in 1815, while the response of Northern Hemisphere (NH) boreal summer temperature is spatially heterogeneous. We test the sensitivity of the climate response simulated by the MPI Earth system model to a range of volcanic forcing estimates constructed using estimated volcanic stratospheric sulfur injections (VSSIs) and uncertainties from ice-core records. Three of the forcing reconstructions represent a tropical eruption with an approximately symmetric hemispheric aerosol spread but different forcing magnitudes, while a fourth reflects a hemispherically asymmetric scenario without volcanic forcing in the NH extratropics. Observed and reconstructed post-volcanic surface NH summer temperature anomalies lie within the range of all the scenario simulations. Therefore, assuming the model climate sensitivity is correct, the VSSI estimate is accurate within the uncertainty bounds. Comparison of observed and simulated tropical temperature anomalies suggests that the most likely VSSI for the 1809 eruption would be somewhere between 12 and 19 Tg of sulfur. Model results show that NH large-scale climate modes are sensitive to both volcanic forcing strength and its spatial structure. While spatial correlations between the N-TREND NH temperature reconstruction and the model simulations are weak in terms of the ensemble-mean model results, individual model simulations show good correlation over North America and Europe, suggesting the spatial heterogeneity of the 1810 cooling could be due to internal climate variability.

To advance the understanding of the interplay among clouds, convection, and circulation, and its role in climate change, the Elucidating the role of clouds–circulation coupling in climate campaign (EUREC4A) and Atlantic Tradewind Ocean–Atmosphere Mesoscale Interaction Campaign (ATOMIC) collected measurements in the western tropical Atlantic during January and February 2020. Upper-air radiosondes were launched regularly (usually 4-hourly) from a network consisting of the Barbados Cloud Observatory (BCO) and four ships within 6–16∘ N, 51–60∘ W. From 8 January to 19 February, a total of 811 radiosondes measured wind, temperature, and relative humidity. In addition to the ascent, the descent was recorded for 82 % of the soundings. The soundings sampled changes in atmospheric pressure, winds, lifting condensation level, boundary layer depth, and vertical distribution of moisture associated with different ocean surface conditions, synoptic variability, and mesoscale convective organization. Raw (Level 0), quality-controlled 1 s (Level 1), and vertically gridded (Level 2) data in NetCDF format (Stephan et al., 2020) are available to the public at AERIS (https://doi.org/10.25326/137). The methods of data collection and post-processing for the radiosonde data set are described here.

Abstract Warming in Central Asia has been accelerating over the past three decades and is expected to intensify through the end of this century. Here, we develop a summer temperature reconstruction for western Mongolia spanning eight centuries (1269–2004 C.E.) using delta blue intensity measurements from annual rings of Siberian larch. A significant cooling response is observed in the year following major volcanic events and up to five years post‐eruption. Observed summer temperatures since the 1990s are the warmest over the past eight centuries, an observation that is also well captured in Coupled Model Intercomparison Project (CMIP5) climate model simulations. Projections for summer temperature relative to observations suggest further warming of between ∼3°C and 6°C by the end of the century (2075–2099 cf. 1950–2004) under the representative concentration pathways 4.5 and 8.5 (RCP4.5 and RCP8.5) emission scenarios. We conclude that projected future warming lies beyond the range of natural climate variability for the past millennium as estimated by our reconstruction.

