Search

Refractive index (RI) detection using backscatter interferometry (BSI) enables universal detection in capillary electrophoresis (CE). BSI detection is a versatile on-capillary approach that is easily integrated with capillary or microfluidic channels, straightforward to miniaturize, and inexpensive. The focused BSI light source can also double as the excitation source for fluorescence, enabling simultaneous universal (BSI) and specific (fluorescence) signals from the same detection volume. To improve BSI detection and expand orthogonal content, we integrate photothermal absorption with BSI detection. Nonradiative relaxation of an excited analyte releases heat into the surroundings, which modifies both the local RI and conductivity (viscosity) of the analyte zone. We recently showed that the BSI signal is sensitive to both RI and conductivity, which makes photothermal absorption a promising route to signal enhancement. Here, we use coaxially delivered BSI and photothermal absorption beams to characterize BSI, photothermal BSI, and fluorescence detection using the separation of test samples. We show that photothermal absorption leads to 3 orders of magnitude improvement in BSI detection limits at the powers studied and provides new opportunities for studying binding interactions with CE.

Deep-sea hydrothermal systems at slow/ultraslow-spreading mid-ocean ridges are often located within ultramafic rocks that are part of oceanic core complexes. These complexes contain lower-crustal and mantle sections exhumed due to detachment faulting. Hydrothermal circulation in these environments leads to massive sulfide deposits, hydration of oceanic lithosphere and conditions resembling early Earth’s life origin. However, the relationship between hydrothermal pathways in these environments and crustal and mantle lithologies, faulting, magmatism, serpentinization and alteration is poorly understood. Here we present seismic models of a Mid-Atlantic Ridge core complex and its ultramafic-hosted hydrothermal system derived from full waveform inversion of controlled-source seismic data and from local earthquake tomography. The models and derived rock properties reveal high-permeability channels within serpentinized peridotite along the flanks of the core complex. These channels converge beneath active and fossil hydrothermal fields and are diverted around mechanically strong, impermeable shallow mafic intrusions (2–3 km wide, ~1 km thick), causing hydrothermal outflow and the formation of massive sulfide deposits around the intrusions’ edges. These mafic intrusions also act as lids that limit fluid downflow—and thus serpentinization—in the centre of the core complex. Our results demonstrate that hydrothermal flow in ultramafic settings is controlled by lithology contacts, with mafic intrusions modulating hydrothermal pathways and extent of mantle serpentinization at depth.

Degradation of estuarine water quality during the Anthropocene has largely resulted from discharges of nutrients leading to eutrophication. Recently, upstream management practices have led to comparatively reduced nutrient input into estuaries. Concurrently, climate cycles and impacts associated with anthropogenic climate warming can affect the long‐term conditions observed within estuaries. Using long‐term monitoring data from adjacent southeastern U.S. estuaries, we show that decadal‐scale trends in nutrient concentrations and phytoplankton standing stock differ between the two connected systems. These contrasting trends appear to result from differences in oceanic influence, the extent of adjacent vegetated marsh, watershed size, and upstream degradation. In the minimally impacted, ocean‐dominated North Inlet estuary, we document increasing ammonium and chlorophyll a(Chl a), while in the adjacent, river‐dominated Winyah Bay, ammonium, and Chl aconcentrations are more variable but do not appear to have increased over the same time period. Surprisingly, total nitrogen exhibits the opposite pattern: temporal stability in North Inlet but increasing in Winyah Bay. We hypothesize that sea level rise associated with climate change has driven a complex set of interactions between salt marsh porewaters and tidal pumping, leading to the spillover of nutrients from salt marshes into tidal creeks in North Inlet. In Winyah Bay, this mechanism is less evident as a driver of ammonium concentrations, likely due to the outsized effect of watershed nutrient input and the narrow fringing marsh platform. The degree to which this mechanism operates in other estuaries, which vary in tidal range, the extent of vegetated marsh, watershed size, and degree of anthropogenic degradation warrants further study.

Research on animal–microbiota interactions has become a central topic in biological sciences because of its relevance to basic eco-evolutionary processes and applied questions in agriculture and health. However, animal hosts and their associated microbial communities are still seldom studied in a systemic fashion. Hologenomics, the integrated study of the genetic features of a eukaryotic host alongside that of its associated microbes, is becoming a feasible — yet still underexploited — approach that overcomes this limitation. Acknowledging the biological and genetic properties of both hosts and microbes, along with the advantages and disadvantages of implemented techniques, is essential for designing optimal studies that enable some of the major questions in biology to be addressed.

Microbes that thrive in premise plumbing can have potentially important effects on human health. Yet, how and why plumbing-associated microbial communities vary across broad spatial scales remain undetermined. We characterized the bacterial communities in 496 showerheads collected from across the continental United States. The overall community structure, determined by 16S rRNA gene amplicon sequencing, revealed high levels of bacterial diversity. Although a large fraction of the observed variation in community composition could not be explained, differences in bacterial community composition were associated with water supply (private well water vs public municipal water), water source (groundwater vs surface water), and associated differences in water chemistry (pH and chlorine). Most notably, showerheads in homes supplied with public water had higher abundances of Blastomonas, Mycobacterium, and Porphyrobacter, while Pseudorhodoplanes, Novosphingobium, and Nitrospirawere more abundant in those receiving private well water. We conducted shotgun metagenomic analyses on 92 of these samples to assess differences in genomic attributes. Public water-sourced showerheads had communities enriched in genes related to lipid and xenobiotic metabolisms, virulence factors, and antibiotic resistance. In contrast, genes associated with oxidative stress and membrane transporters were over-represented in communities from private well water-sourced showerheads compared to those supplied by public water systems. These results highlight the broad diversity of bacteria found in premise plumbing across the United States and the role of the water source and treatment in shaping the microbial community structure and functional potential.

