Preoperative Risk Factors for 1-year Mortality in Patients Undergoing Fenestrated Endovascular Aortic Aneurysm Repair in the US-Aortic Research Consortium.

BACKGROUND: Early survival (1-year) following elective repair of complex abdominal aortic aneurysms (AAA) or thoracoabdominal aortic aneurysms (TAAA) can be utilized as an indicator of successful repair and provides a reasonable countermeasure to the annual rupture risk based on diameter. We aimed to identify preoperative factors associated with 1-year mortality following F/BEVAR and develop a predictive model for 1-year mortality based on patient-specific risk-profiles. METHODS: The US-Aortic Research Consortium (US-ARC) database was queried for all patients undergoing elective F/BEVAR for complex AAA or TAAA from 2005-2022. The primary outcome was 1-year survival based on preoperative risk-profile. Multivariable Cox regression was used to determine preoperative variables associated with 1-year mortality overall and by extent of aortic pathology. Logistic regression was performed to build a predictive model for 1-year mortality based on number of risk factors present. RESULTS: A total of 2,099 patients met the inclusion criteria for this study (complex AAA: N=709, 34.3%; Type 1-3 TAAA: N=777, 37.6%; Type 4-5 TAAA: N=580, 28.1%). Multivariable Cox regression identified the following significant risk factors associated with 1-year mortality: current smoker, chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), Aortic diameter>7cm, Age>75, Extent 1-3, creatinine>1.7mg/dL, and hematocrit<36%. When stratified by extent of aortic involvement, multivariable Cox regression revealed risk factors for 1-year mortality in complex AAA (CHF max aortic diameter>7cm, hematocrit<36mg/dL, and current smoking status), Type 1-3 TAAA (COPD, CHF, and Age>75) and Type 4-5 TAAA (age>75, creatinine>1.7mg/dL, and hematocrit<36mg/dL). Logistic regression was then utilized to develop a predictive model for 1-year mortality based on patient risk-profile. Appraisal of the model revealed an area under the curve of 0.64, p-value<0.001, and observed to expected ratio of 0.85. CONCLUSIONS: This study describes multiple risk factors associated with an increase in 1-year mortality following F/BEVAR. Given that elective repair of complex AAA or TAAA is offered to some patients in whom future rupture risk outweighs operative risk, these findings suggest that highly comorbid patients with smaller aneurysms may not benefit from repair. Descriptive and predictive models for 1-year mortality based on patient risk-profiles can serve as an adjunct in clinical decision-making when considering elective F/BEVAR.

Visual access to an outdoor range early in life, but not environmental complexity, increases meat chicken ranging behavior.

Not all chickens access an outdoor range when the opportunity is provided. This may be related to the abrupt change in environments from the stable rearing conditions to the complexity of the outdoor range. We aimed to prepare chickens to range by increasing the complexity of the indoor environment early in life with the intention to encourage range use. Mixed sex Cobb500 chickens were allocated to 1 of 3 treatment groups: visual access (VA) treatment provided VA to the outdoor range from day old via transparent pop-hole covers; environmental complexity (EC) treatment provided an artificial haybale, fan with streamers and a solid vertical barrier; Control treatment was a representative conventional environment. Chickens were given access to the outdoor range at 21 d of age. Behavior in the home pen was assessed in wk 1, 2 and 5 and individual ranging behavior was monitored through radio frequency identification (RFID) technology. The VA chickens were more active compared to EC (P = 0.006) and Control (P = 0.007) chickens and spent more time foraging than control chickens (P = 0.036) during the first week of life. More VA chickens accessed the range area compared to EC chickens (P = 0.015). VA chickens accessed the range sooner after they were first provided access and spent more time on the range than EC and control chickens (P < 0.001). Mortality was lower in the VA treatment compared to EC (P = 0.024) and control group (P = 0.002). There was evidence that VA chickens weighed less than Control and EC chickens, however results were inconsistent between age and sex. Hence, providing meat chickens with VA to an outdoor range early in life increased activity in early life, decreased latency to first access the range and increased time on the range and lowered mortality. Future work should aim to understand the mechanism behind these changes in behavior to develop recommendations for producers to implement in commercial conditions.

