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The geologic framework of the Seattle fault zone (SFZ) has been extensively studied, but the structure and fault strand locations in the central portion of the fault zone through the city of Seattle have remained controversial. Much of what is known about the SFZ has come from light detection and ranging (lidar)-topographic surveys and paleoseismic investigations of fault scarps primarily west of Puget Sound, regional gravity and aeromagnetic modeling, and multiscale marine seismic imaging in waters both west and east of Seattle. We analyze ∼24 km of land-based P-wave seismic-reflection data that fill in a critical gap in our understanding of the SFZ beneath the urban areas of West Seattle, south-central Seattle, and Mercer Island. These data image deformed strata in the upper 1 km, including upwarped Tertiary rock and younger sediments. Collectively, these data provide evidence for multiple Quaternary-active thrust faults, back thrusts, and sub-basins within the SFZ beneath the city of Seattle. The results indicate that multiple and potentially active back thrusts in the upper ∼500 m extend across the length of the SFZ and the entire urban corridor that may be analogous to those on Bainbridge Island west of Puget Sound.

Abstract High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory‐based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end‐tidal carbon dioxide (PETCO2) against peripheral oxygen saturation (SpO2) to characterize and quantify VA during incremental ascent to HA (n = 46). Secondarily, these participants were compared with a separate group following the identical ascent profile whilst self‐administering a prophylactic oral dose of acetazolamide (Az; 125 mg BID; n = 20) during ascent. First, morning PETCO2 and SpO2 measurements were collected on 46 acetazolamide‐free (NAz) lowland participants during an incremental ascent over 10 days to 5160 m in the Nepal Himalaya. AUC was calculated from individually constructed Fenn diagrams, with a trichotomized split on ranked values characterizing the smallest, medium, and largest magnitudes of AUC, representing high (n = 15), moderate (n = 16), and low (n = 15) degrees of acclimatization. After characterizing the range of response magnitudes, we further demonstrated that AUC magnitudes were significantly smaller in the Az group compared to the NAz group (P = 0.0021), suggesting improved VA. These results suggest that calculating AUC on modified Fenn diagrams has utility in assessing VA in large groups of trekkers during incremental ascent to HA, due to the associated portability and congruency with known physiology, although this novel analytical method requires further validation in controlled experiments. Highlights What is the central question of this study? What are the characteristics of a novel methodological approach to assess ventilatory acclimatization (VA) with incremental ascent to high altitude (HA)? What is the main finding and its importance? Area under the curve (AUC) magnitudes calculated from modified Fenn diagrams were significantly smaller in trekkers taking an oral prophylactic dose of acetazolamide compared to an acetazolamide‐free group, suggesting improved VA. During incremental HA ascent, quantifying AUC using modified Fenn diagrams is feasible to assess VA in large groups of trekkers with ascent, although this novel analytical method requires further validation in controlled experiments.

Abstract Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan–Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06–3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86–3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p

The critical current in a one-dimensional (1D) crossed-field gap is defined by the transition from a cycloidal flow to a near-Brillouin (nB) state characterized by electron flow orthogonal to both the electric and magnetic fields and uniform virtual cathode formation. Motivated by recent studies on space-charge-limited current in non-magnetic diodes, we assess the meaning of critical current in a magentically insulated two-dimensional (2D) planar crossed-field geometry. Particle-in-cell (PIC) simulations demonstrate that binary behavior between a laminar and turbulent state does not occur in 2D because the virtual cathode is nonuniform. Rather than a distinct nB state above the critical current as in 1D, there is an increase in Brillouin contribution with the presence of cycloidal components and noise even at low currents. To evaluate the electron flows in a 2D crossed-field gap in the absence of a binary transition, we developed two metrics to assess the Brillouin and cycloidal components in a 2D planar crossed-field gap for various emission widths and injection current densities by comparing the phase space plots from PIC simulations to analytical solutions for cycloidal and Brillouin flow. For a smaller emission width, less Brillouin contribution occurs for a given injection current, while maximizing the cycloidal noise requires a larger injection current. Once the virtual cathode starts to form and expand with increasing injection current, the cycloidal noise reaches its peak and then decreases while the Brillouin components become significant and increase.

Background The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness.Methods We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes.Results We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p

Background Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings.Methods We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p

Abstract Intrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and the network of antagonistic regulatory elements it encodes. These modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2 binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between the PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.