AimsSpinal deformity surgery carries the risk of neurological injury. Neurophysiological monitoring allows early identification of intraoperative cord injury which enables early intervention resulting in a better prognosis. Although multimodal monitoring is the ideal, resource constraints make surgeon-directed intraoperative transcranial motor evoked potential (TcMEP) monitoring a useful compromise. Our experience using surgeon-directed TcMEP is presented in terms of viability, safety, and efficacy.MethodsWe carried out a retrospective review of a single surgeon’s prospectively maintained database of cases in which TcMEP monitoring had been used between 2010 and 2017. The upper limbs were used as the control. A true alert was recorded when there was a 50% or more loss of amplitude from the lower limbs with maintained upper limb signals. Patients with true alerts were identified and their case history analyzed.ResultsOf the 299 cases reviewed, 279 (93.3%) had acceptable traces throughout and awoke with normal clinical neurological function. No patient with normal traces had a postoperative clinical neurological deficit. True alerts occurred in 20 cases (6.7%). The diagnoses of the alert group included nine cases of adolescent idiopathic scoliosis (AIS) (45%) and six of congenital scoliosis (30%). The incidence of deterioration based on diagnosis was 9/153 (6%) for AIS, 6/30 (20%) for congenital scoliosis, and 2/16 (12.5%) for spinal tuberculosis. Deterioration was much more common in congenital scoliosis than in AIS (p = 0.020). Overall, 65% of alerts occurred during rod instrumentation: 15% occurred during decompression of the internal apex in vertebral column resection surgery. Four alert cases (20%) awoke with clinically detectable neurological compromise.ConclusionSurgeon-directed TcMEP monitoring has a 100% negative predictive value and allows early identification of physiological cord distress, thereby enabling immediate intervention. In resource constrained environments, surgeon-directed TcMEP is a viable and effective method of intraoperative spinal cord monitoring.Level of evidence: IIICite this article: Bone Joint J2021;103-B(3):547–552.

High speed capillary electrophoresis (HSCE) combined with refractive index (RI) detection is developed for the rapid separation and detection of inorganic ions and amino acids. A mixture of three inorganic ions (K+, Na+, Li+) and eight amino acids (Lys, Arg, Ala, Gly, Val, Thr, Trp, Asp) are detected using back scatter interferometry (BSI), without the need for chemical modifications or contrast. A thin-walled separation capillary (50 μm i.d. by 80 μm o.d.) helps mitigate Joule heating at the high field strengths required for rapid separations. This, combined with a short 8 cm length-to-detector (10 cm total length), enables separations on the seconds time scale. Using a background electrolyte (BGE) of 4 M acetic acid (pH 1.6) and a field strength of 900 V cm−1, all 11 analytes are separated in less than 40 s. Moreover, peaks in the BSI signal arising from the sample injection and EOF, enable electrophoretic mobilities to readily be obtained from apparent mobilities. This leads to excellent repeatability, with analyte electrophoretic mobilities varying from 0.39 to 1.56 % RSD over eight consecutive separations. The universal detection of inorganic ions and amino acids without prior chemical modification or additives in the BGE is an advantage of refractive index detection. A disadvantage arises from modest detection limits. Here, however, we show that submicromolar detection is possible with careful thermostatting of the thin separation capillary. A series of electropherograms are used to quantify arginine concentrations from 700 nM to 500 μM, using 50 μM Li+as an internal standard. The resulting calibration curve leads to a calculated LOD of 376 nM and a LOQ of 1.76 μM. Diagnostically relevant amino acid panels are also separated, illustrating the potential for future applications in neurodegenerative and metabolic disease diagnostics. HSCE combined with BSI detection, therefore, is shown to be a rapid, sensitive, and universal approach for analyzing sample mixtures.

•The fosfomycin resistance gene FosA7was detected in Escherichia coliisolated from an urban environment.•Most of the bacterial isolates were recovered from the urban environment.•E. coliisolates predominantly clustered under phylogroups B1, B2 and D.•Antimicrobial resistance and virulence-associated plasmids pCoo, pB171, col(156) and pHN7A8 were identified in the subset.

Rising atmospheric [CO2] has been shown to impact plant primary metabolism and the severity of Fusariumhead blight (FHB) in wheat. In this study, we evaluated how changes in grain nutritional content due to growth at elevated [CO2] affected Fusarium graminearumgrowth and mycotoxin production. Susceptible (Norm) and moderately resistant (Alsen) hard spring wheat grains that had been grown at ambient (400 ppm) or elevated [CO2] (800 ppm) were independently inoculated with two F. graminearumfungal strains, which produce the trichothecene mycotoxin, deoxynivalenol. Under higher [CO2], FHB-susceptible and moderately resistant wheat had disproportionate losses in protein and mineral contents, with Alsen being more severely impacted. Furthermore, the F. graminearumstrain 9F1 had increased mycotoxin biosynthesis in response to the loss of wheat nutritional content in Alsen. Our results demonstrate that future [CO2] conditions may provide a strain-specific pathogenic advantage on hosts, with greater losses in nutritional content.