Abstract Background The AMBER (Assessment, Management, Best Practice, Engagement, Recovery Uncertain) care bundle is a complex intervention used in UK hospitals to support patients with uncertain recovery. However, it has yet to be evaluated in a randomised controlled trial (RCT) to identify potential benefits or harms. The aim of this trial was to investigate the feasibility of a cluster RCT of the AMBER care bundle. Methods This is a prospective mixed-methods feasibility cluster RCT. Quantitative data collected from patients (or proxies if patients lack capacity) were used (i) to examine recruitment, retention and follow-up rates; (ii) to test data collection tools for the trial and determine their optimum timing; (iii) to test methods to identify the use of financial resources; and (iv) to explore the acceptability of study procedures for health professionals and patients. Descriptive statistical analyses and thematic analysis used the framework approach. Results In total, 894 patients were screened, of whom 220 were eligible and 19 of those eligible (8.6%) declined to participate. Recruitment to the control arm was challenging. Of the 728 patients screened for that arm, 647 (88.9%) were excluded. Overall, 65 patients were recruited (81.3% of the recruitment target of 80). Overall, many were elderly (≥80 years, 46.2%, n = 30, mean = 77.8 years, standard deviation [SD] = 12.3 years). Over half (53.8%) had a non-cancer diagnosis, with a mean of 2.3 co-morbidities; 24.6% patients (n = 16) died during their hospital stay and 35.4% (n = 23) within 100 days of discharge. In both trial arms, baseline IPOS subscale scores identified moderate patient anxiety (control: mean 13.3, SD 4.8; intervention: mean 13.3, SD 5.1), and howRwe identified a good care experience (control: mean 13.1, SD 2.5; intervention: mean 11.5, SD 2.1). Collecting quantitative service use and quality of life data was feasible. No patient participants regarded study involvement negatively. Focus groups with health professionals identified concerns regarding (i) the subjectivity of the intervention’s eligibility criteria, (ii) the need to prognosticate to identify potential patients and (iii) consent procedures and the length of the questionnaire. Conclusions A full trial of the AMBER care bundle is technically feasible but impractical due to fundamental issues in operationalising the intervention’s eligibility criteria, which prevents optimal recruitment. Since this complex intervention continues to be used in clinical care and advocated in policy, alternative research approaches must be considered and tested. Trial registration International Standard Randomised Controlled Trial Number (ISRCTN) Register, ISRCTN36040085.

Abstract Background In England, influenza and pertussis vaccination has been recommended for all pregnant women since 2010 and 2012 respectively. However, in some areas, vaccination uptake rates have been low. A qualitative study was conducted to gain a contextualised understanding of factors influencing vaccination acceptance during pregnancy in Hackney, a borough in north-east London, UK. This paper draws on in-depth insights gained from the above study, to provide recommendations for increasing long-term maternal vaccination acceptance. Methods Hackney was chosen as the study site because it has one of the lowest vaccination coverage rates in pregnancy in the UK. A maximum variation sampling method was used to recruit 47 pregnant and recently pregnant women from a wide range of backgrounds, as well as ten healthcare professionals from three general practices; two community antenatal clinics; nine parent-toddler groups; and four community centres. In-depth interviews and a video-recording of a pregnant patient’s consultation, explored experiences of care within the National Health Service during pregnancy, and women’s views about maternal vaccination. In-depth interviews with healthcare professionals explored their views towards, and how they discuss and provide maternal vaccination. Study data were analysed both deductively, through drawing on insights from anthropological works that address diverse conceptualisations and practices around vaccination; and inductively, with a thematic analysis approach. Results The findings of this study and the recommendations based on them were divided into five broad themes: access to maternal vaccination; healthcare institution rhetoric and its effect on maternal vaccination acceptance; community and family influences on maternal vaccination decisions; healthcare professionals’ views towards maternal vaccination; and the influence of patient-healthcare professional relationships on maternal vaccination acceptance. Conclusions The strategies to improve maternal vaccination acceptance recommended in this paper would engender a more open and democratised healthcare system.

Introduction Multiple hospitalisations towards the end of life is an indicator of poor-quality care. Understanding the characteristics of patients who experience hospitalisations at the end-of-life and how they vary is important for improved care planning. Objectives To describe socio-demographic and clinical characteristics of patients diagnosed with serious mental illness who experienced multiple hospitalisations in the last 90 days of life. Methods Data for all adult patients with a diagnosis of serious mental illness who died in 2018-2019 in England, UK were extracted from the National Mental Health Services Data Set linked with Hospital Episode Statistics and death registry data. Variables of interest included age, gender, marital status, underlying and contributory cause of death, ethnicity, place of death, deprivation status, urban-rural indicator, and patient’s region of residence. The number of hospitalisations and patient’s sociodemographic & clinical were described using descriptive statistics and percentages, respectively. Results Of the 45924 patients, 38.1% (n=17505, Male=42.9%, Female=57.1%, Mean age:78.4) had at least one hospitalisation in the last 90 days of life. The median number of hospitalisations was 2(StdDev:1.64, Minimum=1,Maximum=23). Most of those hospitalised (n=11808, 67.5%), died in a health care establishment (e.g. Hospital or hospice). There were marked geographic differences in the proportions of hospitalisations.The North West region of England recorded the most hospitalisations (n= 2906,16.6%), compared to other regions. Conclusions Further analysis is needed to understand factors independently associated with hospitalisations in people with serious mental illness. Funding: This project is supported by the National Institute for Health Research (NIHR) Applied Research Collaborations (ARC) South London.

It is a challenge to scale up laser-ion acceleration to higher ion energies. Here the authors demonstrate a hybrid acceleration scheme based on the relativistic induced transparency mechanism using linearly polarised laser interaction with foil targets and its future implication in using high power lasers.

