Monitoring the Evolution of Relative Product Populations at Early Times during a Photochemical Reaction.

Identifying multiple rival reaction products and transient species formed during ultrafast photochemical reactions and determining their time-evolving relative populations are key steps toward understanding and predicting photochemical outcomes. Yet, most contemporary ultrafast studies struggle with clearly identifying and quantifying competing molecular structures/species among the emerging reaction products. Here, we show that mega-electronvolt ultrafast electron diffraction in combination with ab initio molecular dynamics calculations offer a powerful route to determining time-resolved populations of the various isomeric products formed after UV (266 nm) excitation of the five-membered heterocyclic molecule 2(5H)-thiophenone. This strategy provides experimental validation of the predicted high (∼50%) yield of an episulfide isomer containing a strained three-membered ring within ∼1 ps of photoexcitation and highlights the rapidity of interconversion between the rival highly vibrationally excited photoproducts in their ground electronic state.

Photodissociation of dicarbon: How nature breaks an unusual multiple bond.

The dicarbon molecule (C2) is found in flames, comets, stars, and the diffuse interstellar medium. In comets, it is responsible for the green color of the coma, but it is not found in the tail. It has long been held to photodissociate in sunlight with a lifetime precluding observation in the tail, but the mechanism was not known. Here we directly observe photodissociation of C2 From the speed of the recoiling carbon atoms, a bond dissociation energy of 602.804(29) kJ·mol[Formula: see text] is determined, with an uncertainty comparable to its more experimentally accessible N2 and O2 counterparts. The value is within 0.03 kJ·mol-1 of high-level quantum theory. This work shows that, to break the quadruple bond of C2 using sunlight, the molecule must absorb two photons and undergo two "forbidden" transitions.

Drug-Induced dermatomyositis following COVID-19 vaccination.

Dermatomyositis (DM) is a multi-organ idiopathic inflammatory myopathy that presents with proximal symmetric muscle weakness accompanied by characteristic cutaneous findings. Most individuals present with skin manifestations prior to muscle involvement and its course can involve the blood vessels, joints, esophagus, and lungs and can be paraneoplastic, making a malignancy assessment imperative. Although its etiology is unknown, type I interferon appears to be a component in evoking the characteristic inflammatory response and patients with DM often have an increase in type I inducible genes. Suspected triggers for DM are environmental factors, drugs, viral infections, and vaccines. The association of DM with vaccination poses a new conundrum within the medical community as people continue to get vaccinated and boosted with SARS-CoV2 vaccines, though it is worth noting that the most common challenges arose as type I hypersensitivity reactions and new onset autoimmune disorders are rare. Presented here is a 53-year-old man who was diagnosed with DM after receiving the second dose of the Pfizer vaccine. His case highlights the importance of the potential onset of autoimmune diseases following the COVID-19 vaccine, a phenomenon that clinicians should be aware of as the discourse concerning the pandemic continues.

Arrest of mouse preterm labor until term delivery by combination therapy with atosiban and mundulone, a natural product with tocolytic efficacy.

There is a lack of FDA-approved tocolytics for the management of preterm labor (PL). In prior drug discovery efforts, we identified mundulone and mundulone acetate (MA) as inhibitors of in vitro intracellular Ca2+-regulated myometrial contractility. In this study, we probed the tocolytic potential of these compounds using human myometrial samples and a mouse model of preterm birth. In a phenotypic assay, mundulone displayed greater efficacy, while MA showed greater potency and uterine-selectivity in the inhibition of intracellular-Ca2+ mobilization. Cell viability assays revealed that MA was significantly less cytotoxic. Organ bath and vessel myography studies showed that only mundulone exerted inhibition of myometrial contractions and that neither compounds affected vasoreactivity of ductus arteriosus. A high-throughput combination screen identified that mundulone exhibits synergism with two clinical-tocolytics (atosiban and nifedipine), and MA displayed synergistic efficacy with nifedipine. Of these combinations, mundulone+atosiban demonstrated a significant improvement in the in vitro therapeutic index compared to mundulone alone. The ex vivo and in vivo synergism of mundulone+atosiban was substantiated, yielding greater tocolytic efficacy and potency on myometrial tissue and reduced preterm birth rates in a mouse model of PL compared to each single agent. Treatment with mundulone after mifepristone administration dose-dependently delayed the timing of delivery. Importantly, mundulone+atosiban permitted long-term management of PL, allowing 71% dams to deliver viable pups at term (>day 19, 4-5 days post-mifepristone exposure) without visible maternal and fetal consequences. Collectively, these studies provide a strong foundation for the development of mundulone as a single or combination tocolytic for management of PL.

