Analysis of Anonymous Student Narratives About Experiences with Emergency Medicine Residency Programs.

Background: Academic emergency medicine (EM) communities have viewed anonymous online communities (AOC) such as Reddit or specialty-specific "applicant spreadsheets" as poor advising resources. Despite this, robust EM AOCs exist, with large user bases and heavy readership. Insights about applicants' authentic experiences can be critical for applicants and program leadership decision-making. To date, there are no EM studies to qualitatively assess EM AOC narratives during the application cycle. Our goal was to perform a qualitative analysis of students' EM program experiences through a publicly available AOC. Methods: This was a qualitative analysis of a publicly available, time-stamped, user-locked AOC dataset: "Official 2020-2021 Emergency Medicine Applicant Spreadsheet." We extracted and then de-identified all data from selected sub-sheets entitled "Virtual Interview Impressions" and "Rotation Impressions." Four investigators used constant comparative method to analyze the data inductively, and they subsequently met to generate common themes discussed by students. Preliminary thematic analysis was conducted on a random sample of 37/183 (20%) independent narratives to create the initial codebook. This was used and updated iteratively to analyze the entire narrative set consisting of 841 discrete statements. Finally, two unique codes were created to distinguish whether the identified sub-themes, or program attributes, were likely "modifiable" or "non-modifiable." Results: We identified six major themes: living and working conditions; interpersonal relationships; learning experiences, postgraduate readiness, and online/virtual supplements. Common sub-themes included patient population (13%); resident personality (7%); program leadership personality (7%); relationship with faculty/leadership (6%); geography (4%); practice setting (4%); program reputation (4%), and postgraduate year-3 experiences (4%). Modifiable sub-themes outnumbered non-modifiable sub-themes, 60.7% to 39.3%. Conclusion: In this analysis of selected medical students' narratives in an AOC, the majority of identified themes represented topics that may serve as external feedback for EM residency programs and their clerkships. Selective use of AOCs may set a precedent for future program assessments by applicants and inform program leadership of important programmatic elements in the eyes of applicants. It elucidates important themes in their interactions or learning experiences with programs and creates opportunities for learner-centric program improvement.

Delayed Presentation of Popliteal Artery Injury after Salter-Harris III Proximal Tibia Fracture.

Introduction: Proximal tibia physeal fractures in children are not very common but can be dangerous because they can harm popliteal fossa structures, especially the popliteal artery. Popliteal artery injuries (PAI) are most commonly the result of trauma to the lower extremity, including blunt force, hyperextension injuries, complex fractures, and knee dislocations that can compromise popliteal neurovascular structures. Case Presentation. A 14-year-old boy presents to the emergency department after being transferred from an outside hospital 24 hours after a left lower extremity hyperextension injury. Radiographs demonstrated a Salter-Harris III proximal tibia fracture with posterior displacement. ABIs were deferred due to palpable distal pulses and no evidence of compartment syndrome. Closed reduction and percutaneous pinning were planned to correct the fracture. Intraoperatively, it was discovered that knee extension decreased lower extremity perfusion while knee flexion returned perfusion. An angiography revealed a popliteal artery occlusion with no distal flow. Based on this, an above-knee to below-knee popliteal bypass using the contralateral great saphenous vein was performed followed by closed reduction and percutaneous pinning of the proximal tibia. Conclusion: Proximal tibia physeal injuries, especially the Salter-Harris III and IV injuries, warrant a high index of suspicion of popliteal artery injuries. Palpable pulses and delayed presentation in the distal lower extremity do not rule out a PAI because collateral flow to the anterior and posterior tibial arteries may mask signs of an avascular limb, highlighting the need for a thorough history and physical exam. The authors present this case to reaffirm the importance of an ankle-brachial index when evaluating hyperextension injuries with proximal tibial epiphyseal fractures.

Drug resistance and vaccine target surveillance of Plasmodium falciparum using nanopore sequencing in Ghana.

Malaria results in over 600,000 deaths annually, with the highest burden of deaths in young children living in sub-Saharan Africa. Molecular surveillance can provide important information for malaria control policies, including detection of antimalarial drug resistance. However, genome sequencing capacity in malaria-endemic countries is limited. We designed and implemented an end-to-end workflow to detect Plasmodium falciparum antimalarial resistance markers and diversity in the vaccine target circumsporozoite protein (csp) using nanopore sequencing in Ghana. We analysed 196 clinical samples and showed that our method is rapid, robust, accurate and straightforward to implement. Importantly, our method could be applied to dried blood spot samples, which are readily collected in endemic settings. We report that P. falciparum parasites in Ghana are mostly susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine resistance and no evidence of artemisinin resistance. Multiple single nucleotide polymorphisms were identified in csp, but their significance is uncertain. Our study demonstrates the feasibility of nanopore sequencing for malaria genomic surveillance in endemic countries.

