scholarly journals Thirty clues to the exceptional diversification of flowering plants

2018 ◽  
Author(s):  
Susana Magallón ◽  
Luna L. Sánchez-Reyes ◽  
Sandra L. Gómez-Acevedo

SummaryAs angiosperms became one of the megadiverse groups of macroscopic eukaryotes, they forged modern ecosystems and promoted the evolution of extant terrestrial biota. Unequal distribution of species among lineages suggests that diversification, the process which ultimately determines species-richness, acted differentially through angiosperm evolution.We investigate how angiosperms became megadiverse by identifying the phylogenetic and temporal placement of exceptional radiations, by combining the most densely fossil-calibrated molecular clock phylogeny with a Bayesian model that identifies diversification shifts among evolutionary lineages and through time. We evaluate the effect of the prior number of expected shifts in the phylogenetic tree.Major diversification increases took place over 100 Ma, from the Early Cretaceous to the end Paleogene, and are distributed across the angiosperm phylogeny. Angiosperm long-term diversification trajectory shows moderate rate variation, but is underlain by increasing speciation and extinction, and results from temporally overlapping, independent radiations and depletions in component lineages.The identified deep time diversification shifts are clues to identify ultimate drivers of angiosperm megadiversity, which probably involve multivariate interactions among intrinsic traits and extrinsic forces. An enhanced understanding of angiosperm diversification will involve a more precise phylogenetic location of diversification shifts, and integration of fossil information.


2019 ◽  
Vol 104 (7) ◽  
pp. e2.49-e2
Author(s):  
Susie Gage

AimThe National Patient Safety Agency (NPSA)1 identified heparin as a major cause of adverse events associated with adverse incidents, including some fatalities. By ensuring good communication, this should be associated with risk reduction.1 The aim of this study was to ensure there is clear anticoagulation communication on discharge, from the paediatric intensive care unit (PICU) electronic prescribing system (Philips), to the paediatric cardiac high dependency unit and paediatric cardiac ward. To investigate whether the heparin regimen complies with the hospital’s anticoagulant guidelines and if there is any deviation; that this is clearly documented. To find out if there is an indication documented for the heparin regimen chosen and if there is a clear long term plan documented for the patient, after heparin cessation.MethodsA report was generated for all patients who were prescribed a heparin infusion on PICU, between 1st January 2018 and 30th June 2018, from the Philips system. All discharge summaries from the PICU Philips system were reviewed. Only paediatric cardiac patients were included that had a heparin infusion prescribed on discharge, all other discharge summaries were excluded from the study. Each discharge summary was reviewed in the anticoagulant section; for the heparin regimen chosen, whether it complies with the hospital’s anticoagulant guidelines and if there was any deviation whether this was documented. The indication documented of which heparin regimen was chosen and whether a clear long term plan was documented after heparin cessation; for example if the patient is to be transferred onto aspirin, clopidogrel, warfarin or enoxaparin.Results82 discharge summaries were reviewed over the 6 month period between 1st January 2018 and 30th June 2018; 16 were excluded as were not paediatric cardiac, leaving 66 paediatric cardiac discharge summaries that were reviewed. 45 out of 66 (68%) complied with the hospital’s heparin anticoagulation guidelines. Of the 32% that deviated from the protocol; only 33% (7 out of 21) had a reason documented. Only 50% (33) of the summaries reviewed had an indication for anticoagulation noted on the discharge summary and 91% of discharge summaries had a long term anticoagulant plan documented.ConclusionThe electronic prescribing system can help to ensure a clear anticoagulation communication as shown by 91% of the anticoagulation long term plan being clearly documented; making it a more seamless patient transfer. On the Philips PICU electronic prescribing system there is an anticoagulant section on the discharge summary that has 3 boxes that need to be completed; heparin regimen, indication and anticoagulation long term plan. However, despite these boxes; deviations from the anticoagulant protocol were poorly documented as highlighted by only 33% having the reason highlighted in the discharge summary, only 50% of the indications were documented. Despite having prompts for this information on the discharge summary, the medical staffs needs to be aware to complete this information, in order to reduce potential medication errors and risk.ReferenceThe National Patient Safety Agency (NPSA). Actions that make anticoagulant therapy safer. NPSA; March 2007.



Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.