ABSTRACTBackground The introduction of low titer group O whole blood (LTOWB) that contains potentially ABO-incompatible plasma and the increasing use of group A plasma, due to shortages of AB plasma, in trauma patients whose ABO group is unknown could put the recipients of incompatible plasma at risk of increased morbidity and mortality. This study evaluated civilian trauma patient outcomes following receipt of incompatible plasma.Methods One trauma center’s patient contributions to three multicenter studies of different trauma resuscitation strategies was analyzed; these patients were separated into two groups based on receipt of only compatible plasma versus receipt of any quantity of incompatible plasma. Multivariate analysis was performed to determine if receipt of incompatible plasma was associated with 24-hour or 30-day mortality.Results There were 347 patients eligible for this secondary analysis with 167 recipients of only compatible plasma and 180 recipients of incompatible plasma. The two groups were well matched demographically and on both prehospital and hospital arrival vital signs. The median (IQR) volume of incompatible plasma received by these patients was 684 ml (342, 1229). There was not a significant difference between the groups in 24-hour and 30-day mortality, nor in in-hospital or intensive care unit lengths of stay. In the Cox proportional-hazards regression model for both 24-hour and 30-day survival, receipt of incompatible plasma was not independently predictive of either mortality endpoint.Conclusion Receipt of incompatible plasma was not independently associated with increased mortality in trauma patients. Prospective studies are needed to confirm these findings.

Polynuclear heterobimetallic coordination cages in which different metal cations are connected within a ligand scaffold are known to adopt a variety of polyhedral architectures, many of which display interesting functions. Within the extensive array of coordination cages incorporating Fe(II) centres reported so far, the majority contain low-spin (LS) Fe(II), with high-spin (HS) Fe(II) being less common. Herein, we present the synthesis and characterisation of a new tetradecanuclear heterobimetallic [Fe8Pd6L8](BF4]28 (1) cubic cage utilising the metalloligand approach. Use of the tripodal tris-imidazolimine derivative (2) permitted the formation of the tripodal HS Fe(II) metalloligand [FeL](BF4)2·CH3OH (3) that was subsequently used to form the coordination cage 1. Magnetic and structural analyses gave insight into the manner in which the HS environment of the metalloligand was transferred into the cage architecture along with the structural changes that accompanied its occupancy of the eight corners of the discrete cubic structure.

Hybrid organic–inorganic phosphazane macrocycles have been studied for their potentially useful host–guest chemistries, but synthetic routes capable of controlling their size have yet to be reported. Here, a two-step route that exploits pre-arranged building blocks enables the design of an unfolded tetrameric macrocycle.

Melatonin (N-acetyl-5-methoxytryptamine, MEL), its kynurenic (N1-acetyl-N2-formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to N-phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.

Abstract Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady‐state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady‐state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady‐state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude‐related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n = 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n = 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady‐state measurements of resting ventilation (V̇I; L/min), pressure of end‐tidal (PET)CO2 (Torr), and peripheral oxygen saturation (SpO2; %) were measured. A stimulus index (SI; PETCO2/SpO2) was calculated, and SSCD was calculated by indexing V̇I against SI. We found that (a) both V̇I and SSCD increased with ascent to 4240 m (day seven; V̇I: +39%, p

Background: Major League Baseball (MLB) was among the first professional team sports leagues to resume play in the United States after public health measures related to the appearance of coronavirus disease 2019 caused interruptions to preseason training and major alterations to regular season play. There was a high level of concern that these athletes were ill-prepared for competition and would experience an increased risk of injury under the restricted play rules. Methods: The data in our study were compiled using publicly accessible records of players placed on injured lists from 2015 to 2020. These records came from 4 open access websites: rotoworld.com, fangraphs.com, foxsports.com, and spotrac.com. All injuries were confirmed using the transaction database found on the official MLB website (mlb.com). Results: A greater proportion of pitchers were injured during the first 30 days of the 2020 season compared to the first 30 days of any of the 5 prior seasons (29.74% vs. 11.72%, n=2190, P