Atom probe tomography using an extreme ultraviolet trigger pulse.

Atom probe tomography (APT) is a powerful materials characterization technique capable of measuring the isotopically resolved three-dimensional (3D) structure of nanoscale specimens with atomic resolution. Modern APT instrumentation most often uses an optical pulse to trigger field ion evaporation-most commonly, the second or third harmonic of a Nd laser is utilized (∼λ = 532 nm or λ = 355 nm). Herein, we describe an APT instrument that utilizes ultrafast extreme ultraviolet (EUV) optical pulses to trigger field ion emission. The EUV light is generated via a commercially available high harmonic generation system based on a noble-gas-filled capillary. The centroid of the EUV spectrum is tunable from around 25 eV (λ = 50 nm) to 45 eV (λ = 28 nm), dependent on the identity of the gas in the capillary (Xe, Kr, or Ar). EUV pulses are delivered to the APT analysis chamber via a vacuum beamline that was optimized to maximize photon flux at the APT specimen apex while minimizing complexity. We describe the design of the beamline in detail, including the various compromises involved. We characterize the spectrum of the EUV light and its evolution as it propagates through the various optical elements. The EUV focus spot size is measured at the APT specimen plane, and the effects of misalignment are simulated and discussed. The long-term stability of the EUV source has been demonstrated for more than a year. Finally, APT mass spectra are shown, demonstrating the instrument's ability to successfully trigger field ion emission from semiconductors (Si, GaN) and insulating materials (Al2O3).

Temporal trends in microplastic accumulation in placentas from pregnancies in Hawai'i.

Microplastics are created for commercial use, are shed from textiles, or result from the breakdown of larger plastic items. Recent reports have shown that microplastics accumulate in human tissues and may have adverse health consequences. Currently, there are no standardized environmental monitoring systems to track microplastic accumulation within human tissues. Using Raman spectroscopy, we investigated the temporal exposures to plastic pollution in Hawai'i and noted a significant increase in the accumulation of microplastics in discarded placentas over the past 15 years, with changes in the size and chemical composition of the polymers. These findings provide a rare insight into the vulnerability and sensitivity of Pacific Island residents to plastic pollution and illustrate how discarded human tissues can be used as an innovative environmental plastic pollution monitoring system.

Pf7: an open dataset of Plasmodium falciparum genome variation in 20,000 worldwide samples.

We describe the MalariaGEN Pf7 data resource, the seventh release of Plasmodium falciparum genome variation data from the MalariaGEN network.  It comprises over 20,000 samples from 82 partner studies in 33 countries, including several malaria endemic regions that were previously underrepresented.  For the first time we include dried blood spot samples that were sequenced after selective whole genome amplification, necessitating new methods to genotype copy number variations.  We identify a large number of newly emerging crt mutations in parts of Southeast Asia, and show examples of heterogeneities in patterns of drug resistance within Africa and within the Indian subcontinent.  We describe the profile of variations in the C-terminal of the csp gene and relate this to the sequence used in the RTS,S and R21 malaria vaccines.  Pf7 provides high-quality data on genotype calls for 6 million SNPs and short indels, analysis of large deletions that cause failure of rapid diagnostic tests, and systematic characterisation of six major drug resistance loci, all of which can be freely downloaded from the MalariaGEN website.

Tuning the photodynamics of sub-nanometer neutral chromium oxide clusters through sequential oxidation.

Sub-nanometer neutral chromium oxide clusters were produced in the gas phase through laser ablation and their low-lying excited state lifetimes were measured using femtosecond pump-probe spectroscopy. Time-dependent density functional theory calculations relate the trends in experimental lifetimes to the cluster's electronic structure. The photoexcited (CrO2)n (n < 5) cluster transients with the absence of up to four O atoms (CrnO2n-x, x < 5) exhibit a ∼30 fs and sub-ps lifetime, attributed to instantaneous metallic e-e scattering and vibrationally mediated charge carrier relaxation, respectively. A long-lived (>2 ps) response is found in both small and clusters with low O content, indicating that terminal CrO bonds facilitate efficient excited state relaxation. The ∼30 fs transient signal fraction grows nearly linearly with oxidation, matching the amount of O-2p to Cr-3d charge transfer character of the photoexcitation and suggesting a gradual transition between semiconducting and metallic behavior in chromium oxide clusters at the molecular level. The results presented herein suggest that the photocatalytic properties of chromium oxides can be tunable based on size and oxidation.