2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A454-A454
Author(s):  
Georgina Long ◽  
Reinhard Dummer ◽  
Douglas Johnson ◽  
Olivier Michielin ◽  
Salvador Martin-Algarra ◽  
...  

BackgroundPrevious findings from the MASTERKEY-265 phase 1b study showed that the combination of T-VEC and pembrolizumab was well tolerated and produced a high complete response (CR) rate of 43% in patients with advanced melanoma.1 The 3-year progression-free survival (PFS) and overall survival (OS) rates at that time were 53.6% and 71%, respectively. Here, we report the results of the long-term follow-up efficacy analyses.MethodsThe MASTERKEY-265 phase 1b trial (NCT02263508) was an open-label, single-arm study that enrolled patients who had unresectable, stage IIIB-IVM1c melanoma with injectable, measurable lesions and no prior systemic treatment. T-VEC was administered intralesionally at the approved dosing starting day 1 of week 1. Pembrolizumab (200 mg) was administered intravenously Q2W beginning on day 1 of week 6. The maximum treatment period was 2 years. The primary endpoint was dose-limiting toxicities; key secondary endpoints included objective response rate and PFS per modified irRC, OS, and safety.ResultsAs of the data cutoff (Mar 2, 2020), all 21 patients enrolled were off treatment; 6 died and 15 are in long-term follow-up. The median follow-up time was 58.6 months (range: 1.4–61.6). The CR rate remained 43% (9/21 patients). Twelve of the 13 responders (92.3%) are still in response, including all 9 patients with a CR. Median duration of response was not reached (range: 2.8+–54.3+ months). Median PFS and OS were not reached at the data cutoff. KM estimates of 4-year PFS and OS rates were 55.9% and 71.4%, respectively, which have held stable since the 3-year analysis. Patients who achieved a CR or partial response had better OS (p=0.0056) compared to those who did not respond. Median OS for non-responders was 24.4 months and was not reached for responders. No additional safety signals were detected.ConclusionsAt almost 5 years of follow-up, median PFS and OS were not reached for patients treated with the combination of T-VEC and pembrolizumab in this phase 1b study of unresectable metastatic melanoma. 92% of responders remained in response with improved OS observed in responders compared with non-responders. The corresponding randomized phase 3 trial has completed enrollment and is currently ongoing.Trial RegistrationNCT02263508Ethics ApprovalThe study was approved by the Ethics Board of each institution involved in this study and can be produced upon request.ReferenceLong G, Dummer R, Andtbacka R, et al. Follow-up analysis of MASTERKEY-265 Phase 1b (ph1b) trial of talimogene laherparepvec (T-VEC) in combination (combo) with pembrolizumab (pembro) in patients (pts) with unresectable stage IIIB–IVM1c melanoma (MEL). Pigment Cell Melanoma Res 2019;32:133–134.



2021 ◽  
Vol 92 (8) ◽  
pp. A11.2-A11
Author(s):  
Ewelina de Leon ◽  
Graeme Yorston

Objectives/AimsTraumatic brain injury is a common cause of permanent or long-term disability,1 and up to 80% of people with moderate to severe brain injury have some degree of pituitary insufficiency. Endocrine disruption has been documented in medical literature since the 1940s,2-4 where central diabetes insipidus has been described as a common transient complication which causes polydipsia (insatiable thirst). However, polydipsia can be caused by other conditions. It is classified into dipsogenic, in a syndrome of disordered thirst-regulating mechanism in patients without psychiatric disease called dipsogenic diabetes insipidus, psychogenic, as a compulsive water drinking in patients with psychiatric conditions referred to as psychogenic polydipsia or psychogenic diabetes insipidus and iatrogenic where large quantities of water are consumed for health benefits. All of which are referred to as primary polydipsia if these conditions cannot be distinguished. Dipsogenic diabetes insipidus and psychogenic polydipsia can be easily mixed up, misdiagnosed or even unrecognised, mainly because their pathophysiology is still unclear. Are these conditions different, or is there anything that can relate them to each other? With this literature review, we are aiming to find the link between subsets of polydipsia after brain trauma, to compare proposed differential diagnosis and their functionality in clinical settings.MethodA literature review was conducted following a search of MEDLINE, CINAHL Plus, APA PsycArticles, APA PsycBooks, APA PsycInfo databases from 1858 onwards.ResultsWe will present our findings from the literature review.ConclusionPolydipsia is a common clinical problem and requires careful evaluation and management to prevent long term neurological sequelae, and there are no evidence-based treatment guidelines.References National Institute of Health and Care Excellence (NICE). (2019). Head Injury. CG176. Retrieved from: https://www.nice.org.uk/guidance/cg176 Escamilla RF, Lisser H. Simmonds disease: A clinical study with revie of the literature; Differentiation from anorexia nervosa by statistical analysis of 595 cases, 101 of which were provided pathologically. The Journal of Clinical Endocrinology & Metabolism 1942;2(2):6596. Porter RJ, Miller RA. Diabetes insipidus following closed head injury. Journal of Neurology, Neurosurgery, and Psychiatry 1946;11:528562. Webb NE, Little B, Loupee-Wilson S, Power EM. Traumatic brain injury and neuro-endocrine disruption: medical and psychosocial rehabilitation. NeuroRehabilitation (Reading, Mass.) 2014;34(4):625636.



