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1.
Conserv Biol ; : e14296, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38770838

ABSTRACT

Marine protected areas (MPAs) globally serve conservation and fisheries management goals, generating positive effects in some marine ecosystems. Surf zones and sandy beaches, critical ecotones bridging land and sea, play a pivotal role in the life cycles of numerous fish species and serve as prime areas for subsistence and recreational fishing. Despite their significance, these areas remain understudied when evaluating the effects of MPAs. We compared surf zone fish assemblages inside and outside MPAs across 3 bioregions in California (USA). Using seines and baited remote underwater videos (BRUVs), we found differences in surf zone fish inside and outside MPAs in one region. Inside south region MPAs, we observed higher abundance (Tukey's honest significant difference [HSD] = 0.83, p = 0.0001) and richness (HSD = 0.22, p = 0.0001) in BRUVs and greater biomass (HSD = 0.32, p = 0.0002) in seine surveys compared with reference sites. Selected live-bearing, fished taxa were positively affected by MPAs. Elasmobranchs displayed greater abundance in BRUV surveys and higher biomass in seine surveys inside south region MPAs (HSD = 0.35, p = 0.0003 and HSD = 0.23, p = 0.008, respectively). Although we observed no overall MPA signal for Embiotocidae, abundances of juvenile and large adult barred surfperch (Amphistichus argenteus), the most abundant fished species, were higher inside MPAs (K-S test D = 0.19, p < 0.0001). Influence of habitat characteristics on MPA performance indicated surf zone width was positively associated with fish abundance and biomass but negatively associated with richness. The south region had the largest positive effect size on all MPA performance metrics. Our findings underscored the variability in species richness and composition across regions and survey methods that significantly affected differences observed inside and outside MPAs. A comprehensive assessment of MPA performance should consider specific taxa, their distribution, and the effects of habitat factors and geography.


Evaluación de la influencia de las áreas marinas protegidas sobre los peces de la zona de rompientes Resumen Las áreas marinas protegidas (AMP) cumplen los objetivos de conservación y manejo de pesquerías a nivel mundial, lo que genera efectos positivos en algunos ecosistemas marinos. Las zonas de rompientes y las playas arenosas, ecotonos importantes que conectan la tierra con el mar, tienen un papel esencial en el ciclo de vida de varios peces y fungen como áreas óptimas para la pesca recreativa y de sustento. A pesar de su importancia, estas áreas están poco estudiadas con respecto a la evaluación del efecto de las AMP. Comparamos la composición de peces del área de rompientes dentro y fuera de las AMP de tres bioregiones de California, EUA. Usamos chinchorros y videos submarinos con carnada (BRUVs) y descubrimos diferencias en los peces de la zona de rompientes dentro y fuera de las AMP en una región. Dentro de las AMP de la región sur observamos una mayor abundancia (diferencia significativa honesta de Tukey [DSH]  =  0.83, p = 0.0001) y riqueza (DSH  =  0.22, p = 0.0001) en los BRUV y una mayor biomasa (DSH  =  0.32, p = 0.0002) en los censos con chinchorro en comparación con los sitios de referencia. Los taxones seleccionados de peces de sustento fueron afectados de manera positiva por las AMP. Los elasmobranquios mostraron una mayor abundancia en los BRUV y una mayor biomasa en los censos con chinchorro dentro de las AMP de la región sur (DSH  =  0.35, p = 0.0003 y DSH  =  0.23, p = 0.008, respectivamente). Aunque no observamos una señal generalizada de las AMP para la familia Embiotocidae, la abundancia de Amphistichus argenteus juveniles y adultos, la especie pescada más abundante, fue mayor dentro de las AMP (prueba K­S D  =  0.19, p < 0.0001). La influencia de las características del hábitat sobre el desempeño de las AMP indicó que el ancho de la zona de rompientes está asociado de forma positiva con la abundancia y biomasa de los peces, pero de forma negativa con la riqueza. La región sur tuvo el mayor tamaño de efecto positivo sobre todas las medidas de desempeño de las AMP. Nuestros hallazgos destacan la variabilidad en la riqueza y composición de especies en todas las regiones y los censos que afectan significativamente las diferencias observadas dentro y fuera de las AMP. Una evaluación completa del desempeño de las AMP debe considerar taxones específicos, su distribución y el efecto de los factores de hábitat y la geografía.