Light scattering in a three-phase photosensitive system via Monte Carlo approach.

Digital light processing (DLP)-based additive manufacturing has emerged as a powerful technique for fabricating structures from filled resin systems, in which the light scattering behavior is critical to the dimensional fidelity of the cured part. Recently created low density filled resins that incorporate hollow microspheres introduce a third optically active phase, producing yet more complex scattering and cure behaviours that existing empirical relationships cannot predict. This study simulates light scattering in these systems via Mie theory and a novel Monte Carlo model, providing insight into the relationship between filler volume fraction and cured dimensions, and proposes an inversion parameter for predicting film dimensions. Cured resin geometry dimensions such as cured depth (CD) and cured width (CW) are predicted using the developed model for 10, 30, and 50 vol% hollow glass microsphere filled resin systems. In contrast to standard two-phase models, our three-phase model predicts a positive relationship between cured depths and half-widths and the filler volume fraction, consistent with experimental data. By elucidating the intricacies of light scattering in three-phase systems, this work provides valuable insights for advancing DLP-based additive manufacturing and designing filled resin formulations to achieve the desired cured dimensions.

Improving evaluation for TTR amyloidosis by interactive filtering of Tc-99 m PYP SPECT images. The role for "clean blood pool" imaging.

BACKGROUND: Myocardial imaging with bone agents such as Tc-99 m PYP and HMDP has assumed a central role in the evaluation of patients with suspected transthyretin (TTR) amyloidosis. Visual scoring (VS) (0-3 +) and the heart to contralateral lung ratio (HCL) classify many patients as equivocal when mediastinal uptake is apparent but cannot be further differentiated into myocardial uptake versus blood pool. SPECT imaging has been recommended but current reconstruction protocols frequently produce amorphous mediastinal activity that also fails to discriminate between myocardial activity and blood pool. We hypothesized that interactive filtering interactively using a deconvolving filter would improve this. METHODS: We identified 176 sequential patients referred for TTR amyloid imaging. All patients had planar imaging, 101 had planar imaging with a large field of view camera that allowed HCL measurements. SPECT imaging was performed on a 3-headed digital camera with lead fluorescence attenuation correction. One study was excluded for technical reasons. We created software to allow interactive filtering while reconstructing the images then overlay them on attenuation mu maps to assist localization of myocardial/mediastinal uptake. Conventional Butterworth and an interactive inverse Gaussian filters were employed to differentiate myocardial uptake from residual blood pool. We defined "clean blood pool" (CBP) as recognizable blood pool with no activity in the surrounding myocardium. A scan was determined diagnostic if it showed CBP, positive uptake or no identifiable mediastinal uptake. RESULTS: 76/175 (43%) were equivocal (1 +) by visual uptake. Of these 22 (29%) were diagnostic by Butterworth but 71 (93%) were by inverse gaussian (p < .0001). 71/101 (70%) were equivocal by HCL (1-1.5). Of these, 25 (35%) were diagnostic by Butterworth but 68 (96%) were diagnostic by inverse gaussian (p < .0001). This was driven by a greater than threefold increase in the identification of CBP by inverse gaussian filtering. CONCLUSION: CBP can be identified in the vast majority of patients with equivocal PYP scans using optimized reconstruction and can greatly reduce the number of equivocal scans.

Differences in Health Care Experiences among Transgender and Gender Diverse Youth by Gender Identity and Race/Ethnicity.

