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The liquid-liquid transition (LLT), in which a single-component liquid transforms into another one via a first-order phase transition, is an intriguing phenomenon that has changed our perception of the liquid state. LLTs have been predicted from computer simulations of water1,2, silicon3, carbon dioxide4, carbon5, hydrogen6 and nitrogen7. Experimental evidence has been found mostly in supercooled (that is, metastable) liquids such as Y2O3-Al2O3 mixtures8, water9 and other molecular liquids10-12. However, the LLT in supercooled liquids often occurs simultaneously with crystallization, making it difficult to separate the two phenomena13. A liquid-liquid critical point (LLCP), similar to the gas-liquid critical point, has been predicted at the end of the LLT line that separates the low- and high-density liquids in some cases, but has not yet been experimentally observed for any materials. This putative LLCP has been invoked to explain the thermodynamic anomalies of water1. Here we report combined in situ density, X-ray diffraction and Raman scattering measurements that provide direct evidence for a first-order LLT and an LLCP in sulfur. The transformation manifests itself as a sharp density jump between the low- and high-density liquids and by distinct features in the pair distribution function. We observe a non-monotonic variation of the density jump with increasing temperature: it first increases and then decreases when moving away from the critical point. This behaviour is linked to the competing effects of density and entropy in driving the transition. The existence of a first-order LLT and a critical point in sulfur could provide insight into the anomalous behaviour of important liquids such as water.
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High-pressure (>1â GPa) torsion apparatus can be coupled with in situ X-ray tomography (XRT) to study microstructures in materials associated with large shear strains. Here, deformation experiments were carried out on multi-phase aggregates at â¼3-5â GPa and â¼300-500°C, using a rotational tomography Paris-Edinburgh press (RoToPEc) with in situ absorption contrast XRT on the PSICHE beamline at Synchrotron SOLEIL. The actual shear strain reached in the samples was quantified with respect to the anvil twisting angles, which is γ ≤ 1 at 90° anvil twist and reaches γ ≃ 5 at 225° anvil twist. 2D and 3D quantifications based on XRT that can be used to study in situ the deformation microfabrics of two-phase aggregates at high shear strain are explored. The current limitations for investigation in real time of deformation microstructures using coupled synchrotron XRT with the RoToPEc are outlined.
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Flowers are essential but vulnerable plant organs, exposed to pollinators and florivores; however, flower chemical defenses are rarely investigated. We show here that two clustered terpene synthase and cytochrome P450 encoding genes (TPS11 and CYP706A3) on chromosome 5 of Arabidopsis (Arabidopsis thaliana) are tightly coexpressed in floral tissues, upon anthesis and during floral bud development. TPS11 was previously reported to generate a blend of sesquiterpenes. By heterologous coexpression of TPS11 and CYP706A3 in yeast (Saccharomyces cerevisiae) and Nicotiana benthamiana, we demonstrate that CYP706A3 is active on TPS11 products and also further oxidizes its own primary oxidation products. Analysis of headspace and soluble metabolites in cyp706a3 and 35S:CYP706A3 mutants indicate that CYP706A3-mediated metabolism largely suppresses sesquiterpene and most monoterpene emissions from opening flowers, and generates terpene oxides that are retained in floral tissues. In flower buds, the combined expression of TPS11 and CYP706A3 also suppresses volatile emissions and generates soluble sesquiterpene oxides. Florivory assays with the Brassicaceae specialist Plutella xylostella demonstrate that insect larvae avoid feeding on buds expressing CYP706A3 and accumulating terpene oxides. Composition of the floral microbiome appears also to be modulated by CYP706A3 expression. TPS11 and CYP706A3 simultaneously evolved within Brassicaceae and form the most versatile functional gene cluster described in higher plants so far.plantcell;31/12/2947/FX1F1fx1.