Researchers in science education lacks valid and reliable instruments to assess students' "disciplinary" and "epistemic" reading of scientific texts. The main purpose of this study was to develop and validate a Reading in Science Holistic Assessment (RISHA) to assess students' holistic reading of scientific texts. RISHA measures students' content, procedural, and epistemic domains of reading two texts, one history-of-science text and another socio-scientific text. The initial 24-item RISHA was administered to 161 Grade 9 students from 3 schools. The multidimensional Rasch partial credit model was used to analyze the reliability and validity of RISHA. All items demonstrated good fit and reliability. According to logit scores generated for each domain in Rasch analysis, students in our study performed better in content domain and less well in the epistemic domain. Students also performed significantly better in the epistemic domain of the socio-scientific text than in the history-of-science text. RISHA provides accurate measures in various domains of reading scientific texts and various contexts of scientific texts. We propose that RISHA could potentially be applied to studying the effect of reading-science intervention or predictors of students' performance in each domain of reading scientific texts.

ChatGPT becomes a prominent tool for students' learning of science when students "read" its scientific texts. Students read to learn about climate change misinformation using ChatGPT, while they develop critical awareness of the content, linguistic features as well as nature of AI and science to comprehend these texts. In this exploratory study, we investigated students' reading performance in comprehending two ChatGPT-generated socio-scientific texts, with one focusing on cognitive-epistemic aspects of climate science and another one focusing on social-institutional aspects of climate science. We theorized such reading of ChatGPT-generated outputs as encompassing the content-interpretation, genre-reasoning and epistemic-evaluation domains. Combining Rasch partial-credit model and qualitative analysis, we explored and investigated how a total of 117 junior secondary students (grades 8 to 9) read such texts. Moreover, we also examined how 55 students' holistic reading of socio-scientific texts on climate change in a ChatGPT scenario changes after a reading-science intervention. Our findings indicate that the content-interpretation was the easiest while the epistemic-evaluation domains were the most difficult. Interestingly, after the reading-science intervention, many students developed their tentative view on nature of science when they evaluated ChatGPT's claims; while a small increase in number of students discussed reliability and non-epistemic nature of AI when they evaluated ChatGPT's claims in relation to climate change. The findings also drive a pedagogical model that improves students' holistic reading of socio-scientific texts generated by ChatGPT.

Perovskite single crystals are commonly grown in organic solvents, which require relatively high temperature condition. Here, the authors develop a low-temperature crystallisation strategy to grow CsPbBr3 single crystals in water with improved charge transport properties and stability.

Abstract Treatments for ‘superbug’ infections are the focus for innovative research, as drug resistance threatens human health and medical practices globally. In particular, Acinetobacter baumannii (Ab) infections are repeatedly reported as difficult to treat due to increasing antibiotic resistance. Therefore, there is increasing need to identify novel targets in the development of different antimicrobials. Of particular interest is fatty acid synthesis, vital for the formation of phospholipids, lipopolysaccharides/lipooligosaccharides, and lipoproteins of Gram-negative envelopes. The bacterial type II fatty acid synthesis (FASII) pathway is an attractive target for the development of inhibitors and is particularly favourable due to the differences from mammalian type I fatty acid synthesis. Discrete enzymes in this pathway include two reductase enzymes: 3-oxoacyl-acyl carrier protein (ACP) reductase (FabG) and enoyl-ACP reductase (FabI). Here, we investigate annotated FabG homologs, finding a low-molecular weight 3-oxoacyl-ACP reductase, as the most likely FASII FabG candidate, and high-molecular weight 3-oxoacyl-ACP reductase (HMwFabG), showing differences in structure and coenzyme preference. To date, this is the second bacterial high-molecular weight FabG structurally characterized, following FabG4 from Mycobacterium. We show that ΔAbHMwfabG is impaired for growth in nutrient rich media and pellicle formation. We also modelled a third 3-oxoacyl-ACP reductase, which we annotated as AbSDR. Despite containing residues for catalysis and the ACP coordinating motif, biochemical analyses showed limited activity against an acetoacetyl-CoA substrate in vitro. Inhibitors designed to target FabG proteins and thus prevent fatty acid synthesis may provide a platform for use against multidrug-resistant pathogens including A. baumannii.

