Search

Patients with myeloma often face significant diagnostic delay, with up to one-third of UK patients diagnosed after an emergency presentation (EP). Compared with other routes, patients presenting as an emergency have more advanced disease, increased complications, and poorer prognosis. An economic model was developed using a decision-tree framework and lifetime time horizon to estimate costs related to different presentation routes (EP, general practitioner [GP] 2-week wait, GP urgent, GP routine, and consultant to consultant) for UK patients diagnosed as having myeloma. After diagnosis, patients received one of 3 first-line management options (observation, active treatment, or end-of-life care). Inputs were derived from UK health technology assessments and targeted literature reviews, or based on authors' clinical experience where data were unavailable. Active treatment, complication, and end-of-life care costs were included. The average per-patient cost of treating myeloma (across all routes) was estimated at £146 261. The average per-patient cost associated with EP (£152 677) was the highest; differences were minimal compared with GP 2-week wait (£149 631) and consultant to consultant (£147 237). GP urgent (£140 025) and GP routine (£130 212) were associated with marginally lower costs. Complication (£42 252) and end-of-life care (£11 273) costs were numerically higher for EP than other routes (£25 021-£38 170 and £9772-£10 458, respectively). An economic benefit may be associated with earlier diagnosis, gained via reduced complication and end-of-life care costs. Strategies to expedite myeloma diagnosis and minimize EPs have the potential to improve patient outcomes and may result in long-term savings that could offset any upfront costs associated with their implementation. • Patients with multiple myeloma who present as an emergency have a poorer prognosis and additional complications compared with those diagnosed via other routes. • This analysis evaluates the cost associated with various routes of presentation for patients with multiple myeloma and explores the economic impact of diagnosis via emergency presentation, which can be associated with diagnostic delay. • The costs resulting from complications and end-of-life care are higher for patients presenting as an emergency than other routes, suggesting the potential to reduce these costs with earlier diagnosis. Therefore, strategies to expedite myeloma diagnosis and minimize emergency presentations not only have the potential to improve patient outcomes but may also result in long-term cost savings that could offset any upfront costs associated with their implementation. [ABSTRACT FROM AUTHOR]

• Females have lower range in legibility scores in comparison to males. • Lateral grips generated greater upper trapezius activity than the DT grip style. • The LQ grip style generated longer stroke durations than the DT grip style. This study aimed to explore the differences in muscle activity, handwriting legibility, and consistency when using the 4 primary handwriting grip styles: dynamic quadrupod (DQ), dynamic tripod, lateral quadrupod (LQ) and lateral tripod. Thirty-four 18-22-year-old participants completed a handwriting legibility test on paper as well as consistency and metrics tests using both surface electromyography and a digital writing tablet. Electromyography was used to measure the activity of 6 muscles associated with handwriting, and the tablet measured stroke duration, length, velocity, and pen pressure. Subjects used each grip style with all protocols and scores were normalized to their native grip. Significance was set at P <.05. Females had a lower range in legibility scores than males by 3.5% ± 1.7% (p =.046, d = 0.713), but grip style did not impact legibility. The upper trapezius (UT) was more active in the lateral tripod and LQ grips compared to DQ by 16.8% ± 5.2% and by 13.8% ± 5.2%, (p =.007, p =.012, respectively, partial η2 = 0.188). The stroke duration was greater in the LQ grip style than dynamic tripod and DQ grip styles (p =.008, p =.023, respectively; partial η2 = 0.123). Lateral grip styles involve more whole-arm, stabilizing movements while dynamic grip styles require fine dexterous movements. Furthermore, females are likely to be able to employ any grip with minimal effect on legibility. For a patient needing guidance in rehabilitation, understanding the differences in grips could aid selection of the optimum grip style to employ based on their muscular control deficits. [ABSTRACT FROM AUTHOR]

The modern ethos of burn care requires a holistic approach that helps patients to not only survive but also maintain a good quality of life. Bromelain-based enzymatic debridement with Nexobrid™ (NXB) has been shown to selectively debride burnt tissue and allow dermal preservation, which has the potential to reduce surgical burden and improve scarring. In this study, early experience with the use of Nexobrid™ at a tertiary burns centre between July 2016 and December 2019 is presented. In particular, the study assessed whether NXB had changed the acute care delivered to this cohort. A retrospective analysis of the patients' records was performed. Results were analysed and presented in the context of current literature. Twenty adult patients (17 male, 3 female) underwent enzymatic debridement with NXB. Median age was 42.5 years. Mean total burn surface area (TBSA) on admission was 20%. Twelve patients were admitted to the intensive care unit, and eight were admitted to the adult burns ward. Mean TBSA treated with NXB was 8.2%, usually within 24 h of admission (mean). All patients had anaesthetist-led analgesia. NXB debridement was successful in 55% of patients, obviating the need for escharotomy in some patients. Sixty percent of all patients required further surgery, and 80% of facial burns treated with NXB required further surgery. Inotrope support was associated with NXB failure (p = 0.015). Mean length of stay was 29 days. Current evidence, including our own findings, cannot justify replacing the current surgical standard of care with NXB, but it certainly solidifies enzymatic debridement as a useful adjunct that should form part of the modern burn surgeon's armamentarium. [ABSTRACT FROM AUTHOR]