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Alquil e Aril Transferases/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Flores/metabolismo , Terpenos/antagonistas & inibidores , Alquil e Aril Transferases/genética , Animais , Arabidopsis/enzimologia , Arabidopsis/genética , Arabidopsis/microbiologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Flores/genética , Flores/microbiologia , Expressão Gênica , Larva , Microbiota , Modelos Moleculares , Simulação de Acoplamento Molecular , Monoterpenos/metabolismo , Mariposas , Família Multigênica , Filogenia , Sesquiterpenos/metabolismo , Terpenos/química , Terpenos/metabolismo , Nicotiana/metabolismo , Leveduras/metabolismoRESUMO
OBJECTIVE: We examined the predictive relation between childhood-diagnosed ADHD and trajectories of body mass index (BMI) from childhood to adulthood in an all-female sample, accounting for socioeconomic status (SES), childhood comorbidities (e.g., depression/anxiety), and stimulant usage. Childhood executive functioning (i.e., planning, sustained attention, and response inhibition) was also evaluated as a possible predictor of BMI trajectories. METHOD: We utilized longitudinal data from a full sample of 140 girls diagnosed with ADHD in childhood and 88 comparison girls matched on age and ethnicity. Girls were 6-12 years old at the first assessment and followed prospectively for 16 years. Data were collected on their BMI and stimulant medication usage across four evaluation waves. Using latent growth curve modeling, we evaluated the BMI trajectories of girls with ADHD and the comparison sample from childhood to adulthood. RESULTS: Although there was no significant difference in initial childhood BMI, girls with ADHD increased in BMI at a significantly faster rate than comparison girls across development, even when adjusting for covariates. Significant differences in BMI first emerged in adolescence; by adulthood, 40.2% of the ADHD sample met criteria for obesity versus 15.4% of the comparison sample. When covarying ADHD diagnosis, executive functioning measures were not significantly predictive of BMI increase. Adjusting for stimulant medication usage within the ADHD sample did not alter core findings. CONCLUSIONS: We discuss health-related implications for girls with ADHD, potential underlying mechanisms, and how our findings may inform both ADHD and obesity interventions.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Índice de Massa Corporal , Criança , Função Executiva/fisiologia , Feminino , Humanos , Estudos Longitudinais , Obesidade , Adulto JovemRESUMO
Background: SBIRT (Screening, Brief Intervention, and Referral to Treatment) is an effective early intervention approach for individuals with substance misuse. The purpose of this study was to determine if medical learners are more adept at learning a brief substance use intervention compared to non-medical learners (e.g., social work students). The dissemination of SBIRT training among many helping professions can increase service delivery for substance use problems. Methods: A total of 2,488 participants completed SBIRT training, representing 15 different disciplines and over 20 different institutions. General linear models and paired t-tests were used to investigate the effects of SBIRT training on changes in knowledge and attitude of alcohol and drug use and satisfaction. Results: There were no statistical differences in the change of satisfaction, knowledge, and attitude between medical and non-medical discipline participants. Both medical and non-medical participants had greater improvement in attitude and knowledge scores post-training. Similar improvements in attitude, knowledge, and satisfaction were observed in all the health-care discipline participants. Discussion: SBIRT skills may be transferable to disciplines including non-prescribing professionals (e.g., social work, nursing, physical therapy, rehabilitation science, and pharmacy). In an effort to expand treatment, health-care training institutions adopt SBIRT as a core competency for professional practice.
