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Apoptosis and necroptosis overlap in their initial signaling but diverge to produce non-inflammatory and pro-inflammatory outcomes, respectively. High glucose pushes signaling in favor of necroptosis producing a hyperglycemic shift from apoptosis to necroptosis. This shift depends on receptor-interacting protein 1 (RIP1) and mitochondrial reactive oxygen species (ROS). Here, we show that RIP1, mixed lineage kinase domain-like (MLKL) protein, Bcl-2 agonist/killer (Bak), Bcl-2 associated x (Bax) protein, and dynamin-related protein 1 (Drp1) traffic to the mitochondria in high glucose. RIP1 and MLKL appear in the mitochondria in their activated, phosphorylated states while Drp1 appears in its activated, dephosphorylated state in high glucose. Mitochondrial trafficking is prevented in rip1 KO cells and upon treatment with N-acetylcysteine. Induction of ROS replicated the mitochondrial trafficking seen in high glucose. MLKL forms high MW oligomers in the outer and inner mitochondrial membranes while Bak and Bax form high MW oligomers in the outer mitochondrial membrane in high glucose, suggesting pore formation. MLKL, Bax, and Drp1 promoted cytochrome c release from the mitochondria as well as a decrease in mitochondrial membrane potential in high glucose. These results indicate that mitochondrial trafficking of RIP1, MLKL, Bak, Bax, and Drp1 are key events in the hyperglycemic shift from apoptosis to necroptosis. This is also the first report to show oligomerization of MLKL in the inner and outer mitochondrial membranes and dependence of mitochondrial permeability on MLKL.

Contains fulltext : 251517.pdf (Publisher’s version ) (Open Access) OBJECTIVE: International guidelines recommend supervised exercise therapy (SET) as primary treatment for all patients with intermittent claudication (IC), yet primary endovascular revascularisation (ER) might be more effective in patients with iliac artery obstruction. METHODS: This was a multicentre RCT including patients with IC caused by iliac artery stenosis or occlusion (NCT01385774). Patients were allocated randomly to SET or ER stratified for maximum walking distance (MWD) and concomitant SFA disease. Primary endpoints were MWD on a treadmill (3.2 km/h, 10% incline) and disease specific quality of life (VascuQol) after one year. Additional interventions during a mean follow up of 5.5 years were recorded. RESULTS: Between November 2010 and May 2015, 114 patients were allocated to SET, and 126 to ER. The trial was terminated prematurely after 240 patients were included. Compliance with SET was 57/114 (50%) after six months. Ten patients allocated to ER (8%) did not receive this intervention. One year follow up was complete for 90/114 (79%) SET patients and for 104/126 (83%) ER patients. The mean MWD improved from 187 to 561 m in SET patients and from 196 to 574 m in ER patients (p = .69). VascuQol sumscore improved from 4.24 to 5.58 in SET patients, and from 4.28 to 5.88 in ER patients (p = .048). Some 33/114 (29%) SET patients had an ER within one year, and 2/114 (2%) surgical revascularisation (SR). Some 10/126 (8%) ER patients had additional ER within one year and 10/126 (8%) SR. After a mean of 5.5 years, 49% of SET patients and 27% of ER patients underwent an additional intervention for IC. CONCLUSION: Taking into account the many limitations of the SUPER study, both a strategy of primary SET and primary ER improve MWD on a treadmill and disease specific Qol of patients with IC caused by an iliac artery obstruction. It seems reasonable to start with SET in these patients and accept a 30% failure rate, which, of course, must be discussed with the patient. Patients continue to have interventions beyond one year.

Understanding the mechanisms that promote the coexistence of hundreds of species over small areas in tropical forest remains a challenge. Many tropical tree species are presumed to be functionally equivalent shade tolerant species that differ in performance trade-offs between survival in shade and the ability to quickly grow in sunlight.Variation in plant functional traits related to resource acquisition is thought to predict variation in performance among species, perhaps explaining community assembly across habitats with gradients in resource availability. Many studies have found low predictive power, however, when linking trait measurements to species demographic rates.Seedlings face different challenges recruiting on the forest floor and may exhibit different traits and/or performance trade-offs than older individuals face in the eventual adult niche. Seed mass is the typical proxy for seedling success, but species also differ in cotyledon strategy (reserve vs photosynthetic) or other seedling traits. These can cause species with the same average seed mass to have divergent performance in the same habitat.We combined long-term studies of seedling dynamics with functional trait data collected at a standard developmental stage in three diverse neotropical forests to ask whether variation in coordinated suites of traits predicts variation among species in demographic performance.Across hundreds of species in Ecuador, Panama, and Puerto Rico, we found seedlings displayed correlated suites of leaf, stem, and root traits, which strongly correlated with seed mass and cotyledon strategy. Variation among species in seedling functional traits, seed mass, and cotyledon strategy were strong predictors of trade-offs in seedling growth and survival.Our findings highlight the importance of cotyledon strategy in addition to seed mass as a key component of seed and seedling biology. These results also underscore the importance of matching the ontogenetic stage of the trait measurement to the stage of demographic dynamics.Synthesis:With strikingly consistent patterns across three tropical forests, we find strong evidence for the promise of functional traits to provide mechanistic links between seedling form and demographic performance.

Contains fulltext : 293881.pdf (Publisher’s version ) (Open Access) PURPOSE: To study the prevalence, level, and nature of sleep problems and fatigue experienced by Usher syndrome type 2a (USH2a) patients. DESIGN: Cross-sectional study. PARTICIPANTS: Fifty-six genetically confirmed Dutch patients with syndromic USH2a and 120 healthy controls. METHODS: Sleep quality, prevalence, and type of sleep disorders, chronotype, fatigue, and daytime sleepiness were assessed using 5 questionnaires: (1) Pittsburgh Sleep Quality Index, (2) Holland Sleep Disorders Questionnaire, (3) Morningness-Eveningness Questionnaire, (4) Checklist Individual Strength, and (5) Epworth Sleepiness Scale. For a subset of patients, recent data on visual function were used to study the potential correlation between the outcomes of the questionnaires and disease progression. MAIN OUTCOME MEASURES: Results of all questionnaires were compared between USH2a and control cohorts, and the scores of the patients were compared with disease progression defined by age, visual field size, and visual acuity. RESULTS: Compared with the control population, patients with USH2a experienced a poorer quality of sleep, a higher incidence of sleep disorders, and higher levels of fatigue and daytime sleepiness. Intriguingly, the sleep disturbances and high levels of fatigue were not correlated with the level of visual impairment. These results are in accordance with the patients' experiences that their sleep problems already existed before the onset of vision loss. CONCLUSIONS: This study demonstrates a high prevalence of fatigue and poor sleep quality experienced by patients with USH2a. Recognition of sleep problems as a comorbidity of Usher syndrome would be a first step toward improved patient care. The absence of a relationship between the level of visual impairment and the severity of reported sleep problems is suggestive of an extraretinal origin of the sleep disturbances. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found after the references. 01 december 2023

