For more than 400 years, the Catholic Church's 'Index Librorum Prohibitorum' struck terror into the hearts of authors, publishers, and booksellers around the world, while arousing ridicule and ...contempt from many others, especially those in Protestant and non-Christian circles. Biased, inconsistent, and frequently absurd in its attempt to ban objectionable texts of every conceivable description - with sometimes fatal consequences - the index also reflected the deep learning and careful consideration of many hundreds of intellectual contributors over the long span of its storied evolution. This book examines the reasons behind the Church's attempts to censor religious, scientific, and artistic works, and considers not only why this most sustained of campaigns failed, but what lessons can be learned for today's debates over freedom of expression and cancel culture.
Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or ...refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL).
Patients received oral lenalidomide 25 mg on days 1–21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR).
Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months 95% confidence interval (CI) 2.7–5.1. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0–NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively.
Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma.
Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma with poor overall prognosis, requiring the development of new therapies. Lenalidomide is an immunomodulatory agent demonstrating ...antitumor and antiproliferative effects in MCL. We report results from a long-term subset analysis of 57 patients with relapsed/refractory MCL from the NHL-003 phase II multicenter study of single-agent lenalidomide in patients with aggressive lymphoma
Lenalidomide was administered orally 25 mg daily on days 1–21 every 28 days until progressive disease (PD) or intolerability. The primary end point was overall response rate (ORR).
Fifty-seven patients with relapsed/refractory, advanced-stage MCL had a median of three prior therapies. The ORR was 35% complete response (CR)/CR unconfirmed (CRu) 12%, with a median duration of response (DOR) of 16.3 months (not yet reached in patients with CR/CRu) by blinded independent central review. The median time to first response was 1.9 months. Median progression-free survival was 8.8 months, and overall survival had not yet been reached. The most common grade 3/4 adverse events (AEs) were neutropenia (46%), thrombocytopenia (30%), and anemia (13%).
These results show the activity of lenalidomide in heavily pretreated, relapsed/refractory MCL. Responders had a durable response with manageable side-effects. Clinical trial number posted on www.clinicaltrials.gov NCT00413036.
•Data from a single tower are used to characterize advection regimes in a new site in complex terrain.•Positive vertical advection was associated with cold-air drainage.•Horizontal advection driven ...by landscape heterogeneity was inferred in mid- to late-morning.•Roughly 50% of observations, collected when advection is significant, will need to be filtered.•Similar physiological functioning in morning and afternoon periods simplifies gapfilling.
Multiple data streams from a new flux tower located in complex and heterogeneous terrain at the Coweeta Hydrologic Laboratory (North Carolina, USA) were integrated to identify periods of advective flow regimes. Drainage flows were expected a priori, due to the location of the measurement site at the base of a long, gently-sloping valley. Drainage flow was confirmed by examining vertical profile measurements of wind direction and by estimating vertical advection fluxes. The vertical advection flux of CO2 was most significant in early morning (000–0600h) during the growing season, when it averaged ∼5μmolm−2s−1. Horizontal advection flux of CO2 was not directly measured in this study; however, an expected exponential relationship between nocturnal ecosystem respiration (RE) and air temperature was recovered when horizontal advection of CO2 was assumed to be negatively correlated to vertical advection, or when data were limited to periods when measured vertical advection fluxes were small. Taken together, these data imply the presence of a negative horizontal advection CO2 flux during nocturnal periods characterized by positive vertical advection of CO2. Daytime periods were characterized by consistent anabatic (up-valley) flows in mid- to late-morning (0500–1200h) and consistent katabatic (down-valley) flows in the afternoon. A combination of above-canopy flux profile measurements, energy balance closure estimates, and flux footprint estimates suggest that during periods of up-valley wind flow, the flux footprint frequently exceeds the ecosystem dimensions, and horizontal advection fluxes related to landscape heterogeneity were a significant component of the total ecosystem flux of CO2. We used sap flux from individual trees beneath the tower to explore diurnal patterns in stomatal conductance in order to evaluate gapfilling approaches for the unreliable morning data. The relationship between stomatal conductance and vapor pressure deficit was similar in morning and afternoon periods, and we conclude that gapfilling morning data with models driven by afternoon data is a reasonable approach at this site. In general, results were consistent with other studies showing that the advection and wind flow regimes in complex terrain are highly site specific; nonetheless, the site characterization strategy developed here, when used together with independent estimates of components of the ecosystem carbon flux, could be generally applied in other sites to better understand the contribution of advection to the total ecosystem flux.