Purpose: To compare the utility of low-dose versus standard cone-beam computed tomography (CT) angiography protocols in identifying nontarget embolization (NTE) during prostatic artery embolization (PAE).Materials and Methods: A prospective, single-center, Phase-1 study (NCT02592473) was conducted for lower urinary tract symptoms in benign prostatic hyperplasia. Prostate volume, international prostate symptom score (IPSS), quality of life score (QoL), International Index of Erectile Function (IIEF), peak flow rate, UCLA Prostate Cancer Index (UCLA-PCI), and postvoid residual were recorded at baseline and 1, 3, 6, 12, and 24-months after PAE. Six-second (standard protocol, n = 29) or 5-second (low-dose protocol n = 45) rotations were made. Images were selected and matched in pairs by areas of NTE and compared by readers using a binomial generalized estimating equation model. Procedural outcomes were analyzed using a linear mixed model.Results: Seventy-four cone-beam CT angiographies were performed in 21 patients. IPSS and QoL scores significantly improved (P <.05). There was no change in UCLA-PCI or IIEF scores. Dose area product of the low- and standard-dose protocol were 37,340.82 mGy·cm2 ± 104.66 and 62,645.66 mGy·cm2 ± 12,711.48, respectively, representing a dose reduction of 40.4%. A total of 120 comparisons showed no preference between the 2 protocols (P =.24). Observers identified 76 and 69 instances of NTE in the standard- and low-dose protocols, respectively (P =.125).Conclusions: Low-dose cone-beam CT angiography achieved equivalent clinical utility in identifying NTE during PAE, with the advantage of a lower radiation dose. [ABSTRACT FROM AUTHOR]

Conventional karyotype is one of the most relevant prognostic factors in MDS. However, about 50% of patients with MDS have a normal karyotype. Usually, 20–25 normal metaphases (nMP) are considered to be optimal to exclude small abnormal clones which might be associated with poor prognosis. This study evaluated the impact of examining a suboptimal number of metaphases in patients recruited to the EUMDS Registry with low and intermediate-1 risk according to IPSS. Only 179/1049 (17%) of patients with a normal karyotype had a suboptimal number of nMP, defined as less than 20 metaphases analyzed. The outcome (overall survival and progression-free survival) of patients with suboptimal nMP was not inferior to those with higher numbers of analyzed MP both in univariate and multivariate analyses. For patients with an abnormal karyotype, 224/649 (35%) had a suboptimal number of MP assessed, but this did not impact on outcome. For patients with a normal karyotype and suboptimal numbers of analyzable metaphases standard evaluation might be acceptable for general practice, but we recommend additional FISH-analyses or molecular techniques, especially in candidates for intensive interventions. [ABSTRACT FROM AUTHOR]

The assessment of a cap for remediation of sediments requires long-term monitoring because of the slow migration of contaminants in porous media. In this study, coring and passive sampling tools were used to assess the transport and degradation of polycyclic aromatic hydrocarbons (PAHs) in an amended cap (sand + Organoclay® PM-199) in the Grand Calumet River (Indiana, USA) during four sampling events from 2012 to 2019. Measurements of three PAHs (phenanthrene (Phe), pyrene (Pyr) and benzo[a]pyrene (BaP), representing low, medium, and high molecular weight compounds, respectively) showed a difference of at least two orders of magnitude between bulk concentrations in the native sediments and the remediation cap. Averages of pore water measurements also showed lower levels in the cap respective to the native sediments by a factor of at least 7 for Phe and 3 for Pyr. In addition, between the baseline (BL), which corresponds to observations from 2012 to 2014, and the measurements in 2019, there was a decrease in depth-averaged pore water concentrations of Phe (C 2019 / C B L = 0.20 − 0.07 + 0.12 in sediments and 0.27 − 0.10 + 0.15 in cap) and Pyr (C 2019 / C B L = 0.47 − 0.12 + 0.16 in sediments and 0.71 − 0.20 + 0.28 in the cap). In the case of BaP in pore water, no change was observed in native sediments (C 2019 / C B L = 1.0 − 0.24 + 0.32) and there was an increase in the cap (C 2019 / C B L = 2.0 − 0.54 + 0.72). Inorganic anions and estimates of pore water velocity along with measurements of PAHs were used to model the fate and transport of contaminants. The modeling suggested that degradation of Phe (t 1 / 2 = 1.12 − 0.11 + 0.16 years) and Pyr (t 1 / 2 = 5.34 − 1.8 + 5.3 years) in the cap is faster than migration, thus the cap is expected to be protective of the sediment-water interface indefinitely for these constituents. No degradation was noted in BaP and the contaminant is expected to reach equilibrium in the capping layer over approximately 100 years if there exists sufficient mass of BaP in the sediments and there is no deposition of clean sediment at the surface. [Display omitted] • Remediation cap effectively isolates contaminated solids from surface water • Passive sampling measurements are statistically consistent over multiple years • Passive sampling of conservative tracers can aid in conceptual model development • Observations indicate larger attenuation rates for low molecular weight compounds [ABSTRACT FROM AUTHOR]