Transgender and gender diverse (TGD) youth experience significant risk for negative health outcomes, yet few studies exist that address TGD youth's experiences of health care. This paper explores the equitable access and utilization of health care in a sample of TGD youth of diverse gender and racial/ethnic identities. Data for this analysis are from the TGD subsample (n = 1415) of the 2018 Survey of Today's Adolescent Relationships and Transitions (START) Project. We assessed five health care experiences: being insured, having a current health care provider, being out to one's provider, believing your provider was knowledgeable about transgender issues, and barriers to accessing care due to gender identity/expression. We examined the proportion of TGD youth who reported each of these outcomes and within-group differences by gender identity and race/ethnicity using descriptive statistics, logistic regression, and predicted probabilities. When differences were examined by gender identity, barriers to equitable care were consistently more present among transgender females than youth of other gender identities. There were few significant differences by race/ethnicity; however, dual referent models demonstrated barriers to equitable care were particularly evident among Black and Hispanic transgender women. We discuss these findings through the lens of intersectionality and highlight the importance of research and intervention work focused on reducing barriers to equitable care for TGD youth.

Perceptually Discriminating the Highest Priority Alarms Reduces Response Time: A Retrospective Pre-Post Study at Four Hospitals.

OBJECTIVE: Reduce nurse response time for emergency and high-priority alarms by increasing discriminability between emergency and all other alarms and suppressing redundant and likely false high-priority alarms in a secondary alarm notification system (SANS). BACKGROUND: Emergency alarms are the most urgent, requiring immediate action to address a dangerous situation. They are clinician-triggered and have higher positive predictive value (PPV). High-priority alarms are automatically triggered and have lower PPV. METHOD: We performed a retrospective pre-post study, analyzing data 15 months before and 25 months after a SANS redesign was implemented in four hospitals. For emergency alarms, we incorporated digitized human speech to distinguish them from automatically triggered alarms, leaving their onset and escalation pathways unchanged. For automatically triggered alarms, we suppressed some by delaying initial onset and escalation by 20 s. We used linear mixed models to assess the change in response time, Fisher's exact test for the proportion of response times longer than 120 s, and control charts for process stability. RESULTS: Response time for emergency alarms decreased at all hospitals (main, from 26.91 s to 22.32 s, p < .001; cardiac, from 127.10 s to 52.43 s, p < .001; cancer, from 18.03 s to 15.39 s, p < .001). Improvements were sustained. Automatically triggered alarms decreased 25.0%. Response time for the three automatically triggered cardiac alarms increased at the four hospitals. CONCLUSION: Auditory sound disambiguation was associated with a sustained reduced nurse response time for emergency alarms, but suppressing some high-priority automatically triggered alarms was not. APPLICATION: Distinguishing and escalating urgent, actionable alarms with higher PPV improves response time.

POPTARTS: A New Method to Determine Quantum Yields in a Molecular Beam.

A new technique is reported to determine absolute photodissociation quantum yields, ϕdiss, in a molecular beam. The technique relies on a molecule having two available product channels, where a species in channel A can be converted photolytically to a species in channel B. The relative decrease in the species from channel A and the relative increase in species from B provide a direct measure of the relative product yield of each channel, with no external calibration required. In the event that only channels A and B exist, or at least dominate, then the sum rule ϕA + ϕB = 1 can be used to convert relative quantum yields into absolute yields. The technique is demonstrated using the well-understood and characterized photochemistry of HCHO. Formaldehyde photolysis at wavelengths near 310 nm produces either H + HCO (channel A) or H2 + CO (channel B). HCO can then be photolyzed with high efficiency into H + CO. The product state distributions for HCO from channel A, CO from channel B, and CO from the secondary HCO photolysis event are all well-known; this is not a requirement but is utilized here to demonstrate the veracity of the technique. The zero-pressure quantum yields of HCO from HCHO photolysis via the 2341 and 2151 states of HCHO are determined to be 0.66 and 0.74, respectively, which are in excellent agreement with the established quantum yields at atmospheric pressure and support the conclusion that HCHO quantum yields at these photolysis energies are not pressure dependent.

Performance of the APACHE II and SOFA Scores in Diabetic Ketoacidosis.