High-speed capillary electrophoresis (HSCE) is implemented using a 10 cm total length fused-silica capillary (50 μm i.d., 80 μm o.d.) combined with refractive index (RI) detection using backscatter interferometry (BSI). The short capillary length reduces analysis time while the ultrathin wall (15 μm) efficiently dissipates heat from the separation channel, mitigating the deleterious effects of Joule heating. The separation capillary is mounted on a temperature-controlled heat sink that stabilizes the temperature to ±0.004 °C. This temperature stabilization improves separation efficiency and enhances RI detection. Ohm’s Law plots confirm the superior heat dissipation of the HSCE capillary compared to a similarly prepared conventional CE capillary (50 μm i.d., 363 μm o.d.). The speed and efficiency of HSCE combined with universal RI detection is illustrated through the separation of K+, Ba2+, Mg2+, Na+, Li+, and Tris+in approximately 30 s, with efficiencies greater than 500 000 plates/m. Run-to-run repeatability is explored using nine consecutive electrokinetic injections of a K+, Na+, and Li+mixture. The average migration times and %RSD for K+, Na+, and Li+were measured to be 22.04 s (1.59%), 26.81 s (1.38%), and 29.80 s (2.21%), respectively. Finally, we show that the BSI signal is sensitive to the separation voltage through the Kerr mechanism. This leads to peaks in the electropherogram from the injection process that are useful for precisely defining the start of each separation and quantifying the amount of sample injected onto the capillary.

Biodiesel is a renewable alternative diesel fuel made from plant oils, waste cooking greases, and animal fats. Its most common form is fatty acid methyl esters (FAME) from transesterification of lipids and methanol. Biodiesel has physical properties that compare well with conventional diesel fuel (petrodiesel). However, biodiesel has poor cold flow properties that must be monitored in cold weather. In this work, three correlation models are introduced that accurately calculate the cold filter plugging point (CFPP) of biodiesel. The models were developed using measured CFPP data from neat (unblended) biodiesel fuels and 24 binary biodiesel admixtures. The biodiesel fuels studied were from canola, palm, and soybean oils and yellow grease (CaME, PME, SME, and YGME). The solid–liquid equilibrium (SLE) model required accurate concentration, melting point (MP), and enthalpy of fusion (ΔHfus) data for each FAME species in the mixture. These data were used to infer the SLE phase transition temperature (TSLE) of the biodiesel mixtures. The TSLEdemonstrated a linear correlation (R2= 0.977) with CFPP. The MODified Empirical Correlation (MODEC) model (R2= 0.980) was obtained by analysis of (CFPP)−1versus ln(yC16) data where yC16is the mass fraction of methyl palmitate (MeC16). Finally, a second-order polynomial (R2= 0.982) was derived to calculate the CFPP from the modified long-chain saturation factor (LCSFmod), which was defined as a weighted average mass fraction of C16+ saturated-FAME (SFAME) in the mixtures. Weight factors were the MP of the corresponding SFAME species. Prevalidation tests on these models yielded good results for the calculated CFPP data. These performances exceeded those obtained by using 26 models from the scientific literature. The MODEC model performed better by a small margin than the other two new models. The main benefit of the MODEC model is that it requires just the yC16value instead of the complete compositional analyses needed to apply the SLE or LCSFmodmodels.

Study Design Retrospective cohort study.Objectives To identify predictors for early mortality following traumatic spinal cord injury (TSCI), as recognition of factors associated with early mortality is essential for public resource allocation and optimized acute care.Methods Retrospective Analysis of SCI patients admitted to the acute SCI ward from 2003 to 2022 was performed. Days elapsing from the date of injury to date of death established the survival time. Early mortality was defined as survival time ≤ 365 days. Multivariable logistic regression was used in modeling of early death following TSCI with age, gender, neurologic deficit, type of neurologic injury, ventilation status, and count of complications as covariates.Results Simple logistic regression indicated a significant association of early mortality with the number of complications (P< .0001), neurological deficit (P< .0001), complete neurological injury (P< .0001), ventilation status (P< .0001), and age group (P< .0003). After adjusting for other covariates, complete neurological injury (OR: 1.75, P< .0001), ventilation (OR: 2.80, P< .0001), and Age group (over 60 OR: 17.71, P< .0001) were significantly associated with early mortality. The multivariable model showed a good overall fit (Hosmer-Lemeshow P= .315; AUC 0.85).Conclusions Predictors of early mortality after TSCI are high complete spinal cord injury, age, number of complications, and the need for ventilation. Identification of high-risk patients is crucial to rationalize and improve acute care to potentially reduce mortality rates.

Biodiesel is a renewable alternative diesel fuel made from plant oils and animal fats. In the form of fatty acid methyl esters (FAMEs), it is usually obtained by transesterification of plant oil or animal fat with methanol in the presence of catalyst. Most of the fuel properties of biodiesel compare well with conventional diesel fuel (petrodiesel). One major disadvantage of biodiesel is its relatively poor cold flow properties which must be monitored during cold weather in moderate temperature climates. Two correlation models were developed to accurately calculate the cloud point (CP) of biodiesel. Both models were developed using measured CP data from binary admixtures of biodiesel fuels made from canola, palm, and soybean oils and yellow grease (CaME, PME, SME, and YGME). One model was based on solid–liquid equilibrium (SLE) thermodynamics in organic mixtures. This model required fatty acid concentrations (FA profile) and melting point (MP) and enthalpy of fusion (ΔHfus) data for each FAME species in the mixture. A high degree of correlation (R2= 0.949) was found between CP and the calculated mixture SLE transition temperature (TSLE). Regression analysis yielded an equation for calculating the CP of FAME mixtures. The modified empirical correlation (MODEC) model (R2= 0.893) was derived from (1/CP) versus ln(yC16) data where yC16is the mass fraction of methyl palmitate (MeC16) in the mixture. The performances of both models in predicting the CP of multicomponent FAME mixtures (biodiesel) were compared against results from six empirical correlation models from the literature. The SLE model performed best by having close to a 1:1 correlation between calculated (CP-calc) and measured CP data and the highest accuracy with respect to average deviations. Although the MODEC model did not exhibit a 1:1 correlation, it performed nearly as well as the SLE model in accurately calculating the CP of biodiesel. The main benefit of the MODEC model is that it requires only a measured yC16value vis-à-vis complete analysis of the FA profile in order to apply the SLE model.