3.
N Engl J Med ; 390(13): 1196-1206, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38598574

ABSTRACT

BACKGROUND: Despite the availability of effective therapies for patients with chronic kidney disease, type 2 diabetes, and hypertension (the kidney-dysfunction triad), the results of large-scale trials examining the implementation of guideline-directed therapy to reduce the risk of death and complications in this population are lacking. METHODS: In this open-label, cluster-randomized trial, we assigned 11,182 patients with the kidney-dysfunction triad who were being treated at 141 primary care clinics either to receive an intervention that used a personalized algorithm (based on the patient's electronic health record [EHR]) to identify patients and practice facilitators to assist providers in delivering guideline-based interventions or to receive usual care. The primary outcome was hospitalization for any cause at 1 year. Secondary outcomes included emergency department visits, readmissions, cardiovascular events, dialysis, and death. RESULTS: We assigned 71 practices (enrolling 5690 patients) to the intervention group and 70 practices (enrolling 5492 patients) to the usual-care group. The hospitalization rate at 1 year was 20.7% (95% confidence interval [CI], 19.7 to 21.8) in the intervention group and 21.1% (95% CI, 20.1 to 22.2) in the usual-care group (between-group difference, 0.4 percentage points; P = 0.58). The risks of emergency department visits, readmissions, cardiovascular events, dialysis, or death from any cause were similar in the two groups. The risk of adverse events was also similar in the trial groups, except for acute kidney injury, which was observed in more patients in the intervention group (12.7% vs. 11.3%). CONCLUSIONS: In this pragmatic trial involving patients with the triad of chronic kidney disease, type 2 diabetes, and hypertension, the use of an EHR-based algorithm and practice facilitators embedded in primary care clinics did not translate into reduced hospitalization at 1 year. (Funded by the National Institutes of Health and others; ICD-Pieces ClinicalTrials.gov number, NCT02587936.).


Subject(s)
Diabetes Mellitus, Type 2 , Hospitalization , Hypertension , Renal Insufficiency, Chronic , Humans , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Hospitalization/statistics & numerical data , Hypertension/epidemiology , Hypertension/therapy , Renal Dialysis , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/therapy , Precision Medicine , Electronic Health Records , Algorithms , Primary Health Care/statistics & numerical data
4.
bioRxiv ; 2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38617258

ABSTRACT

Transcription factor (TF)-cofactor (COF) interactions define dynamic, cell-specific networks that govern gene expression; however, these networks are understudied due to a lack of methods for high-throughput profiling of DNA-bound TF-COF complexes. Here we describe the Cofactor Recruitment (CoRec) method for rapid profiling of cell-specific TF-COF complexes. We define a lysine acetyltransferase (KAT)-TF network in resting and stimulated T cells. We find promiscuous recruitment of KATs for many TFs and that 35% of KAT-TF interactions are condition specific. KAT-TF interactions identify NF-κB as a primary regulator of acutely induced H3K27ac. Finally, we find that heterotypic clustering of CBP/P300-recruiting TFs is a strong predictor of total promoter H3K27ac. Our data supports clustering of TF sites that broadly recruit KATs as a mechanism for widespread co-occurring histone acetylation marks. CoRec can be readily applied to different cell systems and provides a powerful approach to define TF-COF networks impacting chromatin state and gene regulation.