[German S1 Guideline Long-/Post-COVID]. / S1-Leitlinie Long-/Post-COVID.

The German Society of Pneumology initiated 2021 the AWMF S1 guideline Long COVID/Post-COVID. In a broad interdisciplinary approach, this S1 guideline was designed based on the current state of knowledge.The clinical recommendations describe current Long COVID/Post-COVID symptoms, diagnostic approaches, and therapies.In addition to the general and consensus introduction, a subject-specific approach was taken to summarize the current state of knowledge.The guideline has an explicit practical claim and will be developed and adapted by the author team based on the current increase in knowledge.

Free energy landscape within the hysteresis regime for fluids confined in disordered mesoporous solids.

Adsorption/desorption and melting/freezing in structurally disordered nanoporous solids exhibit strongly non-equilibrium behavior as revealed by the formation of a hysteresis region populated by the multitude of different states. Many questions concerning the free energy spectrum of these states, including the existence of the equilibrium transition, if any, their accessibility in the experiments, and internal relaxation dynamics toward the global energy minimum, still remain poorly addressed. By using a serially connected pore model with the statistical disorder as a minimal model of the pore networks, we explore the system free energies along the solid-liquid and liquid-gas transitions in the pore systems. The rigorous results obtained with this model shed light on the occurrence and nature of the equilibrium transition line in porous solids with arbitrary pore topology. We discuss further the free energies along the experimentally measured boundary and scanning transitions and how close the equilibrium states can be approached in these experiments.

Quantitating Diffusion Enhancement in Pore Hierarchies.

A microporous continuum traversed by a set of mutually perpendicular channels is considered to be a model for a hierarchically porous system of the mesoporous zeolite type. Transient profiles of molecular uptake as determined by kinetic Monte Carlo (kMC) simulation are found to be in excellent agreement with the result attained by the application of the two-region model (the Kärger model) of molecular diffusion. In particular, it is found that, in the two limiting cases referred to as fast exchange and slow exchange, there exist two simple analytical expressions for the rate of molecular uptake and hence for the quantification of transport enhancement in comparison with the purely microporous adsorbent. In the general case, transport enhancement is simply recognized by the reciprocal addition of the expressions in the two limiting cases.

Membrane Structure of Aquaporin Observed with Combined Experimental and Theoretical Sum Frequency Generation Spectroscopy.

High-resolution structural information on membrane proteins is essential for understanding cell biology and for the structure-based design of new medical drugs and drug delivery strategies. X-ray diffraction (XRD) can provide angstrom-level information about the structure of membrane proteins, yet for XRD experiments, proteins are removed from their native membrane environment, chemically stabilized, and crystallized, all of which can compromise the conformation. Here, we describe how a combination of surface-sensitive vibrational spectroscopy and molecular dynamics simulations can account for the native membrane environment. We observe the structure of a glycerol facilitator channel (GlpF), an aquaporin membrane channel finely tuned to selectively transport water and glycerol molecules across the membrane barrier. We find subtle but significant differences between the XRD structure and the inferred in situ structure of GlpF.

Analysis of nanoscale fluid inclusions in geomaterials by atom probe tomography: Experiments and numerical simulations.

The spatial correlation between defects in crystalline materials and trace element segregation plays a fundamental role in determining the physical and mechanical properties of a material, which is particularly important in naturally deformed materials. Herein, we combine electron backscatter diffraction, electron channelling contrast imaging, scanning transmission electron microscopy and atom probe tomography on a naturally occurring metal sulphide in an attempt to document mechanisms of element segregation in a brittle-dominated deformation regime. Within APT reconstructions, features with a high point density comprising O-rich discs stacked over As-rich spherules are observed. The combined microscopy data allow us to interpret these as nanoscale fluid inclusions. Our observations are confirmed by simulated APT experiments of core-shell particles with a core exhibiting a very low evaporation field and the shell emulating a segregated layer at the inclusion interface. Our data has significant trans-disciplinary implications to the geosciences, the material sciences, and analytical microscopy.