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Intervenção em Crise , Transtornos Relacionados ao Uso de Substâncias , Humanos , Programas de Rastreamento , Encaminhamento e Consulta , Serviço Social , Estudantes , Transtornos Relacionados ao Uso de Substâncias/diagnóstico , Transtornos Relacionados ao Uso de Substâncias/terapiaRESUMO
BACKGROUND: This study is a longitudinal follow-up to prior work examining the important pragmatic skill of communication repair (i.e., the ability to respond effectively to a request for clarification of an unclear message) across three neurodevelopmental disabilities in which language skills are impaired: fragile X syndrome with and without autism spectrum disorder (FXS-ASD; FXS-O), idiopathic ASD (ASD-O), Down syndrome (DS) and controls with typical development (TD). Prior work examining communication repair skills at younger ages indicated impairments in boys with FXS-ASD and ASD-O, with females performing comparably with each other across groups. AIMS: To characterize communication repair skills in young individuals with FXS-ASD, FXS-O, ASD-O, DS and TD, across groups and over development. A secondary aim included documenting sex differences in FXS (with and without ASD) and DS. METHODS & PROCEDURES: Sixty young individuals with FXS-ASD (49 males, 11 females), 38 with FXS-O (13 males, 25 females), 38 with ASD-O (males only), 42 with DS (21 males, 21 females) and 41 with TD (21 males, 20 females) participated in the study, with a subsample reported on here who were retested at a second time point 2.7 years later on average. Participants completed a structured, picture-based task designed to assess the ability to repair breakdowns in communication. Participants' responses were compared across groups and sexes at the second time point, and interpreted with respect to previously published (Time 1) findings. OUTCOMES & RESULTS: Key findings included that, with age, male groups (including those with FXS-ASD and ASD-O, who showed difficulty at Time 1) performed more comparably, decreasing their use of inappropriate responses, in spite of relatively little change observed in general cognitive or structural language abilities in the clinical groups. However, girls with FXS and DS became more non-responsive with age, and differences between boys and girls with FXS-ASD emerged over time as well. CONCLUSIONS & IMPLICATIONS: Findings suggest that impairments in a critical pragmatic skill-the ability to repair communication breakdown-show significant change with age across three neurodevelopmental disabilities, with important sex-specific patterns. These developments were often observed in spite of a relative plateau in cognitive and language growth, suggesting that repair skills may be more malleable and therefore an excellent target for intervention. Findings not only inform the nature of pragmatic impairment across groups but also can importantly inform clinical practice, suggesting that clinicians should monitor pragmatic skills such as repairs throughout development and also consider the role of sex in clinical efforts.
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Transtorno do Espectro Autista/complicações , Transtornos da Comunicação/reabilitação , Síndrome de Down/complicações , Síndrome do Cromossomo X Frágil/complicações , Adolescente , Fatores Etários , Estudos de Casos e Controles , Criança , Pré-Escolar , Transtornos da Comunicação/etiologia , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Fatores SexuaisRESUMO
Squamous cell carcinoma of a thyroglossal duct cyst is exceedingly rare, with less than 30 cases reported across the literature. Herein, we present a case of squamous cell carcinoma (SCC) of a thyroglossal duct cyst (TGDC) and discuss the utility of a level IA neck dissection in these cases. In 2018, a 62-year-old female presented to a university-affiliated otolaryngologist with symptoms of dysphagia and a palpable anterior midline neck mass. MRI demonstrated a 3.1 × 2.0-cm mass concerning an invasive TGDC. She was referred to our institution for further management. Preoperative imaging demonstrated an invasive TGDC but no pathological nodes. A Sistrunk procedure and a IA neck dissection were performed. Pathology demonstrated one pathological node in the neck dissection specimen. In summary, a bilateral IA neck dissection was performed on a clinically node zero (N0) patient, and a pathological node was ultimately identified. We hope that by introducing this idea of a IA neck dissection for SCC of a TGDC, we can prompt further investigation into the utility of this procedure for these uniquely rare cases.