In developed countries, diabetes is the leading cause of chronic kidney disease (CKD) and accounts for 50% of incidence of end stage kidney disease. Despite declining prevalence of micro- and macrovascular complications, there are rising trends in renal replacement therapy in diabetes. Optimal glycemic control may reduce risk of progression of CKD and related death. However, assessing glycemic control in patients with advanced CKD and on dialysis (G4-5) can be challenging. Laboratory biomarkers, such as glycated haemoglobin (HbA1c), may be biased by abnormalities in blood haemoglobin, use of iron therapy and erythropoiesis-stimulating agents and chronic inflammation due to uraemia. Similarly, glycated albumin and fructosamine may be biased by abnormal protein turnover. Patients with advanced CKD exhibited heterogeneity in glycemic control ranging from severe insulin resistance to ‘burnt-out’ beta-cell function. They also had high risk of hypoglycaemia due to reduced renal gluconeogenesis, frequent use of insulin and dysregulation of counterregulatory hormones. Continuous glucose monitoring (CGM) systems measure glucose in interstitial fluid every few minutes and provide an alternative and more reliable method of glycemic assessment, including asymptomatic hypoglycaemia and hyperglycaemic excursions. Recent international guidelines recommended use of CGM-derived Glucose Management Index (GMI) in patients with advanced CKD although data are scarce in this population. Using CGM, patients with CKD were found to experience marked glycemic fluctuations with hypoglycemia due to loss of glucose and insulin during haemodialysis (HD) followed by hyperglycemia in the post-HD period. On the other hand, during peritoneal dialysis, patients may experience glycemic excursions with influx of glucose from dialysate solutions. These undesirable glucose exposure and variability may accelerate decline of residual renal function. Although CGM may improve the quality of glycemic monitoring and control in populations with CKD, further studies are needed to confirm the accuracy, optimal mode and frequency of CGM as well as their cost-effectiveness and user-acceptability in patients with advanced CKD and dialysis.

Abstract Background There is a growing interest in exploring the nature of communication in veterinary medicine and understanding how veterinary practitioners communicate with their clients and other professionals. This is the first integrative review of literature on veterinary communication. Applying the PRISMA model, the PubMed, PsychInfo and ERIC databases were searched using keywords such as ‘veterinary’, ‘vet’, ‘communication’ and ‘interaction’ for related articles published between 1 January 2000 and 31 December 2018. Results Keyword searching through the databases yielded 1572 related studies. Only 48 of these studies were included in our analysis after an in-depth review by two independent reviewers using the critical appraisal skills Programme frameworks with high inter-rater reliability (Cohen’s kappa coefficient κ > 0.8). The existing body of research on veterinary communication can be classified into three major areas: (a) client–veterinarian communication, (b) cross-disciplinary communication in a professional veterinarian team and (c) training of veterinary communication skills. This review details the complexity and heterogeneity of agenda in the field of veterinary communication. The included studies indicate that veterinary practitioners are not equipped with specific communication skills to address different agendas in veterinary communication. The veterinary curriculum should include a component on communication training that can help veterinary students acquire necessary communication skills that allow them to effectively communicate with clients and other professionals Conclusion This review detailed the complexity of agendas in the field of veterinary communication. The results indicate that veterinary practitioners can further benefit from training on specific communication skills that address the agendas found in veterinary communication research. Furthermore, the veterinary curriculum should include a component on communication training that equips veterinary students with the necessary communication skills that allow them to effectively communicate with different stakeholders such as clients and colleagues with and across the field of veterinary science.

Abstract Background In metabolically stable horses, alpha‐2‐agonists suppress insulin secretion with transient hyperglycemia and rebound hyperinsulinemia. In horses with insulin dysregulation (ID), the effect of alpha‐2‐agonists has not been investigated; however, both the alpha‐2‐agonist‐induced suppression of insulin secretion and rebound hyperinsulinemia could have clinical relevance. Hypothesis/Objectives In horses with ID, alpha‐2‐agonists will alter insulin and glucose dynamics. Animals Seven horses with ID and 7 control horses. Methods In this randomized crossover study, xylazine hydrochloride (1.1 mg/kg) or detomidine hydrochloride (30 μg/kg) were administered IV, and blood was collected for glucose and insulin concentrations at 0, 15, 30, 45, 60, 90, 120, 150, 180, and 300 minutes after administration. Horses received each drug in a random order with a 24‐hour washout period between drugs. Percent change in glucose and insulin concentrations was compared between groups, drugs, and over time with P