Evaluation of Mechanical Properties of Porous OSG Films by PFQNM AFM and Benchmarking with Traditional Instrumentation.

Characterization of mechanical properties of thin porous films with nanoscale resolution remains a challenge for instrumentation science. In this work, atomic force microscopy (AFM) in the PeakForce quantitative nanomechanical mapping (PFQNM) mode is used for Young's modulus measurements of porous organosilicate glass films. The test samples were prepared by sol-gel techniques using silicon alkoxide and methyl-modified silicon alkoxide to prepare films with different CH3/Si ratios. The film porosity was engineered by using a Brij 30 template and the evaporation-induced self-assembly technique. The chemical composition, pore structure, and modification during air storage and thermal annealing were studied using FTIR spectroscopy and ellipsometric porosimetry (EP). Since PFQNM AFM was first used for evaluation of Young's modulus of thin porous films, the obtained results are benchmarked using nanoindentation (NI), surface acoustic wave (SAW) spectroscopy, and EP. The results have good agreement with each other, but PFQNM and NI give slightly larger values than SAW and EP. The difference is in agreement with previously reported data and reflects the different physical meaning of the obtained values. It is shown that the presence of physically adsorbed water strongly influences the results generated by PFQNM AFM, and therefore, reliable water removal from the studied materials is necessary.

The association between range usage and tibial quality in commercial free-range laying hens.

1. Bone tissue adapts continuously to metabolic calcium demands, as well as to external forces due to physical weight loading subject to hen movement. Limited calcium metabolism and, subsequently, its availability from the medullary bone, is a major factor contributing to reduced eggshell quality in hens in the late laying period (>60 weeks of age). 2. Increasing physical activity and biomechanical loading during hen rearing has been demonstrated to increase skeletal strength, enhancing bone mass as well as endocortical and periosteal bone metabolism. Presently, the consequences of range use during lay on bone quality characteristics in laying hens remain unknown. 3.The aims of this study were to characterise tibiotarsal bone indices and evaluate the impact of range access during lay on tibia bone quality in commercial free-range laying hens. 4. This exploratory study described and analysed the volumetric measurements, morphological mechanical and trabeculae indices of the tibiotarsal bone of 48 Lohmann Brown laying hens at 74 weeks of age. All bone parameters were obtained using micro-computed tomography and correlated with individual hen range use. 5. Range usage throughout lay was not associated with tibial trabecular architecture (bone volume and fraction, trabecular thickness, trabecular connectivity density and structural model index), or any other morphological characteristics (breaking strength, diaphyseal diameter, bone weight and bone mineral density) of the tibia (P > 0.05) when hens were 74 weeks of age. 6. The results demonstrated a large variation in individual bone characteristics and suggested that range usage was not associated with bone quality in commercial free-range laying hens used in this study. In conclusion, the bone health of free-range commercial laying hens may be positively impacted by other features, such as hen genetics, feed, the quality of pullet rearing, perch availability or other shed equipment, and the benefits of these variables exceed the benefit of range use.

The Genomics of Cannabis and Its Close Relatives.

Cannabis sativa L. is an important yet controversial plant with a long history of recreational, medicinal, industrial, and agricultural use, and together with its sister genus Humulus, it represents a group of plants with a myriad of academic, agricultural, pharmaceutical, industrial, and social interests. We have performed a meta-analysis of pooled published genomics data, andwe present a comprehensive literature review on the evolutionary history of Cannabis and Humulus, including medicinal and industrial applications. We demonstrate that current Cannabis genome assemblies are incomplete, with ∼10% missing, 10-25% unmapped, and 45S and 5S ribosomal DNA clusters as well as centromeres/satellite sequences not represented. These assemblies are also ordered at a low resolution, and their consensus quality clouds the accurate annotation of complete, partial, and pseudogenized gene copies. Considering the importance of genomics in the development of any crop, this analysis underlines the need for a coordinated effort to quantify the genetic and biochemical diversity of this species.

Prevention of anastomotic leak in rectal cancer surgery with local antibiotic decontamination: a prospective, randomized, double-blind, placebo-controlled single center trial.