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Carcinoma Papilar , Carcinoma de Células Escamosas , Cisto Tireoglosso , Neoplasias da Glândula Tireoide , Carcinoma Papilar/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Pessoa de Meia-Idade , Esvaziamento Cervical , Cisto Tireoglosso/diagnóstico por imagem , Cisto Tireoglosso/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgiaRESUMO
Terpenoids, compounds found in all domains of life, represent the largest class of natural products with essential roles in their hosts. All terpenoids originate from the five-carbon building blocks, isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP), which can be derived from the mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways. The absence of two components of the MVA pathway from archaeal genomes led to the discovery of an alternative MVA pathway with isopentenyl phosphate kinase (IPK) catalyzing the final step, the formation of IPP. Despite the fact that plants contain the complete classical MVA pathway, IPK homologs were identified in every sequenced green plant genome. Here, we show that IPK is indeed a member of the plant terpenoid metabolic network. It is localized in the cytosol and is coexpressed with MVA pathway and downstream terpenoid network genes. In planta, IPK acts in parallel with the MVA pathway and plays an important role in regulating the formation of both MVA and MEP pathway-derived terpenoid compounds by controlling the ratio of IP/DMAP to IPP/DMAPP. IP and DMAP can also competitively inhibit farnesyl diphosphate synthase. Moreover, we discovered a metabolically available carbon source for terpenoid formation in plants that is accessible via IPK overexpression. This metabolite reactivation approach offers new strategies for metabolic engineering of terpenoid production.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimologia , Archaea/enzimologia , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Terpenos/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Citosol/metabolismo , Regulação da Expressão Gênica de Plantas , Técnicas de Inativação de Genes , Genes de Plantas , Hemiterpenos/metabolismo , Cinética , Redes e Vias Metabólicas/genética , Ácido Mevalônico/metabolismo , Compostos Organofosforados/metabolismo , Plantas Geneticamente Modificadas , Plastídeos/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Homologia de Sequência de Aminoácidos , Sesquiterpenos/metabolismo , Nicotiana/genéticaRESUMO
In forensic sciences, body fluids, or biological traces, are a major source of information, and their identification can play a decisive role in criminal investigations. Currently, the nature of biological fluids is assessed using immunological, physico-chemical, mRNA and epigenetic methods, but these have limits in terms of sensitivity and specificity. The emergence of next-generation sequencing technologies offers new opportunities to identify the nature of body fluids by determining bacterial communities. The aim of this pilot study was to assess whether analysis of the bacterial communities in isolated and mixed biological fluids could reflect the situation observed in real forensics labs. Several samples commonly encountered in forensic sciences were tested from healthy volunteers: saliva, vaginal fluid, blood, semen and skin swabs. These samples were analyzed alone or in combination in a ratio of 1:1. Sequencing was performed on the Ion Gene StudioTM S5 automated sequencer. Fluids tested alone revealed a typical bacterial signature with specific bacterial orders, enabling formal identification of the fluid of interest, despite inter-individual variations. However, in biological fluid mixtures, the predominance of some bacterial microbiomes inhibited interpretation. Oral and vaginal microbiomes were clearly preponderant, and the relative abundance of their bacterial communities and/or the presence of common species between samples made it impossible to detect bacterial orders or genera from other fluids, although they were distinguishable from one another. However, using the beta diversity, salivary fluids were identified and could be distinguished from fluids in combination. While this method of fluid identification is promising, further analyses are required to consolidate the protocol and ensure reliability.
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Black phosphorus (bP) is a crystalline material that can be seen as an ordered stacking of two-dimensional layers, which results in outstanding anisotropic physical properties. The knowledge of its pressure (P)-temperature (T) phase diagram, and in particular, of its melting curve is fundamental for a better understanding of the synthesis and stability conditions of this element. Despite the numerous studies devoted to this subject, significant uncertainties remain regarding the determination of the position and slope of its melting curve. Here we measured the melting curve of bP in an extended P, T region from 0.10(3) to 5.05(40) GPa and from 914(25) to 1788(70) K, using in situ high-pressure and high-temperature synchrotron X-ray diffraction. We employed an original metrology based on the anisotropic thermoelastic properties of bP to accurately determine P and T. We observed a monotonic increase of the melting temperature with pressure and the existence of two distinct linear regimes below and above 1.35(15) GPa, with respective slopes of 348 ± 21 and of 105 ± 12 K·GPa-1. These correspond to the melting of bP toward the low-density liquid and the high-density liquid, respectively. The triple point at which solid bP and the two liquids meet is located at 1.35(15) GPa and 1350(25) K. In addition, we have characterized the solid phases after crystallization of the two liquids and found that, while the high-density liquid transforms back to solid bP, the low-density liquid crystallizes into a more complex, partly crystalline and partly amorphous solid. The X-ray diffraction pattern of the crystalline component could be indexed as a mixture of red and violet P.