Ring-width (RW) records from the Gulf of Alaska (GOA) have yielded a valuable long-term perspective for North Pacific changes on decadal to longer timescales in prior studies but contain a broad winter to late summer seasonal climate response. Similar to the highly climate-sensitive maximum latewood density (MXD) proxy, the blue intensity (BI) parameter has recently been shown to correlate well with year-to-year warm-season temperatures for a number of sites at northern latitudes. Since BI records are much less labour intensive and expensive to generate than MXD, such data hold great potential value for future tree-ring studies in the GOA and other regions in mid- to high latitudes. Here we explore the potential for improving tree-ring-based reconstructions using combinations of RW- and BI-related parameters (latewood BI and delta BI) from an experimental subset of samples at eight mountain hemlock (Tsuga mertensiana) sites along the GOA. This is the first study for the hemlock genus using BI data. We find that using either inverted latewood BI (LWBinv) or delta BI (DB) can improve the amount of explained temperature variance by > 10 % compared to RW alone, although the optimal target season shrinks to June–September, which may have implications for studying ocean–atmosphere variability in the region. One challenge in building these BI records is that resin extraction did not remove colour differences between the heartwood and sapwood; thus, long term trend biases, expressed as relatively warm temperatures in the 18th century, were noted when using the LWBinv data. Using DB appeared to overcome these trend biases, resulting in a reconstruction expressing 18th–19th century temperatures ca. 0.5 °C cooler than the 20th–21st centuries. This cool period agrees well with previous dendroclimatic studies and the glacial advance record in the region. Continuing BI measurement in the GOA region must focus on sampling and measuring more trees per site (> 20) and compiling more sites to overcome site-specific factors affecting climate response and using subfossil material to extend the record. Although LWBinv captures the inter-annual climate signal more strongly than DB, DB appears to better capture long-term secular trends that agree with other proxy archives in the region. Great care is needed, however, when implementing different detrending options and more experimentation is necessary to assess the utility of DB for different conifer species around the Northern Hemisphere.

Global ocean circulation, governed by the salinity of seawater, is a key contributor in supporting marine life and in regulating climate. Biologging has enabled researchers to record in-situ ocean parameters from free-ranging animals, as they swim through their environment. Current salinity sensors are bulky, expensive, highly intrusive and also susceptible to corrosion and biofouling. We present a four-electrode conductivity cell based on laser-induced graphene (LIG) on a polyimide substrate for salinity measurements. The flexible, lightweight and cost-efficient sensors operate under various bending conditions with an accuracy of ±0.5 psu. The sensors offer a linear response to salinity, as well as a high sensitivity of 0.85 mS/psu, and they operate over a wide range of frequencies (10 kHz–100 kHz). These characteristics considerably relax the requirements for the circuit of the data logger. A four electrodes configuration reduces the dependency on the electrical double layer, since the electrodes used to drive a current are different from the electrodes measuring the voltage drop. The sensors’ deployment in the Red Sea has revealed its capability to withstand the harsh seawater environment. The mechanical flexibility and low thickness and weight of the conductivity cell allow for a less-intrusive attachment of this sensor to marine animals, while the versatile fabrication process enables customization of the sensor to a wide range of applications.

Aim. We investigated use of mastectomy as treatment for early breast cancer in the US and applied the resulting information to estimate the minimum and maximum rates at which mastectomy could plausibly be undergone by patients with overdiagnosed breast cancer. Little is currently known about overtreatments undergone by overdiagnosed patients. Methods. In the US, screening is often recommended at ages ≥40. The study population was women age ≥40 diagnosed with breast cancer in the US SEER 9 cancer registries during 2013 (n=26,017). We evaluated first-course surgical treatments and their associations with case characteristics. Additionally, a model was developed to estimate probability of mastectomy conditional on observed case characteristics. The model was then applied to evaluate possible rates of mastectomy in overdiagnosed patients. To obtain minimum and maximum plausible rates of this overtreatment, we respectively assumed the cases that were least and most likely to be treated by mastectomy had been overdiagnosed. Results. Of women diagnosed with breast cancer at age ≥40 in 2013, 33.8% received mastectomy. Mastectomy was common for most investigated breast cancer types, including for the early breast cancers among which overdiagnosis is thought to be most widespread: mastectomy was undergone in 26.4% of in situ and 28.0% of AJCC stage-I cases. These rates are substantively higher than in many European nations. The probability-based model indicated that between >0% and 0% and 3% and