Abstract The high metabolic demand of cerebral tissue requires that local perfusion is tightly coupled with local metabolic rate (neurovascular coupling; NVC). During chronic altitude exposure, where individuals are exposed to the antagonistic cerebrovascular effects of hypoxia and hypocapnia, pH is maintained through renal compensation and NVC remains stable. However, the potential independent effect of acute hypocapnia and respiratory alkalosis on NVC remains to be determined. We hypothesized that acute steady‐state hypocapnia via voluntary hyperventilation would attenuate the magnitude of NVC. We recruited 17 healthy participants and insonated the posterior cerebral artery (PCA) with transcranial Doppler ultrasound. NVC was elicited using a standardized strobe light stimulus (6 Hz; 5 × 30 s on/off) where absolute delta responses from baseline (BL) in peak, mean, and total area under the curve (tAUC) were quantified. From a BL end‐tidal (PET)CO2 level of 36.7 ± 3.2 Torr, participants were coached to hyperventilate to reach steady‐state hypocapnic steps of Δ‐5 Torr (31.6 ± 3.9) and Δ‐10 Torr (26.0 ± 4.0; p

Antimicrobial resistance is an emerging global health crisis. Consequently, we have a critical need to prolong our current arsenal of antibiotics, in addition to the development of novel treatment options.

Acinetobacter baumannii

Abstract Background Diseases associated with insulin dysregulation (ID), such as equine metabolic syndrome and pituitary pars intermedia dysfunction, are of interest to practitioners because of their association with laminitis. Accurate insulin concentration assessment is critical in diagnosing and managing these diseases. Hypothesis/Objectives To determine the effect of time, temperature, and collection tube type on insulin concentrations in horses at risk of ID. Animals Eight adult horses with body condition score >6/9. Methods In this prospective study, subjects underwent an infeed oral glucose test 2 hours before blood collection. Blood samples were divided into ethylenediaminetetraacetic acid, heparinized, or serum tubes and stored at 4 or 20°C. Tubes were centrifuged and analyzed for insulin by a chemiluminescent assay over 8 days. Changes in insulin concentrations were compared with a linear mixed effects model. Results An overall effect of time, tube type and temperature was identified (P = .01, P = 0.001, and P = 0.001, respectively). Serum and heparinized samples had similar concentrations for 3 days at 20°C and 8 days at 4°C; however, after 3 days at 20°C, heparinized samples had significantly higher insulin concentrations (P = .004, P = .03, and P = .03 on consecutive days). Ethylenediaminetetraacetic acid samples had significantly lower insulin concentrations regardless of time and temperature (P = .001 for all comparisons). Conclusions and Clinical Importance These results suggest an ideal protocol to determine insulin concentrations involves using serum or heparinized samples with analysis occurring within 3 days at 20°C or 8 days at 4°C.

Abstract Ligand and strain effects can tune the adsorption energy of key reaction intermediates on a catalyst surface to speed up rate‐limiting steps of the reaction. As novel fields like high‐entropy alloys emerge, understanding these effects on the atomic structure level is paramount: What atoms near the binding site determine the reactivity of the alloy surface? By statistical analysis of 2000 density functional theory calculations and subsequent host/guest calculations, it is shown that three atomic positions in the third layer of an fcc(111) metallic structure fourth‐nearest to the adsorption site display significantly increased influence on reactivity over any second or third nearest atomic positions. Subsequently observed in multiple facets and host metals, the effect cannot be explained simply through the d‐band model or a valence configuration model but rather by favorable directions of interaction determined by lattice geometry and the valence difference between host and guest elements. These results advance the general understanding of how the electronic interaction of different elements affect adsorbate–surface interactions and will contribute to design principles for rational catalyst discovery of better, more stable and energy efficient catalysts to be employed in energy conversion, fuel cell technologies, and industrial processes.