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In the present study, in-situ observation of Hot Isostatic Pressure (HIP) procedure of laser powder bed fusion manufactured Ti-6Al-4V parts was performed to quantitatively estimate the densification rate of the material and the influence of the defect initial size and shape on such rate. The observations were performed in-situ using the Ultrafast Tomography Paris-Edinburgh Cell and the combination of fast phase-contrast synchrotron X-ray tomography and energy dispersive diffraction. With this strategy, we could quantify how the effectiveness of HIP depends on the characteristics of a defect. Smaller defects showed a higher densification rate, while the defect shape did not have significant effect on such rate.
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BACKGROUND: The extended endonasal approach has been utilized in the resection of anterior skull base lesions in the pediatric population. There are unique challenges to these patients in the post-operative setting, including patient compliance with medical therapy and post-operative debridements, and a smaller nasal airway that may increase propensity toward scarring. Our objective for this study is to evaluate the incidence of post-operative radiographic inflammation in this patient population using the Lund-Mackay (LM) score. METHODS: A single-center, retrospective review of pediatric patients undergoing endoscopic approach to the skull base between 2009 and 2021 was performed. Demographic and clinicopathologic data and pre- and post-operative imaging were analyzed. One-way ANOVA followed by Tukey multiple pairwise comparisons statistical tests were used to compare mean LM scores between groups. RESULTS: Seventy-two patients (52 males, 20 females) were identified with a median follow-up of 27 months. All patients underwent an extended endonasal approach for resection of skull base lesions. The mean LM scores were compared between pre-operative MRI, first post-operative MRI > 30 days after surgery, and most recent post-operative MRI. One-way ANOVA was performed with significant differences noted between the groups (p < 0.001). Tukey multiple pairwise comparisons test was then performed and noted significant differences between the pre-operative and first post-operative LM (p < 0.0001) and the first post-operative and most recent LM (p < 0.0001). There was no significant difference noted between the pre-operative LM score and most recent LM score (p = 0.14). CONCLUSION: Despite concerns regarding possible subsequent development of chronic rhinosinusitis following endoscopic skull base surgery in pediatric patients, the current study suggests that transient radiographic evidence of sinus inflammation can be seen up to six months postoperatively, which appears to resolve by approximately two years after surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2014-2017, 2023.
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Sinusite , Base do Crânio , Masculino , Feminino , Humanos , Criança , Incidência , Base do Crânio/diagnóstico por imagem , Base do Crânio/cirurgia , Endoscopia/efeitos adversos , Nariz/cirurgia , Sinusite/cirurgia , Estudos Retrospectivos , Inflamação/epidemiologia , Inflamação/etiologiaRESUMO
Purpose: This study aimed to determine the impact of uttering the word "quiet" on clinical workload during the overnight otolaryngology call shift and understand the factors contributing to resident busyness. Materials and Methods: A multicenter, single-blind, randomized-controlled trial was conducted. A total of 80 overnight call shifts covered by a pool of 10 residents were randomized to the quiet or to the control group. At the start of shift, residents were asked to state aloud, "Today will be a quiet night" (quiet group) or "Today will be a good night" (control group). Clinical workload, as measured by number of consults, was the primary outcome. Secondary measures included number of sign-out tasks, unplanned inpatient and operating room visits, number of phone calls and hours of sleep, and self-perceived busyness. Results: There was no difference in the number of total (P = 0.23), nonurgent (P = 0.18), and urgent (P = 0.18) consults. Tasks at signout, total phone calls, unplanned inpatient visits, and unplanned operating room visits did not differ between the control and quiet groups. While there were more unplanned operating room visits in the quiet group (29, 80.6%) compared to the control group (34, 94.4%), this was not found to be significant (P = 0.07). The majority of residents reported feeling "not busy" during control nights (18, 50.0%) compared to feeling "somewhat busy" during quiet nights (17, 47.2%; P = 0.42). Conclusion: Contrary to popular belief, there is no clear evidence that uttering the word "quiet" significantly increases clinical workload.