1. Describe the impact of spousal death on survival in people with dementia, chronic organ failure, and cancer. 2. Identify the potential mechanisms by which spousal death may affect survival in people with serious illness and consider potential implications for clinical or community-based interventions for these populations. The "widowhood effect," in which mortality rises in the period following death of a spouse, may be heightened in people with serious illnesses, like dementia, cancer, and chronic organ failure, in which support needs are high and for whom spouses typically provide extensive caregiving support. Yet there are limited data on widowhood and mortality that account for these serious illnesses. To determine the relative mortality risk of widowhood among those with dementia, cancer, and chronic organ failure. Retrospective cohort study among community-dwelling, married/partnered persons, ≥65 years, enrolled in the Health and Retirement Study, a longitudinal nationally representative survey of older adults linked to Medicare claims, from 2000-2018. We used cox proportional hazards model to determine short- and long-term mortality in people with dementia (PWD), heart failure (PWHF), and cancer (PWC). We identified 2,091 PWD (846 experienced widowhood), 463 PWHF (170 experienced widowhood), and 744 PWC (215 experienced widowhood). Compared to those with serious illness alone, those with serious illness and widowhood had increased 1-year mortality in PWD (7% vs. 5%; RR 1.4) and PWHF (11% vs. 7%; RR 1.5) and decreased 1-year mortality in PWC (10% vs. 11%; RR 0.9). These effects were diminished beyond 1 year following the widowhood event (1-year mortality rate 6% for PWD [RR 1.2], 10% for PWHF [RR 1.4], and 8% for PWC [RR 0.73]). Widowhood increases the risk of dying for those with serious illness within the first year following the event and is most pronounced in those with illnesses that have prolonged periods of poor function, such as in dementia and heart failure. Widowhood may be an important disruptive event that may deserve further clinical or community-based interventions. [ABSTRACT FROM AUTHOR]

Smallholder farmers in Malawi must cope with small farm size, low soil fertility and production risks associated with rainfed agriculture. Integration of legumes into maize-based cropping systems is advocated as a means to increase production of diverse nutrient-dense grains and improve soil fertility. It is difficult to achieve both aims simultaneously, however. Short-duration grain legumes rarely produce enough biomass to appreciatively improve soils, and long duration pigeonpea, commonly grown in Malawi as a dual purpose crop, produces little or no edible grain as a consequence of grain-filling into the dry season. A novel technology is the doubled-up legume rotation (DLR) system in which two legumes with complementary phenology are intercropped and grown in rotation with maize. Initial performance from on-farm research is favorable; however, it is crucial to understand competition for resources in mixed cropping systems under variable soil and climate conditions. We used soil and crop yield data from farmer participatory trials to parameterize the Agricultural Production Systems Simulator (APSIM) and evaluate its performance in simulating observed treatments at three locations in central Malawi. We used the calibrated APSIM model to investigate the performance of DLR and other maize-based systems across 26 growing seasons (1979–2005) in the three agroecologies. We simulated two DLR systems (maize rotated with a groundnut/pigeonpea or soybean/pigeonpea intercrop), maize rotated with groundnut or soybean, maize intercropped with pigeonpea, and continuous maize under a range of N fertilizer inputs. We extended findings to the household level by determining calorie and protein yields of these systems, and calculating the chance that an average household could meet their food requirements by dedicating all available farmland to a given system. Simulated maize grain yields in DLR and maize-grain legume rotations were essentially equivalent, and exceeded yields in maize/pigeonpea intercrop and sole cropped maize receiving comparable fertility inputs. All rotation systems were more likely to meet household calorie and protein needs than other systems receiving equivalent inputs. DLR systems accumulated higher total soil C and N over time than traditional rotation systems in areas where pigeonpea performed well. However, the effects of improved soil fertility on maize yields were counterbalanced by factors including N immobilization and water availability. We conclude that where growing conditions allow, DLR can harness the complementary phenology of pigeonpea to build soil quality for the future without reducing maize yields or compromising household food production in the immediate term. [ABSTRACT FROM AUTHOR]