Accurate prediction of severity and mortality in diabetic ketoacidosis (DKA) is important for allocation of resources. The APACHE II and SOFA scores are used to predict mortality in critically ill patients, however neither has been tested exclusively in DKA. We sought to determine if these scoring systems can accurately predict mortality in patients with DKA. This was an observational study of patients presenting to an urban tertiary care center with a diagnosis of DKA. Adult patients (age ≥ 18 years) with glucose > 250 mg/dL, bicarbonate ≤ 20 mEg/L, an anion gap ≥ 16 mEg/L, pH ≤ 7.30, and urine ketones were included. Predicted mortality based upon APACHE II and SOFA scores were compared to observed mortality. A total of 50 patients were included. There was no observed mortality in our population. The median APACHE II score was 10 (IQR: 6, 15) which predicted a mortality of 15% and the median SOFA score was 1 (IQR: 0, 2) which predicted a mortality of 0%. In summary, we found the APACHE II illness severity score does not accurately predict mortality in a population of patients with DKA, while the SOFA score appears to predict mortality in the same population.

Questions raised by a case of adult-onset linear nodular scleroderma.

Morphea presenting clinically with nodular or keloidal skin changes is extremely rare. Nodular scleroderma or keloidal morphea presenting in a linear distribution is even more uncommon. We present an otherwise healthy young woman with unilateral, linear, nodular scleroderma and review the somewhat confounding earlier literature in this area. To date, this young woman's skin changes have proven refractory to oral hydroxychloroquine and ultraviolet A1 phototherapy. Several aspects of this case including the patient's family history of Raynaud disease, her nodular sclerodermatous skin lesions, and the presence of U1RNP autoantibodies raised concern about her management with respect to future risk of developing systemic sclerosis.

A rapid dynamic in vivo near-infrared fluorescence imaging assay to track lung vascular permeability after acute radiation injury.

To develop a dynamic in vivo near-infrared (NIR) fluorescence imaging assay to quantify sequential changes in lung vascular permeability-surface area product (PS) in rodents. Dynamic NIR imaging methods for determining lung vascular permeability-surface area product were developed and tested on non-irradiated and 13 Gy irradiated rats with/without treatment with lisinopril, a radiation mitigator. A physiologically-based pharmacokinetic (PBPK) model of indocyanine green (ICG) pulmonary disposition was applied to in vivo imaging data and PS was estimated. In vivo results were validated by five accepted assays: ex vivo perfused lung imaging, endothelial filtration coefficient (Kf) measurement, pulmonary vascular resistance measurement, Evan's blue dye uptake, and histopathology. A PBPK model-derived measure of lung vascular permeability-surface area product increased from 2.60 ± 0.40 [CL: 2.42-2.78] mL/min in the non-irradiated group to 6.94 ± 8.25 [CL: 3.56-10.31] mL/min in 13 Gy group after 42 days. Lisinopril treatment lowered PS in the 13 Gy group to 4.76 ± 6.17 [CL: 2.12-7.40] mL/min. A much higher up to 5× change in PS values was observed in rats exhibiting severe radiation injury. Ex vivo Kf (mL/min/cm H2O/g dry lung weight), a measure of pulmonary vascular permeability, showed similar trends in lungs of irradiated rats (0.164 ± 0.081 [CL: 0.11-0.22]) as compared to non-irradiated controls (0.022 ± 0.003 [CL: 0.019-0.025]), with reduction to 0.070 ± 0.035 [CL: 0.045-0.096] for irradiated rats treated with lisinopril. Similar trends were observed for ex vivo pulmonary vascular resistance, Evan's blue uptake, and histopathology. Our results suggest that whole body dynamic NIR fluorescence imaging can replace current assays, which are all terminal. The imaging accurately tracks changes in PS and changes in lung interstitial transport in vivo in response to radiation injury.

Nonadiabatic Coupling Effects in the 800 nm Strong-Field Ionization-Induced Coulomb Explosion of Methyl Iodide Revealed by Multimass Velocity Map Imaging and Ab Initio Simulation Studies.