Sodium triacetoxyborohydride (STAB) is a common reducing agent with potency that degrades over time and is not uniformly assigned. A simple assay based on an aldehyde reduction has been developed to determine the active borohydride content of this reagent. The HPLC assay yield of a salicylaldehyde reduction has been shown to accurately determine this potency and has been validated against the H2evolution method as well as yields obtained from a reductive amination. The use of these assay data to adjust the STAB charge as well to optimize a reductive amination has been demonstrated.

The authors conducted an experiment to determine the effects of gender, race, online video gaming experience, and the experimental context in which participants played the video game (online vs. offline vs. no information control) on avatar selection. The qualities of the avatar compared were based on eight objective differences between avatars and individuals: attractiveness, skin tone, height, girth chest size, waist size, hip size, and height. As predicted, those with online gaming experience selected avatars that were taller, thinner, and more attractive relative to their real selves than did participants with no prior online game experience. Non-white participants selected avatars with lighter skin-tones, whereas white participants selected avatars with darker skin-tones. Surprisingly, male participants selected shorter avatars than female counterparts did.

Study Design: Systematic review.Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, ultimately resulting in paralysis and death. The condition is considered to be caused by a complex interaction between environmental and genetic factors. Although vast genetic research has deciphered many of the molecular factors in ALS pathogenesis, the environmental factors have remained largely unknown. Recent evidence suggests that participation in certain types of sporting activities are associated with increased risk for ALS.Objective: To test the hypothesis that competitive sports at the highest level that involve repetitive concussive head and cervical spinal trauma result in an increased risk of ALS compared with the general population or nonsport controls.Methods: Electronic databases from inception to November 22, 2017 and reference lists of key articles were searched to identify studies meeting inclusion criteria.Results: Sixteen studies met the inclusion criteria. Sports assessed (professional or nonprofessional) included soccer (n = 5), American football (n = 2), basketball (n = 1), cycling (n = 1), marathon or triathlon (n = 1), skating (n = 1), and general sports not specified (n = 11). Soccer and American football were considered sports involving repetitive concussive head and cervical spinal trauma. Professional sports prone to repetitive concussive head and cervical spinal trauma were associated with substantially greater effects (pooled rate ratio [RR] 8.52, 95% CI 5.18-14.0) compared with (a) nonprofessional sports prone to repetitive concussive head and cervical spinal trauma (pooled RR 0.60, 95% CI 0.12-3.06); (b) professional sports not prone to repetitive head and neck trauma (pooled RR 1.35, 95% CI 0.67-2.71); or (c) nonprofessional sports not prone to repetitive concussive head and cervical spinal trauma (pooled RR 1.17, 95% CI 0.79-1.71).Conclusions: Our review suggests that increased susceptibility to ALS is significantly and independently associated with 2 factors: professional sports and sports prone to repetitive concussive head and cervical spinal trauma. Their combination resulted in an additive effect, further increasing this association to ALS.

Refractive index (RI) sensing in microfluidics has the advantage of universal detection, capable of sensing all species from simple monoatomic ions to complex proteins without external labels or additional contrast agents. Various forms of interferometry have been developed for RI sensing in microfluidics. In particular, backscatter interferometry (BSI) is easily implemented and well-suited for miniaturization. This is important for future applications in point-of-care or point-of-interest measurements, where the total analysis system needs to be easily deployed. The optical arrangement in BSI is similar to that used in optical pickup heads (OPHs), found in CD and DVD drives. This offers intriguing possibilities for repurposing OPHs for miniaturized RI detection in microfluidics. To explore the feasibility of this approach, commercially available OPHs are modified for RI detection in 75 μm i.d. (363 μm o.d.) fused silica capillaries. BSI interference patterns measured using a modified OPH positioned near the capillary are compared with simulations as a function of wavelength. Once characterized, the modified OPH is used to measure refractive index changes as sucrose solutions are injected through the 75 μm i.d. capillary. Signal level changes were recorded following the introduction of solutions ranging in concentration from 67 μM to 19.3 mM and the resulting calibration plot (67 μM to 4.8 mM) exhibited good linearity (R2= 0.9993). Finally, a modified OPH was used to detect the electrophoretic separation of Na+and Li+using RI detection. While the measurements reported here used modified OPHs that bypassed the built-in photodiode detector, eventually all on-board components could be utilized for a completely self-contained, inexpensive, universal detector for field deployable microfluidic applications.

The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

Study Design: Bibliometric review of the literature.Objective: This bibliometric analysis aims to give an overview of the most influential academic literature written on spinal tuberculosis.Methods: All databases included in the Thomson Reuters Web of Knowledge were searched for the most influential publications in spinal tuberculosis. The most cited articles published between 1950 and 2015, with the main focus on orthopedic surgery, were identified using a multistep approach, and a total of 100 articles were included. The publications were then analyzed in this bibliometric analysis.Results: The number of citations ranged from 243 to 36, with an average of 77.11. The articles were published in 34 different journals, and the studies were conducted in 20 different countries. The top 3 countries, India, the United States, and China, published a total of 51% (n = 51) of all articles. Low-burden countries produced 60% (n = 60) of all articles in our list. African centers produced only 4% (n = 4) of all included articles.Conclusions: Indian and Chinese researchers dominate evidence in spinal tuberculosis. Other areas with high disease burden, such as Africa, do not feature. Most publications are retrospective studies with a low level of evidence.