2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Binhao Wang ◽  
Huihua Li ◽  
Xu Han ◽  
Yiheng Yang ◽  
Yue Chen ◽  
...  


Author(s):  
Sophie Comte-Perret ◽  
Anne Zanchi ◽  
Fulgencio Gomez

Summary Medical therapy for Cushing's syndrome due to bilateral macronodular adrenal hyperplasia (BMAH) is generally administered for a limited time before surgery. Aberrant receptors antagonists show inconsistent efficacy in the long run to prevent adrenalectomy. We present a patient with BMAH, treated for 10 years with low doses of ketoconazole to control cortisol secretion. A 48-year-old woman presented with headaches and hypertension. Investigations showed the following: no clinical signs of Cushing's syndrome; enlarged lobulated adrenals; normal creatinine, potassium, and aldosterone; normal urinary aldosterone and metanephrines; elevated urinary free cortisol and steroid metabolites; and suppressed plasma renin activity and ACTH. A screening protocol for aberrant adrenal receptors failed to show any illegitimate hormone dependence. Ketoconazole caused rapid normalisation of cortisol and ACTH that persists over 10 years on treatment, while adrenals show no change in shape or size. Ketoconazole decreases cortisol in patients with Cushing's syndrome, and may prevent adrenal overgrowth. Steroid secretion in BMAH is inefficient as compared with normal adrenals or secreting tumours and can be controlled with low, well-tolerated doses of ketoconazole, as an alternative to surgery. Learning points Enlarged, macronodular adrenals are often incidentally found during the investigation of hypertension in patients harboring BMAH. Although laboratory findings include low ACTH and elevated cortisol, the majority of patients do not display cushingoid features. Bilateral adrenalectomy, followed by life-long steroid replacement, is the usual treatment of this benign condition, and alternative medical therapy is sought. Therapy based on aberrant adrenal receptors gives disappointing results, and inhibitors of steroidogenesis are not always well tolerated. However, ketoconazole at low, well-tolerated doses appeared appropriate to control adrenal steroid secretion indefinitely, while preventing adrenal overgrowth. This treatment probably constitutes the most convenient long-term alternative to surgery.