5.
Struct Dyn ; 11(2): 024309, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38595978

ABSTRACT

For time-resolved diffraction studies of irreversible structural dynamics upon photoexcitation, there are constraints on the number of perturbation cycles due to thermal effects and accumulated strain, which impact the degree of crystal order and spatial resolution. This problem is exasperated for surface studies that are more prone to disordering and defect formation. Ultrafast electron diffraction studies of these systems, with the conventional stroboscopic pump-probe protocol, require repetitive measurements on well-prepared diffraction samples to acquire and average signals above background in the dynamic range of interest from few tens to hundreds of picoseconds. Here, we present ultrafast streaked low-energy electron diffraction (LEED) that demands, in principle, only a single excitation per nominal data acquisition timeframe. By exploiting the space-time correlation characteristics of the streaking method and high-charge 2 keV electron bunches in the transmission geometry, we demonstrate about one order of magnitude reduction in the accumulated number of the excitation cycles and total electron dose, and 48% decrease in the root mean square error of the model fit residual compared to the conventional time-scanning measurement. We believe that our results demonstrate a viable alternative method with higher sensitivity to that of nanotip-based ultrafast LEED studies relying on a few electrons per a single excitation, to access to all classes of structural dynamics to provide an atomic level view of surface processes.

6.
Meat Sci ; 214: 109516, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38678864

ABSTRACT

Millennials have been shown to have distinctly different behaviors; however, factors affecting their liking of beef, pork and chicken has not been fully elucidated. As millennials are current and future animal protein consumers, the question of if they have different drivers of liking for beef, pork, and chicken has not been answered. Top loin steaks cooked to 58.3 or 80 °C; and pork loin chops and chicken breasts cooked to 62.7 or 80 °C were cooked on a flat grill. Beef bottom round roasts cooked to 58.3 or 80°; and pork inside ham roasts and chicken thighs were cooked to 62.7 or 80 °C in a Crock-pot®. A descriptive flavor and texture attribute panel and a consumer central location test in four cities were used to evaluated flavor and texture attributes. Consumers were either millennials or non-millennials, and light or heavy beef-eaters. Meat descriptive flavor and texture attributes differed by cooking method, cut, and internal temperature (P < 0.05). Consumers preferred grilled meat more than meat cooked in the Crock-pot® (P > 0.05). Consumers rated grill flavor, juiciness, and tenderness (P ≥ 0.05) higher in grilled meat. Light beef-eaters, those who ate beef 2 to 4 times per month, rated overall, flavor, and species flavor lower (P < 0.05) than heavy beef-eaters, but consumers liked beef regardless of generational segment or their consumption of beef; however, millennials rated overall, overall flavor, and tenderness liking slightly lower than non-millennials. These results indicate that millennials have similar drivers of liking as non-millennials across beef, pork, and chicken protein sources.


Subject(s)
Chickens , Consumer Behavior , Cooking , Red Meat , Taste , Animals , Humans , Cattle , Adult , Male , Female , Young Adult , Middle Aged , Red Meat/analysis , Swine , United States , Adolescent , Meat/analysis , Food Preferences , Pork Meat/analysis , Aged
7.
Struct Dyn ; 11(2): 024301, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38433875

ABSTRACT

Understanding the chemical reactions that give rise to functional biological systems is at the core of structural biology. As techniques are developed to study the chemical reactions that drive biological processes, it must be ensured that the reaction occurring is indeed a biologically relevant pathway. There is mounting evidence indicating that there has been a propagation of systematic error in the study of photoactive biological processes; the optical methods used to probe the structural dynamics of light activated protein functions have failed to ensure that the photoexcitation prepares a well-defined initial state relevant to the biological process of interest. Photoexcitation in nature occurs in the linear (one-photon per chromophore) regime; however, the extreme excitation conditions used experimentally give rise to biologically irrelevant multiphoton absorption. To evaluate and ensure the biological relevance of past and future experiments, a theoretical framework has been developed to determine the excitation conditions, which lead to resonant multiphoton absorption (RMPA) and thus define the excitation limit in general for the study of structural dynamics within the 1-photon excitation regime. Here, we apply the theoretical model to bacteriorhodopsin (bR) and show that RMPA occurs when excitation conditions exceed the linear saturation threshold, well below typical excitation conditions used in this class of experiments. This work provides the guidelines to ensure excitation in the linear 1-photon regime is relevant to biological and chemical processes.