The bile salt export pump (BSEP) is expressed at the canalicular domain of hepatocytes, where it mediates the elimination of monovalent bile salts into the bile. Inhibition of BSEP is considered a susceptibility factor for drug-induced liver injury that often goes undetected during nonclinical testing. Although in vitro assays exist for screening BSEP inhibition, a reliable and specific method for confirming Bsep inhibition in vivo would be a valuable follow up to a BSEP screening strategy, helping to put a translatable context around in vitro inhibition data, incorporating processes such as metabolism, protein binding, and other exposure properties that are lacking in most in vitro BSEP models. Here, we describe studies in which methods of quantitative intravital microscopy were used to identify dose-dependent effects of two known BSEP/Bsep inhibitors, 2-[4-[4-(butylcarbamoyl)-2-[(2,4-dichlorophenyl)sulfonylamino]phenoxy]-3-methoxyphenyl]acetic acid (AMG-009) and bosentan, on hepatocellular transport of the fluorescent bile salts cholylglycyl amidofluorescein and cholyl-lysyl-fluorescein in rats. Results of these studies demonstrate that the intravital microscopy approach is capable of detecting Bsep inhibition at drug doses well below those found to increase serum bile acid levels, and also indicate that basolateral efflux transporters play a significant role in preventing cytosolic accumulation of bile acids under conditions of Bsep inhibition in rats. Studies of this kind can both improve our understanding of exposures needed to inhibit Bsep in vivo and provide unique insights into drug effects in ways that can improve our ability interpret animal studies for the prediction of human drug hepatotoxicity.

Scanning resonator microscopy (SRM) is a scanning probe technique that uses a small, optical resonator attached to the end of a conventional atomic force microscopy cantilever to simultaneously measure optical and topography properties of sample surfaces. In SRM, whispering gallery mode (WGM) resonances excited in the attached optical resonator shift in response to changes in surface refractive index (RI), providing a mechanism for mapping RI with high spatial resolution. In our initial report, the SRM tip was excited with a fixed excitation wavelength during sample scanning, which limits the approach. An improved method based on a wavelength modulation coupled with phase sensitive detection is reported here. This results in real-time characterization of WGM spectral shifts while eliminating complications arising from measurements based solely on signal intensity. This improved approach, combined with a modified tip design enabling integration of smaller resonators, is shown to enhance signal-to-noise and lead to sub-100 nm spatial resolution in the SRM optical image. The improved capabilities are demonstrated through measurements on thin dielectric and polymer films.

To test models of tectonic, magmatic, and hydrothermal processes along slow‐spreading mid‐ocean ridges, we analyzed seismic refraction data from the Mid‐Atlantic Ridge INtegrated Experiments at Rainbow (MARINER) seismic and geophysical mapping experiment. Centered at the Rainbow area of the Mid‐Atlantic Ridge (36°14'N), this study examines a section of ridge with volcanically active segments and a relatively amagmatic ridge offset that hosts the ultramafic Rainbow massif and its high‐temperature hydrothermal vent field. Tomographic images of the crust and upper mantle show segment‐scale variations in crustal structure, thickness, and the crust‐mantle transition, which forms a vertical gradient rather than a sharp boundary. There is little definitive evidence for large regions of sustained high temperatures and melt in the lower crust or upper mantle along the ridge axes, suggesting that melts rising from the mantle intrude as small intermittent magma bodies at crustal and subcrustal levels. The images reveal large rotated crustal blocks, which extend to mantle depths in some places, corresponding to off‐axis normal fault locations. Low velocities cap the Rainbow massif, suggesting an extensive near‐surface alteration zone due to low‐temperature fluid‐rock reactions. Within the interior of the massif, seismic images suggest a mixture of peridotite and gabbroic intrusions, with little serpentinization. Here diffuse microearthquake activity indicates a brittle deformation regime supporting a broad network of cracks. Beneath the Rainbow hydrothermal vent field, fluid circulation is largely driven by the heat of small cooling melt bodies intruded into the base of the massif and channeled by the crack network and shallow faults. We present tomographic images of the crust and upper mantle of the Mid‐Atlantic Ridge (Rainbow area) made from Pwave refraction dataAlong ridge segments, the crust is cold, brittle, and ~4‐5 km thick and probably forms by repeated injection of small melt bodiesRainbow massif is capped by cool, altered mantle rocks; the interior is hot and relatively unaltered and deforms in the brittle regime

Study Design: Retrospective, descriptive study.Objectives: Managing early surgical site infection following elective lumbar spine surgery remains a challenge with controversy regarding retention of instrumentation and bone graft. Wound closure may also pose considerable challenges. We aim to report on our method of managing deep surgical site infections complicating elective spine surgery with surgeon assembled deep vacuum dressings. Identification of causative organisms with their sensitivities was a secondary objective.Methods: Patients were identified from a prospectively maintained, single-surgeon database from 2003-2015. Patients who had an infective or trauma related diagnosis, cervical procedures, and were younger than 18 years were excluded. Records were reviewed to identify bacteriology, laboratory tests performed, antibiotics administered, and type and frequency of surgical management. One thousand two hundred twenty patients qualified for inclusion, with 19 identified as having developed acute wound sepsis.Results: All patients had surgical debridement on the day of presentation and the majority of wounds were managed with a vacuum dressing. In all but 1 patient was instrumentation retained. Specimens for culture were taken at each debridement and antibiotics changed accordingly. Patients received a minimum 6 weeks of antibiotics.Conclusions: The management of deep surgical site infection is labor intensive and frustrating for both surgeon and patient due to the unexpected prolonged admission. Management goals are identification and eradication of the causative organism with subsequent healing of the surgical wound. This process is enhanced with the use of negative-suction dressings made from theatre stock replaced at regular intervals and allows retention of bone graft and instrumentation in the majority of cases.