PURPOSE: Anastomotic leak and other infectious complications are septic complications of rectal cancer surgery caused by bacteria. Data from registry analysis show a beneficial effect of local antimicrobial administration on anastomotic leaks, but data are inconsistent in recent clinical trials. Therefore, our aim was to study the efficacy of topical antibiotic treatment on the incidence of anastomotic leaks in rectal cancer surgery. METHODS: A prospective, randomized, double-blind and placebo-controlled, single center trial was conducted. Patients received either placebo and amphotericin B or decontamination with polymyxin B, tobramycin, vancomycin, and amphotericin B four times per day starting the day before surgery until postoperative day 7. If a protective ileostomy was created, a catheter was placed transanally and the medication was administered locally to the anastomotic site. All patients received an intravenous perioperative antibiotic prophylaxis. RESULTS: The trial had to be stopped for ethical reasons after first interim analysis with 80 patients instead of the initially planned 280 patients. Of the 40 patients randomized to receive placebo, eight (20%) developed anastomotic leak compared to only 2 (5%) in the treatment group of 40 patients (decontamination) with significant difference in the χ2 test (p = 0.0425). Twenty percent of the placebo group and 12.5% in the treatment group developed infectious complications not associated with anastomotic leak (p = 0.5312). One patient (2.5%) in the placebo group died (p = 0.3141). CONCLUSION: Local decontamination with polymyxin, tobramycin, vancomycin, and amphotericin B is safe and effective in the prevention of anastomotic leak in rectal cancer surgery.

Flock use of the range is associated with the use of different components of a multi-tier aviary system in commercial free-range laying hens.

1. The objective of this study was to investigate the association of using a multi-tier aviary system and access to range on flock uniformity in free-range laying hens, and to determine whether the extent of range use or flock uniformity can be predicted from the use of different levels of the aviary system.2. A total of 13,716 Lohmann Brown hens from five commercial free-range flocks housed in identical houses on the same farm were individually weighed at 16 weeks of age and allocated to five replicate areas within each house. Hen movement in the multi-tier aviary system and on the range was individually monitored using radio frequency identification (RFID). All hens had access to the range from 18 to 22 weeks of age and were exposed to the same management conditions.3. Whilst only one flock significantly changed its flock uniformity with time, they differed from each other in uniformity and body weight (P = 0.001).4. Hens spent most of their available time on the lower aviary tier (7.29 ± 0.029 h/hen/day) and on the upper aviary tier (4.29 ± 0.024 h/hen/day) while the least amount of time was spent on the range and in the nest boxes (0.93 ± 0.005 h/hen/day and 1.48 ± 0.007 h, respectively, P = 0.001).5. Range use was negatively correlated (r = -0.30) to the time spent on the upper aviary tier and positively correlated (r = 0.46) to the time spent on the lower aviary tier (P = 0.001). Bivariate analysis revealed that range and upper aviary resp. lower aviary tier usage had a significant curvilinear association.6. In conclusion, the study showed that range use was associated to the time hens spent on the different tiers of the aviary system. Flock uniformity varied between flocks but was not associated with either range and aviary system usage.

Neutron Time-of-Flight Measurements of Charged-Particle Energy Loss in Inertial Confinement Fusion Plasmas.

Neutron spectra from secondary ^{3}H(d,n)α reactions produced by an implosion of a deuterium-gas capsule at the National Ignition Facility have been measured with order-of-magnitude improvements in statistics and resolution over past experiments. These new data and their sensitivity to the energy loss of fast tritons emitted from thermal ^{2}H(d,p)^{3}H reactions enable the first statistically significant investigation of charged-particle stopping via the emitted neutron spectrum. Radiation-hydrodynamic simulations, constrained to match a number of observables from the implosion, were used to predict the neutron spectra while employing two different energy loss models. This analysis represents the first test of stopping models under inertial confinement fusion conditions, covering plasma temperatures of k_{B}T≈1-4 keV and particle densities of n≈(12-2)×10^{24} cm^{-3}. Under these conditions, we find significant deviations of our data from a theory employing classical collisions whereas the theory including quantum diffraction agrees with our data.