2018 ◽  
Author(s):  
Pascal O. Title ◽  
Daniel L. Rabosky

AbstractSpecies-specific diversification rates, or “tip rates”, can be computed quickly from phylogenies and are widely used to study diversification rate variation in relation to geography, ecology, and phenotypes. These tip rates provide a number of theoretical and practical advantages, such as the relaxation of assumptions of rate homogeneity in trait-dependent diversification studies. However, there is substantial confusion in the literature regarding whether these metrics estimate speciation or net diversification rates. Additionally, no study has yet compared the relative performance and accuracy of tip rate metrics across simulated diversification scenarios.We compared the statistical performance of three model-free rate metrics (inverse terminal branch lengths; node density metric; DR statistic) and a model-based approach (BAMM). We applied each method to a large set of simulated phylogenies that had been generated under different diversification processes; scenarios included multi-regime time-constant and diversity-dependent trees, as well as trees where the rate of speciation evolves under a diffusion process. We summarized performance in relation to the type of rate variation, the magnitude of rate heterogeneity and rate regime size. We also compared the ability of the metrics to estimate both speciation and net diversification rates.We show decisively that model-free tip rate metrics provide a better estimate of the rate of speciation than of net diversification. Error in net diversification rate estimates increases as a function of the relative extinction rate. In contrast, error in speciation rate estimates is low and relatively insensitive to extinction. Overall, and in particular when relative extinction was high, BAMM inferred the most accurate tip rates and exhibited lower error than non-model-based approaches. DR was highly correlated with true speciation rates but exhibited high error variance, and was the best metric for very small rate regimes.We found that, of the metrics tested, DR and BAMM are the most useful metrics for studying speciation rate dynamics and trait-dependent diversification. Although BAMM was more accurate than DR overall, the two approaches have complementary strengths. Because tip rate metrics are more reliable estimators of speciation rate, we recommend that empirical studies using these metrics exercise caution when drawing biological interpretations in any situation where the distinction between speciation and net diversification is important.



2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A980-A980
Author(s):  
Domenico Mallardo ◽  
Giosuè Scognamiglio ◽  
Khrystyna North ◽  
Mariaelena Capone ◽  
Michael Bailey ◽  
...  

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer with neuroendocrine features, and it is associated with elevated mortality. The pathogenesis is associated with presence of clonally integrated Merkel cell polyomavirus (MCPyV) or ultraviolet light (UV) exposure.1 The MCPyV causes up to 80% of MCC tumors in North America and Europe.2–4 Recently immunotherapy is having good results,5 the phase 2 trial JAVELIN Merkel 200 indicated that treatment with Avelumab (PDL1 inhibitor) in patients with metastatic MCC pre-treated have a meaningful long-term survival outcomes respect chemotherapy. Moreover, ORRs were highest in patients with high TMB that were also MCPyV−, PD-L1+ or had a greater CD8+ T cell density at the invasive margin.6 In this study, we investigated the biological signatures in patients with MCPyV or not.MethodsFrom April 2011 to June 2018, we collected retrospectively 50 FFPE (Formalin-Fixed Paraffin-Embed) from 37 patients with metastatic MCC and 13 tissues from a secondary metastatic site. All patients have appropriately signed informed consent. We performed an immunohistochemistry assays (IHC) for MCPyV and PDL1. In addition, through the NanoString GeoMx DSP (Digital Spatial Profiling), we analysed 11 patients (6 MCPyV+; 5 MCPyV-) with cutaneous metastasis using a 44-plex antibody cocktail. For each slide we selected three different areas: Intratumoral, extratumoral and tumour border, in each area we selected CD4+ and CD8+ cells in 4 different ROIs (Region of Interest). Statistical analysis was performed via Bonferroni correction, P< 0.05 was considered statistically significant for median stratification.ResultsThe DSP analysis showed that the tumour border cells have an overexpression of IDO respect intratumoral area (adj. p<0.01). Instead, extratumoral area of MCPyV- patients have a higher expression of B7-H3 respect MCPyV+ as well as FOXP3 is higher in the tumour border of MCPyV+ patients and EpCAM in the intratumoral area (p<0.05). PDL1 is overexpressed in MCPyV+ CD4+ cells respect CD8+ (p<0.05). The IHC assay shown that viral status does not change in multiple metastases and PDL1 is elevated in the tumour border (p<0.05).ConclusionsIn this retrospective study, our preliminary data shown that tumour edge have an important role in the modulations of immune infiltrate and patients with Merkel cell polyomavirus could have a different pathway of immunosuppression compared to patients with non-virus related etiology. Further investigations are needed to get additional information.AcknowledgementsThe study was supported by the Institutional Project ”Ricerca Corrente” of Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli, Italy.ReferencesKaae J, Hansen AV, Biggar RJ, et al. Merkel cell carcinoma: incidence, mortality, and risk of other cancers. J Natl Cancer Inst 2010 June 2;102(11):793–801.Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 2008 February 22;319(5866):1096–100.Garneski KM, Warcola AH, Feng Q, et al. Merkel cell polyomavirus is more frequently present in North American than Australian Merkel cell carcinoma tumors. J Invest Dermatol 2009 January;129(1):246–8.Goh G, Walradt T, Markarov V, et al. Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy. Oncotarget 2016 January 19;7(3):3403–15.Bichakjian CK, Olencki T, Aasi SZ, et al. Merkel cell carcinoma, version 1.2018, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2018 June;16(6):742–774.D’Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer 2020 May;8(1):e000674.Ethics ApprovalThe study was approved by internal ethics board of the Istituto Nazionale Tumori IRCCS Fondazione ”G. Pascale” of Napoli Italy, approval number of registry 33/17 OSS.ConsentWritten informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.