Background: Population-based information on cancer incidence, prevalence and outcome are required to inform clinical practice and research; but contemporary data are lacking for many myeloid malignancy subtypes. Methods: Set within a socio-demographically representative UK population of ∼4 million, myeloid malignancy data (N=5231 diagnoses) are from an established patient cohort. Information on incidence, survival (relative & overall), transformation/progression, and prevalence is presented for >20 subtypes. Results: The median diagnostic age was 72.4years (InterQuartile Range 61.6-80.2), but there was considerable subtype heterogeneity, particularly among the acute myeloid leukaemias (AML) where medians ranged from 20.3 (IQR 13.9-43.8) for AML 11q23 through to 73.7 (IQR 57.3-79.1) for AML with no recurrent genetic changes. Five-year Relative Survival (RS) estimates varied hugely; from <5% for aggressive entities like therapy-related AML (2.6%, 95% Confidence Interval 0.4-9.0) to >85% for indolent/treatable conditions like chronic myeloid leukaemia (89.8%, 95% CI 84.0-93.6). With a couple of notable exceptions, males experienced higher rates and worse survival than females: the age-standardized incidence rates of several conditions was 2-4 higher in males than females, and the 5-year RS for all subtypes combined was 48.8% (95% CI 46.5-51.2) and 60.4% (95% CI 57.7-62.9) for males and females respectively. During follow-up (potential minimum 2 years and maximum 11years) myelodysplastic syndrome (MDS) progression to AML ranged from 25% for refractory anaemia with excess blasts through to 5% for refractory anaemia with ring sideroblasts: the median interval between MDS and AML diagnosis was 9.0 months (IQR 4.8-17.4months). Conclusions: The marked incidence and outcome variations seen by subtype, sex and age, confirm the requirement for "real-world" longitudinal data to inform aetiological hypotheses, healthcare planning, and future monitoring of therapeutic change. Several challenges for routine cancer registration were identified, including the need to link more effectively to diagnostic and clinical data sources, and to review policies on the recording of progressions and transformations. [ABSTRACT FROM AUTHOR]

Coastal systems on the Laurentian Great Lakes are highly affected by meter scale variability in water levels that occur across a range of temporal scales, from hourly wind set-up and seiches to inter-annual highs and lows driven by longer-term patterns of precipitation and evaporation. High lake level periods are often associated with increased coastal erosion and flooding, stress on sensitive wetland ecosystems, and damage to infrastructure. During the late 2010s, water levels on the Great Lakes neared or exceeded record highs, initiating a renewed interest in coastal management across the region. The objective of this study was to inform and engage regional experts and local interest groups and to examine their perspectives on the important processes, coastal management solutions, and applied research needed for the conservation of the Point Pelee (PP) foreland in Lake Erie. A virtual conference, the Point Pelee 'Hackathon,' used a crowd-sourced approach to problem solving where participants were presented 'the sum of the discourse,' or the current state of knowledge on coastal processes and management affecting the region. The conference covered a range of topics through invited speaker presentations, followed by individual surveys and moderated group discussions. Q-methodology surveys incorporated concepts informed by the sum of the discourse and identified statistically significant sources of agreement and disagreement on management challenges and solutions among 'like-minded' individuals. Common viewpoints identified harbours & jetties and sediment nourishment projects as an important cause of erosion and mitigation strategy, whereas highly opposed viewpoints were held on the importance of sediment supply and adopting a 'do-nothing' approach for coastal management. Emergent and more nuanced viewpoints were also found within group discussions, highlighting important considerations that can be used to advance the discourse on proposed management solutions. The results of this study can be used to guide the development of a regional coastal management strategy, and a similar methodology can be used to inform and engage stakeholders and examine perspectives on a range of issues affecting the world's marine and lacustrine coasts. • Coastal systems on the Laurentian Great Lakes are highly influenced by short- and longer-term lake level fluctuations. • High lake level periods are cause increased coastal erosion, flooding, stress on ecosystems, and damage to infrastructure. • Regional experts and local interest groups were engaged to examine perspectives on coastal management strategies. • Communal and opposing views were identified from Q-methodology surveys and moderated group discussions. • Results indicate significant sources of agreement and disagreement that can be used to guide a regional management strategy. [ABSTRACT FROM AUTHOR]

Conveyor belt fires in an underground mine pose a serious life threat to miners. Water sprinkler systems are usually used to extinguish underground conveyor belt fires, but because of the complex interaction between conveyor belt fires and mine ventilation airflow, more effective engineering designs are needed for the installation of water sprinkler systems. A computational fluid dynamics (CFD) model was developed to simulate the interaction between the ventilation airflow, the belt flame spread, and the water spray system in a mine entry. The CFD model was calibrated using test results from a large-scale conveyor belt fire suppression experiment. Simulations were conducted using the calibrated CFD model to investigate the effects of sprinkler location, water flow rate, and sprinkler activation temperature on the suppression of conveyor belt fires. The sprinkler location and the activation temperature were found to have a major effect on the suppression of the belt fire, while the water flow rate had a minor effect. [ABSTRACT FROM AUTHOR]