Various bone parameters are positively correlated with hen body weight while range access has no beneficial effect on tibia health of free-range layers.

The aim of this study was to determine if body weight or range use has a significant impact on bone health in commercial free-range laying hens, and to correlate tibia bone quality parameters with individual range usage and body weight. A total of 30 Lohmann Brown hens at 74 wk of age were selected from a commercial free-range farm and were either classified as heavy (mean ± SEM body weight 2.11 ± 0.034 kg, n = 14) or light (1.68 ± 0.022 kg, n = 16) body weight, and also classified as rangers (accessed the range for 86.7% of available days, n = 16) or stayers (accessed the range for 5.00% of available days, n = 14). The left tibiae of all individuals were analyzed for morphological parameters using computed tomography, evaluated for bone breaking strength, and ashed to determine mineral composition. Keel bone scoring was performed based on observation. Data were analyzed using a 2 × 2 factorial ANOVA, and regression analysis was performed. There was no measurable effect of range usage on any of the tibia parameters investigated. The body weight was significantly correlated with tibia breaking strength (r = 0.59), tibia weight (r = 0.56), tibia length (r = 0.64), diaphyseal diameter (r = 0.61), and total tibia volume (r = 0.67). In conclusion, range access had no beneficial effect on bone health. The impact of internal hen house furnishing and movement on bone health needs further investigation.

The German trial on Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE): a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Comprehensive treatment of Herpes-simplex-virus-encephalitis (HSVE) remains a major clinical challenge. The current therapy gold standard is aciclovir, a drug that inhibits viral replication. Despite antiviral treatment, mortality remains around 20% and a majority of survivors suffer from severe disability. Experimental research and recent retrospective clinical observations suggest a favourable therapy response to adjuvant dexamethasone. Currently there is no randomized clinical trial evidence, however, to support the routine use of adjuvant corticosteroid treatment in HSVE. METHODS: The German trial of Aciclovir and Corticosteroids in Herpes-simplex-virus-Encephalitis (GACHE) studied the effect of adjuvant dexamethasone versus placebo on top of standard aciclovir treatment in adult patients aged 18 up to 85 years with proven HSVE in German academic centers of Neurology in a randomized and double blind fashion. The trial was open from November 2007 to December 2012. The initially planned sample size was 372 patients with the option to increase to up to 450 patients after the second interim analysis. The primary endpoint was a binary functional outcome after 6 months assessed using the modified Rankin scale (mRS 0-2 vs. 3-6). Secondary endpoints included mortality after 6 and 12 months, functional outcome after 6 months measured with the Glasgow outcome scale (GOS), functional outcome after 12 months measured with mRS and GOS, quality of life as measured with the EuroQol 5D instrument after 6 and 12 months, neuropsychological testing after 6 months, cranial magnetic resonance imaging findings after 6 months, seizures up to day of discharge or at the latest at day 30, and after 6 and 12 months. RESULTS: The trial was stopped prematurely for slow recruitment after 41 patients had been randomized, 21 of them treated with dexamethasone and 20 with placebo. No difference was observed in the primary endpoint. In the full analysis set (n = 19 in each group), 12 patients in each treatment arm achieved a mRS of 0-2. Similarly, we did not observe significant differences in the secondary endpoints (GOS, mRS, quality of life, neuropsychological testing). CONCLUSION: GACHE being prematurely terminated demonstrated challenges encountered performing randomized, placebo-controlled trials in rare life threatening neurological diseases. Based upon our trial results the use of adjuvant steroids in addition to antiviral treatment remains experimental and is at the decision of the individual treating physician. Unfortunately, the small number of study participants does not allow firm conclusions. TRIAL REGISTRATION: EudraCT-Nr. 2005-003201-81.

Structural and functional studies of the metalloregulator Fur identify a promoter-binding mechanism and its role in Francisella tularensis virulence.