Author(s):  
Elda Kara ◽  
Elisa Della Valle ◽  
Sara De Vincentis ◽  
Vincenzo Rochira ◽  
Bruno Madeo

Summary Spontaneous or fine-needle aspiration (FNAB)-induced remission of primary hyperparathyroidism (PHPT) may occur, especially for cystic lesions. However, the disease generally relapses over a short time period. We present a case of PHPT due to an enlarged hyperfunctioning parathyroid that underwent long-term (almost 9 years) clinical and ultrasonographic remission after the disappearance of the lesion following ultrasound (US)-assisted FNAB. A 67-year-old woman with PHPT underwent biochemical and US examinations that confirmed the diagnosis and showed a lesion suggestive for parathyroid adenoma or hyperplasia. US-FNAB of the lesion confirmed its parathyroid nature by means of elevated levels of parathyroid hormone within the needle washing fluid. At the second visit, the patient referred slight neck swelling that resolved spontaneously in the days after the US-FNAB. At subsequent follow-up, the enlarged parathyroid was not found; it was visible neither with US nor with magnetic resonance imaging. Biochemical remission persists after 9 years. This is the first reported case of cure of PHPT after US-FNAB performed on a hyperfunctioning parathyroid resulting in its complete disappearance over a period of 9 years of negative biochemical and ultrasonographic follow-up. Learning points: Spontaneous or fine-needle aspiration-induced remission of primary hyperparathyroidism can occur. Both circumstances may present disease relapse over a variable time period, but definite remission is also possible even though long-term periodic follow-up should be performed. Parathyroid damage should be ruled out in case of neck symptomatology after parathyroid fine-needle aspiration or spontaneous symptomatology in patients with history of primary hyperparathyroidism.



2020 ◽  
Author(s):  
Orsolya Valkó ◽  
Balázs Deák ◽  
Péter Török ◽  
Katalin Tóth ◽  
Réka Kiss ◽  
...  

AbstractSowing grass seeds generally supports the rapid development of a closed perennial vegetation, which makes the method universally suitable for fast and effective landscape-scale restoration of grasslands. However, sustaining the recovered grasslands, and increasing their diversity is a challenging task. Understanding the role of seed bank compositional changes and vegetation dynamics contributes to designating management regimes that support the establishment of target species and suppress weeds. Our aim was to reveal the effect of post-restoration management on the vegetation and seed bank dynamics in grasslands restored in one of the largest European landscape-scale restoration projects. Eight years after restoration we sampled the vegetation and seed bank in a total of 96 plots located in 12 recovered grasslands in the Great Hungarian Plain. In each recovered grassland stand we designated a mown (mown from Year 1 to Year 8) and an abandoned sample site (mown from Year 1 to Year 3 then abandoned from Year 4 to Year 8). Mown and abandoned sites showed divergent vegetation and seed bank development. Abandonment led to the decline of sown grasses and higher cover of weeds, especially in the alkaline grasslands. Our study confirmed that seed bank has a limited contribution to the maintenance of biodiversity in both grassland types. We found that five years of abandonment had a larger effect on the seed bank than on the vegetation. We stress that long-term management is crucial for controlling the emergence of the weeds from their dense seed bank in restored grasslands.Implications for practiceSeed sowing of grass mixtures can be a feasible tool for restoring grasslands at large scales. However, the developed vegetation usually has low biodiversity and a high seed density of weeds is typical in the soil seed bank even several years after the restoration. Therefore, post-restoration management is necessary for suppressing weeds both aboveground and belowground.We recommend to design the long-term management of the sites subjected to grassland restoration already in the planning phase of the restoration projects and ensure that the management plan is ecologically and economically feasible.We recommend to complement the monitoring of vegetation with the analysis of soil seed bank for evaluating restoration success.



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