Diagenetic processes are important drivers of water column biogeochemistry in coastal areas. For example, sediment oxygen consumption can be a significant contributor to oxygen depletion in hypoxic systems, and sediment–water nutrient fluxes support primary productivity in the overlying water column. Moreover, nonlinearities develop between bottom water conditions and sediment–water fluxes due to loss of oxygen-dependent processes in the sediment as oxygen becomes depleted in bottom waters. Yet, sediment–water fluxes of chemical species are often parameterized crudely in coupled physical–biogeochemical models, using simple linear parameterizations that are only poorly constrained by observations. Diagenetic models that represent sediment biogeochemistry are available, but rarely are coupled to water column biogeochemical models because they are computationally expensive. Here, we apply a method that efficiently parameterizes sediment–water fluxes of oxygen, nitrate and ammonium by combining in situ measurements, a diagenetic model and a parameter optimization method. As a proof of concept, we apply this method to the Louisiana Shelf where high primary production, stimulated by excessive nutrient loads from the Mississippi–Atchafalaya River system, promotes the development of hypoxic bottom waters in summer. The parameterized sediment–water fluxes represent nonlinear feedbacks between water column and sediment processes at low bottom water oxygen concentrations, which may persist for long periods (weeks to months) in hypoxic systems such as the Louisiana Shelf. This method can be applied to other systems and is particularly relevant for shallow coastal and estuarine waters where the interaction between sediment and water column is strong and hypoxia is prone to occur due to land-based nutrient loads.

Laser-driven proton acceleration from ultrathin foils is investigated experimentally using f/3 and f/1 focusing. Higher energies achieved with f/3 are shown via simulations to result from self-focusing of the laser light in expanding foils that become relativistically transparent, enhancing the intensity. The increase in proton energy is maximized for an optimum initial target thickness, and thus expansion profile, with no enhancement occurring for targets that remain opaque, or with f/1 focusing to close to the laser wavelength. The effect is shown to depend on the drive laser pulse duration.

The present paper addresses the detection of turbulence based on the Thorpe (1977) method applied to an atmosphere where saturation of water vapor occurs. The detection method proposed by Thorpe relies on the sorting in ascending order of a measured profile of a variable conserved through adiabatic processes, (e.g. potential temperature). For saturated air, the reordering should be applied to a moist-conservative potential temperature, θm, which is analogous to potential temperature for a dry (subsaturated) atmosphere. Here, θm is estimated from the Brunt–Väisälä frequency derived by Lalas and Einaudi (1974) in a saturated atmosphere. The application to balloon data shows that the effective turbulent fraction of the troposphere can dramatically increase when saturation is taken into account. Preliminary results of comparisons with data simultaneously collected from the VHF Middle and Upper atmosphere radar (MUR, Japan) seem to give credence to the proposed approach.

Ground surveys and remote sensing are integral to establishing fair and equitable property valuations necessary for real property taxation. The International Association of Assessing Officers (IAAO) has embraced aerial and street-view imaging as part of its standards related to property tax assessments and audits. New technologies, including unmanned aerial systems (UAS) paired with imaging sensors, will become more common as local governments work to ensure their cadastre and tax rolls are both accurate and complete. Trends in mapping technology have seen an evolution in platforms from large, expensive manned aircraft to very small, inexpensive UAS. Traditional methods of photogrammetry have also given way to new equipment and sensors: digital cameras, infrared imagers, light detection and ranging (LiDAR) laser scanners, and now synthetic aperture radar (SAR). At the University of Alaska Fairbanks (UAF), we work extensively with unmanned aerial systems equipped with each of these newer sensors. UAF has significant experience flying unmanned systems in the US National Airspace, having begun in 1969 with scientific rockets and expanded to unmanned aircraft in 2003. Ongoing field experience allows UAF to partner effectively with outside organizations to test and develop leading-edge research in UAS and remote sensing. This presentation will discuss our research related to various sensors and payloads for mapping. We will also share our experience with UAS and optical systems for creating some of the first cadastral surveys in rural Alaska.