Passive sampling for hydrophobic organics in soils and sediments is typically accomplished by measuring the equilibrium accumulation of the target compounds onto a sorbing polymer. Because the samplers do not often achieve equilibrium in the environment, the release of performance reference compounds (PRCs) pre-loaded on the sampler is used to estimate the extent of equilibrium uptake of a similar target compound. In this work, we evaluate the effect of non-equilibrium loading of PRCs on the estimated equilibration of target compounds. A numerical transport model considering both internal and external mass transfer resistances to the polymer during loading from a finite reservoir was constructed to predict PRC distribution polymer sheets. An analytical internal diffusion, external mass transfer limited model is then employed to simulate the release of the PRCs and predict both the apparent and actual approach to equilibration for the uptake of target compounds. Partial equilibration during loading of PRCs does not lead to inaccuracies in target compound equilibration except when internal resistances control both PRC release and target compound uptake, under which conditions the PRCs overestimate the extent of equilibration of target compounds. This is likely to occur during short PRC loading times (e.g., <1 month) and thick polymer sheets (e.g., >100 µm in thickness). If external mass transfer resistances control PRC release and target compound uptake, even partially loaded PRCs can accurately indicate the extent of equilibration of target compounds as long as the initial PRC loading is adequately characterized. [Display omitted] • Nonuniform loading of PRCs can lead to over-estimation of target compound equilibration. • PRCs indicate degree of equilibration if external resistances control target compound uptake. • PRCs indicate target compound equilibration if time of field exposure exceeds L2/D p. • PRC equilibration errors only likely in thick (>100 µm) LDPE or POM and exposure times < L2/D p. [ABSTRACT FROM AUTHOR]

Objectives: We present a new method for determining prevalence estimates together with estimates of their precision, from incidence and survival data using Monte-Carlo simulation techniques. The algorithm also provides for the incidence process to be marked with the values of subject level covariates, facilitating calculation of the distribution of these variables in prevalent cases. Methods: Disease incidence is modelled as a marked stochastic process and simulations are made from this process. For each simulated incident case, the probability of remaining in the prevalent sub-population is calculated from bootstrapped survival curves. This algorithm is used to determine the distribution of prevalence estimates and of the ancillary data associated with the marks of the incidence process. This is then used to determine prevalence estimates and estimates of the precision of these estimates, together with estimates of the distribution of ancillary variables in the prevalent sub-population. This technique is illustrated by determining the prevalence of acute myeloid leukaemia from data held in the Haematological Malignancy Research Network (HMRN). In addition, the precision of these estimates is determined and the age distribution of prevalent cases diagnosed within twenty years of the prevalence index date is calculated. Conclusion: Determining prevalence estimates by using Monte-Carlo simulation techniques provides a means of calculation more flexible that traditional techniques. In addition to automatically providing precision estimates for the prevalence estimates, the distribution of any measured subject level variables can be calculated for the prevalent sub-population. Temporal changes in incidence and in survival offer no difficulties for the method. [ABSTRACT FROM AUTHOR]

Abstract: Carbon monoxide (CO) and carbon dioxide (CO2) emissions during a spontaneous heating event in a coal mine are important gases to monitor for detecting the spontaneous heating at an early stage. However, in underground coal mines, the CO and CO2 concentrations and their related fire ratios may be affected by mine ventilation. In this study, CO and CO2 emissions from spontaneous heating of a U.S. coal sample were evaluated in an isothermal oven under different airflow ventilation rates ranging from 100 to 500cm3/min. Laboratory experiments were conducted at oven temperatures of 70, 90, and 100°C. The temperature at the center of the coal sample was continually monitored, while the CO, CO2, and oxygen (O2) concentrations of the exit gas were continually measured. The results indicate that CO was generated immediately after the airflow passed through the coal, while CO2 was generated in a late phase. The amounts of CO generated under different airflow rates were approximately the same at the initial temperature of 70°C, while the amounts of CO generated increased significantly as the airflow rates and initial temperatures increased. The ratio of CO/CO2 was found to be independent of airflow rate and initial temperature, approaching a constant value of 0.2 quickly if there was no thermal runaway. The value tended to decrease when a thermal runaway took place. The CO/O2 deficiency ratio was dependent on both airflow rates and the initial temperature. The experimental results are in qualitative agreement with some large-scale test and field monitoring results. [Copyright &y& Elsevier]

