The thirteen species of Dryopteris in North America have long been suspected of having undergone a complicated history of reticulate evolution via allopolyploid hybridization. Various explanations ...for the origins of the allopolyploid taxa have been suggested, and though most lines of evidence have supported the so-called "semicristata" hypothesis, contention over the group's history has continued in several recent, conflicting studies.
Sequence data from nine plastid and two nuclear markers were collected from 73 accessions representing 35 species of Dryopteris. Sequences from each of the allopolyploids are most closely related to their progenitor species as predicted by the "semicristata" hypothesis. Allotetraploid D. campyloptera appears to be derived from a hybrid between diploid D. expansa and D. intermedia; D. celsa, from diploid D. ludoviciana x D. goldiana; and D. carthusiana and D. cristata, from diploid "D. semicristata" x D. intermedia and D. ludoviciana, respectively. Allohexaploid D. clintoniana appears to be derived from D. cristata x D.goldiana. The earliest estimated dates of formation of the allopolyploids, based on divergence time analyses, were within the last 6 Ma. We found no evidence for recurrent formation of any of the allopolyploids. The sexual allopolyploid taxa are derived from crosses between parents that show intermediate levels of genetic divergence relative to all pairs of potential progenitors. In addition, the four allotetraploids are transgressive with respect to geographic range relative to one or both of their parents (their ranges extend beyond those of the parents), suggesting that ecological advantages in novel habitats or regions may promote long-term regional coexistence of the hybrid taxa with their progenitors.
This study provides the first thorough evaluation of the North American complex of woodferns using extensive sampling of taxa and genetic markers. Phylogenies produced from each of three datasets (one plastid and two nuclear) support the "semicristata" hypothesis, including the existence of a missing diploid progenitor, and allow us to reject all competing hypotheses. This study demonstrates the value of using multiple, biparentally inherited markers to evaluate reticulate complexes, assess the frequency of recurrent polyploidization, and determine the relative importance of introgression vs. hybridization in shaping the histories of such groups.
Premise of the study: Dryopteris is a large, cosmopolitan fern genus ideal for addressing questions about diversification, biogeography, hybridization, and polyploidy, which have historically been ...understudied in ferns. We constructed a highly resolved, well-supported phylogeny for New World Dryopteris and used it to investigate biogeographic patterns and divergence times. Methods: We analyzed relationships among 97 species of Dryopteris, including taxa from all major biogeographic regions, with analyses based on 5699 aligned nucleotides from seven plastid loci. Phylogenetic analyses used maximum parsimony, maximum likelihood, and Bayesian inference. We conducted divergence time analyses using BEAST and biogeographic analyses using maximum parsimony, maximum likelihood, Bayesian, and S-DIVA approaches. We explored the monophyly of subgenera and sections in the most recent generic classification and of geographic groups of taxa using Templeton tests. Key results: The genus Dryopteris arose ca. 42 million years ago (Ma). Most of the Central and South American species form a well-supported clade which arose 32 Ma, but the remaining New World species are the result of multiple, independent dispersal and vicariance events involving Asia, Europe, and Africa over the last 15 Myr. We identified six long-distance dispersal events and three vicariance events in the immediate ancestry of New World species; reconstructions for another four lineages were ambiguous. Conclusions: New World Dryopteris are not monophyletic; vicariance has dominated the history of the North American species, while long-distance dispersal prevails in the Central and South American species, a pattern not previously seen in plants.
This review explores the concept of futility timeouts and the use of traumatic brain injury (TBI) as an independent predictor of the futility of resuscitation efforts in severely bleeding trauma ...patients. The national blood supply shortage has been exacerbated by the lingering influence of the COVID-19 pandemic on the number of blood donors available, as well as by the adoption of balanced hemostatic resuscitation protocols (such as the increasing use of 1:1:1 packed red blood cells, plasma, and platelets) with and without early whole blood resuscitation. This has underscored the urgent need for reliable predictors of futile resuscitation (FR). As a result, clinical, radiologic, and laboratory bedside markers have emerged which can accurately predict FR in patients with severe trauma-induced hemorrhage, such as the Suspension of Transfusion and Other Procedures (STOP) criteria. However, the STOP criteria do not include markers for TBI severity or transfusion cut points despite these patients requiring large quantities of blood components in the STOP criteria validation cohort. Yet, guidelines for neuroprognosticating patients with TBI can require up to 72 h, which makes them less useful in the minutes and hours following initial presentation. We examine the impact of TBI on bleeding trauma patients, with a focus on those with coagulopathies associated with TBI. This review categorizes TBI into isolated TBI (iTBI), hemorrhagic isolated TBI (hiTBI), and polytraumatic TBI (ptTBI). Through an analysis of bedside parameters (such as the proposed STOP criteria), coagulation assays, markers for TBI severity, and transfusion cut points as markers of futilty, we suggest amendments to current guidelines and the development of more precise algorithms that incorporate prognostic indicators of severe TBI as an independent parameter for the early prediction of FR so as to optimize blood product allocation.