It has been recently proposed by Clayson and Kantha (2008) to evaluate the climatology of atmospheric turbulence through the detection of overturns in the free atmosphere by applying a Thorpe analysis on relatively low vertical resolution (LR) profiles collected from standard radiosoundings. Since then, several studies based on this idea have been published. However, the impact of instrumental noise on the detection of turbulent layers was completely ignored in these works. The present study aims to evaluate the feasibility of overturns detection from radiosoundings. For this purpose, we analyzed data of two field campaigns during which high-resolution (HR) soundings (10–20 cm) were performed simultaneously with standard LR soundings. We used the raw data of standard meteorological radiosondes, the vertical resolution ranging from 5 to 9 m. A Thorpe analysis was applied to both LR and HR potential temperature profiles. A denoising procedure was first applied in order to reduce the probability of occurrence of artificial overturns, i.e. potential temperature inversions due to instrumental noise only. We then compared the empirical probability density functions (pdf) of the sizes of the selected overturns from LR and HR profiles. From HR profiles measured in the troposphere, the sizes of the detected overturns range from 4 to ~1000 m. The shape of the size pdf of overturns is found to sharply decrease with increasing scales. From LR profiles, the smallest size of detected overturns is ~32 m, a similar decrease in the shape of the pdf of sizes being observed. These results suggest that overturns, resulting either from small-scale turbulence or from instabilities, can indeed be detected from meteorological radiosonde measurements in the troposphere and in the stratosphere as well. However they are rather rare as they belong to the tail of the size distribution of overturns: they only represent the 7 % largest events in the troposphere, and 4 % in the stratosphere.

The debate about the importance of bacterial infection in chronic obstructive pulmonary disease will continue. About half of exacerbations yield positive sputum bacteriology, and the isolation rate can be increased by selection of purulent samples. However, bacteria are also isolated in the stable state. The presence of bacteria in sputum alone during an exacerbation does not prove causation. Bacteria have been associated with airway inflammation both in the stable state, when the level of inflammation is related to the size of the bacterial load, and during exacerbations, when resolution of the inflammation is related to bacterial eradication. New evidence has been obtained from epidemiological, immunological and antibiotic studies that supports a role for bacterial infection in causing neutrophilic airway inflammation in chronic obstructive pulmonary disease, and if accepted should lead to new research in the use of antibiotics.

The actual impact on vertical transport of small-scale turbulence in the free atmosphere is still a debated issue. Numerous estimates of an eddy diffusivity exist, clearly showing a lack of consensus. MST radars were, and continue to be, very useful for studying atmospheric turbulence, as radar measurements allow one to estimate the dissipation rates of energy (kinetic and potential) associated with turbulent events. The two commonly used methods for estimating the dissipation rates, from the backscattered power and from the Doppler width, are discussed. The inference methods of a local diffusivity (local meaning here "within" the turbulent patch) by using the dissipation rates are reviewed, with some of the uncertainty causes being stressed. Climatological results of turbulence diffusivity inferred from radar measurements are reviewed and compared. As revealed by high resolution MST radar measurements, atmospheric turbulence is intermittent in space and time. Recent theoretical works suggest that the effective diffusivity of such a patchy turbulence is related to statistical parameters describing the morphology of turbulent events: filling factor, lifetime and height of the patches. It thus appears that a statistical description of the turbulent patches' characteristics is required in order to evaluate and parameterize the actual impact of small-scale turbulence on transport of energy and materials. Clearly, MST radars could be an essential tool in that matter.

Very high resolution radar measurements were performed in the troposphere and lower stratosphere by means of the PROUST radar. The PROUST radar operates in the UHF band (961 MHz) and is located in St. Santin, France (44°39’ N, 2°12’ E). A field campaign involving high resolution balloon measurements and the PROUST radar was conducted during April 1998. Under the classical hypothesis that refractive index inhomogeneities at half radar wavelength lie within the inertial subrange, assumed to be isotropic, kinetic energy and temperature variance dissipation rates were estimated independently in the lower stratosphere. The dissipation rate of temperature variance is proportional to the dissipation rate of available potential energy. We therefore estimate the ratio of dissipation rates of potential to kinetic energy. This ratio is a key parameter of atmospheric turbulence which, in locally homogeneous and stationary conditions, is simply related to the flux Richardson number, Rf .Key words. Meteorology and atmospheric dynamics (turbulence) – Radio science (remote sensing)