The Coulomb explosion (CE) of jet-cooled CH3I molecules using ultrashort (40 fs), nonresonant 805 nm strong-field ionization at three peak intensities (260, 650, and 1300 TW cm-2) has been investigated by multimass velocity map imaging, revealing an array of discernible fragment ions, that is, Iq+ (q ≤ 6), CHn+ (n = 0-3), CHn2+ (n = 0, 2), C3+, H+, H2+, and H3+. Complementary ab initio trajectory calculations of the CE of CH3IZ+ cations with Z ≤ 14 identify a range of behaviors. The CE of parent cations with Z = 2 and 3 can be well-described using a diatomic-like representation (as found previously) but the CE dynamics of all higher CH3IZ+ cations require a multidimensional description. The ab initio predicted Iq+ (q ≥ 3) fragment ion velocities are all at the high end of the velocity distributions measured for the corresponding Iq+ products. These mismatches are proposed as providing some of the clearest insights yet into the roles of nonadiabatic effects (and intramolecular charge transfer) in the CE of highly charged molecular cations.

Variation in SOFA (Sequential Organ Failure Assessment) Score Performance in Different Infectious States.

INTRODUCTION: In this study, we investigated whether the Sequential Organ Failure Assessment (SOFA) score performance differs based on the type of infection among patients admitted to the intensive care unit (ICU) with infection. MATERIALS AND METHODS: Single-center, retrospective study of adult ICU patients admitted with infection between January 2008 and April 2018 at an urban tertiary care center. Patients were uniquely classified into different infection types based on International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes. Infection types included were pneumonia, meningitis, bacteremia, cellulitis, cholangitis/cholecystitis, intestinal and diarrheal disease, endocarditis, urinary tract infection (UTI), and peritonitis. The SOFA score performance and mortality in relation to SOFA score were compared across infection types. RESULTS: A total of 12 283 patients were included. Of these, 50.6% were female and the median age was 70 years (interquartile range: 57-82). The most common infection types were pneumonia (32.2%) and UTI (31.0%). Overall, 1703 (13.9%) patients died prior to hospital discharge. The median baseline SOFA score (within 24 hours of ICU admission) for the cohort was 5 (3-8). Patients with peritonitis had the highest median SOFA score, 7 (4-9), and patients with cellulitis and UTI had the lowest median SOFA score, 4 (2-7). The SOFA score discrimination to predict mortality was highest among patients with endocarditis (area under the receiver operating characteristic [AUC]: 0.79, 95% CI: 0.69-0.90) and lowest for patients with isolated bacteremia (AUC: 0.59, 95% CI: 0.49-0.70). Observed mortality by quartile of SOFA score differed substantially across infection types. CONCLUSIONS: Type of infection is an important consideration when interpreting the SOFA score. This is relevant as SOFA emerges as an important tool in the definition and prognostication of sepsis.

Photodissociation dynamics of CF3CHO: C-C bond cleavage.

The photodissociation dynamics of jet-cooled trifluoroacetaldehyde (CF3CHO) into radical products, CF3 + HCO, was explored using velocity mapped ion imaging over the wavelength range 297.5 nm ≤λ≤ 342.8 nm (33 613-29 172 cm-1) covering the entire section of the absorption spectrum accessible with solar actinic wavelengths at the ground level. After initial excitation to the first excited singlet state, S1, the radical dissociation proceeds largely via the first excited triplet state, T1, at excitation energies above the T1 barrier. By combining velocity-mapped ion imaging with high-level theory, we place this barrier at 368.3 ± 2.4 kJ mol-1 (30 780 ± 200 cm-1). After exciting to S1 at energies below this barrier, the dissociation proceeds exclusively via the ground electronic state, S0. The dissociation threshold is determined to be 335.7 ± 1.8 kJ mol-1 (28 060 ± 150 cm-1). Using laser-induced fluorescence spectroscopy, the origin of the S1 ← S0 transition is assigned at 28 903 cm-1. The S0 dissociation channel is active at the S1 origin, but the yield significantly increases above 29 100 cm-1 due to enhanced intersystem crossing or internal conversion.

The effect of an electronic medical record intervention on hydroxychloroquine prescribing habits and surveyed providers' opinions of the 2016 American Academy of Ophthalmology guidelines in the rheumatology and dermatology practices of an academic institutionle.