The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ...ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of therapeutic response. Here we investigated the expression of PD-L1 on tumor cells (TC) and tumor-infiltrating immune cells (IC) by IHC in 68 NEN samples with a high proliferation rate (Ki-67 >20%) from 57 patients and in 22 samples we correlated it with TAIC density by assessing intratumoral infiltration of CD3+, CD8+, and CD68+ cells. Furthermore, the tumor microenvironment was evaluated according to the classification of Teng et al. We detected PD-L1 expression in 31.6% of NEN G3. Its expression usually was weak and more IC than TC expressed PD-L1. The proportion of tumors positive for PD-L1 was comparable in NEN from different sites of origin but varied depending on tumor differentiation and disease extension. No positive IHC staining was found in 3 well-differentiated neuroendocrine tumors (NETs) with a proliferation rate above 20% (NET G3). When analyzing TAIC, we rarely (18.2%) detected intratumoral CD8+ cells, whereas infiltration by CD3+ and CD68+ cells was more common (45.5 and 59.1%, respectively). By combining CD3+ cells and PD-L1 status, we identified the immune ignorant phenotype of tumor microenvironment as being the most common phenotype, supporting the concept of a preferably combined immunotherapeutic approach in neuroendocrine carcinoma (NEC).
Angiosarcoma of the adrenal gland is a very rare malignant vascular neoplasm. The clinical symptoms are atypical or completely absent. Angiosarcomas of the adrenal gland are therefore often ...discovered incidentally, and the diagnosis is made histologically after resection.
A 46-year-old white Spanish male who was a previous smoker and nondrinker and was slightly overweight (92 kg, 176 cm, body mass index 29.7 kg/m
) with no relevant medical history presented to the internal medicine emergency department of our hospital with an unclear 12 cm tumor of the right adrenal gland. Prior to the computed tomography scan, he had had persistent evening fevers for 4 months and unintentional weight loss of 5 kg. The laboratory results showed anemia and an elevated C-reactive protein, but no hormone production. We performed an open adrenalectomy of the right adrenal gland. Finally, the histologic findings revealed an angiosarcoma of the adrenal gland.
Even though angiosarcomas of the adrenal gland are rare, the differential diagnosis of an angiosarcoma should be considered if a malignant tumor of the adrenal gland is suspected. Treatment decisions should be made on an interdisciplinary basis and preferably in a specialized center. Owing to the rarity of angiosarcomas of the adrenal gland, it is necessary to continue to share clinical experience to gain a better understanding of this particular tumor entity.
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► We produce the largest nuclear phylogeny to date for Dryopteris. ► Plastid and nuclear datasets are used to study branching vs. reticulate evolution. ► Our data support an existing ...hypothesis for the origin of North American polyploids. ► Our data reveal extensive reticulation in the Latin American taxa. ► Latin American species are the result of transcontinental hybridization events.
Reticulate, or non-bifurcating, evolution is now recognized as an important phenomenon shaping the histories of many organisms. It appears to be particularly common in plants, especially in ferns, which have relatively few barriers to intra- and interspecific hybridization. Reticulate evolutionary patterns have been recognized in many fern groups, though very few have been studied rigorously using modern molecular phylogenetic techniques in order to determine the causes of the reticulate patterns. In the current study, we examine patterns of branching and reticulate evolution in the genus Dryopteris, the woodferns. The North American members of this group have long been recognized as a classic example of reticulate evolution in plants, and we extend analysis of the genus to all 30 species in the New World, as well as numerous taxa from other regions. We employ sequence data from the plastid and nuclear genomes and use maximum parsimony (MP), maximum likelihood (ML), Bayesian inference (BI), and divergence time analyses to explore the relationships of New World Dryopteris to other regions and to reconstruct the timing and events which may have led to taxa displaying reticulate rather than strictly branching histories. We find evidence for reticulation among both the North and Central/South American groups of species, and our data support a classic hypothesis for reticulate evolution via allopolyploid speciation in the North America taxa, including an extinct diploid progenitor in this group. In the Central and South American species, we find evidence of extensive reticulation involving unknown ancestors from Asia, and we reject deep coalescent processes such as incomplete lineage sorting in favor of more recent intercontinental hybridization and chloroplast capture as an explanation for the origin of the Latin American reticulate taxa.
More than 36,000 people in the United States die from suicide annually, and suicide is the third leading cause of death in adolescence. Adolescence is a time of high risk for suicidal behavior, as ...well as a time that intervention and treatment may have the greatest impact because of structural brain changes and significant psychosocial development during this period. Functional and structural neuroimaging studies in adults who have attempted suicide suggest distinct gray matter volume abnormalities in cortical regions, as well as prefrontal cortical and dorsal anterior cingulate gyrus neural circuitry differences compared with affective and healthy adult controls. Recent functional neuroimaging studies in adolescents with a history of suicide attempt suggest differences in the attention and salience networks compared with adolescents with depression and no history of suicide attempt and healthy controls when viewing angry faces. In contrast, no abnormalities are seen in these areas in the absence of emotional stimuli. These networks may represent promising targets for future neuroimaging studies to identify markers of risk for future suicide attempt in adolescents.