We describe outcomes after allogeneic hematopoietic cell transplantation (HCT) for mycosis fungoides and Sezary syndrome (MF/SS). Outcomes of 129 subjects with MF/SS reported to the Center for the ...International Blood and Marrow Transplant from 2000-2009. Median time from diagnosis to transplant was 30 (4-206) months and most subjects were with multiply relapsed/ refractory disease. The majority (64%) received non-myeloablative conditioning (NST) or reduced intensity conditioning (RIC). NST/RIC recipients were older in age compared with myeloablative recipients (median age 51 vs 44 years, P=0.005) and transplanted in recent years. Non-relapse mortality (NRM) at 1 and 5 years was 19% (95% confidence interval (CI) 12-27%) and 22% (95% CI 15-31%), respectively. Risk of disease progression was 50% (95% CI 41-60%) at 1 year and 61% (95% CI 50-71%) at 5 years. PFS at 1 and 5 years was 31% (95% CI 22-40%) and 17% (95% CI 9-26%), respectively. OS at 1 and 5 years was 54% (95% CI 45-63%) and 32% (95% CI 22-44%), respectively. Allogeneic HCT in MF/SS results in 5-year survival in approximately one-third of patients and of those, half remain disease-free.
Gene expression profiling of diffuse large B-cell lymphoma (DLBCL) has revealed biologically and prognostically distinct subgroups: germinal center B-cell-like (GCB), activated B-cell-like (ABC) and ...primary mediastinal (PM) DLBCL. The BCL6 gene is often translocated and/or mutated in DLBCL. Therefore, we examined the BCL6 molecular alterations in these DLBCL subgroups, and their impact on BCL6 expression and BCL6 target gene repression. BCL6 translocations at the major breakpoint region (MBR) were detected in 25 (18.8%) of 133 DLBCL cases, with a higher frequency in the PM (33%) and ABC (24%) subgroups than in the GCB (10%) subgroup. Translocations at the alternative breakpoint region (ABR) were detected in five (6.4%) of 78 DLBCL cases, with three cases in ABC and one case each in the GCB and the unclassifiable subgroups. The translocated cases involved IgH and non-IgH partners in about equal frequency and were not associated with different levels of BCL6 mRNA and protein expression. BCL6 mutations were detected in 61% of DLBCL cases, with a significantly higher frequency in the GCB and PM subgroups (>70%) than in the ABC subgroup (44%). Exon-1 mutations were mostly observed in the GCB subgroup. The repression of known BCL6 target genes correlated with the level of BCL6 mRNA and protein expression in GCB and ABC subgroups but not with BCL6 translocation and intronic mutations. No clear inverse correlation between BCL6 expression and p53 expression was observed. Patients with higher BCL6 mRNA or protein expression had a significantly better overall survival. The biological role of BCL6 in translocated cases where repression of known target genes is not demonstrated is intriguing and warrants further investigation.
Shallow landslides are a significant hazard in steep, soil‐mantled landscapes. During intense rainfall events, the distribution of shallow landslides is controlled by variations in landscape ...gradient, the frictional and cohesive properties of soil and roots, and the subsurface hydrologic response. While gradients can be estimated from digital elevation models, information on soil and root properties remains sparse. We investigated whether geomorphically controlled variations in ecology affect the spatial distribution of root cohesion by measuring the distribution and tensile strength of roots from soil pits dug downslope of 15 native trees in the southern Appalachian Mountains, North Carolina, United States. Root tensile strengths from different hardwood tree species were similar and consistently higher than the only native shrub species measured (Rhododendron maximum). Roots were stronger in trees found on noses (areas of divergent topography) relative to those in hollows (unchanneled, convergent topography) coincident with the variability in cellulose content. This cellulose variability is likely related to topographic differences in soil water potential. For all species, roots were concentrated close to the soil surface, with roots in hollows being more evenly distributed in the soil column than those on noses. Trees located on noses had higher mean root cohesion than those in hollows because of a higher root tensile force. R. maximum had the shallowest, weakest roots suggesting that recent expansion of this species due to fire suppression has likely lowered the root cohesion of some hollows. Quantification of this feedback between physiologic controls on root growth and slope hydrology has allowed us to create a curvature‐based model of root cohesion that is a significant improvement on current models that assume a spatially averaged value.