8.
J Phys Chem B ; 128(13): 3249-3257, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38507573

ABSTRACT

Spin-casting of molecularly doped polymer solution mixtures is one of the commonly used methods to obtain conductive organic semiconductor films. In spin-casted films, electronic interaction between the dopant and polymer is one of the crucial factors that dictates the doping efficiency. Here, we investigate excitonic couplings using ultrafast two-dimensional electronic spectroscopy to examine the different types of electronic interactions in ion pairs of the prototype F4TCNQ-doped P3HT polymer system in a precursor solution mixture for spin-casting. Off-diagonal peaks in the 2D spectra clearly establish the excitonic coupling between P3HT+ and F4TCNQ- ions in solution. The observed excitonic coupling is the direct manifestation of a Coulombic interaction between the ion pair. The excited-state lifetime of F4TCNQ- in ion pairs shows biexponential decay at 30 and 200 fs, which hints toward the presence of a heterogeneous population with different interaction strengths. To examine the nature of these different types of interactions in solution mixtures, we study the system using molecular dynamics simulations on a fully solvated model employing the generalized Amber force field. We retrieve three dominant interaction modes of F4TCNQ anions with P3HT: side chain, π-stack, and slipped stack. To quantify these interactions, we complement our studies with electronic structure calculations, which reveal the excitonic coupling strengths of ∼ 75 cm-1 for side chain, ∼ 150 cm-1 for π-π-stack, and ∼69 cm-1 for slipped stack. These various interaction modes provide information about the key geometries of the seed structures in precursor solution mixtures, which may determine the final structures in spin-casted films. The insights gained from our study may guide new strategies to control and ultimately tune Coulomb interactions in polymer-dopant solutions.

9.
Sci Adv ; 10(10): eadk1312, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38446882

ABSTRACT

Photosystem II (PSII) reaction center (RC) is a unique complex that is capable of efficiently separating electronic charges across the membrane. The primary energy- and charge-transfer (CT) processes occur on comparable ultrafast timescales, which makes it extremely challenging to understand the fundamental mechanism responsible for the near-unity quantum efficiency of the transfer. Here, we elucidate the role of quantum coherences in the ultrafast energy and CT in the PSII RC by performing two-dimensional (2D) electronic spectroscopy at the cryogenic temperature of 20 kelvin, which captures the distinct underlying quantum coherences. Specifically, we uncover the electronic and vibrational coherences along with their lifetimes during the primary ultrafast processes of energy and CT. We construct an excitonic model that provides evidence for coherent energy and CT at low temperature in the 2D electronic spectra. The principles could provide valuable guidelines for creating artificial photosystems with exploitation of system-bath coupling and control of coherences to optimize the photon conversion efficiency to specific functions.

10.
J Chem Phys ; 160(10)2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38456529

ABSTRACT

We propose a quantum tomography (QT) approach to retrieve the temporally evolving reduced density matrix in electronic state basis, where the populations and coherence between the ground state and excited state are reconstructed from the ultrafast electron diffraction signal. In order to showcase the capability of the proposed QT approach, we simulate the nuclear wavepacket dynamics and ultrafast electron diffraction of photoexcited pyrrole molecules using the ab initio quantum chemical CASSCF method. From the simulated time-resolved diffraction data, we retrieve the evolving density matrix in a crude diabatic representation basis and reveal the symmetry of the excited pyrrole wavepacket. Our QT approach opens the route to make a quantum version of "molecular movie" that covers the electronic degree of freedom and equips ultrafast electron diffraction with the power to reveal the coherence between electronic states, relaxation, and dynamics of population transfer.