Context: Weight loss is known to improve health, however the influence of variability in body weight around the overall trajectory on these outcomes is unknown. Few studies have measured body weight frequently enough to accurately estimate the variability component. Objective: To investigate the association of 12-month weight variability and concurrent weight change with changes in health markers and body composition. Methods: This study was a secondary analysis of the NoHoW trial, a 2 × 2 factorial randomised controlled trial promoting evidence-based behaviour change for weight loss maintenance. Outcome measurements related to cardiometabolic health and body composition were taken at 0, 6 and 12 months. Participants were provided with Wi-Fi connected smart scales (Fitbit Aria 2) and asked to self-weigh regularly over this period. Associations of weight variability and weight change with change in outcomes were investigated using multiple linear regression with multiple levels of adjustment in 955 participants. Results: Twelve models were generated for each health marker. Associations between weight variability and changes in health markers were inconsistent between models and showed no evidence of a consistent relationship, with all effects explaining

The effect of different leaving groups on the substitution versus elimination outcomes with C-5 d-glucose derivatives was investigated. The stereochemical configurations of 3-O-benzyl-1,2-O-isopropylidene-5-O-methanesulfonyl-6-O-triphenylmethyl-α-d-glucofuranose, C36H38O8S (3) [systematic name: 1-[(3aR,5R,6S,6aR)-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-(trityloxy)ethyl methanesulfonate], a stable intermediate, and 5-azido-3-O-benzyl-5-deoxy-1,2-O-isopropylidene-6-O-triphenylmethyl-β-l-idofuranose, C35H35N3O5 (4) [systematic name: (3aR,5S,6S,6aR)-5-[1-azido-2-(trityloxy)ethyl]-6-benzyloxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxole], a substitution product, were examined and the inversion of configuration for the azido group on C-5 in 4 was confirmed. The absolute structures of the molecules in the crystals of both compounds were confirmed by resonant scattering. In the crystal of 3, neighbouring molecules are linked by C—H...O hydrogen bonds, forming chains along the b-axis direction. The chains are linked by C—H...π interactions, forming layers parallel to the ab plane. In the crystal of 4, molecules are also linked by C—H...O hydrogen bonds, forming this time helices along the a-axis direction. The helices are linked by a number of C—H...π interactions, forming a supramolecular framework.

Although optogenetic techniques have proven to be invaluable for manipulating and understanding complex neural dynamics over the past decade, they still face practical and translational challenges in targeting networks involving multiple, large, or difficult-to-illuminate areas of the brain. We utilized inhibitory luminopsins to simultaneously inhibit the dentate gyrus and anterior nucleus of the thalamus of the rat brain in a hardware-independent and cell-type specific manner. This approach was more effective at suppressing behavioral seizures than inhibition of the individual structures in a rat model of epilepsy. In addition to elucidating mechanisms of seizure suppression never directly demonstrated before, this work also illustrates how precise multi-focal control of pathological circuits can be advantageous for the treatment and understanding of disorders involving broad neural circuits such as epilepsy.

Extracts of the mantle and viscera of the Indo-Pacific nudibranchs Goniobranchus aureopurpureus and Goniobranchus sp. 1 afforded 11 new diterpenoids (1–11), all of which possess a tetracyclic spongian-16-one scaffold with extensive oxidation at C-6, C-7, C-11, C-12, C-13, and/or C-20. The structures and relative configuration were investigated by NMR experiments, while X-ray crystallography provided the absolute configuration of 1, including a 2′S configuration for the 2-methylbutanoate substituent located at C-7. Dissection of animal tissue revealed that the mantle and viscera tissues differed in their metabolite composition with diterpenes 1–11 present in the mantle tissue of the two nudibranch species.

Background: Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR . Methods: This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR . The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry. Results: Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively. Conclusions: Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival.

In classrooms worldwide, the use of English to teach science subjects is becoming increasingly common. There is an increasing number of English-as-a-second/foreign-language learners studying science in English. This review examines 66 empirical studies on this topic published from 2000 to 2021. We critically review and synthesise evidence of the language challenges faced by teachers and students in secondary and tertiary English medium instruction (EMI) science courses, as well as proposed coping strategies. By adopting a multidisciplinary approach, we examine our findings from three fields of research: science education, language policy and applied linguistics. Our study extends EMI research by combining language learning and canonical content learning. Our synthesis of previous findings enhances understanding of content teaching in a second/foreign language in language immersion classrooms (e.g. content and language integrated learning, content-based instruction) and provides evidence-based pedagogical suggestions for enhancing EMI science teachers' instructional practices worldwide.