Health State Utilities for Adverse Events Associated with Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma.

BACKGROUND: Chimeric antigen receptor (CAR) T-cell therapy provides effective treatment for large B-cell lymphoma (LBCL). Cost-utility analyses examining and comparing the value of these treatments require health state utilities representing key characteristics to differentiate among therapies. This study estimated utilities for adverse events (AEs) associated with CAR T-cell therapy, including cytokine release syndrome (CRS) and neurological events (NEs). METHODS: Health state vignettes were drafted based on literature review, AE reports from a trial of CAR T-cell therapy, and clinician input. Health states were valued in time trade-off interviews with general population participants in the UK. The first vignette described relapsed/refractory LBCL treated with CAR T-cell therapy without AEs. Five other vignettes had the same LBCL and treatment description, with the addition of an AE. Disutilities (i.e., utility decrease) associated with these AEs were calculated by subtracting the utility of the health state without AEs from those of the other health states. RESULTS: Interviews were completed with 218 participants (50% male; mean age 49 years). Mean (standard deviation [SD]) utility for CAR T-cell therapy without AEs was 0.73 (0.30). Mean (SD) disutilities associated with CRS were -0.01 (0.04) for grade 1, -0.05 (0.09) for grade 2, and -0.23 (0.24) for grade 3/4. Mean (SD) disutilities associated with NEs were -0.04 (0.07) for grade 1/2 and -0.18 (0.22) for grade 3/4. CONCLUSIONS: More severe AEs were associated with greater disutilities. Health state utilities estimated in this study may be useful in cost-effectiveness models examining the value of CAR T-cell therapy in patients with LBCL.

Orbital-dependent photodynamics of strongly correlated nickel oxide clusters.

The ultrafast electronic relaxation dynamics of neutral nickel oxide clusters were investigated with femtosecond pump-probe spectroscopy and supported with theoretical calculations to reveal that their excited state lifetimes are strongly dependent on the nature of the electronic transition. Absorption of a UV photon produces short-lived (lifetime ∼ 110 fs) dynamics in stoichiometric (NiO)n clusters (n < 6) that are attributed to a ligand to metal charge transfer (LMCT) and produces metallic-like electron-electron scattering. Oxygen vacancies introduce excitations with Ni-3d → Ni-4s and 3d → 4p character, which increases the lifetimes of the sub-picosecond response by up to 80% and enables the formation of long-lived (lifetimes >2.5 ps) states. The atomic precision and tunability of gas phase clusters are employed to highlight a unique reliance on the Ni orbital contributions to the photoexcited lifetimes, providing new insights to the analogous band edge excitation dynamics of strongly correlated bulk-scale NiO materials.

Oxygen Deficiencies in Titanium Oxide Clusters as Models for Bulk Defects.

TD-DFT calculations were performed on neutral TinO2n, TinO2n-1, and TinO2n-2 clusters, where n ≤ 7. Calculations show the TinO2n clusters are closed shell systems containing empty d orbitals and that the partially filled d orbitals of the suboxide clusters have a profound effect on their structural, electronic, and topological properties. The low energy photoexcitations of TinO2n clusters are all O-2p to Ti-3d transitions, while the open-shell suboxide clusters are all characterized by d-d transitions that occur at a much smaller optical gap. Upon low energy photoabsorption, the localization of the hole is accompanied by a local bond elongation, i.e., polaron formation, whereas d-electrons are generally delocalized around the cluster. The properties of the clusters, including the oxygen binding energies and structures, were calculated to account for the variation in relative populations found in experimental cluster distributions. Several TinO2n-2 clusters contain higher symmetry which is reflected in their relative stability. In particular, the tetrahedral symmetry of Ti4O6 inhibits charge carrier localization and therefore exhibits higher stability.

Principles of Hypotensive Shock: A Video Introduction to Pathophysiology and Treatment Strategies.