11.
J Struct Biol ; 216(2): 108073, 2024 Mar 02.
Article in English | MEDLINE | ID: mdl-38432598

ABSTRACT

Cryo-electron microscopy has become a powerful tool to determine three-dimensional (3D) structures of rigid biological macromolecules from noisy micrographs with single-particle reconstruction. Recently, deep neural networks, e.g., CryoDRGN, have demonstrated conformational and compositional heterogeneity of complexes. However, the lack of ground-truth conformations poses a challenge to assess the performance of heterogeneity analysis methods. In this work, variational autoencoders (VAE) with three types of deep generative priors were learned for latent variable inference and heterogeneous 3D reconstruction via Bayesian inference. More specifically, VAEs with "Variational Mixture of Posteriors" priors (VampPrior-SPR), non-parametric exemplar-based priors (ExemplarPrior-SPR) and priors from latent score-based generative models (LSGM-SPR) were quantitatively compared with CryoDRGN. We built four simulated datasets composed of hypothetical continuous conformation or discrete states of the hERG K + channel. Empirical and quantitative comparisons of inferred latent representations were performed with affine-transformation-based metrics. These models with more informative priors gave better regularized, interpretable factorized latent representations with better conserved pairwise distances, less deformed latent distributions and lower within-cluster variances. They were also tested on experimental datasets to resolve compositional and conformational heterogeneity (50S ribosome assembly, cowpea chlorotic mottle virus, and pre-catalytic spliceosome) with comparable high resolution. Codes and data are available: https://github.com/benjamin3344/DGP-SPR.

12.
Struct Dyn ; 11(1): 014302, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38304443

ABSTRACT

Samples suitable for electron diffraction studies must satisfy certain characteristics such as having a thickness in the range of 10-100 nm. We report, to our knowledge, the first successful synthesis technique of nanometer-thin sheets of single-crystalline thymine suitable for electron diffraction and spectroscopy studies. This development provides a well-defined system to explore issues related to UV photochemistry of DNA and high intrinsic stability essential to maintaining integrity of genetic information. The crystals are grown using the evaporation technique, and the nanometer-thin sheets are obtained via microtoming. The sample is characterized via x-ray diffraction and is subsequently studied using electron diffraction via a transmission electron microscope. Thymine is found to be more radiation resistant than similar molecular moieties (e.g., carbamazepine) by a factor of 5. This raises interesting questions about the role of the fast relaxation processes of electron scattering-induced excited states, extending the concept of radiation hardening beyond photoexcited states. The high stability of thymine in particular opens the door for further studies of these ultrafast relaxation processes giving rise to the high stability of DNA to UV radiation.

13.
Antimicrob Agents Chemother ; 68(3): e0127923, 2024 Mar 06.
Article in English | MEDLINE | ID: mdl-38299818

ABSTRACT

Invasive primary Candida surgical site infections (IP-SSIs) are a common complication of liver transplantation, and targeted antifungal prophylaxis is an efficient strategy to limit their occurrence. We performed a retrospective single-center cohort study among adult single liver transplant recipients at Duke University Hospital in the period between 1 January 2015 and 31 December 2020. The study aimed to determine the rate of Candida IP-SSI according to the peri-transplant antifungal prophylaxis received. Of 470 adult single liver transplant recipients, 53 (11.3%) received micafungin prophylaxis, 100 (21.3%) received fluconazole prophylaxis, and 317 (67.4%) did not receive systemic antifungal prophylaxis in the peri-transplant period. Ten Candida IP-SSIs occurred among 5 of 53 (9.4%) micafungin recipients, 1 of 100 (1.0%) fluconazole recipients, and 4 of 317 (1.3%) recipients who did not receive antifungal prophylaxis. Our study highlights the limitations of antifungal prophylaxis in preventing invasive Candida IP-SSI after liver transplant surgery. We hypothesize that pathogen, host, and pharmacokinetic-related factors contributed to the occurrence of Candida IP-SSI despite antifungal prophylaxis. Our study reinforces the need for a risk-based, multi-pronged approach to fungal prevention, including targeted antifungal administration in patients with risks for invasive candidiasis and close monitoring, especially among patients with surgically complex procedures, with timely control of surgical leaks.