The 2021 IPCC report found that most studies show declining trends for the global diurnal temperature range (DTR) since the 1950s, decreasing mainly during 1960–1980. This issue is revisited here using an up‐to‐date in‐situ data set, Hadley Center Integrated Surface Database, constrained by rigorous station selection conditions. The global observed DTR trend was found to reverse during 1980–2021, increasing significantly at a rate of 0.091 ± 0.008°C decade−1. The trend was dominated by a faster rate of increasing daily maximum air temperature. This increasing observed trend in the past four decades was not fully captured in raw CMIP6 models, as models only partially capture the spatial patterns. With global CMIP6 outputs and regionally‐available observations, the global land DTR was then estimated, through emergent constraints, to be 0.063 ± 0.012°C decade−1. The study raises concern for risks of increasing DTR globally and provides new insights into global DTR assessment. In 2021, the IPCC reported a decrease in the near‐surface diurnal air temperature range (DTR) since the 1950s. However, using the in‐situ surface air temperature observations, the global DTR trend was found to reverse after the 1980s, as daily maximum air temperature increased faster than the daily minimum air temperature did between 1980 and 2021. The observed results for 1980–2014 were used to assess the historical simulations within CMIP6. Models generally depicted similar spatial variability as observed results but high variation existed between models. Most of the models did not capture the reversal of the global DTR trend and underestimated regional results. To narrow down the uncertainty and produce a complete global land DTR estimation, we applied the emergent constraint approach by combining observation data and model results. The global DTR trend from 1980 to 2014 was 0.063 ± 0.012°C decade−1. The constraining data was also used at a regional scale. It was shown that DTR trends for North America retained high uncertainty (−0.011 ± 0.026°C decade−1), while Europe and Asia showed reduced uncertainty with increasing DTR. The up‐to‐date Hadley Center Integrated Surface Database (HadISD) in‐situ data reveals a reversed global diurnal air temperature range (DTR) trend, increasing for 1980–2021The observed spatial patterns are partially captured but the reversal trends are not shown by CMIP6 modelsThe emergent constraint for CMIP6 models with HadISD estimates increasing DTR at the global scale The up‐to‐date Hadley Center Integrated Surface Database (HadISD) in‐situ data reveals a reversed global diurnal air temperature range (DTR) trend, increasing for 1980–2021 The observed spatial patterns are partially captured but the reversal trends are not shown by CMIP6 models The emergent constraint for CMIP6 models with HadISD estimates increasing DTR at the global scale

Radiological contamination of coastal habitats poses potential risk for native fauna, but the bioavailability of aqueous radium (Ra) and other dissolved metals to marine bivalves remains unclear. This study was the first to examine the tissue-specific disposition of aqueous 226Ra in a coastal mussel, specifically the Atlantic ribbed mussel Geukensia demissa. Most organ groups reached steady-state concentrations within 7 days during experimental exposure, with an average uptake rate constant of 0.0013 mL g–1d–1. When moved to Ra-free synthetic seawater, mussels rapidly eliminated aqueous 226Ra (average elimination rate constant 1.56 d–1). The biological half-life for aqueous 226Ra ranged from 8.9 h for the gills and labial palps to 15.4 h for the muscle. Although previous field studies have demonstrated notable 226Ra accumulation in the soft tissues of marine mussels and that, for freshwater mussels, tissue-incorporated 226Ra derives primarily from the aqueous phase, our tissue-specific bioconcentration factors (BCFs) were on the order of (8.3 ± 1.5) × 10–4indicating low accumulation potential of aqueous 226Ra in estuarine mussels. This suggests marine and estuarine mussels obtain 226Ra from an alternate route, such as particulate-sorbed Ra ingested during filter-feeding or from a contaminated food source.

•Rapid environmental change requires our understanding of large scale evolutionary trends.•Modern technology makes it easier to engage the public in the scientific process.•Recent insect-based citizen science has expanded our understanding of global trends.•Successful citizen science empowers the public to study life's diversity around them.

Study Design Systematic review.Objectives To determine the incidence of catastrophic cervical spine injuries (CCSIs) among elite athletes participating in contact team sports and whether the incidence varies depending on the use of protective gear or by player position.Methods Electronic databases and reference lists of key articles published from January 1, 2000, to January 29, 2016, were searched.Results Fourteen studies were included that reported CCSI in rugby (n?=?10), American football (n?=?3), and Irish hurling (n?=?1). Among Rugby Union players, incidence of CCSI was 4.1 per 100,000 player-hours. Among National Football League players, the CCSI rate was 0.6 per 100,000 player-exposures. At the collegiate level, the CCSI rate ranged from 1.1 to 4.7 per 100,000 player-years. Mixed populations of elite and recreational rugby players in four studies report a CCSI rate of 1.4 to 7.2 per 100,000 player-years. In this same population, the scrum accounted for 30 to 51% of total reported CCSIs in Rugby Union versus 0 to 4% in Rugby League. The tackle accounted for 29 to 39% of injuries in Rugby Union and 78 to 100% of injuries in Rugby League. Making a tackle was responsible for 29 to 80% of injuries in American football.Conclusion CCSIs are infrequent among elite athletes. There is insufficient evidence to determine the effect of protective gear (e.g., helmets, padding) on CCSI incidence. Scrum and tackle in rugby and tackling in American football account for the majority of CCSIs in each respective sport.