Anthropogenic activities have altered historical disturbance regimes, and understanding the mechanisms by which these shifting perturbations interact is essential to predicting where they may erode ecosystem resilience. Emerging infectious plant diseases, caused by human translocation of nonnative pathogens, can generate ecologically damaging forms of novel biotic disturbance. Further, abiotic disturbances, such as wildfire, may influence the severity and extent of disease‐related perturbations via their effects on the occurrence of hosts, pathogens and microclimates; however, these interactions have rarely been examined. The disease ‘sudden oak death’ (SOD), associated with the introduced pathogen Phytophthora ramorum, causes acute, landscape‐scale tree mortality in California's fire‐prone coastal forests. Here, we examined interactions between wildfire and the biotic disturbance impacts of this emerging infectious disease. Leveraging long‐term datasets that describe wildfire occurrence and P. ramorum dynamics across the Big Sur region, we modelled the influence of recent and historical fires on epidemiological parameters, including pathogen presence, infestation intensity, reinvasion, and host mortality. Past wildfire altered disease dynamics and reduced SOD‐related mortality, indicating a negative interaction between these abiotic and biotic disturbances. Frequently burned forests were less likely to be invaded by P. ramorum, had lower incidence of host infection, and exhibited decreased disease‐related biotic disturbance, which was associated with reduced occurrence and density of epidemiologically significant hosts. Following a recent wildfire, survival of mature bay laurel, a key sporulating host, was the primary driver of P. ramorum infestation and reinvasion, but younger, rapidly regenerating host vegetation capable of sporulation did not measurably influence disease dynamics. Notably, the effect of P. ramorum infection on host mortality was reduced in recently burned areas, indicating that the loss of tall, mature host canopies may temporarily dampen pathogen transmission and ‘release’ susceptible species from significant inoculum pressure. Synthesis. Cumulatively, our findings indicate that fire history has contributed to heterogeneous patterns of biotic disturbance and disease‐related decline across this landscape, via changes to the both the occurrence of available hosts and the demography of epidemiologically important host populations. These results highlight that human‐altered abiotic disturbances may play a foundational role in structuring infectious disease dynamics, contributing to future outbreak emergence and driving biotic disturbance regimes.

OBJECTIVE: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR).METHODS: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests.RESULTS: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively).CONCLUSION: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair.

Additional file 1. Inter-task correlations.

Epidemiological models are important for the understanding of disease progression in plants and for the design of control strategies.

Background: To compare hospital outcomes of aortic aneurysm surgery, casemix correction for preoperative variables is essential. Most of these variables can be deduced from mortality risk prediction models. Our aim was to identify the optimal set of preoperative variables associated with mortality to establish a relevant and efficient casemix model.Methods: All patients prospectively registered between 2013 and 2016 in the Dutch Surgical Aneurysm Audit (DSAA) were included for the analysis. After multiple imputation for missing variables, predictors for mortality following univariable logistic regression were analyzed in a manual backward multivariable logistic regression model and compared with three standard mortality risk prediction models: Glasgow Aneurysm Score (GAS, mainly clinical parameters), Vascular Biochemical and Haematological Outcome Model (VBHOM, mainly laboratory parameters), and Dutch Aneurysm Score (DAS, both clinical and laboratory parameters). Discrimination and calibration were tested and considered good with a C-statistic > 0.8 and Hosmer-Lemeshow (H-L) P > 0.05.Results: There were 12,401 patients: 9,537 (76.9%) elective patients (EAAA), 913 (7.4%) acute symptomatic patients (SAAA), and 1,951 (15.7%) patients with acute rupture (RAAA). Overall postoperative mortality was 6.5%; 1.8% after EAAA surgery, 6.6% after SAAA, and 29.6% after RAAA surgery. The optimal set of independent variables associated with mortality was a mix of clinical and laboratory parameters: gender, age, pulmonary comorbidity, operative setting, creatinine, aneurysm size, hemoglobin, Glasgow coma scale, electrocardiography, and systolic blood pressure (C-statistic 0.871). External validation overall of VBHOM, DAS, and GAS revealed C-statistics of 0.836, 0.782, and 0.761, with an H-L of 0.028, 0.00, and 0.128, respectively.Conclusions: The optimal set of variables for casemix correction in the DSAA comprises both clinical and laboratory parameters, which can be collected easily from electronic patient files and will lead to an efficient casemix model.

Introduction: The number of elective surgeries for patients who are over 70 years of age is continuously growing. At the same time, postoperative delirium (POD) is common in older patients (5–60%) depending on predisposing risk factors, such as multimorbidity, cognitive impairment, neurodegenerative disorders and other dementing disorders, and precipitating factors, such as duration of surgery. Knowledge of individual risk profiles prior to elective surgery may help to identify patients at increased risk for development of POD. In this study, clinical and cognitive risk factors for POD were investigated in patients undergoing various elective cardiac and non-cardiac surgeries.Methods: The PAWEL study is a prospective, interventional trial on delirium prevention. At baseline, 880 inpatients at five surgical centers were recruited for sub-sample PAWEL-R. Multimodal assessments included clinical renal function, medication, American Society of Anesthesiologists (ASA) Physical Status Classification System, geriatric and cognitive assessments, which comprised the Montreal Cognitive Assessment Scale (MoCA), Trail-making Test, and Digit Span backward. Delirium incidence was monitored postoperatively by the Confusion Assessment Method (CAM) and a chart review for up to a week or until discharge. Multivariate regression models and Chi-square Automatic Interaction Detectors (CHAID) analyses were performed using delirium incidence as the primary outcome.Results: Eighteen risk factors were investigated in elective cardiovascular and orthopedic or general surgery. A total of 208 out of 880 patients (24%) developed POD. A global regression model that included all risk variables predicted delirium incidence with high accuracy (AUC = 0.81; 95% CI 0.77, 0.85). A simpler model (clinical and cognitive variables; model CLIN-COG) of 10 factors that only included surgery type, multimorbidity, renal failure, polypharmacy, ASA, cut-to-suture time, and cognition (MoCA, Digit Span backward, and preexisting dementia), however, exhibited similar predictive accuracy (AUC = 0.80; 95% CI 0.76, 0.84).Conclusion: The risk of developing POD can be estimated by preoperative assessments, such as ASA classification, expected cut-to-suture time, and short cognitive screenings. This rather efficient approach predicted POD risk over all types of surgery. Thus, a basic risk assessment including a cognitive screen can help to stratify patients at low, medium, or high POD risk to provide targeted prevention and/or management strategies for patients at risk.