Subject(s)
Candidiasis, Invasive , Candidiasis , Liver Transplantation , Adult , Humans , Antifungal Agents/therapeutic use , Fluconazole/therapeutic use , Liver Transplantation/adverse effects , Micafungin/therapeutic use , Retrospective Studies , Cohort Studies , Surgical Wound Infection/prevention & control , Surgical Wound Infection/drug therapy , Candidiasis, Invasive/drug therapy , Candidiasis, Invasive/prevention & control , Candida
14.
Nature ; 626(8000): 720-722, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38355996

Subject(s)
Light , Proteins , X-Rays , Radiography , Lasers
15.
Anaesthesia ; 79(2): 193-202, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38088443

ABSTRACT

Each year approximately one million people suffer spinal cord injury, which has significant physical, psychosocial and economic impacts on patients and their families. Spinal cord rehabilitation centres are a well-established part of the care pathway for patients with spinal cord injury and facilitate improvements in functional independence and reductions in healthcare costs. Within the UK, however, there are a limited number of spinal cord injury centres, which delays admission. Patients and their families often perceive that they are not receiving specialist care while being treated in non-specialist units. This review aimed to provide clinicians who work in non-specialist spinal injury centres with a summary of contemporary studies relevant to the critical care management of patients with cervical spinal cord injury. We undertook a targeted literature review including guidelines, systematic reviews, meta-analyses, clinical trials and randomised controlled trials published in English between 1 June 2017 and 1 June 2023. Studies involving key clinical management strategies published before this time, but which have not been updated or repeated, were also included. We then summarised the key management themes: acute critical care management approaches (including ventilation strategies, blood pressure management and tracheostomy insertion); respiratory weaning techniques; management of pain and autonomic dysreflexia; and rehabilitation.


Subject(s)
Cervical Cord , Spinal Cord Injuries , Humans , Cervical Cord/injuries , Spinal Cord Injuries/therapy , Intensive Care Units , Hospitalization , Critical Care
16.
Chem Phys Lipids ; 258: 105365, 2024 01.
Article in English | MEDLINE | ID: mdl-38092233

ABSTRACT

Layers of pulmonary lipids on an aqueous substrate at non-equilibrium conditions can decrease the surface tension of water to quite low values. This is connected with different relaxation processes occurring at the interface and the associated changes in the surface layer structure. Results of measurements by the combination of methods like surface rheology, ellipsometry, Brewster angle microscopy, and IRRAS for spread layers of lipid mixtures open a possibility to specify the dynamics of structural changes at conditions close to the physiological state. At sufficiently low surface tension values (below 5 mN/m) significant changes in the ellipsometric signal were observed for pure DPPC layers, which can be related to a transition from 2D to 3D structures caused by the layer folding. The addition of other lipids can accelerate the relaxation processes connected with squeezing-out of molecules or multilayer stacks formation hampering thereby a decrease of surface tension down to low values corresponding to the folding of the monolayer.


Subject(s)
Lung , Microscopy , Surface Tension , Lung/chemistry , Lipids/chemistry , Surface Properties , Water/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry
17.
J Community Health ; 49(1): 17-25, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37314631

ABSTRACT

BACKGROUND: Despite being disproportionately impacted by COVID-19 due to a lack of structural support, marginalized communities have been largely ignored in the politically polarized debate over school masking. In response to this, we sought to explore masking attitudes by centering the voices of parents and children at historically marginalized, predominantly Hispanic schools in southern California. METHODS: We conducted a mixed-methods study with parents and children attending 26 low-income predominantly Hispanic-serving elementary schools. A random sample of parents was asked to provide a freelist of words they associate with masking. A subset of parents with children aged 4-6 was recruited from these surveys to participate in parent-child interviews (PCI). We calculated Smith's salience index for all unique items, stratifying by language (English/Spanish). Item salience guided PCI thematic analysis for additional context and meaning. RESULTS: 648 participants provided 1118 unique freelist items in English and Spanish. 19 parent-child pairs were interviewed, 11 in Spanish and 8 in English. The most salient words were "safety"(0.37), "protection"(0.12), "prevention"(0.05), "health"(0.04), "good"(0.03), "can't breathe"(0.03), "necessary"(0.02), "care"(0.02), "precaution"(0.02), and "unnecessary"(0.02). Spanish speakers had a more favorable view of masking than English speakers, particularly regarding "protection" (0.20 vs 0.08) and "prevention" (0.10 vs 0.02). DISCUSSION: Masking is an affordable individual-level risk mitigation that protects the communities that have inequitably shouldered the burdens of the COVID-19 pandemic. We recommend that policymakers prioritize the views of those most impacted when deciding on risk mitigation policies like school masking.