BACKGROUND: Retinal toxicity is a rare adverse event related to the use of hydroxychloroquine (HCQ). To address this, in 2016, the American Academy of Ophthalmology (AAO) issued guidelines recommending that HCQ not exceed 5 mg/kg/day. We analyzed HCQ prescribing habits at our institution, compared to these guidelines, and used surveys to determine the opinions on these guidelines. We then introduced, in a prospective and non-controlled study, a clinical decision support (CDS) tool into the electronic medical record (EMR) to study how this intervention might affect adherence with or opinions on these guidelines. METHODS: Data were collected pre-intervention (June 2017-January 2019) and post-intervention (March 2019-April 2020). In January 2019 we released our CDS tool. Results were analyzed using descriptive statistics for demographic data and Fisher's exact tests for comparisons of proportions between groups. RESULTS: Pre-intervention, we reviewed 1128 rheumatology charts and 282 dermatology charts. 31.0 and 39.7% respectively (32.8% combined) were prescribed HCQ > 5 .0 mg/kg/day. Post-intervention, we reviewed 1161 rheumatology charts and 110 dermatology charts. 23.0 and 25.5% respectively (23.2% combined) were prescribed HCQ > 5.0 mg/kg/day. Post-intervention, 9.6% fewer patients were prescribed HCQ > 5 mg/kg/day (P < .001). Pre-intervention, we compiled 18 rheumatology surveys and 12 dermatology surveys. Post-intervention, we compiled 16 rheumatology surveys and 12 dermatology surveys. Post-intervention, fewer rheumatologists incorrectly described the AAO weight-based guidelines. Combined, there was an overall reduction but not of statistical significance (P = .47). The majority of providers surveyed believed that the CDS tool was useful (72.2%). CONCLUSIONS: At our academic institution, there remains unfamiliarity with and hesitation to comply with the 2016 AAO guidelines. Prescribed doses often exceed what is recommended in these guidelines. A CDS tool can improve adherence with these guidelines and might improve providers' familiarity with these guidelines.

Photofragment Translational Spectroscopy Studies of H Atom Loss Following Ultraviolet Photoexcitation of Methimazole in the Gas Phase.

The ultraviolet (UV) photodissociation of gas-phase methimazole has been investigated by H Rydberg atom photofragment translational spectroscopy methods at many wavelengths in the range of 222.5-275 nm and by complementary electronic structure calculations. Methimazole is shown to exist predominantly as the thione tautomer, 1-methyl-2(3 H)-imidazolinethione, rather than the commonly given thiol form, 2-mercapto-1-methylimidazole. The UV absorption spectrum of methimazole is dominated by the S4 ← S0 transition of the thione tautomer, which involves electron promotion from an a' (p y) orbital localized on the sulfur atom to a σ* orbital localized around the N-H bond. Two H atom formation pathways are identified following UV photoexcitation. One, involving prompt, excited-state N-H bond fission, yields vibrationally cold but rotationally excited methimazolyl (Myl) radicals in their first excited (Ã) electronic state. The second yields H atoms with an isotropic recoil velocity distribution peaking at low kinetic energies but extending to the energetic limit allowed by energy conservation given a ground-state dissociation energy D0(Myl-H) ∼24 000 cm-1. These latter H atoms are attributed to the unimolecular decay of highly vibrationally excited S0 parent molecules. The companion electronic structure calculations provide rationales for both fragmentation pathways and the accompanying product energy disposals and highlight similarities and differences between the UV photochemistry of methimazole and that of other azoles (e.g., imidazole) and with molecules like thiourea and thiouracil that contain similar N-C═S motifs.

Communication: Multi-mass velocity map imaging study of the ultraviolet photodissociation of dimethyl sulfide using single photon ionization and a PImMS2 sensor.

This study of the photodissociation of dimethyl sulfide at λ = 227.5 nm demonstrates the opportunities (and some of the challenges) of product detection using vacuum ultraviolet photoionization combined with recently developed multi-mass imaging methods. The capability of imaging different charged products simultaneously allows determination of the primary fragmentation dynamics through, for example, product fragment momentum and angular distribution matching and reveals potential complications from dissociative ionization, product alignment-dependent photoionization probabilities, and the effects of space charging.