Genomewide association studies (GWAS) have improved our understanding of the genetic architecture of common complex diseases such as osteoporosis. Nevertheless, to attribute functional skeletal contributions of candidate genes to osteoporosis-related traits, there is a need for efficient and cost-effective in vivo functional testing. This can be achieved through CRISPR-based reverse genetic screens, where phenotyping is traditionally performed in stable germline knockout (KO) mutants. Recently it was shown that first-generation (F0) mosaic mutant zebrafish (so-called crispants) recapitulate the phenotype of germline KOs. To demonstrate feasibility of functional validation of osteoporosis candidate genes through crispant screening, we compared a crispant to a stable KO zebrafish model for the lrp5 gene. In humans, recessive loss-of-function mutations in LRP5, a co-receptor in the Wnt signaling pathway, cause osteoporosis-pseudoglioma syndrome. In addition, several GWAS studies identified LRP5 as a major risk locus for osteoporosis-related phenotypes. In this study, we showed that early stage lrp5 KO larvae display decreased notochord mineralization and malformations of the head cartilage. Quantitative micro-computed tomography (micro-CT) scanning and mass-spectrometry element analysis of the adult skeleton revealed decreased vertebral bone volume and bone mineralization, hallmark features of osteoporosis. Furthermore, regenerating fin tissue displayed reduced Wnt signaling activity in lrp5 KO adults. We next compared lrp5 mutants with crispants. Next-generation sequencing analysis of adult crispant tissue revealed a mean out-of-frame mutation rate of 76%, resulting in strongly reduced levels of Lrp5 protein. These crispants generally showed a milder but nonetheless highly comparable skeletal phenotype and a similarly reduced Wnt pathway response compared with lrp5 KO mutants. In conclusion, we show through faithful modeling of LRP5-related primary osteoporosis that crispant screening in zebrafish is a promising approach for rapid functional screening of osteoporosis candidate genes. (C) 2021 American Society for Bone and Mineral Research. (C) 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Plant defense chemistry is often hypothesized to drive ecological and evolutionary success in diverse tropical forests, yet detailed characterizations of plant secondary metabolites in tropical plants are logistically challenging. Here, we explore a new integrative approach that combines visible‐to‐shortwave infrared (VSWIR) spectral reflectance data with detailed plant metabolomics data from 19 Protium (Burseraceae) tree species. Building on the discovery that different Protium species have unique chemistries yet share many secondary metabolites, we devised a method to test for associations between metabolites and VSWIR spectral data. Given species‐level variation in metabolite abundance, we correlated the concentration of particular chemicals with the reflectance of the spectral bands in a wavelength band per secondary metabolite matrix. We included 45 metabolites that were shared by at least 5 Protium species and correlated their per‐species foliar abundances against each one of 210 wavelength bands of field‐measured VSWIR spectra. Finally, we tested whether classes of similar metabolites showed similar relationships with spectral patterns. We found that many secondary metabolites yielded strong correlations with VSWIR spectra of Protium. Furthermore, important Protium metabolite classes such as procyanidins (condensed tannins) and phytosterols were grouped together in a hierarchical clustering analysis (Ward’s algorithm), confirming similarity in their associations with plant spectral patterns. We also found a significant correlation in the phenolics content between juvenile and canopy trees of the same species, suggesting that species‐level variation in defense chemistry is consistent across life stages and geographic distribution. We conclude that the integration of spectral and metabolic approaches could represent a powerful and economical method to characterize important aspects of tropical plant defense chemistry.

BACKGROUND: Colonic ischemia remains a severe complication after abdominal aortic aneurysm (AAA) repair and is associated with a high mortality. With open repair being one of the main risk factors of colonic ischemia, deciding between endovascular or open aneurysm repair should be based on tailor-made medicine. This study aims to identify high-risk patients of colonic ischemia, a risk that can be taken into account while deciding on AAA treatment strategy.METHODS: A nationwide population-based cohort study of 9,433 patients who underwent an AAA operation between 2014 and 2016 was conducted. Potential risk factors were determined by reviewing prior studies and univariate analysis. With logistic regression analysis, independent predictors of intestinal ischemia were established. These variables were used to form a prediction model.RESULTS: Intestinal ischemia occurred in 267 patients (2.8%). Occurrence of intestinal ischemia was seen significantly more in open repair versus endovascular aneurysm repair (7.6% vs. 0.9%; P < 0.001). This difference remained significant after stratification by urgency of the procedure, in both intact open (4.2% vs. 0.4%; P < 0.001) and ruptured open repair (15.0% vs. 6.2%); P < 0.001). Rupture of the AAA was the most important predictor of developing intestinal ischemia (odds ratio [OR], 5.9, 95% confidence interval [CI] 4.4-8.0), followed by having a suprarenal AAA (OR 3.4; CI 1.1-10.6). Associated procedural factors were open repair (OR 2.8; 95% CI 1.9-4.2), blood loss >1L (OR 3.6; 95% CI 1.7-7.5), and prolonged operating time (OR 2.0; 95% CI 1.4-2.8). Patient characteristics included having peripheral arterial disease (OR 2.4; 95% CI 1.3-4.4), female gender (OR 1.7; 95% CI 1.2-2.4), renal insufficiency (OR 1.7; 1.3-2.2), and pulmonary history (OR 1.6; 95% CI 1.2-2.2). Age CONCLUSIONS: One of the main risk factors is open repair. Several other risk factors can contribute to developing colonic ischemia after AAA repair. The proposed prediction model can be used to identify patients at high risk for developing colonic ischemia. With the current trend in AAA repair leaning toward open repair for better long-term results, our prediction model allows a better informed decision can be made in AAA treatment strategy.

The zebrafish is an appealing model organism for investigating the genetic (G) and environmental (E) factors, as well as their interactions (GxE), which contribute to craniofacial malformations. Here, we review zebrafish studies on environmental factors involved in the etiology of craniofacial malformations in humans including maternal smoking, alcohol consumption, nutrition and drug use. As an example, we focus on the (cleft) palate, for which the zebrafish ethmoid plate is a good model. This review highlights the importance of investigating ExE interactions and discusses the variable effects of exposure to environmental factors on craniofacial development depending on dosage, exposure time and developmental stage. Zebrafish also promise to be a good tool to study novel craniofacial teratogens and toxin mixtures. Lastly, we discuss the handful of studies on gene–alcohol interactions using mutant sensitivity screens and reverse genetic techniques. We expect that studies addressing complex interactions (ExE and GxE) in craniofacial malformations will increase in the coming years. These are likely to uncover currently unknown mechanisms with implications for the prevention of craniofacial malformations. The zebrafish appears to be an excellent complementary model with high translational value to study these complex interactions.

Zebrafish scales are mineralised plates that can regenerate involvingde novobone formation. This presents an opportunity to uncover genes and pathways relevant to human musculoskeletal disease relevant to impaired bone formation. To investigate this hypothesis, we defined transcriptomic profiles of ontogenetic and regenerating scales, and identified 604 differentially expressed genes (DEGs) that were enriched for extracellular matrix, ossification, and cell adhesion pathways. Next, we showed that human orthologues of DEGs were 2.8 times more likely to cause human monogenic skeletal diseases (P−11), and they showed enrichment for human orthologues associated with polygenetic disease traits including stature, bone density and osteoarthritis (PCOL11A2) or bone density only (SPP1) developed skeletal abnormalities consistent with our genetic association studies.Col11a2Y228X/Y228Xmutants showed endoskeletal features consistent with abnormal growth and osteoarthritis, whereasspp1P160X/P160Xmutants had elevated bone density (P

Contains fulltext : 226469.pdf (Publisher’s version ) (Open Access) BACKGROUND: Long-term secondary aortic reinterventions (SARs) can be a sign of (lack of) effectiveness of abdominal aortic aneurysm (AAA) surgery. This study provides insight into the national number of SARs after primary AAA repair by endovascular aneurysm repair (EVAR) or by open surgical repair in the Netherlands. METHODS: Observational study included all patients undergoing SAR between 2016 and 2017, registered in the compulsory Dutch Surgical Aneurysm Audit (DSAA). The DSAA started in 2013, SARs are registered from 2016. Characteristics of SAR and postoperative outcomes (mortality/complications) were analyzed, stratified by urgency of SAR. Data of SARs were merged with data of their preceded primary AAA repair, registered in the DSAA after January 2013. In these patients undergoing SAR, treatment characteristics of the preceded primary AAA repair were additionally described, with focus on differences between stent grafts. RESULTS: Between 2016 and 2017, 691 patients underwent SAR, this concerned 9.3% of all AAA procedures (infrarenal/juxtarenal/suprarenal) in the Netherlands (77% elective/11% acute symptomatic/12% ruptured). Endoleak (60%) was the most frequent indication for SAR. SARs were performed with EVAR in 66%. Postoperative mortalities after SAR were 3.4%, 11%, and 29% in elective, acute symptomatic, and ruptured patients, respectively. In 26% (n = 181) of the patients undergoing SAR their primary AAA repair was performed after January 2013 and data of primary and SAR procedures could be merged. In 93% (n = 136), primary AAA repair was EVAR. Endografts primarily used were nitinol/polyester (62%), nitinol/polytetrafluoroethylene (8%), endovascular sealing (21%), and others (9%), compared with their national market share of 76% (odds ratio [OR], 0.52; 95% confidence interval [CI], 0.38-0.71), 15% (OR, 0.50; CI, 0.29-0.89), 4.9% (OR, 5.04; CI, 3.44-7.38), and 4.1% (OR, 2.81; CI, 1.66-4.74), respectively. CONCLUSIONS: In the Netherlands, about one-tenth of the annual AAA procedures concerns an SAR. A quarter of this cohort had an SAR within 1-5 years after their primary AAA repair. Most SARs followed after primary EVAR procedures, in which an overrepresentation of endovascular sealing grafts was seen. Postoperative mortality after SAR is comparable with primary AAA repair.