A campaign devoted to stratosphere-troposphere exchange mechanisms studies has been held on 4–5 March 1995, during a tropopause folding passage over western Europe. The observational network included 1 UHF and 3 VHF radar, 1 temperature lidar, and 1 ozone lidar, deployed in the south of France. The fold is associated with a strong quasi meridional jet stream running along the west side of an upper level trough forming a potential vorticity (PV) anomaly. During this campaign, the PV anomaly is advected east-wards without major deformations, with an average velocity of about 30 km per hour. Therefore, a frozen field hypothesis has been used in order to compare the results obtained in the different sites of the network. Under this hypothesis, the same structures associated with the anomaly are observed by each radar or lidar, at the same time relative to this anomaly. The fold is put into evidence by the ozone lidar of the network and by the VHF radars when computing the aspect ratio. The turbulent activity observed by the OHP VHF radar and by the high resolution UHF PROUST radar (30 m altitude resolution) is concentrated in the wind shear regions generated by the jet stream above and below its axis. In the lower level wind shear, turbulent layers are detected within the fold and across its anticyclonic boundary, thus allowing turbulent exchanges with the tropospheric air masses. A large area of aspect ratio greater than 3 is observed in the troposphere during more than ten hours after the passage of the fold by the VHF radars. This particular signature is tentatively analyzed as the progressive dilution of air masses of stratospheric origin extruded from the fold by the turbulent processes. In the upper level wind shears, turbulent layers parallel to the wind isotachs are observed, whose thickness is often smaller than 100 m and are separated by non turbulent regions. A good correlation is found between the spatio-temporal evolution of these turbulent structures observed by the PROUST radar, and the stability structures observed at the same relative time by the temperature lidar. In addition the same turbulent structures are observed to be parallel to the isophase lines of the wind fluctuations, observed at the same relative time by the Lannemezan radar. These characteristics are compatible with the presence of unstable inertia-gravity waves, generated by the jet stream while the turbulent layers could be the signature of their saturation processes.Key words. Atmospheric composition and structure (evolution of the atmosphere) – Meteorology and atmospheric dynamics (middle atmosphere dynamics; turbulence)

The narrator of Antonio Tabucchi’s 1991 novel Requiem has an appointment with a dead poet. During the twenty-four hours which he spends in Lisbon waiting to keep his appointment, he undertakes a physical journey through the city, which turns out to be also a parallel journey of the anima through memory. The journey is initiated by a book, Livro do Desassossego (The book of disquietude), by Fernando Pessoa, the “great poet” who awaits the narrator in the city of this novel. This paper examines Tabucchi's "dialogue with the dead", both within this text and across other Tabucchi texts. It endeavours to show how Tabucchi’s recuperation of Pessoa becomes the recognition of the Other's voices within one’s own unconscious, enabling the exploration of repressed discourse.