Neurovascular coupling (NVC) is the temporal link between neuronal metabolic activity and regional cerebral blood flow (CBF), supporting adequate delivery of nutrients. Exposure to high altitude (HA) imposes several stressors, including hypoxia and hypocapnia, which modulate cerebrovascular tone in an antagonistic fashion. Whether these contrasting stressors and subsequent adaptations affect NVC during incremental ascent to HA is unclear. The aim of this study was to assess whether incremental ascent to HA influences the NVC response. Given that CBF is sensitive to changes in arterial blood gasses, in particular PaCO2, we hypothesized that the vasoconstrictive effect of hypocapnia during ascent would decrease the NVC response. 10 healthy study participants (21.7 ± 1.3 years, 23.57 ± 2.00 kg/m2, mean ± SD) were recruited as part of a research expedition to HA in the Nepal Himalaya. Resting posterior cerebral artery velocity (PCAv), arterial blood gasses (PaO2, SaO2, PaCO2, [HCO3-], base excess and arterial blood pH) and NVC response of the PCA were measured at four pre-determined locations: Calgary/Kathmandu (1045/1400 m, control), Namche (3440 m), Deboche (3820 m) and Pheriche (4240 m). PCAv was measured using transcranial Doppler ultrasound. Arterial blood draws were taken from the radial artery and analyzed using a portable blood gas/electrolyte analyzer. NVC was determined in response to visual stimulation (VS; Strobe light; 6 Hz; 30 s on/off × 3 trials). The NVC response was averaged across three VS trials at each location. PaO2, SaO2, and PaCO2 were each significantly decreased at 3440, 3820, and 4240 m. No significant differences were found for pH at HA (P > 0.05) due to significant reductions in [HCO3-] (P < 0.043). As expected, incremental ascent to HA induced a state of hypoxic hypocapnia, whereas normal arterial pH was maintained due to renal compensation. NVC was quantified as the delta (Δ) PCAv from baseline for mean PCAv, peak PCAv and total area under the curve (ΔPCAv tAUC) during VS. No significant differences were found for Δmean, Δpeak or ΔPCAv tAUC between locations (P > 0.05). NVC remains remarkably intact during incremental ascent to HA in healthy acclimatized individuals. Despite the array of superimposed stressors associated with ascent to HA, CBF and NVC regulation may be preserved coincident with arterial pH maintenance during acclimatization.

Social sciences research about Suriname is euro-centric. It is dominated by the Dutch and evolved in the context of academic colonialism. From the Surinamese point of view, this situation is undesired. Some lessons can be learned from others, e.g. South East Asian and New Zealand/Maori scientific communities. In order to decolonize research it is suggested that the Surinamese social scientists community is strengthened and that cooperation with institutions in the South-American and Caribbean region is intensified. To achieve sustainability in a regional context concerted action of social scientists and academic institutions is required. The focus in this article is on cooperation with Brazil, the Southern neighbor of Suriname and a leading nation in the region. Referring to common factors in history and current social developments in Suriname and Brazil, it is suggested that the cooperation that started in the last decades of the 20th century is intensified.

Platinum nanomaterials provide an excellent catalytic activity for diverse applications and given its high cost, platinum alloys and bi-metallic nanomaterials with transition metals are appealing for low cost and catalytic specificity. Here the synthesis of hierarchically porous Pt−Cu macrobeams and macrotubes templated from Magnus’s salt derivative needles is demonstrated. The metal composition was controlled through the combination of [PtCl4]2− with [Pt(NH3)4]2+ and [Cu(NH3)4]2+ ions in different ratios to form salt needle templates. Polycrystalline Pt−Cu porous macrotubes and macrobeams 10’ s−100’ s μm long with square cross-sections were formed through chemical reduction with dimethylamine borane (DMAB) and NaBH4, respectively. Specific capacitance as high as 20.7 F/g was demonstrated with cyclic voltammetry. For macrotubes and macrobeams synthesized from Pt2−:Pt2+:Cu2+ salt ratios of 1:1:0, 2:1:1, 3:1:2, and 1:0:1, DMAB reduced 3:1:2 macrotubes demonstrated the highest ethanol oxidation peak currents of 12.0 A/g at 0.5 mV/s and is attributed to the combination of a highly porous structure and platinum enriched surface. Salt templates with electrochemical reduction are suggested as a rapid, scalable, and tunable platform to achieve a wide range of 3-dimensional porous metal, alloy, and multi-metallic nanomaterials for catalysis, sensor, and energy storage applications.