Contains fulltext : 226467.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Composite measures may better objectify hospital performance than individual outcome measures (IOM). Textbook outcome (TO) is an outcome measure achieved for an individual patient when all undesirable outcomes are absent. The aim of this study was to assess TO as an additional outcome measure to evaluate quality of care in symptomatic patients treated by carotid endarterectomy (CEA). METHODS: All symptomatic patients treated by CEA in 2018, registered in the Dutch Audit for Carotid Interventions, were included. TO was defined as a composite of the absence of 30 day mortality, neurological events (any stroke or transient ischaemic attack [TIA]), cranial nerve deficit, haemorrhage, 30 day readmission, prolonged length of stay (LOS; > 5 days) and any other surgical complication. Multivariable logistic regression was used to identify covariables associated with achieving TO, which were used for casemix adjustment for hospital comparison. For each hospital, an observed vs. expected number of events ratio (O/E ratio) was calculated and plotted in a funnel plot with 95% control limits. RESULTS: In total, 70.7% of patients had a desired outcome within 30 days after CEA and therefore achieved TO. Prolonged LOS was the most common parameter (85%) and mortality the least common (1.1%) for not achieving TO. Covariates associated with achieving TO were younger age, the absence of pulmonary comorbidity, higher haemoglobin levels, and TIA as index event. In the case mix adjusted funnel plot, the O/E ratios between hospitals ranged between 0.63 and 1.27, with two hospitals revealing a statistically significantly lower rate of TO (with O/E ratios of 0.63 and 0.66). CONCLUSION: In the Netherlands, most patients treated by CEA achieve TO. Variation between hospitals in achieving TO might imply differences in performance. TO may be used as an additive to the pre-existing IOM, especially in surgical care with low baseline risk such as CEA.

Valproic acid (VPA) is an anti-epileptic drug known to cause congenital craniofacial abnormalities, including orofacial clefts (OFC). The exact mechanisms by which VPA leads to craniofacial skeletal malformations are poorly understood. In this study, we investigated the effects of VPA on cartilage and bone formation in the zebrafish larval head during 1-13 hpf (early) and 25-37 hpf (late) development in which cranial neural crest cells (CNCCs) arise and then proliferate and differentiate, respectively. Double-staining for cartilage and bone at 5 dpf revealed that VPA reduced cartilage and bone formation in a dose-dependent manner after both early or late exposure. Several different CNCC-derived cartilage and bone elements were affected in both groups. In the early group (100 μM VPA), the posterior head length and the ethmoid plate were reduced in length (both p 0.01), while mineralization of 4 out of 9 bone elements was often lacking (all p 0.01). In the late group (100 μM VPA), also the posterior head length was reduced as well as the length of the ceratohyals (both p 0.01). Similar to early exposure, mineralization of 3 out of 9 bone elements was often lacking (all p 0.01). These results indicate that both CNCC formation (early) and differentiation (late) are hampered by VPA treatment, of which the consequences for bone and cartilage formation are persistent at 5 dpf. Indeed, we also found that the expression of several genes related to cartilage and bone was upregulated at 5 dpf. These data indicate a compensatory reaction to the lack of cartilage and bone. Altogether, VPA seems to induce craniofacial malformations via disturbed CNCC function leading to defects in cartilage and bone formation.

Epidemiological models are important for the understanding of disease progression in plants and for the design of control strategies. Phytophthora ramorum, the pathogen responsible for the disease known as Sudden Oak Death, causes lethal infection on several oaks but relies on California bay laurels for transmission. Here, repeated surveys of bay laurels and oaks indicated that bay laurel disease incidence was positively correlated with rainfall, bay laurel density, and an eastern aspect, and negatively correlated with bay laurel basal area. Oak infection only occurred in years when rainfall was higher than the 30-year average, and although infection rates were greater among larger trees, mortality was greater among smaller trees. Additionally, larger oaks closer to infected bay laurels exhibited greater infection rates. Disease incidence differed among sites, and only a fraction of bay laurels were disease superspreaders, while even fewer individuals were refugial trees harboring active infections during dry periods. Based on this study, reducing bay laurel density in denser stands and the number of superspreaders or refugial trees in less dense stands may reduce disease incidence. However, the selective removal of bay laurel trees 0–10 m from oaks is likely to be more effective in preventing infection of specific oaks.

Direct ink writing of silicone elastomers enables printing with precise control of porosity and mechanical properties of ordered cellular solids, suitable for shock absorption and stress mitigation applications. With the ability to manipulate structure and feedstock stiffness, the design space becomes challenging to parse to obtain a solution producing a desired mechanical response. Here, we derive an analytical design approach for a specific architecture. Results from finite element simulations and quasi-static mechanical tests of two different parallel strand architectures were analyzed to understand the structure-property relationships under uniaxial compression. Combining effective stiffness-density scaling with least squares optimization of the stress responses yielded general response curves parameterized by resin modulus and strand spacing. An analytical expression of these curves serves as a reduced order model, which, when optimized, provides a rapid design capability for filament-based 3D printed structures. As a demonstration, the optimal design of a face-centered tetragonal architecture is computed that satisfies prescribed minimum and maximum load constraints.

We present the first copper iridium binary metal oxide with the chemical formula Cu2IrO3. The material is synthesized from the parent compound Na2IrO3 by a topotactic reaction where sodium is exchanged with copper under mild conditions. Cu2IrO3 has the same monoclinic space group (C2/c) as Na2IrO3 with a layered honeycomb structure. The parent compound Na2IrO3 is proposed to be relevant to the Kitaev spin liquid on the basis of having Ir4+ with an effective spin of 1/2 on a honeycomb lattice. Remarkably, whereas Na2IrO3 shows a long-range magnetic order at 15 K and fails to become a true spin liquid, Cu2IrO3 remains disordered until 2.7 K, at which point a short-range order develops. Rietveld analysis shows less distortions in the honeycomb structure of Cu2IrO3 with bond angles closer to 120° compared to Na2IrO3. Thus, the weak short-range magnetism combined with the nearly ideal honeycomb structure places Cu2IrO3 closer to a Kitaev spin liquid than its predecessors.