Multiple stressors to a shallow lake ecosystem have the ability to control the relative stability of alternative states (clear, macrophyte-dominated or turbid, algal-dominated). As a consequence, the ...use of remedial biomanipulations to induce trophic cascades and shift a turbid lake to a clear state is often only a temporary solution. Here we show the instability of short-term manipulations in the shallow Lake Christina (Minnesota, USA) is governed by the long-term state following a regime shift in the lake. During the modern, managed period of the lake, three top-down manipulations (fish kills) were undertaken inducing temporary (5-10 years) unstable clear-water states. Paleoecological remains of diatoms, along with proxies of primary production (total chlorophyll
a
and total organic carbon accumulation rate) and trophic state (total P) from sediment records clearly show a single regime shift in the lake during the early 1950s; following this shift, the functioning of the lake ecosystem is dominated by a persistent turbid state. We find that multiple stressors contributed to the regime shift. First, the lake began to eutrophy (from agricultural land use and/or increased waterfowl populations), leading to a dramatic increase in primary production. Soon after, the construction of a dam in 1936 effectively doubled the depth of the lake, compounded by increases in regional humidity; this resulted in an increase in planktivorous and benthivorous fish reducing phytoplankton grazers. These factors further conspired to increase the stability of a turbid regime during the modern managed period, such that switches to a clear-water state were inherently unstable and the lake consistently returned to a turbid state. We conclude that while top-down manipulations have had measurable impacts on the lake state, they have not been effective in providing a return to an ecosystem similar to the stable historical period. Our work offers an example of a well-studied ecosystem forced by multiple stressors into a new long-term managed period, where manipulated clear-water states are temporary, managed features.
Multiple stressors to a shallow lake ecosystem have the ability to control the relative stability of alternative states (clear, macrophyte-dominated or turbid, algal-dominated). As a consequence, the ...use of remedial biomanipulations to induce trophic cascades and shift a turbid lake to a clear state is often only a temporary solution. Here we show the instability of short-term manipulations in the shallow Lake Christina (Minnesota, USA) is governed by the long-term state following a regime shift in the lake. During the modern, managed period of the lake, three top-down manipulations (fish kills) were undertaken inducing temporary (5-10 years) unstable clear-water states. Paleoecological remains of diatoms, along with proxies of primary production (total chlorophyll
a
and total organic carbon accumulation rate) and trophic state (total P) from sediment records clearly show a single regime shift in the lake during the early 1950s; following this shift, the functioning of the lake ecosystem is dominated by a persistent turbid state. We find that multiple stressors contributed to the regime shift. First, the lake began to eutrophy (from agricultural land use and/or increased waterfowl populations), leading to a dramatic increase in primary production. Soon after, the construction of a dam in 1936 effectively doubled the depth of the lake, compounded by increases in regional humidity; this resulted in an increase in planktivorous and benthivorous fish reducing phytoplankton grazers. These factors further conspired to increase the stability of a turbid regime during the modern managed period, such that switches to a clear-water state were inherently unstable and the lake consistently returned to a turbid state. We conclude that while top-down manipulations have had measurable impacts on the lake state, they have not been effective in providing a return to an ecosystem similar to the stable historical period. Our work offers an example of a well-studied ecosystem forced by multiple stressors into a new long-term managed period, where manipulated clear-water states are temporary, managed features.
Abstract
Background
Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data ...about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.
Methods
In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients, including those receiving chemotherapy for hematologic malignancies or hematopoietic stem cell transplantation.
Results
Among 389 organisms causing BSI in 343 patients, there was an equal distribution of gram-negative (GN) and gram-positive (GP) bacteria, with variability across centers. Cefepime and piperacillin-tazobactam were the most commonly prescribed empirical antibiotics for FN, at 62% and 23%, respectively; a GP-directed agent was empirically included in nearly half of all FN episodes within the first 24 hours. Susceptibility to fluoroquinolones, cefepime, piperacillin-tazobactam, and carbapenems was 49%, 84%, 88%, and 96%, respectively, among GN isolates. Critical illness (CrI), defined as a new requirement for mechanical ventilation, vasopressor, or death within 30 days, occurred in 15% and did not correlate with fluoroquinolone prophylaxis, organism type, initial antibiotics, or adequacy of coverage. Only severity of illness at presentation, signified by a Pitt bacteremia score ≥2, predicted for critical illness within 30 days. Mortality was 4% by day 7 and 10% overall.
Conclusions
In accordance with US guidelines, cefepime or piperacillin-tazobactam remain effective agents or empirical treatment for high-risk cancer patients with FN who are stable at presentation, maintaining high GN pathogen susceptibility and yielding excellent outcomes.
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