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Bacterial nitric-oxide synthase (NOS)-like proteins are believed to be genuine NOSs. As for cytochromes P450 (CYPs), NOS-proximal ligand is a thiolate that exerts a push effect crucial for the process of dioxygen activation. Unlike CYPs, this catalytic electron donation seems controlled by a hydrogen bond (H-bond) interaction between the thiolate ligand and a vicinal tryptophan. Variations of the strength of this H-bond could provide a direct way to tune the stability along with the electronic and structural properties of NOS. We generated five different mutations of bsNOS Trp66, which can modulate this proximal H-bond. We investigated the effects of these mutations on different NOS complexes (FeIII, FeIICO, and FeIINO), using a combination of UV-visible absorption, EPR, FTIR, and resonance Raman spectroscopies. Our results indicate that (i) the proximal H-bond modulation can selectively decrease or increase the electron donating properties of the proximal thiolate, (ii) this modulation controls the σ-competition between distal and proximal ligands, (iii) this H-bond controls the stability of various NOS intermediates, and (iv) a fine tuning of the electron donation by the proximal ligand is required to allow at the same time oxygen activation and to prevent uncoupling reactions.
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Bacillus subtilis/enzimologia , Óxido Nítrico Sintase/química , Óxido Nítrico Sintase/metabolismo , Espectroscopia de Ressonância de Spin Eletrônica , Ligação de Hidrogênio , Estresse Oxidativo , Estrutura Secundária de Proteína , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral RamanRESUMO
Objectives: Determine variability in intra- and post-operative management of tracheostomies (trachs) at our institution as existing literature suggests that trachs are a frequent trigger for airway-related emergencies. Catalyze the development of an institution-wide protocols for trach care. Methods: A 39-question online survey was sent to 55 providers who perform open and percutaneous trachs at three of the hospitals within our large, urban, academic medical center. These providers were identified by surveillance of the operating room schedules for 1 year. Results: The survey was completed by 40 of the 53 eligible providers (75.5%). Response rate by question varied. Respondents included members of all departments that perform trachs at our institution (Otorhinolaryngology, Trauma Surgery, Thoracic Surgery, General Surgery, Cardiovascular Surgery and Interventional Pulmonology).While most responses demonstrated uniformity in practice, notable variations included the following: 80% of percutaneous trach providers stated that morbid obesity was not a contraindication to performing a trach outside of the operating room (n = 20) while 58% of open trach providers stated that morbid obesity was a contraindication; only 35% of open trach providers perform a Bjork flap (n = 350). The survey also identified significant variability in practice with regards to timing of trach suture removal. Discussion: Lack of uniformity was identified in several practices related to intra- and post-operative tracheostomy care. Results did, however, trend toward consensus in many areas. The results are being used to establish a more consistent approach to tracheostomy management across our institution to ensure standardization of practice amidst the rapidly evolving practices of trach placement. Implications for practice: With ongoing evolution in the methods of trach placement and its management, the concepts put forth here will be a resource for health care providers at other institutions to consider intra-institutional analysis and establishment of practice standardization.