The tropical forests of Borneo and Amazonia may each contain more tree species diversity in half a square kilometre than do all the temperate forests of Europe, North America, and Asia combined. Biologists have long been fascinated by this disparity, using it to investigate potential drivers of biodiversity. Latitudinal variation in many of these drivers is expected to create geographic differences in ecological and evolutionary processes, and evidence increasingly shows that tropical ecosystems have higher rates of diversification, clade origination, and clade dispersal. However, there is currently no evidence to link gradients in ecological processes within communities at a local scale directly to the geographic gradient in biodiversity. Here, we show geographic variation in the storage effect, an ecological mechanism that reduces the potential for competitive exclusion more strongly in the tropics than it does in temperate and boreal zones, decreasing the ratio of interspecific-to-intraspecific competition by 0.25% for each degree of latitude that an ecosystem is located closer to the Equator. Additionally, we find evidence that latitudinal variation in climate underpins these differences; longer growing seasons in the tropics reduce constraints on the seasonal timing of reproduction, permitting lower recruitment synchrony between species and thereby enhancing niche partitioning through the storage effect. Our results demonstrate that the strength of the storage effect, and therefore its impact on diversity within communities, varies latitudinally in association with climate. This finding highlights the importance of biotic interactions in shaping geographic diversity patterns, and emphasizes the need to understand the mechanisms underpinning ecological processes in greater detail than has previously been appreciated.

We assessed the effects of (a) stimulus fading, (b) verbal feedback, and (c) superimposition training on college students’ skill acquisition, maintenance, and generalization of accurate pours of a standard serving of beer (12 oz). Participants were 18 college students who failed to pour within 10% o

Contains fulltext : 226470.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Mycotic aneurysms of the abdominal aorta (MAAA) can be treated by open repair (OR) or endovascular aneurysm repair (EVAR). This nationwide study provides an overview of the situation of MAAA treatment in The Netherlands in 2016. METHODS: A retrospective cohort study was conducted with all centers that registered aortic abdominal aneurysms in the Dutch Surgical Aneurysm Audit in 2016. Questionnaires on 1-year outcomes were sent to all centers that treated patients with MAAA. The primary aim was to determine 30-day and 1-year mortality and morbidity of OR- and EVAR-treated patients. Morbidity was determined by the need for reoperations and the number of readmissions to the hospital. RESULTS: Twenty-six MAAA were detected in the Dutch Surgical Aneurysm Audit database of 2016, resulting in an incidence of 0.7% of all registered abdominal aortic aneurysms. The 30-day mortality for OR and EVAR treated patients was 1 in 13 and 0 in 13, respectively. Major and minor reinterventions within 30 days were needed for two (one OR and one EVAR) and two (one OR and one EVAR) patients, respectively. Two patients (15.4%) in the OR group and one patient (7.7%) in the EVAR group were readmitted to hospital within 30 days. In total, 1-year outcomes of 23 patients were available. In the OR group, one patient (9.1%) died in the first postoperative year. There was one major reintervention (removal of endoprosthesis and spiralvein reconstruction) in the EVAR group. Two patients (18.2%) treated with OR and two (16.7%) treated with EVAR required a minor reintervention. In both groups, four patients (OR, 36.4%; EVAR, 33.3%) were readmitted to hospital within 1 year postoperatively. CONCLUSIONS: Both OR- and EVAR-treated patients show acceptable clinical outcomes after 30 days and at the 1-year follow-up. Depending on the clinical course of the patient, EVAR may be considered in the management of this disease.

Contains fulltext : 229914.pdf (Publisher’s version ) (Open Access) BACKGROUND: While several observational studies suggested a lower postoperative mortality after minimal invasive endovascular aneurysm repair (EVAR) in patients with a ruptured abdominal aortic aneurysm (RAAA) compared to conventional open surgical repair (OSR), landmark randomized controlled trials have not been able to prove the superiority of EVAR over OSR. Randomized controlled trials contain a selected, homogeneous population, influencing external validity. Observational studies are biased and adjustment of confounders can be incomplete. Instrumental variable (IV) analysis (pseudorandomization) may help to answer the question if patients with an RAAA have lower postoperative mortality when undergoing EVAR compared to OSR. METHODS: This is an observational study including all patients with an RAAA, registered in the Dutch Surgical Aneurysm Audit between 2013 and 2017. The risk difference (RD) in postoperative mortality (30 days/in-hospital) between patients undergoing EVAR and OSR was estimated, in which adjustment for confounding was performed in 3 ways: linear model adjusted for observed confounders, propensity score model (multivariable logistic regression analysis), and IV analysis (two-stage least square regression), adjusting for observed and unobserved confounders, with the variation in percentage of EVAR per hospital as the IV instrument. RESULTS: 2419 patients with an RAAA (1489 OSR and 930 EVAR) were included. Unadjusted postoperative mortality was 34.9% after OSR and 22.6% after EVAR (RD 12.3%, 95% CI 8.5-16%). The RD adjusted for observed confounders using linear regression analysis and propensity score analysis was, respectively, 12.3% (95% CI 9.6-16.7%) and 13.2% (95%CI 9.3-17.1%) in favor of EVAR. Using IV analysis, adjusting for observed and unobserved confounders, RD was 8.9% (95% CI -1.1-18.9%) in favor of EVAR. CONCLUSIONS: Adjusting for observed confounders, patients with an RAAA undergoing EVAR had a significant better survival than OSR in a consecutive large cohort. Adjustment for unobserved confounders resulted in a clinical relevant RD. An "EVAR preference strategy" in patients with an RAAA could result in lower postoperative mortality.

Human‐altered disturbance regimes and changing climatic conditions can reduce seed availability and suitable microsites, limiting seedling regeneration in recovering forest systems. Thus, resprouting plants, which can persist in situ, are expected to expand in dominance in many disturbance‐prone forests. However, resprouters may also be challenged by changing regimes, and the mechanisms determining facultative seedling recruitment by resprouting species, which will determine both the future spread and current persistence of these populations, are poorly understood. In the resprouter‐dominated forests of coastal California, interactions between wildfire and an emerging disease, sudden oak death (SOD), alter disturbance severity and tree mortality, which may shift forest regeneration trajectories. We examine this set of compound disturbances to (1) assess the influence of seed limitation, biotic competition, and abiotic conditions on seedling regeneration in resprouting populations; (2) investigate whether disease‐fire interactions alter postfire seedling regeneration, which have implications for future disease dynamics and shifts in forest composition. Following a wildfire that impacted a preexisting plot network in SOD‐affected forests, we monitored seedling abundances and survival over eight years. With pre‐ and postfire data, we assessed relationships between regeneration dynamics and disturbance severity, biotic, and abiotic variables, using Bayesian generalized linear models and mixed models. Our results indicate that postfire seedling regeneration by resprouting species was shaped by contrasting mechanisms reflecting seed limitation and competitive release. Seedling abundances declined with decreasing postfire survival of mature, conspecific stems, while belowground survival of resprouting genets had no effect. However, where seed sources persisted, seedling abundances and survival generally increased with the prefire severity of disease impacts, suggesting that decreased competition with adults may enhance seedling recruitment in this resprouter‐dominated system. Species’ regeneration responses varied with their relative susceptibility to SOD and suggest compositional shifts, which will determine future disease management and forest restoration actions. These results additionally highlight that mechanisms related to biotic competition, seed limitation, and opportunities for seedling recruitment beneath mature canopies may determine possible shifts in the occurrence of resprouting traits. This result has broad applications to other systems impacted by human‐altered regimes where asexual persistence may be predicted to be a beneficial life history strategy.

The global mechanisms that regulate and potentially coordinate cell proliferation & death in developing neural regions are not well understood. In particular, it is not clear how or whether clonal relationships between neural progenitor cells and their progeny influence the growing brain. We have developed an approach using Brainbow in the developing zebrafish to visualize and follow multiple clones of related cells in vivo over time. This allows for clear visualization of many dividing clones of cells, deep in proliferating brain regions. As expected, in addition to undergoing interkinetic nuclear migration and cell division, cells also periodically undergo apoptosis. Interestingly, cell death occurs in a non-random manner: clonally related cells are more likely to die in a progressive fashion than cells from different clones. Multiple members of an individual clone die while neighboring clones appear healthy and continue to divide. Our results suggest that clonal relationships can influence cellular fitness and survival in the developing nervous system, perhaps through a competitive mechanism whereby clones of cells are competing with other clones. Clonal cell competition may help regulate neuronal proliferation in the vertebrate brain.