Recently, ruthenium-catalyzed isomerization–decarboxylation of fatty acids to give alkene mixtures was reported. When the substrate was oleic acid, the reaction yielded a mixture consisting of heptadecene isomers. In this work, we report the compositional analysis of the mixture obtained by triruthenium dodecacarbonyl catalyzed decarboxylation of oleic acid. Surprisingly, the most prominent single compound identified was heptadecane at approximately 18 wt %. A mixture of heptadecene isomers constituted the greatest percentage of the product (>75%), where all positional isomers were confirmed by GC–MS analysis of dimethyl disulfide derivatives of the product. Besides these components, minor amounts of alkyl aromatics, each with a total of 17 carbons atoms, among them undecyl benzene, were observed. Minor amounts of other compounds, such as shorter-chain hydrocarbons and polyunsaturated C17 compounds, were also observed. A reaction pathway to explain the existence of these products is proposed. Heptadecenes first cyclize to the observed alkyl aromatics under liberation of hydrogen with the formed hydrogen, then in turn hydrogenating some heptadecenes to heptadecane. Thus, triruthenium dodecacarbonyl is suggested to also promote dehydrogenation, aromatization, and hydrogenation under the present conditions. Since the product mixture consisted mainly of long-chain hydrocarbons, its properties regarding diesel fuel application were studied and compared to biodiesel and petroleum diesel. The cetane number (86.9) was high, but oxidative stability (3.4 h; EN 15751) and cold flow (cloud point −1 °C) would require improvement to meet fuel specifications. All other fuel properties were within the limits prescribed in the petrodiesel standards.

The biological diversity and composition of microorganisms influences both human health outcomes and ecological processes; therefore, understanding the factors that influence microbial biodiversity is key to creating healthy, functional landscapes in which to live. In general, biological diversity is predicted to be limited by habitat size, which for green areas is often reduced in cities, and by chronic disturbance (stress). These hypotheses have not previously been tested in microbial systems in direct comparison to macroorganisms. Here we analyzed bacterial, fungal and ant communities in small road medians (average area 0.0008?km2) and larger parks (average area 0.64?km2) across Manhattan (NYC). Bacterial species richness was not significantly different between medians and parks, but community composition was significantly distinct. In contrast, ant communities differed both in composition and richness with fewer ant species in medians than parks. Fungi showed no significant variation in composition or richness but had few shared taxa between habitats or sites. The diversity and composition of microbes appears less sensitive to habitat patchiness or urban stress than those of macroorganisms. Microbes and their associated ecosystem services and functions may be more resilient to the negative effects of urbanization than has been previously appreciated.

The biological diversity and composition of microorganisms influences both human health outcomes and ecological processes; therefore, understanding the factors that influence microbial biodiversity is key to creating healthy, functional landscapes in which to live. In general, biological diversity is predicted to be limited by habitat size, which for green areas is often reduced in cities, and by chronic disturbance (stress). These hypotheses have not previously been tested in microbial systems in direct comparison to macroorganisms. Here we analyzed bacterial, fungal and ant communities in small road medians (average area 0.0008 km2) and larger parks (average area 0.64 km2) across Manhattan (NYC). Bacterial species richness was not significantly different between medians and parks, but community composition was significantly distinct. In contrast, ant communities differed both in composition and richness with fewer ant species in medians than parks. Fungi showed no significant variation in composition or richness but had few shared taxa between habitats or sites. The diversity and composition of microbes appears less sensitive to habitat patchiness or urban stress than those of macroorganisms. Microbes and their associated ecosystem services and functions may be more resilient to the negative effects of urbanization than has been previously appreciated.

Traditional in vitro human liver cell culture models lose key hepatic functions such as metabolic activity during short-term culture. Advanced three-dimensional (3D) liver coculture platforms offer the potential for extended hepatocyte functionality and allow for the study of more complex biologic interactions, which can improve and refine human drug safety evaluations. Here, we use a perfusion flow 3D microreactor platform for the coculture of cryopreserved primary human hepatocytes and Kupffer cells to study the regulation of cytochrome P450 3A4 isoform (CYP3A4) activity by chronic interleukin 6 (IL-6)–mediated inflammation over 2 weeks. Hepatocyte cultures remained stable over 2 weeks, with consistent albumin production and basal IL-6 levels. Direct IL-6 stimulation that mimics an inflammatory state induced a dose-dependent suppression of CYP3A4 activity, an increase in C-reactive protein (CRP) secretion, and a decrease in shed soluble interleukin-6 receptor (IL-6R) levels, indicating expected hepatic IL-6 bioactivity. Tocilizumab, an anti-IL-6R monoclonal antibody used to treat rheumatoid arthritis, has been demonstrated clinically to impact small molecule drug pharmacokinetics by modulating cytochrome P450 enzyme activities, an effect not observed in traditional hepatic cultures. We have now recapitulated the clinical observation in a 3D bioreactor system. Tocilizumab was shown to desuppress CYP3A4 activity while reducing the CRP concentration after 72 hours in the continued presence of IL-6. This change in CYP3A4 activity decreased the half-life and area under the curve up to the last measurable concentration (AUClast) of the small molecule CYP3A4 substrate simvastatin hydroxy acid, measured before and after tocilizumab treatment. We conclude that next-generation in vitro liver culture platforms are well suited for these types of long-term treatment studies and show promise for improved drug safety assessment.