Subject(s)
Hispanic or Latino , Masks , Pandemics , Humans , Attitude , Pandemics/prevention & control , Parents , Schools , Surveys and Questionnaires , Health Policy
18.
Clin Oncol (R Coll Radiol) ; 36(1): e1-e10, 2024 01.
Article in English | MEDLINE | ID: mdl-37923688

ABSTRACT

AIMS: New treatment options for advanced ovarian cancer have the potential to significantly change the treatment pathway in the UK. Understanding the structures and responsibilities of multidisciplinary teams/tumour boards (MDT) and regional variations will enable services to adapt more effectively to these changes. MATERIALS AND METHODS: The KNOW-OC survey was conducted in 2020 to understand the views of a selected group of 66 healthcare professionals (HCPs) involved in advanced ovarian cancer care in UK hospitals. RESULTS: The results showed that MDT involvement in the management of advanced ovarian cancer varied depending on pathway stage and line of relapse, with 98.5% of HCPs responding that the MDT was involved in decisions at initial presentation, but only 40.9% for patients with multiple relapses. The MDT was mostly responsible for determining whether the patients would undergo primary or interval cytoreductive surgery according to 75.8% of respondents, and most HCPs (80.3%) stated that tumour dissemination patterns were the most important factor influencing this decision. The most commonly assessed biomarkers at the time of the survey were CA125, gBRCA and tBRCA. Homologous recombination deficiency was viewed as the second most important factor for determining prognosis, but few centres had access to testing at the time of survey completion. The use of active surveillance was expected to decrease in favour of first-line targeted therapies. Nearly all (98.5%) HCPs agreed there is a role for secondary cytoreductive surgery for the treatment of recurrence (for carefully selected patients). CONCLUSIONS: The results highlighted UK-specific geographical variation in the views of HCPs on MDT involvement and specific practices, such as molecular biomarker testing, and the overall treatment approach. Together, these findings improve the understanding of reported clinical practice across the UK for ovarian cancer and provide insight into decision-making associated with updates to recommendations for best practice (e.g. European Society for Medical Oncology/European Society of Gynaecological Oncology consensus statements) and the introduction of new treatment options.


Subject(s)
Ovarian Neoplasms , Humans , Female , Surveys and Questionnaires , Ovarian Neoplasms/drug therapy , Carcinoma, Ovarian Epithelial/therapy , Delivery of Health Care , United Kingdom
19.
IUCrJ ; 11(Pt 1): 62-72, 2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38038991

ABSTRACT

Serial electron diffraction (SerialED), which applies a snapshot data acquisition strategy for each crystal, was introduced to tackle the problem of radiation damage in the structure determination of beam-sensitive materials by three-dimensional electron diffraction (3DED). The snapshot data acquisition in SerialED can be realized using both transmission and scanning transmission electron microscopes (TEM/STEM). However, the current SerialED workflow based on STEM setups requires special external devices and software, which limits broader adoption. Here, we present a simplified experimental implementation of STEM-based SerialED on Thermo Fisher Scientific STEMs using common proprietary software interfaced through Python scripts to automate data collection. Specifically, we utilize TEM Imaging and Analysis (TIA) scripting and TEM scripting to access the STEM functionalities of the microscope, and DigitalMicrograph scripting to control the camera for snapshot data acquisition. Data analysis adapts the existing workflow using the software CrystFEL, which was developed for serial X-ray crystallography. Our workflow for STEM SerialED can be used on any Gatan or Thermo Fisher Scientific camera. We apply this workflow to collect high-resolution STEM SerialED data from two aluminosilicate zeolites, zeolite Y and ZSM-25. We demonstrate, for the first time, ab initio structure determination through direct methods using STEM SerialED data. Zeolite Y is relatively stable under the electron beam, and STEM SerialED data extend to 0.60 Å. We show that the structural model obtained using STEM SerialED data merged from 358 crystals is nearly identical to that using continuous rotation electron diffraction data from one crystal. This demonstrates that accurate structures can be obtained from STEM SerialED. Zeolite ZSM-25 is very beam-sensitive and has a complex structure. We show that STEM SerialED greatly improves the data resolution of ZSM-25, compared with serial rotation electron diffraction (SerialRED), from 1.50 to 0.90 Å. This allows, for the first time, the use of standard phasing methods, such as direct methods, for the ab initio structure determination of ZSM-25.