Ecological memory is central to how ecosystems respond to disturbance and is maintained by two types of legacies – information and material. Species life-history traits represent an adaptive response to disturbance and are an information legacy; in contrast, the abiotic and biotic structures (such as seeds or nutrients) produced by single disturbance events are material legacies. Disturbance characteristics that support or maintain these legacies enhance ecological resilience and maintain a “safe operating space” for ecosystem recovery. However, legacies can be lost or diminished as disturbance regimes and environmental conditions change, generating a “resilience debt” that manifests only after the system is disturbed. Strong effects of ecological memory on post-disturbance dynamics imply that contingencies (effects that cannot be predicted with certainty) of individual disturbances, interactions among disturbances, and climate variability combine to affect ecosystem resilience. We illustrate these concepts and introduce a novel ecosystem resilience framework with examples of forest disturbances, primarily from North America. Identifying legacies that support resilience in a particular ecosystem can help scientists and resource managers anticipate when disturbances may trigger abrupt shifts in forest ecosystems, and when forests are likely to be resilient.

Background: Medication regimen complexity describes multiple characteristics of a patient’s prescribed drug regimen. Heart transplant recipients must comply with a lifelong regimen that consists of numerous medications. However, a systematic assessment of medication regimen complexity over time has not been conducted in this, or any other, transplant population. Objective: The objective of this study was to quantify patient-level medication regimen complexity over time following primary heart transplantation and heart retransplantation, using the validated patient-level Medication Regimen Complexity Index (pMRCI) tool. Methods: Medication lists were reviewed at transplant discharge and years 1, 3, and 5 post–primary heart transplant, and at transplant discharge and years 1 and 3 post–heart retransplantation. Medications were categorized as transplant-specific, other prescription, and over-the-counter (OTC). Results: In primary heart transplant recipients (n = 60), mean total medication count was 14.3 ± 3.4 at transplant discharge and did not change significantly over time ( P = 0.64). Transplant-specific medication count decreased significantly from discharge (2.9 ± 0.4) to year 5 (2.3 ± 0.6); P = 0.02. However, 32% of patients were taking 16 or more total medications at year 5 posttransplant. More than 70% of the pMRCI score was attributed to other prescription and OTC medications, which was largely driven by dosing frequency in this cohort. Medication complexity did not differ significantly between heart retransplant recipients (n = 11) and matched primary heart transplant controls (n = 22). Conclusion: Together, these data highlight the substantial medication burden after heart transplantation and reveal opportunities to address medication regimen complexity in this, and other, transplant populations.

Craniofacial development is tightly regulated and therefore highly vulnerable to disturbance by genetic and environmental factors. Fibroblast growth factors (FGFs) direct migration, proliferation and survival of cranial neural crest cells (CNCCs) forming the human face. In this study, we analyzed bone and cartilage formation in the head of five dpf fgf8ati282 zebrafish larvae and assessed gene expression levels for 11 genes involved in these processes. In addition, in situ hybridization was performed on 8 and 24 hours post fertilization (hpf) larvae (fgf8a, dlx2a, runx2a, col2a1a). A significant size reduction of eight out of nine craniofacial cartilage structures was found in homozygous mutant (6–36%, P, Summary: A function-blocking mutation in fgf8a causes craniofacial malformations in zebrafish larvae due to impaired cranial neural crest cell migration and survival.

Objectives: Failure to rescue (FTR) is a composite quality indicator, defined as the proportion of deceased patients following major complications. The aims of this study were to compare FTR with mortality for hospital comparisons in abdominal aortic aneurysm (AAA) surgery in The Netherlands and investigate hospital volume and associated factors.Methods: Patients prospectively registered between 2013 and 2015 in the Dutch Surgical Aneurysm Audit (DSAA) were analysed. FTR was analysed for AAA patients and subgroups elective (EAAA) and acute (AAAA; symptomatic or ruptured) aneurysms. Variables and hospital volume were analysed by uni- and multivariable regression analysis. Adjusted hospital comparisons for mortality, major complications, and FTR were presented in funnel plots. Isomortality lines were constructed when presenting FTR and major complication rates.Results: A total of 9258 patients were analysed in 61 hospitals: 7149 EAAA patients (77.2%) and 2109 AAAA patients (22.8%). There were 2785 (30.1%) patients with complications (unadjusted range 5-65% per hospital): 2161 (77.6%) with major and 624 (28.4%) patients with minor complications. Overall mortality was 6.6% (adjusted range 0-16% per hospital) and FTR was 28.4% (n = 613) (adjusted range 0-60% per hospital). Glasgow Coma Scale, age, pulse, creatinine, electrocardiography, and operative setting were independently associated with FTR. Hospital volume was not associated with FTR. In AAAA patients hospital volume was significantly associated with a lower adjusted major complication and mortality rate (OR 0.62, 95% CI 0.49-0.78; and 0.64, 95% CI 0.48-0.87). Four hospitals had a significant lower adjusted FTR with different major complication rates on different isomortality lines.Conclusions: There was more variation in FTR than in mortality between hospitals. FTR identified the same best performing hospitals as for mortality and therefore was of limited additional value in measuring quality of care for AAA surgery. FTR can be used for internal quality improvement with major complications in funnel plots and diagrams with isomortality lines. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

This work presents an integrated approach to study the crystal chemistry and phonon heat capacity of complex layered oxides. Two quaternary delafossites are synthesized from ternary parent compounds and copper monohalides via a topochemical exchange reaction that preserves the honeycomb ordering of the parent structures. For each compound, Rietveld refinement of the powder X-ray diffraction patterns is examined in both monoclinic C2/ c and rhombohedral R3̅ m space groups. Honeycomb ordering occurs only in the monoclinic space group. Bragg peaks associated with honeycomb ordering acquire an asymmetric broadening known as the Warren line shape that is commonly observed in layered structures with stacking disorder. Detailed TEM analysis confirms honeycomb ordering within each layer in both title compounds and establishes a twinning between the adjacent layers instead of the more conventional shifting or skipping stacking faults. The structural model is then used to calculate phonon dispersions and heat capacity from first principles. In both compounds, the calculated heat capacity accurately describes the experimental data. The integrated approach presented here offers a platform to carefully analyze the phonon heat capacity in complex oxides where the crystal structure can produce magnetic frustration. Isolating phonon contribution from total heat capacity is a necessary and challenging step toward a quantitative study of spin liquid materials with exotic magnetic excitations such as spinons and Majorana fermions. A quantitative understanding of phonon density of states based on crystal chemistry as presented here also paves the way toward higher efficiency thermoelectric materials.