RESUMO: O objectivo do estudo, multicêntrico e multinacional, foi o de comparar a efectividade do tratamento oral de 5 dias de moxifloxacina com o tratamento antibiótico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina) nas EABC.Mil novecentos e trinta e cinco doentes foram seleccionados segundo os seguintes critérios: idade superior a 45 anos com bronquite crónica estável, carga tabágica superior a 20 UMA, 2 ou mais EACB no último ano e FEV1 inferior a 85% da referência (estado basal pré-exacerbação).A randomização de 733 doentes, estratificada por corticoterapia associada ou não, foi efectuada na presença de uma EABC que cumprisse os critérios de Anthonisen de tipo I em dois braços: 5 dias de moxifloxacina (400 mg/d) versus 7 dias de um de 3 antibióticos seleccionados pelo investigador, segundo os seus próprios critérios clínicos; amoxicilina (500 mg 3xd), cefuroxime (250 mg 2xd) ou claritromicina (500 mg 2xd).A avaliação primária de resultados consistiu no sucesso clínico (melhoria clínica e não haver necessidade de mudança de antibiótico) e as secundárias, cura clínica (regresso ao estado basal pré-exacerbação), necessidade subsequente de antibioterapia, tempo até à próxima exacerbação e sucesso bacteriológico.As avaliações subsequentes à randomização foram efectuadas 7 a 10 dias após o início do tratamento e mensalmente até a uma nova exacerbação ou decorridos 9 meses.A moxifloxacina foi equivalente aos outros antibióticos na variável primária â sucesso clínico (87,6% vs 83%).No entanto, a moxifloxacina foi significativamente superior na cura clínica (70,9% vs 62,8%) e sucesso bacteriológico (91,5% vs 81%). Cerca do dobro dos doentes no braço antibiótico convencional (14,1%) necessitaram de antibioterapia sistémica subsequente contra 7,6% no braço moxifloxacina.A superioridade da moxifloxacina em relação à terapêutica de referência manteve-se quando se consideraram os subgrupos de prognóstico, nomea-damente o número de exacerbações no ano anterior, idade dos doentes, obstrução das vias aéreas, duração da doença e doenças concomitantes (nomeadamente cardíaca)A moxifloxacina demonstrou uma erradicação bacteriológica superior na população microbiologicamente válida (devido, em grande parte, à persistência de H. influenzae nos grupos de referência).Foi utilizado um número significativamente maior de antibióticos para tratamento das exacerbações no grupo dos fármacos de referência durante o período de seguimento, devido a falências terapêuticas neste grupo, comparativamente com a moxifloxacina.O tempo até à próxima exacerbação foi significativamente superior com moxifloxacina (131 dias vs 103 dias) e a ocorrência de falência, nova exacerbação ou novo antibiótico foi muito inferior até aos 5 meses. COMENTÃRIOS: Está demonstrada a eficácia da terapêutica antibiótica no tratamento das EABC do tipo I e do tipo II de Anthonisen.à com base nestes critérios que os estudos com antibióticos têm sido realizados comparando a ânão inferioridadeâ (equivalência) clínica e bacteriológica dos mais recentes antibióticos â β-lactâmicos (com inibidores das blactamases), cefalosporinas, macrólidos e quinolonas â relativamente aos mais antigos (ampicilina, tetraciclina e cotrimoxazole).No entanto, estes estudos têm excluído doentes graves, com comorbilidades, assim como não estudam apenas doentes com DPOC (isto é, com obstrução das vias aéreas), pois incluem doentes de idades mais jovens e ainda sem obstrução.Este estudo MOSAIC foi desenhado para avaliar a eficácia do tratamento das exacerbações infecciosas (critérios de Anthonisen) em doentes com DPOC (obstrução) de 5 dias com moxifloxacina comparativamente a um regime terapêutico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina).Este é o primeiro estudo concebido especificamente para avaliar a efectividade de um antibiótico (moxifloxacina) nas exacerbações infecciosas de doentes com DPOC.à de lamentar que estes doentes sejam aqui designados de bronquíticos crónicos, o que não é rigoroso, mas parece que os motivos se prendem com a aprovação pelas entidades reguladoras dos medicamentos.Outro aspecto também ligado à aprovação por essas entidades prende-se com a demonstração de equivalência clínica de um novo antibiótico, o que ficou demonstrado neste estudo.Ora, se é equivalente, porquê utilizar o antibiótico mais recente, se os antibióticos mais convencionais atingem taxas de sucesso iguais quando avaliadas aos 7 a 10 dias?Este é o aspecto fundamental deste estudo, e a utilizar em futuros ensaios, uma vez que fica demonstrado que parâmetros de médio e longo prazos (superiores aos 7 a 10 dias) na DPOC são fundamentais como critérios de avaliação de efectividade clínica de um novo antibiótico nas exacerbações agudas da DPOC.Aguardam-se os resultados deste estudo no que respeita à qualidade de vida e à fármaco-economia.Por fim, é de salientar que este estudo contou com a participação de 2 centros portugueses (H. Pulido Valente Dr.ª Cecília Nunes, e H. S. João Dr. João Almeida), o que nem sempre acontece com outros estudos multinacionais no âmbito da DPOC e asma.