Western blotting is a ubiquitous tool used extensively in the clinical and research settings to identify proteins and characterize their levels. It has rapidly become a mainstay in research laboratories due to its specificity, low cost, and ease of use. The specificity arises from the orthogonal processes used to identify proteins. Samples are first separated based on size and then probed with antibodies specific for the protein of interest. This confirmatory approach helps avoid pitfalls associated with antibody cross-reactivity and specificity issues. While the technique has evolved since its inception, the last decade has witnessed a paradigm shift in western blotting technology. The introduction of capillary and microfluidic platforms has significantly decreased time and sample requirements while enabling high-throughput capabilities. These advances have enabled western analysis down to the single cell level in highly parallel formats, opening vast new opportunities for studying cellular heterogeneity. Recent innovations in microscale western blotting are surveyed, and the potential for enhancing detection using advances in label-free biosensing is briefly discussed.

•Urban development occurs across diverse background climates.•Evident shifts in insect communities across urbanization and background climate.•Insects have shared and unique responses to urbanization and background climate.•We develop a framework for exploring shared and unique features of insect responses.•We illustrate use of the framework drawing on patterns in insect macrophysiology.

Data from three co‐located wide‐angle ocean‐bottom seismograph experiments were used to make a new two‐dimensional tomographic image of the East Pacific Rise at 9°N. The upper half of the crustal magmatic system has a different seismic structure than the lower half, presumably corresponding with differences in melt storage and crustal cooling. The upper region is narrow (∼4.5 km wide at 2–3 km depth bsf) and estimated to contain higher melt fractions; the lower region broadens with depth and contains lower melt fractions. The shape of the system suggests steeply‐dipping isotherms and relatively stronger hydrothermal circulation in the upper gabbroic section of the crust, with moderately flattening isotherms and less circulation in the lower gabbroic section. Along mid‐ocean ridges two lithospheric plates separate, inducing mantle upwelling and pressure‐release melting. The melt buoyantly rises toward the surface where it enters a crustal magmatic system. Hydrothermal circulation and conductive heat loss cool the magmatic system and the melts solidify to form new oceanic crust. A seismological study is used to determine the size and internal structure of the crustal magmatic system, the amount of melt in the mantle as it enters the crust, and the final destination of the melt recorded by crustal thickness and crustal structure. A new seismic tomographic image of the East Pacific Rise reveals the average structure of the sub‐ridge magmatic systemThe upper half of the magmatic system is narrow, melt‐rich, and flanked by steeply‐dipping sub‐solidus isothermsThe lower half has lower melt fractions and widens with depth as isotherms begin to flatten A new seismic tomographic image of the East Pacific Rise reveals the average structure of the sub‐ridge magmatic system The upper half of the magmatic system is narrow, melt‐rich, and flanked by steeply‐dipping sub‐solidus isotherms The lower half has lower melt fractions and widens with depth as isotherms begin to flatten

Geodynamic simulations of the development of lattice preferred orientation in the flowing mantle are used to characterize the seismic anisotropy and shear wave splitting (SWS) patterns expected for the interaction of mantle plumes and lithospheric plates. Models predict that in the deeper part of the plume layer ponding beneath the plate, olivine aaxes tend to align perpendicular to the radially directed plume flow, forming a circular pattern reflecting circumferential stretching. In the shallower part of the plume layer, plate shear is more important and the aaxes tend toward the direction of plate motion. Predicted SWS over intraplate plumes reflects the asymmetric influence of plate shear with fast Swave polarization directions forming a pattern of nested U shapes that open in the direction opposing both plate motion and the parabolic shape often used to describe the flow lines of the plume. Predictions explain SWS observations around the Eifel hot spot with an eastward, not westward, moving Eurasian plate, consistent with global studies that require relatively slow net (westward) rotation of all of the plates. SWS at the Hawaiian hot spot can be explained by the effects of plume‐plate interaction, combined with fossil anisotropy in the Pacific lithosphere. In ridge‐centered plume models, the fast polarization directions angle diagonally toward the ridge axis when the plume is simulated as having low viscosity beneath the thermal lithosphere. Such a model better explains SWS observations in northeast Iceland than a model that incorporates a high‐viscosity layer due to dehydration of the shallow‐most upper mantle. Predicted seismic anisotropy of plumes relates variably to mantle flow and strainFast direction of S wave splitting predicted to be perpendicular to plume flowGeodynamic models of S wave splits at the Eifel, Hawaiian, and Iceland hot spots

The article focuses on the history of the U.S. Naval aviation as of 1986 and its 75th anniversary celebration. It says that 1986 was an important year in the Naval history wherein the Maritime Strategy was designed to defeat the Soviet Navy. It says that after celebrating its Naval Aviation's 75th year in 1989, the Berlin Wall fell down which means that the Cold War was over and that the U.S. and North Atlantic Treaty Organization (NATO) prevailed.

The present research explores the relationships between newspaper circulation size (small vs. large), blog post focus (national vs. local/state), and blog post topic (political vs. government) and whether reporters who blog produce posts that break with journalistic routines or include references to the author. Analysis of 960 blog posts from nine newspapers suggests that smaller newspapers were more likely to produce posts that break with journalistic routines and include self-references than larger newspapers. Posts that focused on national news were more likely to break with journalistic routines but were not more likely to include self-references. Posts about political news were more likely to both break with journalistic routines and to include self-references.

At the end of the dark ages, anatomy was taught as though everything that could be known was known. Scholars learned about what had been discovered rather than how to make discoveries. This was true even though the body (and the rest of biology) was very poorly understood. The renaissance eventually brought a revolution in how scholars (and graduate students) were trained and worked. This revolution never occurred in K–12 or university education such that we now teach young students in much the way that scholars were taught in the dark ages, we teach them what is already known rather than the process of knowing. Citizen science offers a way to change K–12 and university education and, in doing so, complete the renaissance. Here we offer an example of such an approach and call for change in the way students are taught science, change that is more possible than it has ever been and is, nonetheless, five hundred years delayed.