Abstract: A computational fluid dynamics (CFD) study was conducted to model effects of coal properties on the potential for spontaneous heating in longwall gob (mined-out) areas. A two longwall panel district using a bleeder ventilation system was simulated. The permeability and porosity profiles for the longwall gob were generated from a geotechnical model and were used as inputs for the three-dimensional CFD modeling. The spontaneous heating is modeled as the low-temperature oxidation of coal in the gob using kinetic data obtained from previous laboratory-scale spontaneous combustion studies. Heat generated from coal oxidation is dissipated by convection and conduction, while oxygen and oxidation products are transported by convection and diffusion. Unsteady state simulations were conducted for three different US coals and simulation results were compared with some available test results. The effects of coal surface area and heat of reaction on the spontaneous heating process were also examined. [Copyright &y& Elsevier]

Abstract: Data from a national case-control study are used to explore the relationships between childhood leukaemia, infant infection and three markers of infectious exposure – birth order, infant-activity group attendance and area-based deprivation. Amongst controls, clinically diagnosed infection in the first year varied little with birth order and infant-activity group attendance – with 4 in 5 children having at least one infection, and each child averaging around 2.9 (2.8–3.0). Amongst cases of acute lymphoblastic leukaemia (ALL), the levels of infection increased as the indices of infectious exposure increased – for example, odds ratios associated with at least one infection in the first year being 0.9 (95% confidence interval (CI): 0.6–1.4) for birth order one and 1.6 (95% CI: 1.1–2.2) for birth order two or more. By contrast, interview data were misleading, with mothers – particularly case mothers – consistently under-reporting. We conclude that the findings based on clinical data, combined with the markers of infectious exposure, confirm the observation that immune dysregulation among children who develop ALL is detectable from an early age. [Copyright &y& Elsevier]

Abstract: Objectives: To analyze post-androgen depletion (AD) primary tumors to identify markers of treatment failure because AD does not reduce the probability of prostate-specific antigen (PSA) failure after prostatectomy. Methods: Tumors removed by radical prostatectomy after 3 months of AD from 21 patients were analyzed for gene expression using oligonucleotide arrays. Differences between patients with and without relapse were identified using a conservative significance criteria of a threefold change and delta 0.68, ensuring a false discovery rate of less than 11%. Results: At 50 months of follow-up, 7 of the 18 evaluable patients developed a biochemical recurrence. Gleason grade, pretherapy PSA level, T stage, and margin status were similar between the two groups. Patients with recurrence had greater post-AD PSA levels than those without recurrence (0.87 versus 0.19 ng/mL; P = 0.042). Gene expression analysis revealed 35 probe sets overexpressed in tumors from patients who relapsed. Among the highest ranked probe sets were PSA and other androgen-responsive genes. Serum PSA values during AD revealed similar findings. After 40 days of AD, the PSA level in those without recurrence was 1.21 ng/mL versus 4.5 ng/mL in those with recurrence (P = 0.0034). Immunohistochemistry of post-AD tumors also demonstrated a high PSA staining intensity in many tumors that recurred relative to those that didn’t. Conclusions: The results of our study show that early recurrence is associated with expression of androgen-responsive genes. Surprisingly, these could be identified as early as 3 months after the initiation of AD therapy. Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study. [Copyright &y& Elsevier]

Background and Objective: Most advanced cancer patients have multiple tumors. Because the multiple tumors are from the same patient, the tumor sizes are expected to be correlated and the information contained in each additional tumor might not always have significant 'added value' toward the response assessment. Needing to measure only a subset of tumors would reduce workload for the study radiologist but is expected to increase the variability in response outcome. We compute this increment in variability and find a procedure for choosing the minimum number (m) of tumors among some fixed maximum number (M) of correlated tumors that must be considered to ensure precision of at least as high as a specified proportion of the precision obtained if one were to measure all M tumors. Method: The ratio V(m)(R)/V(M)(R) = M2[m + (m2 - m)rho(ICC)]/m2[M + (M2 - M)rho(ICC)] quantifies the percentage increment in variance of the response R, where rho(ICC) is the intra-class between tumors within patient correlation coefficient. The procedure for choosing the minimum number of tumors is demonstrated using data for 42 cancer patients with 10 or more tumors. Results: Using the criterion that >20% increase in variability due to selection of a subset out of M of 10 tumors is unacceptable, we find that m of 9, 6, 5, 3, and 2 tumors are needed when rho(ICC)=0.0 (no correlation), 0.2, 0.4, 0.6, and 0.8, respectively. If the criterion is made stricter to >10%, the number of tumors needed rise to 10, 8, 6, 4, and 3, respectively. For the example, 6 tumors out of 10 are found to provide sufficiently stable response categorization confirming the theoretical result. Conclusion: If cancer research community can agree on a percentage of variability in response outcome that is unacceptable, it is mathematically possible to recommend a minimum number of tumors that should be used for response assessment. [ABSTRACT FROM AUTHOR]