A number of linear coordination polymers have been assembled from lanthanide cations (Ln3+) and cucurbit[7]uril (Q[7]) in the presence of [CuCl4]2−or [CoCl4]2− anions acting as inorganic structure inducers in HCl solution. X-ray diffraction analysis has revealed that they form three groups of isomorphous structures. Generally, the complexes of Q[7] with light lanthanide cations (those with atomic number below that of neodymium (Nd3+)) are in one group. The other two groups, in which the lanthanide cation has atomic number greater than that of europium (Eu3+), seem to follow no obvious rule. For example, the complexes of Q[7] with Eu3+ and Gd3+cations are in the second group in the presence of [CuCl4]2− anions, while they are in the third group in the presence of [CoCl4]2− anions. However, whatever group a given complex belongs to, they all show a common honeycomb-patterned supramolecular assembly, in which [CuCl4]2−or [CoCl4]2− anions form a honeycomb structure. The Ln3+ cations then coordinate to neighboring Q[7] molecules to form 1D coordination polymers that are inserted into the channels of the honeycomb framework, such that each individual coordination polymer is surrounded by [CuCl4]2−or [CoCl4]2− anions.

Em 22 pacientes com sorologia positiva para o vírus da imunodeficiência humana, com ou sem síndrome da imunodeficiência adquirida, dos quais 7 com meningoencefalite toxoplásmica e 15 com meningoencefalite chagásica associadas, procuraram-se dados diferenciais, entre as duas encefalopatias, tanto à anatomia patológica quanto à tomografia computadorizada do crânio. Os resultados observados e os dados da literatura nos permitiram concluir que enquanto na meningoencefalite necrosante focal por Toxoplasma gondii o acometimento dos núcleos da base é freqüente, na meningoencefalite necrosante focal causada pelo Trypanosoma cruzi, lesões dessas estruturas parecem não ocorrer ou ser excepcionais. De outro lado, o acometimento da substância branca parece nitidamente maior na meningoencefalite chagásica que na meningoencefalite toxoplásmica, ao passo que o parasitismo e a hemorragia do tecido nervoso, bem como as lesões das bainhas de mielina são mais freqüentes e intensos na meningoencefalite causada pelo Trypanosoma cruzi que naquela por Toxoplasma.

In the title complex, [Cu(C13H11N2O)(N3)], the CuII cation is four-coordinated by an N2O donor set of the tridentate Schiff base ligand and by the terminal N atom of the azide anion, forming a slightly distorted square-planar configuration.

Background: Constructing knowledge through collaborative practical work is a complex process and involves the use of multiple modalities by group members. In practical work sessions, students often manipulate visual objects or textual materials but do not develop their scientific ideas. Purpose: This study illustrates (a) the challenges that science students face when they create thematic patterns in a laboratory class and (b) characterises the processes of how students make meaning of practical work activities. Sample: Drawing from a video database, we chose to investigate an 80-min chemistry lesson with eight Year 10 students who were unpacking the complex ideas behind practical work. This lesson episode was transcribed multimodally, with snapshots of the pictures of students' actions and gestures. Methods: This study adopts a case-study approach. A multimodal discourse analysis approach was taken to examine the classroom discourse of the students when they were determining the strength of acids and alkalis through electroconductivity. Results: We identified various challenges when students integrated gestures, pictures and verbal discourse during the practical work section. These challenges include those when students realise textual and visual modes and those when students associate components of apparatus into a system of functional set-up. Moreover, students cannot construct thematic patterns because they reorient their focus from the domain of ideas to the domain of objects and observables. The study recorded a number of strategies that students use to overcome these challenges that impede their meaning-making. Conclusion: The findings of this study contribute to the literature by identifying the challenges and strategies faced by students when they were connecting the scientific ideas with the practical work. When science education researchers advocate an inquiry oriented approach, they should provide ample scaffolds for these multimodal challenges.

In the title compound, (C24H20As)2[Co2(C6H6NO6)2(OH)2]·8H2O, the CoIII atom in the binuclear centrosymmetric anion is octahedrally surrounded by one N atom and three O atoms of the tetradentate nitrilotriacetate ligand and two μ-hydroxide ligands. The crystal packing is controlled by C—H...O and O—H...O hydrogen-bonding interactions. The crystal employed in this study proved to be a two-component twin around (0overline 11).