Magnetic van der Waals (vdW) materials are the centerpiece of atomically thin devices with spintronic and optoelectronic functions. Exploring new chemistry paths to tune their magnetic and optical properties enables significant progress in fabricating heterostructures and ultracompact devices by mechanical exfoliation. The key parameter to sustain ferromagnetism in 2D is magnetic anisotropy-a tendency of spins to align in a certain crystallographic direction known as easy-axis. In layered materials, two limits of easy-axis are in-plane (XY) and out-of-plane (Ising). Light polarization and the helicity of topological states can couple to magnetic anisotropy with promising photoluminescence or spin-orbitronic functions. Here, a unique experiment is designed to control the easy-axis, the magnetic transition temperature, and the optical gap simultaneously in a series of CrCl

Human-altered ecological disturbances may challenge system resilience and disrupt biological legacies maintaining ecosystem recovery. Yet, the extent to which novel regimes challenge these legacies varies. This may be partially explained by differences in the vulnerability of life history strategies to disturbance characteristics. In the fire-prone, resprouter-dominated coast redwood forests of California, the introduced disease sudden oak death (SOD) alters fuel profiles, fire behavior, and aboveground tree mortality; however, this system is dominated by resprouting trees that are well-adapted to aboveground damage, and belowground survival of individuals may represent the principal biological legacy connecting pre- and post-fire communities. Much of the research exploring altered disturbances and forest recovery has focused on legacies determined by seed dispersal and aboveground survival of adults. In this work, we use pre- and post-fire data from a long-term monitoring network to assess the impacts of novel disturbance interactions between wildfire and SOD on the belowground survival and vegetative reproduction of resprouters. We found that increasing accumulation of coarse woody surface fuels from SOD-killed hosts decreased the likelihood of belowground survival for resprouting tanoak trees, but not for redwoods. Tanoaks' belowground survival was negatively related to substrate burn severity, which increased with the volume of surface fuels from hosts, suggesting heat damage as a possible mechanism influencing altered patterns of resprouter mortality. These impacts increased with decreasing tree size. By contrast, redwood and tanoak trees that survived both disturbances resprouted more vigorously, regardless of post-fire infection by P. ramorum, and generated similar recruitment at the stand level. Our results demonstrate that disease-fire interactions can narrow recruitment filters for resprouters, which could impact long-term population and demographic structure; yet, compounded disturbance may also reduce stand density and disease pressure, allowing competitive release of survivors. Resprouters displayed vulnerabilities to altered disturbance, but our research suggests that legacies maintained by resprouting may be more resilient to certain compounded disturbances, compared to seed-obligate species, because of high rates of individual survival under increasingly severe events. These trends have important implications for conservation of declining tree species in SOD-impacted forests, as well as predictions of human impacts in other disturbance-prone systems where resprouters are present.

Knowledge of the mechanisms by which fish excrete their metabolic nitrogenous waste and insights into nitrogen cycling in aquaculture systems is of utmost importance to improve the sustainable commercial production of fish. In fish, most nitrogenous waste is excreted via the gills as ammonia, a potentially toxic nitrogenous compound. In this study; activity assays, physiological experiments, molecular analysis and microscopy were used to show that the gills of fish harbor a unique combination of hitherto overlooked nitrogen-cycle microorganisms that can theoretically detoxify excreted ammonia by converting it into inert dinitrogen gas. By doing so, these microorganisms may benefit from the ammonia supply by the host and prevent the build-up of this compound to toxic concentrations. This novel relationship between vertebrates and microorganisms may shed new light on nitrogen handling by ammonotelic fish species.

This study assessed the lasting impact of dexamethasone (DEX) exposure during early development on tissue repair capacity at later life stages (5, 14, and 24 days post fertilization [dpf]) in zebrafish larvae. Using the caudal fin amputation model, we show that prior exposure to DEX significantly delays but does not prevent wound healing at all life stages studied. DEX-induced impairments on wound healing were fully restored to normal levels with longer post amputation recovery time. Further analyses revealed that DEX mainly exerted its detrimental effects in the early phase (0-5 hours) of wound-healing process. Specifically, we observed the following events: (1) massive amount of cell death both by necrosis and apoptosis; (2) significant reduction in the number as well as misplacement of macrophages at the wound site; (3) aberrant migration and misplacement of neutrophils and macrophages at the wound site. These events were accompanied by significant (likely compensatory) changes in the expression of genes involved in tissue patterning, including up-regulation of FKBP5 6 hours post DEX exposure and that of Wnt3a and RARγ at 24 hours post amputation. Taken together, this study provides evidence that DEX exposure during early sensitive periods of development appears to cause permanent alterations in the cellular/molecular immune processes that are involved in the early phase of wound healing in zebrafish. These findings are consistent with previous studies showing that antenatal course of DEX is associated with immediate and lasting alterations of the immune system in rodent models and humans. Therefore, the current findings support the use of the larval zebrafish model to study the impact of stress and stress hormone exposure in immature organisms on health risks in later life.

Deprotonation of 1-benzoylacetone with excess lithium hexamethyldisilazide (LHMDS) or lithium diisopropylamide (LDA) resulted in a dilithium dianion-type intermediate, which underwent a Claisen-type condensation with substituted aromatic esters or an isatoic anhydride to afford unsymmetrical 1,3,5-pentanetriones or a cyclized heterocyclic product when the C-acylated intermediates contained a select ortho-substituted phenacyl pendant group. Spectral data indicated that a particular tautomer, a (1Z,4Z)-1-(4-aryl)-1,5-dihydroxy-5-phenylpenta-1,4-dien-3-one, resulted upon recrystallization of the linear products. Condensation–cyclization of the dianion-type intermediate with methyl thiosalicylate resulted in a phenacyl benzoheterocyclic thiopyranone and with 5-chloroisatoic anhydride in a phenacyl quinolinone. X-ray crystal analysis of several products afforded additional proof of structure, especially regarding which tautomer was isolated.

In Amazonian Peru, the neotropical tree Protium subserratum Engl. (Burseraceae) occurs as distinct ecotypes on low nutrient white-sand (WS), intermediate fertility brown-sand (BS), and nutrient-rich clay (CS) soils. Genetic analysis indicates that these ecotypes are undergoing incipient speciation. Possible drivers of this divergence are habitat-specific herbivore faunas and differing resource availabilities. Protium subserratum, therefore, provides an ideal opportunity to investigate how defense chemistry evolves during lineage divergence. WS and BS races of P. subserratum are host to largely non-overlapping herbivore communities and they differ in chlorogenic acid, flavonoid, and oxidized terpene chemistry. Here, we investigate how another important class of anti-herbivore chemicals, procyanidins (PCs), varies among the ecotypes. We isolated the PCs from leaves of juvenile and adult trees from each ecotype and used spectroscopic and chemical techniques to characterize the chemical structures of their component monomers. We found that WS, BS, and CS ecotypes accumulate ca. 17 % of leaf dry weight as PCs. Within ecotypes, we found very little difference in PC type, neither by site nor by life stage. Among ecotypes, however, we observed a marked divergence in PC composition that arose at least in part from differences in their terminal and extension subunits. In addition, the average polymer length of BS and CS PCs was significantly greater than in WS ecotypes. We conclude that phenotypic differences in PCs in the WS versus BS and CS ecotypes of P. subserratum are consistent with selection by herbivores in different soil types that differ strongly in nutrient availability and may contribute to the evolution of habitat specialization.

Convenient synthetic routes to the compounds WBr4 (1), WBr4(MeCN)2 (2), WBr4(THF)2 (3), WBr4(PPh3)2 (4), WBr4(bpy) (6), and WBr4(dppe) (7) are described via the solution-phase oxidation of W(CO)6 using two equivalents of bromine. These one-pot syntheses use inexpensive and readily available starting materials and produce analytically pure compounds with high yields under mild conditions. Attempts to grow crystals of 1 by heating in a sealed tube at ~200 °C resulted in formation of the previously reported compound WOBr4. Attempts to recrystallize 4 from dichloromethane solution produced [HPPh3]2[WBr6] (5). X-ray crystallographic studies showed that 5 consists of an array of [WBr6]2− anions and [HPPh3]+ cations and that 7·CH2Cl2 has the expected six-coordinate tungsten center. The synthesis of tungsten(IV) bromide compounds via oxidation of W(CO)6 is simple and provides better yields than previously reported methods. This synthetic route also has many advantages over the syntheses of similar tungsten(IV) chloride compounds which involve reduction of WCl6.