Francisella tularensis is a Gram-negative bacterium causing tularaemia. Classified as possible bioterrorism agent, it may be transmitted to humans via animal infection or inhalation leading to severe pneumonia. Its virulence is related to iron homeostasis involving siderophore biosynthesis directly controlled at the transcription level by the ferric uptake regulator Fur, as presented here together with the first crystal structure of the tetrameric F. tularensis Fur in the presence of its physiological cofactor, Fe2+. Through structural, biophysical, biochemical and modelling studies, we show that promoter sequences of F. tularensis containing Fur boxes enable this tetrameric protein to bind them by splitting it into two dimers. Furthermore, the critical role of F. tularensis Fur in virulence and pathogenesis is demonstrated with a fur-deleted mutant showing an attenuated virulence in macrophage-like cells and mice. Together, our study suggests that Fur is an attractive target of new antibiotics that attenuate the virulence of F. tularensis.

Goats singly heterozygous for PRNP S146 or K222 orally inoculated with classical scrapie at birth show no disease at ages well beyond 6 years.

Scrapie is a transmissible spongiform encephalopathy of sheep and goats, and scrapie eradication programs in many parts of the world rely on strong genetic resistance to classical scrapie in sheep. However, the utility of putative resistance alleles in goats has been a focus of research because goats can transmit scrapie to sheep and may serve as a scrapie reservoir. Prior work showed that disease-free survival time was significantly extended in orally inoculated goats singly heterozygous for prion amino acid substitutions S146 or K222, but average durations were only around 3 years post-inoculation. The aim of this study was to investigate whether extended survival would exceed 6 years, which represents the productive lifetimes of most commercial goats. While all control homozygotes were clinically affected by an average of <2 years, none of the NS146 or QK222 goats developed clinical scrapie or had PrPSc-positive rectal biopsies. Several NS146 and QK222 goats developed other conditions unrelated to scrapie, but tissue accumulation of PrPSc was not detected in any of these animals. The NS146 heterozygotes have remained disease-free for an average of 2734days (approximately 7.5 years), the longest duration of any classical scrapie challenge experiment with any genotype to date. The QK222 heterozygotes have remained disease-free for an average of 2450days (approximately 6.7 years), the longest reported average duration for QK222 goats challenged with classical scrapie. This research is ongoing, but the current results demonstrate S146 and K222 confer strong resistance to classical scrapie in goats.

Rivaroxaban reversal with prothrombin complex concentrate or tranexamic acid in healthy volunteers.

Essentials Specific reversal agents for managing severe factor Xa inhibitor-associated bleeding are lacking. We assessed 4-factor-prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA). 4F-PCC, but not TXA, reduced the prothrombin time and increased endogenous thrombin potential. These agents may be viable options for reversal of therapeutic doses of rivaroxaban. SUMMARY: Background Oral activated factor X inhibitors such as rivaroxaban are widely used, but specific reversal agents are lacking. Although four-factor prothrombin complex concentrate (4F-PCC) and tranexamic acid (TXA) are sometimes used to manage serious bleeding, their efficacy is unknown. Prior studies in healthy subjects taking rivaroxaban revealed that 4F-PCC partially reverses the prolonged prothrombin time (PT), and fully restores the endogenous thrombin potential (ETP). The effect of TXA has not been evaluated. Methods In this double-blind, parallel-group study, 147 healthy volunteers given rivaroxaban 20 mg twice daily for 3 days were randomized after their morning dose on day 4 to receive intravenous 4F-PCC (50 IU kg-1 ), TXA (1.0 g), or saline. Standardized punch biopsies were performed at baseline and after 4F-PCC, TXA or saline administration. Reversal was assessed by measuring bleeding duration and bleeding volume at biopsy sites, and by determining the PT and ETP. Results As compared with saline, 4F-PCC partially reversed the PT and completely reversed the ETP, whereas TXA had no effect. Neither 4F-PCC nor TXA reduced bleeding duration or volume. All treatments were well tolerated, with no recorded adverse events. Conclusions Although 4F-PCC reduced the PT and increased the ETP in volunteers given supratherapeutic doses of rivaroxaban, neither 4F-PCC nor TXA influenced punch biopsy bleeding.