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Large igneous provinces (LIPs) resulted from intraplate magmatic events mobilizing volumes of magma up to several million cubic kilometers. LIPs and lavas with deep mantle sources have compositions ranging from komatiites found in Archean greenstone belts to basalts and picrites in Phanerozoic flood basalt and recent oceanic islands. In this study, we identify the mantle conditions appropriate to each type of lava based on an experimental study of the melting of pyrolite. The depth of the mantle source decreases from 600 to 700 km for the oldest komatiites to 100 to 300 km for picrites and basalts, and the extent of mantle melting ranges from 10 to 50%. We develop a geodynamical model that explains the origin of the hot mantle plumes capable of generating these melting P-T conditions. Within a superadiabatic temperature gradient persisting in the deep mantle, the ascent of hot mantle plumes creates excess temperatures up to 250 to 300 K by adiabatic decompression.
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Terpenoids are a large and diverse class of plant metabolites that also includes volatile mono- and sesquiterpenes which are involved in biotic interactions of plants. Due to the limited natural availability of these terpenes and the tight regulation of their biosynthesis, there is strong interest to introduce or enhance their production in crop plants by metabolic engineering for agricultural, pharmaceutical and industrial applications. While engineering of monoterpenes has been quite successful, expression of sesquiterpene synthases in engineered plants frequently resulted in production of only minor amounts of sesquiterpenes. To identify bottlenecks for sesquiterpene engineering in plants, we have used two nearly identical terpene synthases, snapdragon (Antirrhinum majus) nerolidol/linalool synthase-1 and -2 (AmNES/LIS-1/-2), that are localized in the cytosol and plastids, respectively. Since these two bifunctional terpene synthases have very similar catalytic properties with geranyl diphosphate (GPP) and farnesyl diphosphate (FPP), their expression in target tissues allows indirect determination of the availability of these substrates in both subcellular compartments. Both terpene synthases were expressed under control of the ripening specific PG promoter in tomato fruits, which are characterized by a highly active terpenoid metabolism providing precursors for carotenoid biosynthesis. As AmNES/LIS-2 fruits produced the monoterpene linalool, AmNES/LIS-1 fruits were found to exclusively produce the sesquiterpene nerolidol. While nerolidol emission in AmNES/LIS-1 fruits was 60- to 584-fold lower compared to linalool emission in AmNES/LIS-2 fruits, accumulation of nerolidol-glucosides in AmNES/LIS-1 fruits was 4- to 14-fold lower than that of linalool-glucosides in AmNES/LIS-2 fruits. These results suggest that only a relatively small pool of FPP is available for sesquiterpene formation in the cytosol. To potentially overcome limitations in sesquiterpene production, we transiently co-expressed the key pathway-enzymes hydroxymethylglutaryl-CoA reductase (HMGR) and 1-deoxy-D-xylulose 5-phosphate synthase (DXS), as well as the regulator isopentenyl phosphate kinase (IPK). While HMGR and IPK expression increased metabolic flux toward nerolidol formation 5.7- and 2.9-fold, respectively, DXS expression only resulted in a 2.5-fold increase.
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OBJECTIVE: To assess the impact of reconstructive technique on the incidence of cerebrospinal fluid (CSF) leak following retrosigmoid approach to acoustic neuroma resection. STUDY DESIGN: Retrospective case series. SETTING: Academic medical center. PATIENTS: A total of 1,200 patients with acoustic neuromas presented to our institution from 2005 to 2018. Of these, 196 patients underwent surgical resection via a retrosigmoid approach. INTERVENTION: At our institution, internal auditory canal (IAC) reconstruction following a retrosigmoid approach was performed with bone wax and muscle plug or Norian hydroxyapatite bone cement from 2005 to 2013. Starting in 2014, a newer model of bone cement, Cranios hydroxyapatite, was used exclusively for reconstruction. MAIN OUTCOME MEASURES: Rates of CSF leak were evaluated across different methods of IAC reconstruction and types of bone cement. Patients whose leaks were attributable to the craniectomy site were excluded from analysis. RESULTS: The postoperative CSF leak rate among patients who did not receive bone cement for IAC reconstruction was 15.6% (n.5). The leak rate amongst patients who received Norian bone cement was 6.3% (n.4). After introduction of Cranios bone cement, the total leak rate decreased to 1% (n.1). Compared with all other types of closure, Cranios had a significantly reduced rate of postoperative CSF leak (pâ<â0.005). The leak rate following Cranios versus Norian was also significantly reduced (pâ<â0.05). Leak rate was not affected by tumor size (p.0.30) or age (p.0.43). CONCLUSION: CSF leak rate following acoustic neuroma resection was significantly reduced by introduction of Cranios hydroxyapatite bone cement.