Forest ecosystems are subject to a variety of disturbances with increasing intensities and frequencies, which may permanently change the trajectories of forest recovery and disrupt the ecosystem services provided by trees. Fire and invasive species, especially exotic disease-causing pathogens and insects, are examples of disturbances that together could pose major threats to forest health. This study examines the impacts of fire and exotic disease (sudden oak death) on forests, with an emphasis on the assessment of post-fire burn severity in a forest where trees have experienced three stages of disease progression pre-fire: early-stage (trees retaining dried foliage and fine twigs), middle-stage (trees losing fine crown fuels), and late-stage (trees falling down). The research was conducted by applying Geographic Object-Based Image Analysis (GEOBIA) to MASTER airborne images that were acquired immediately following the fire for rapid assessment and contained both high-spatial (4 m) and high-spectral (50 bands) resolutions. Although GEOBIA has gradually become a standard tool for analyzing high-spatial resolution imagery, high-spectral resolution data (dozens to hundreds of bands) can dramatically reduce computation efficiency in the process of segmentation and object-based variable extraction, leading to complicated variable selection for succeeding modeling. Hence, we also assessed two widely used band reduction algorithms, PCA (principal component analysis) and MNF (minimum noise fraction), for the delineation of image objects and the subsequent performance of burn severity models using either PCA or MNF derived variables. To increase computation efficiency, only the top 5 PCA and MNF and top 10 PCA and MNF components were evaluated, which accounted for 10% and 20% of the total number of the original 50 spectral bands, respectively. Results show that if no band reduction was applied the models developed for the three stages of disease progression had relatively similar performance, where both spectral responses and texture contributed to burn assessments. However, the application of PCA and MNF introduced much greater variation among models across the three stages. For the early-stage disease progression, neither band reduction algorithms improved or retained the accuracy of burn severity modeling (except for the use of 10 MNF components). Compared to the no-band-reduction scenario, band reduction led to a greater level of overestimation of low-degree burns and underestimation of medium-degree burns, suggesting that the spectral variation removed by PCA and MNF was vital for distinguishing between the spectral reflectance from disease-induced dried crowns (still retaining high structural complexity) and fire ash. For the middle-stage, both algorithms improved the model R 2 values by 2–37%, while the late-stage models had comparable or better performance to those using the original 50 spectral bands. This could be explained by the loss of tree crowns enabling better signal penetration, thus leading to reduced spectral variation from canopies. Hence, spectral bands containing a high degree of random noise were correctly removed by the band reduction algorithms. Compared to the middle-stage, the late-stage forest stands were covered by large piles of fallen trees and branches, resulting in higher variability of MASTER imagery. The ability of band reduction to improve the model performance for these late-stage forest stands was reduced, because the valuable spectral variation representing the actual late-stage forest status was partially removed by both algorithms as noise. Our results indicate that PCA and MNF are promising for balancing computation efficiency and the performance of burn severity models in forest stands subject to the middle and late stages of sudden oak death disease progression. Compared to PCA, MNF dramatically reduced image spectral variation, generating larger image objects with less complexity of object shapes. Whereas, PCA-based models delivered superior performance in most evaluated cases suggesting that some key spectral variability contributing to the accuracy of burn severity models in diseased forests may have been removed together with true spectral noise through MNF transformations.

Environmental contaminants have previously been demonstrated to cause bone deformities mediated through the aryl hydrocarbon receptor (AhR) in fish and mammals. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment, many of them capable of activating AhR. In the present study, fish scales were utilized as a model system to examine possible AhR‐mediated effects of PAHs on bone forming osteoblasts and bone resorptive osteoclasts, using the AhR‐ligand benzo(a)pyrene (BaP) as a model compound. Elasmoid scales from goldfish and zebrafish were exposed to 0.005–50 μM BaP for up to 48 hr, and the activity of osteoblastic and osteoclastic markers were measured, as well as mRNA levels of bone related genes and cyp1a and cyp3a. Using the sp7:luciferase zebrafish assay, a decrease in sp7 promoter activation was observed at the two highest concentrations (5 and 50 μM). Gelatin zymography revealed significantly reduced activity of the osteoclastic protease matrix metalloproteinase 9 (Mmp9) at the highest concentration. Furthermore, transcriptional analysis showed a dose‐dependent increase in cyp1a, however, no significant differential expression was observed for the bone related genes. The findings indicate that BaP might decrease differentiation and activation of osteoblasts, and reduce osteoclastic activity, and thus ultimately cause decreased bone formation. Further investigation is necessary in order to confirm the role of AhR in mediating these effects.

Background: The Dutch Audit for Carotid Interventions (DACI) registers all patients undergoing interventions for carotid artery stenosis in the Netherlands. This study describes the design of the DACI and results of patients with a symptomatic stenosis undergoing carotid endarterectomy (CEA). It aimed to evaluate variation between hospitals in process of care and (adjusted) outcomes, as well as predictors of major stroke/death after CEA.Methods: All patients with a symptomatic stenosis, who underwent CEA and were registered in the DACI between 2014 and 2016 were included in this cohort. Descriptive analyses of patient characteristics, process of care, and outcomes were performed. Casemix adjusted hospital procedural outcomes as (30 day/in hospital) mortality, stroke/death, and major stroke/death, were compared with the national mean. A multivariable logistic regression model (backward elimination at p > 0.10) was used to identify predictors of major stroke/death.Results: A total of 6459 patients, registered by 52 hospitals, were included. The majority (4,832, 75%) were treated Conclusion: CEA in The Netherlands is associated with an overall low mortality and (major) stroke/death rate. Whereas the indicator time to intervention varied between hospitals, mortality and (major) stroke/death were not significantly distinctive enough to identify worse practices and therefore were unsuitable for hospital comparison in the Dutch setting. Additionally, predictors of major stroke/death at population level could be identified. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

International audience; This work presents an integrated approach to study the crystal chemistry and phonon heat capacity of complex layered oxides. Two quaternary delafossites are synthesized from ternary parent compounds and copper monohalides via a topochemical exchange reaction that preserves the honeycomb ordering of the parent structures. For each compound, Rietveld refinement of the powder X-ray diffraction patterns is examined in both monoclinic C2/c and rhombohedral R (3) over barm space groups. Honeycomb ordering occurs only in the monoclinic space group. Bragg peaks associated with honeycomb ordering acquire an asymmetric broadening known as the Warren line shape that is commonly observed in layered structures with stacking disorder. Detailed TEM analysis confirms honeycomb ordering within each layer in both title compounds and establishes a twinning between the adjacent layers instead of the more conventional shifting or skipping stacking faults. The structural model is then used to calculate phonon dispersions and heat capacity from first principles. In both compounds, the calculated heat capacity accurately describes the experimental data. The integrated approach presented here offers a platform to carefully analyze the phonon heat capacity in complex oxides where the crystal structure can produce magnetic frustration. Isolating phonon contribution from total heat capacity is a necessary and challenging step toward a quantitative study of spin liquid materials with exotic magnetic excitations such as spinons and Majorana fermions. A quantitative understanding of phonon density of states based on crystal chemistry as presented here also paves the way toward higher efficiency thermoelectric materials.