Extreme floods, including those expected to become more frequent in a warming world, may impact nutrient metabolism in streams. However, flood impacts on spatial and temporal variability of nutrient ...dynamics on large rivers (e.g., fourth order and higher) have been understudied. In 2016, Hurricane Matthew provided a unique opportunity to evaluate nitrate retention and processing on the Lumbee River, a blackwater stream in southeastern North Carolina. The 3,000+ km2 watershed received as much as 400 mm of rain in 48 hr as the storm moved across the Atlantic Coastal Plain. Resulting floods in the watershed were the largest on record, based on more than 80 years of continuous streamflow measurements at the watershed outlet. We used a modified Lagrangian sampling method to collect water samples and supporting water quality data at multiple points along three reaches of the Lumbee River for several months before and after Hurricane Matthew. Samples were analyzed for nitrate‐nitrogen and used to estimate retention and areal uptake rates for multiple subsections within each reach. Although nitrate‐nitrogen concentrations did not change significantly after the flood, we found that the spatial variability of within‐reach retention and areal uptake increased substantially following the flood, evidenced by changes to within‐reach interquartile ranges. The spatial variability of areal uptake returned to pre‐flood levels approximately eight months after Hurricane Matthew, but retention variability remained elevated at the end of our field study. These results highlight the potential for extreme flooding to impact biogeochemical processes in large rivers long after flood waters subside.
Plain Language Summary
Large floods, such as those following tropical storms, can radically change streambeds and aquatic environments. These changes can have consequences for nutrient processing in streams. Little is known about the impacts of extreme floods in large rivers, particularly with respect to the longevity of their effects on nutrient processing. In 2016, Hurricane Matthew brought widespread flooding to the Lumbee River watershed, located in southeastern North Carolina. We sampled nitrate‐nitrogen along three reaches of the river before and after flooding and were able to compare nitrate processing before and after to determine if large floods could have lasting influences on these characteristics. Significant differences in percent removal and removal rates before and after flooding were found at only one reach, but we did observe a substantial increase in the variability of nitrogen processing in all three reaches. These results shed new light on nitrogen processing in large rivers by identifying potentially important biogeochemical changes caused by extreme flooding.
Key Points
Spatial variability of Nitrate ‐N retention and areal uptake increased in the months after extreme flooding on a blackwater river
Eight months post flood impacts to nitrate‐N areal uptake could not be detected, but increased spatial variability of retention remained
Results suggest some level of resiliency to flood disturbance within larger rivers
AbstractWe compared precipitation intensity-duration-frequency (PIDF) curves developed for four small forested watersheds to spatially interpolated estimates from the National Oceanic and Atmospheric ...Administration’s (NOAA) Atlas-14. We also evaluated the Rational Method (RM) using on-site PIDFs and USGS Regional Regression Equations by comparing their estimated design discharges with a given exceedance probability p (Qp) to values computed from on-site data fitted to the Log-Pearson (LPIII) distribution. Overall, NOAA’s PIDF estimates were not substantially different from the on-site PIDFs. The 25-year and larger Qp by the RM were in closer alignment with LPIII estimates in the smaller watersheds, whereas Qp by the USGS were a better fit for the larger ones in most cases. Adapting return period-dependent runoff coefficient improved estimates by the RM in the large lowland watershed, but not in the other smaller high-relief watersheds. We recommend RM with 1-h duration NOAA-PIDF for designing road drainage structures in small and possibly the USGS method for large forested watersheds. However, future studies should focus on validation in watersheds of different sizes and topography.
Convergence in interspecific leaf trait relationships across diverse taxonomic groups and biomes would have important evolutionary and ecological implications. Such convergence has been hypothesized ...to result from trade-offs that limit the combination of plant traits for any species. Here we address this issue by testing for biome differences in the slope and intercept of interspecific relationships among leaf traits: longevity, net photosynthetic capacity (Amax) leaf diffusive conductance (Gs) specific leaf area (SLA), and nitrogen (N) status, for more than 100 species in six distinct biomes of the Americas. The six biomes were: alpine tundra-subalpine forest ecotone, cold temperate forest-prairie ecotone, montane cool temperate forest, desert shrubland, subtropical forest, and tropical rain forest. Despite large differences in climate and evolutionary history, in all biomes mass-based leaf N (Nmass), SLA, Gs, and Amax were positively related to one another and decreased with increasing leaf life span. The relationships between pairs of leaf traits exhibited similar slopes among biomes, suggesting a predictable set of scaling relationships among key leaf morphological, chemical, and metabolic traits that are replicated globally among terrestrial ecosystems regardless of biome or vegetation type. However, the intercept (i.e., the overall elevation of regression lines) of relationships between pairs of leaf traits usually differed among biomes. With increasing aridity across sites, species had greater Amax for a given level of Gs and lower SLA for any given leaf life span. Using principal components analysis, most variation among species was explained by an axis related to mass-based leaf traits (Amax, N, and SLA) while a second axis reflected climate, Gs, and other area-based leaf traits.
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