Objective: Tumor shrinkage has been adopted as an end point for evaluating the effectiveness of new anticancer agents. The WHO (World Health Organization) criterion suggested measuring the tumor shrinkage by the change in the product of maximal diameter (MD) and the corresponding largest perpendicular diameter (LPD). The RECIST (Response Evaluation Criteria In Solid Tumor) guideline proposed using the change in MD only, based on the observation that this measure is more linearly related to tumor cell kill than the cross product (MD*LPD). Both criteria classify patients into four categories of response: complete response (CR: total disappearance), partial response (PR), stable disease (SD), and progressive disease (PD) but the criteria used in the definition of PD vary. It was anticipated that patients'' actual response categorization would not be considerably affected by utilizing the RECIST criteria instead of WHO. Empirical evidence supporting this fact was provided by retrospective analysis of several large datasets.Study design and setting: A statistical simulation is performed to generate tumor measurements and patient response data under meaningful probability distributions with parameters based on data from 130 patients on clinical trials at a cancer center. Concordance measures between the two response criteria (Kappa coefficient and percentage disagreement per response category) are assessed systematically over various combinations of the percentage of elliptical tumors at baseline and the percentage of tumors changing shape from baseline to follow-up.Results: The overall percentage of disagreement between the two methods of response assessment is found to be in the range of 14–20%. The patients categorized by WHO in the PR, SD, and PD groups fall into a different category when assessed by RECIST between 8–16%, 3–12%, and 32–35% of the times, respectively. The kappa coefficient ranges between 0.68–0.77. The proportion of elliptical tumors at baseline does not greatly impact the concordance, but the magnitude of the change in the aspect ratio has a large impact.Conclusion: Response assessment as measured by RECIST, with both a change in the underlying metric and change in definition of progression, often results in different categorization of response compared to WHO. The difference in response categorization may be problematic when new experimental therapies are compared to conventional agents whose response rates have been established in historical trials. The apparent lower rate of disease progression with RECIST may mean that more patients remain on therapy. Higher percentages of patients with SD need to be interpreted cautiously by distinguishing those due to the change in the response criterion as opposed to those induced by drugs using pathways such as angiogenesis where disease stabilization is expected rather than shrinkage of tumor. [Copyright &y& Elsevier]

Phase II clinical trials in oncology are performed to evaluate the therapeutic efficacy of a new treatment regimen. A common measure of efficacy for these trials is the proportion of patients who obtain a response measured by tumor shrinkage. It is standard practice to classify this response into the following categories: (1) complete response (CR); (2) partial response (PR); (3) stable disease; and (4) progression of disease. Tumor response is then treated as a binary variable whereby patients who achieve either a CR or a PR are considered responders and all others nonresponders. A two-stage design that allows for early termination of the trial if the treatment shows little efficacy such as Gehan or Simon gives equal weight to a CR and a PR. However, a CR, defined as complete disappearance of the tumor, is more likely than a PR to signal an important antitumor effect and result in a survival advantage. We argue that CRs and PRs should be considered separately, and hence we propose a two-stage design with a multilevel endpoint (i.e., CR, PR, and nonresponders). This design is an extension of Simon''s optimal two-stage design and is based on a trinomial model. For most scenarios the proposed design results in an improvement in expected sample size compared to Simon''s optimal design. Design optimization was performed by a direct search based on enumerating exact trinomial probabilities. Sample size tables are provided for parameter sets commonly used in the oncologic setting. Software is available by contacting the authors. [Copyright &y& Elsevier]

Topographic steering has been observed around Gran Canaria, a high-profile circular island located in the Canary Island Archipelago, Spain, culminating in a complex lee-side wind regime at the Maspalomas dunefield. Maspalomas has experienced rapid environmental changes since the 1960s, coincident with a boom in the tourism industry in the region and requires further examination on the linkages between meso-scale airflow patterns and aeolian processes modifying the landscape. The aim of this work is to simulate mean and turbulent airflow conditions at Maspalomas due to incremental changes in the regional wind direction and to compare these results to the predicted and observed aeolian dynamics taken from meteorological records, a global wind retro-analysis model, and remote sensing data. A Smagorinsky Large Eddy Simulation (S-LES) model was used to identify meso-scale airflow perturbations and turbulence at different locations around the island. Variability in meteorological data was also identified, with sites recording accelerated or retarded velocities and directional distributions ranging between unimodal to bimodal. Using a global retro-analysis model, relatively consistent up-wind conditions were predicted over a period coinciding with three aerial LiDAR surveys (i.e., 2006, 2008, and 2011) at the Maspalomas dunefield. Despite the consistent predicted airflow conditions, dune migration rates dropped from 7.26 m y−1 to 2.80 m y−1 and 28% of dunes experienced crest reversal towards the east, or opposite of the primary westerly migration direction during the second time period. Our results indicate that meso-scale airflow steering alters local wind conditions that can modify sediment transport gradients at Maspalomas. Given the rapidity of environmental changes and anthropogenic impacts at Maspalomas, these findings improve our understanding on the aeolian dynamics at Maspalomas and can be used to inform future management strategies. Lastly, the approach used in this study could be applied to other high-profile island settings or similarly complex aeolian environments. Unlabelled Image • Whole-island airflow bifurcation and topographic steering occurs around a dunefield. • Inconsistency in regional wind patterns and dune migrations rates were observed. • Meteorological observations, wind modelling, and remote sensing data were compared. • Incident winds are perturbed, modifying aeolian transport patterns at the dunefield. • Down-scaling winds may better predict dominate drivers in aeolian environments. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis is an important animal health problem and the predominant cause of zoonotic tuberculosis worldwide. It results in serious economic burden due to losses in productivity and the cost of control programmes. Control could be greatly improved by the introduction of an efficacious cattle vaccine but the most likely candidate, BCG, has several limitations including variable efficacy. Augmentation of BCG with a subunit vaccine booster has been shown to increase protection but the selection of antigens has hitherto been left largely to serendipity. In the present study, we take a rational approach to identify the protective antigens of BCG, selecting a BCG transposon mutant library in naïve and BCG-vaccinated cattle. Ten mutants had increased relative survival in vaccinated compared to naïve cattle, consistent with loss of protective antigen targets making the mutants less visible to the BCG immune response. The immunogenicity of three putative protective antigens, BCG_0116, BCG_0205 (YrbE1B) and BCG_1448 (PPE20) was investigated using peptide pools and PBMCs from BCG vaccinated cattle. BCG vaccination induced PBMC to release elevated levels of IP10, IL-17a and IL-10 in response to all three antigens. Taken together, the data supports the further study of these antigens for use in subunit vaccines. [ABSTRACT FROM AUTHOR]