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Neuroma Acústico , Cimentos Ósseos , Vazamento de Líquido Cefalorraquidiano/epidemiologia , Vazamento de Líquido Cefalorraquidiano/etiologia , Durapatita , Humanos , Hidroxiapatitas/uso terapêutico , Neuroma Acústico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
Anthropogenic noise is an emergent ecological pollutant in both terrestrial and aquatic habitats. Human population growth, urbanisation, resource extraction, transport and motorised recreation lead to elevated noise that affects animal behaviour and physiology, impacting individual fitness. Currently, we have a poor mechanistic understanding of the effects of anthropogenic noise, but a likely candidate is the neuroendocrine system that integrates information about environmental stressors to produce regulatory hormones; glucocorticoids (GCs) and androgens enable rapid individual phenotypic adjustments that can increase survival. Here, we carried out two field-based experiments to investigate the effects of short-term (30 min) and longer-term (48 h) motorboat-noise playback on the behaviour, GCs (cortisol) and androgens of site-attached free-living orange-fin anemonefish (Amphiprion chrysopterus). In the short-term, anemonefish exposed to motorboat-noise playback showed both behavioural and hormonal responses: hiding and aggression increased, and distance moved out of the anemone decreased in both sexes; there were no effects on cortisol levels, but male androgen levels (11-ketotestosterone and testosterone) increased. Some behaviours showed carry-over effects from motorboat noise after it had ceased, and there was no evidence for a short-term change in response to subsequent motorboat-noise playback. Similarly, there was no evidence that longer-term exposure led to changes in response: motorboat noise had an equivalent effect on anemonefish behaviour and hormones after 48 h as on first exposure. Longer-term noise exposure led to higher levels of cortisol in both sexes and higher testosterone levels in males, and stress-responses to an additional environmental challenge in both sexes were impaired. Circulating androgen levels correlated with aggression, while cortisol levels correlated with hiding, demonstrating in a wild population that androgen/glucocorticoid pathways are plausible proximate mechanisms driving behavioural responses to anthropogenic noise. Combining functional and mechanistic studies are crucial for a full understanding of this global pollutant.
Assuntos
Recifes de Corais , Perciformes , Animais , Comportamento Animal , Feminino , Peixes , Humanos , Masculino , RuídoRESUMO
Black phosphorus (bP) is a crystalline material which can be seen as an ordered stacking of two-dimensional layers, referred to as phosphorene. The knowledge of the linear thermal expansion coefficients (LTECs) of bP is of great interest in the field of 2D materials for a better understanding of the anisotropic thermal properties and exfoliation mechanism of this material. Despite several theoretical and experimental studies, important uncertainties remain in the determination of the LTECs of bP. Here, we report accurate thermal expansion measurements along the three crystallographic axes using in situ high temperature X-ray diffraction. From the progressive reduction of the diffracted intensities with temperature, we monitored the loss of the crystal structure of bP across the investigated temperature range, evidencing two thermal expansion regimes at temperature below and above 706 K. Below 706 K, a strong out-of-plane anisotropy can be observed, while at temperatures above 706 K a larger thermal expansion occurs along the a crystallographic direction. From our data and by taking advantage of ab initio optimization, we propose a detailed anisotropic thermal expansion mechanism of bP, which leads to an inter- and intra-layer destabilization. An interpretation of it, based on the high T perturbation of the stabilizing sp orbital mixing effect, is provided, consistent with the high pressure data.