20.
J Vasc Surg ; 79(5): 1034-1043, 2024 May.
Article in English | MEDLINE | ID: mdl-38157993

ABSTRACT

OBJECTIVE: Chronic kidney disease (CKD) and end-stage renal disease are traditionally associated with worse outcomes after endovascular aortic repair (EVAR) and open aneurysm repair (OAR) of abdominal aortic aneurysms (AAAs). However, there needs to be more data on complex AAA repair involving the aorta's visceral segment. This study stratifies complex AAA repair outcomes by CKD severity and dialysis dependence. METHODS: All patients undergoing elective OAR and fenestrated/branched EVAR (F-BEVAR) for complex AAA with preoperative renal function data captured by the Vascular Quality Initiative between January 2003 and September 2020 were analyzed. Patients were stratified by CKD class as follows: normal/mild (CKD 1 and 2), moderate (CKD class 3a), moderate to severe (CKD 3b), severe (CKD class 4 and 5), and dialysis. Only patients with clamp sites above one of the renal arteries were included for complex OAR. For F-BEVAR, patients with proximal landing zones below zone 5 (above celiac artery) were included, and distal landing zones between zones 1 and 5 were excluded. Primary outcomes were perioperative and 1-year mortality. Predictors of mortality were identified by Cox multivariate regression models. RESULTS: We identified 7849 elective complex AAA repairs: 4230 (54%) complex OARs and 3619 (46%) F-BEVARs. Most patients were White (89%) and male (74%), with an average age of 72 ± 8 years. The patients who underwent F-BEVAR were older and had more comorbidities. Elective F-BEVAR for complex AAA started in 2012 and increased from 1.4% in 2012 to 58% in 2020 (P < .001). The OAR cohort had more perioperative complications, but less 1-year mortality. The normal/mild CKD cohort had the highest 1-year survival compared with other groups after both complex OAR and F-BEVAR. On Cox regression analysis, when compared with CKD 1-2, worsening CKD stage (CKD 3b: hazard ratio [HR], 2.5; 95% confidence interval [CI], 1.82-3.40; P < .001; CKD 4-5: HR, 1.9; 95% CI, 1.16-3.26; P = .011; and dialysis: HR, 4.4; 95% CI, 2.53-7.72; P < .001) were independently associated with 1-year survival after F-BEVAR. After complex OAR, worsening CKD stage but not dialysis was associated with 1-year mortality compared with CKD 1-2 (CKD 3b: HR, 1.6; 95% CI, 1.13-2.35; P = .009; CKD 4-5: HR, 3.4; 95% CI, 2.03-5.79; P < .001). CONCLUSIONS: CKD severity is an essential predictor of perioperative and 1-year mortality after complex AAA repair, irrespective of the treatment modality, which may reflect the natural history of CKD. Consideration should be given to raising the threshold for elective AAA repair in patients with moderate to severe CKD and end-stage renal disease, given the high 1-year mortality rate.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Kidney Failure, Chronic , Renal Insufficiency, Chronic , Humans , Male , Middle Aged , Aged , Aged, 80 and over , Risk Factors , Blood Vessel Prosthesis Implantation/adverse effects , Treatment Outcome , Endovascular Procedures/adverse effects , Time Factors , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/therapy , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Retrospective Studies
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