To investigate the experiences of adults living with chronic myeloid leukaemia and treated with tyrosine kinase inhibitors, with particular reference to factors influencing adherence. A thematic synthesis of all published qualitative studies examining adults with chronic myeloid leukaemia, receiving tyrosine kinase inhibitors. Eligible publications were identified by searching five electronic databases using defined criteria. The synthesis involved complete coding of extracted data and inductive theme development. Nine studies were included and three overarching themes defined. Overarching themes were: 1) Disease impacts whole life; 2) Disease management strategies; and 3) Valued aspects of care. Side-effects often required physical and psychological adaptation. Patients developed individual decision-making processes to promote adherence and manage side effects. Unintentional non-adherence occurred due to forgetfulness and system failures. Intentional omission also occurred, which together with side effects, was unlikely to be reported to healthcare professionals (HCPs). HCP reassurance about missed doses could reinforce non-adherence. Information needs varied over time and between individuals. Knowledge among patients about treatment was often lacking and could lead to misunderstandings. Patients valued psychological support from HCPs and suggested an individualised approach, facilitating discussion of symptoms, adherence and their perspectives about living with chronic myeloid leukaemia, would improve care. Patients with chronic myeloid leukaemia experienced significant side-effects from treatment and changes to their psychological and physical well-being. They developed their own strategies to manage their disease and treatment. This should be recognised in interventions to improve education, support and the delivery of care that is compassionate and adequately resourced. • The first qualitative synthesis of chronic myeloid leukaemia patient experiences. • Contrary to trial evidence, CML has significant physical and psychological impact. • Patients develop strategies to manage treatment, often without professional input. • Patients value psychological support, professionals require resources to give this. [ABSTRACT FROM AUTHOR]

• The Shockley-Queisser model is extended to account for all of the spectral energy. • Thermodynamic losses are described and cell temperature is accounted for. • Real spectra can be analyzed, accounting for geographical and climatic variation. Research into the fundamental limitations to photovoltaic power conversion has historically used a single predetermined set of conditions to define device performance limitations. This fails to account for the many variables involved in real-world situations. Previous work describing thermodynamic losses in solar energy conversion has typically used an analytical approach, precluding the use of real-world spectra. This paper describes a model which marries the advantages of the analytical approach with a numerical detailed balance calculation, enabling analysis of maximum attainable power conversion efficiency and associated loss mechanisms in photovoltaics under more representative conditions. Input spectra in the model are treated as separate beam and diffuse components, both in terms of power and subtended angle. Differences in conversion show that diffuse light is effectively under maximum concentration. This does not result in an efficiency gain since the equivalent energy is instead accounted for in the Carnot loss. The Carnot limit for the diffuse portion of the spectrum is therefore lower than that for direct light. Simulated hourly "clear sky" spectra across a year were analysed for five geographically disparate locations. Results showed that at higher latitudes narrower band gap devices have a similar maximum efficiency to those with wider band gaps, whilst at lower latitudes wider band gap devices have a slightly higher maximum efficiency. This is compounded by increased irradiance at lower latitudes. Irrespective of band gap, annual energy conversion shows little variation at lower latitudes, with greater conversion in summer being offset by reductions in winter at higher latitudes. [ABSTRACT FROM AUTHOR]