RESUMO: O objectivo do estudo, multicêntrico e multinacional, foi o de comparar a efectividade do tratamento oral de 5 dias de moxifloxacina com o tratamento antibiótico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina) nas EABC.Mil novecentos e trinta e cinco doentes foram seleccionados segundo os seguintes critérios: idade superior a 45 anos com bronquite crónica estável, carga tabágica superior a 20 UMA, 2 ou mais EACB no último ano e FEV1 inferior a 85% da referência (estado basal pré-exacerbação).A randomização de 733 doentes, estratificada por corticoterapia associada ou não, foi efectuada na presença de uma EABC que cumprisse os critérios de Anthonisen de tipo I em dois braços: 5 dias de moxifloxacina (400 mg/d) versus 7 dias de um de 3 antibióticos seleccionados pelo investigador, segundo os seus próprios critérios clínicos; amoxicilina (500 mg 3xd), cefuroxime (250 mg 2xd) ou claritromicina (500 mg 2xd).A avaliação primária de resultados consistiu no sucesso clínico (melhoria clínica e não haver necessidade de mudança de antibiótico) e as secundárias, cura clínica (regresso ao estado basal pré-exacerbação), necessidade subsequente de antibioterapia, tempo até à próxima exacerbação e sucesso bacteriológico.As avaliações subsequentes à randomização foram efectuadas 7 a 10 dias após o início do tratamento e mensalmente até a uma nova exacerbação ou decorridos 9 meses.A moxifloxacina foi equivalente aos outros antibióticos na variável primária â sucesso clínico (87,6% vs 83%).No entanto, a moxifloxacina foi significativamente superior na cura clínica (70,9% vs 62,8%) e sucesso bacteriológico (91,5% vs 81%). Cerca do dobro dos doentes no braço antibiótico convencional (14,1%) necessitaram de antibioterapia sistémica subsequente contra 7,6% no braço moxifloxacina.A superioridade da moxifloxacina em relação à terapêutica de referência manteve-se quando se consideraram os subgrupos de prognóstico, nomeadamente o número de exacerbações no ano anterior, idade dos doentes, obstrução das vias aéreas, duração da doença e doenças concomitantes (nomeadamente cardíaca)A moxifloxacina demonstrou uma erradicação bacteriológica superior na população microbiologicamente válida (devido, em grande parte, à persistência de H. influenzae nos grupos de referência).Foi utilizado um número significativamente maior de antibióticos para tratamento das exacerbações no grupo dos fármacos de referência durante o período de seguimento, devido a falências terapêuticas neste grupo, comparativamente com a moxifloxacina.O tempo até à próxima exacerbação foi significativamente superior com moxifloxacina (131 dias vs 103 dias) e a ocorrência de falência, nova exacerbação ou novo antibiótico foi muito inferior até aos 5 meses. COMENTÃRIOS: Está demonstrada a eficácia da terapêutica antibiótica no tratamento das EABC do tipo I e do tipo II de Anthonisen.à com base nestes critérios que os estudos com antibióticos têm sido realizados comparando a ânão inferioridadeâ (equivalência) clínica e bacteriológica dos mais recentes antibióticos â β-lactâmicos (com inibidores das blactamases), cefalosporinas, macrólidos e quinolonas â relativamente aos mais antigos (ampicilina, tetraciclina e cotrimoxazole).No entanto, estes estudos têm excluído doentes graves, com comorbilidades, assim como não estudam apenas doentes com DPOC (isto é, com obstrução das vias aéreas), pois incluem doentes de idades mais jovens e ainda sem obstrução.Este estudo MOSAIC foi desenhado para avaliar a eficácia do tratamento das exacerbações infecciosas (critérios de Anthonisen) em doentes com DPOC (obstrução) de 5 dias com moxifloxacina comparativamente a um regime terapêutico convencional de 7 dias (amoxicilina, cefuroxime ou claritromicina).Este é o primeiro estudo concebido especificamente para avaliar a efectividade de um antibiótico (moxifloxacina) nas exacerbações infecciosas de doentes com DPOC.à de lamentar que estes doentes sejam aqui designados de bronquíticos crónicos, o que não é rigoroso, mas parece que os motivos se prendem com a aprovação pelas entidades reguladoras dos medicamentos.Outro aspecto também ligado à aprovação por essas entidades prende-se com a demonstração de equivalência clínica de um novo antibiótico, o que ficou demonstrado neste estudo.Ora, se é equivalente, porquê utilizar o antibiótico mais recente, se os antibióticos mais convencionais atingem taxas de sucesso iguais quando avaliadas aos 7 a 10 dias?Este é o aspecto fundamental deste estudo, e a utilizar em futuros ensaios, uma vez que fica demonstrado que parâmetros de médio e longo prazos (superiores aos 7 a 10 dias) na DPOC são fundamentais como critérios de avaliação de efectividade clínica de um novo antibiótico nas exacerbações agudas da DPOC.Aguardam-se os resultados deste estudo no que respeita à qualidade de vida e à fármaco-economia.Por fim, é de salientar que este estudo contou com a participação de 2 centros portugueses (H. Pulido Valente - Dr.ª Cecília Nunes, e H. S. João Dr. João Almeida), o que nem sempre acontece com outros estudos multinacionais no âmbito da DPOC e asma.

For a number of Italian writers the modem city has come to mean as much a style, a fractured syntax, a paratactic sign-system, as a physical construct with certain demonstrable boundaries. In the works of such authors as halo Calvino and Francesca Duranti the crisis of reason is symbolized by indeterminate aleatory structures - such as the labyrinth or the chessboard - all of which can be considered variations on the theme of the modem city. Calvino and Duranti’s invisible or labyrinthine cities serve as an infinitely malleable poetic dramatization of the mind. The cities are both projections of their respective narrators and images that shape the reader's experience. By analysing the spatial structures of the narratives and by examining the use of space as a locus of fantasy this article shows how these novels chart cityscapes of the mind.