Audience: Emergency medicine interns, medical students, and mid-level providers (physician assistants, nurse practitioners). Introduction: Shock is defined as a state of global tissue hypoxia and is typically the result of hypotension and circulatory system failure. A variety of disease states may ultimately culminate in hypotensive shock through one or more generally recognized mechanisms - hypovolemic, cardiogenic, obstructive, and/or distributive shock.1 These mechanisms differ significantly in terms of their pathophysiology and requisite treatment. While the effects of hypotensive shock are initially reversible, untreated hypotensive shock may rapidly progress to multiorgan failure and death. Hence, the ability to promptly recognize a state of hypotensive shock, identify the underlying mechanism, and administer appropriate therapies are skills required of those caring for critically ill patients.2The evaluation of hypotensive shock in the Emergency Department is relatively commonplace. Mortality rates associated with shock are high, ranging from 22.6% - 56.2%, depending upon the underlying etiology.3 For these reasons, the authors believe that a web-based learning module addressing topics related to hypotensive shock would be beneficial to healthcare professionals who are likely to encounter it in clinical practice. The web-based nature of the module would lend itself to convenient viewing and would allow for utilization as a just-in-time training modality. Presenting these topics in an animated format may also be a useful way of displaying the complex nature of cardiovascular physiology. Educational Objectives: By the end of this module, participants should be able to:Review basic principles of cardiovascular physiologyDescribe the four general pathophysiologic mechanisms of hypotensive shockRecognize various etiologies for each mechanism of hypotensive shockRecognize differences in the clinical presentation of each mechanism of hypotensive shockCite the basic approach to treatment for each mechanism of hypotensive shock. Educational Methods: This is a video podcast which conveys information through animated content. It is available to learners on demand and just-in-time for practice. It may be used as a stand-alone educational tool, as a primer to other instructional methods (eg, simulation, flipped classroom setting, or case discussions), or a just-in-time training tool. Research Methods: A small-scale study was performed to quantify the efficacy of this module as an educational tool. The learner group was comprised of a convenience sample of third-year medical students in the midst of their core clinical clerkships. All third-year students were eligible to participate, regardless of which core clerkship they were currently engaged in. Third-year students were contacted via email regarding participation. Participation was completely optional - no incentive was offered, and students were informed that participation would not in any way affect their clerkship grades. For these reasons, an Instructional Review Board review was not necessary. Ten third-year medical students volunteered to participate. In the course of a single, hour-long session, learners were administered the attached assessment form as a pre-test, shown the video module, and then asked to immediately retake the assessment as a post-test to assess for improvement. Assessments were graded on a 17-point scale, according to the attached answer key. Learners were also given the opportunity to provide subjective feedback on the quality of the module as an educational tool. Results: For this assessment, the maximum possible score was 17 points. The average pre-test score across all learners was 11.75 (69.12%) with a standard deviation of 3.24. The average post-test score across all learners was 15.12 (88.97%) with a standard deviation of 3.31. All learners demonstrated improvement in scores on the post-test, with a maximum and minimum improvement of 6 points and 1 point respectively. On average, learners improved by 3.38 points (p = 0.029, 95% confidence interval, 1.97 to 4.78). Statistical significance was established using a paired student's T-test. All learners agreed with the statement, "This module effectively taught concepts related to hypotensive shock." Learners were also given the opportunity to provide subjective feedback regarding the module and responded with statements like, "comprehensive review of the subject," and "very helpful review for clinical clerkships." Discussion: Data from learner assessments suggest that this module is effective in communicating concepts related to hypotensive shock. Learner satisfaction with the module was unanimous. These results suggest that this module would be effective as a standalone educational tool, or as a primer to other instructional methods. Areas of further investigation may include assessment of a larger learner population, assessment of learners at additional stages of clinical training, and assessment of long-term knowledge retention. Topics: Shock, hypotension, cardiovascular physiology, pulmonary artery catheterization, flipped classroom, asynchronous learning, emergency medicine.

Effect of oxidation on excited state dynamics of neutral TinO2n-x (n < 10, x < 4) clusters.

Excited state lifetimes of neutral titanium oxide clusters (TinO2n-x, n < 10, x < 4) were measured using a sequence of 400 nm pump and 800 nm probe femtosecond laser pulses. Despite large differences in electronic properties between the closed shell stoichiometric TinO2n clusters and the suboxide TinO2n-x (x = 1-3) clusters, the transient responses for all clusters contain a fast response of 35 fs followed by a sub-picosecond (ps) excited state lifetime. In this non-scalable size regime, subtle changes in the sub-ps lifetimes are attributed to variations in the coordination of Ti atoms and localization of charge carriers following UV photoexcitation. In general, clusters exhibit longer lifetimes with increased size and also with the addition of O atoms. This suggests that the removal of O atoms develops stronger Ti-Ti interactions as the system transitions from a semiconducting character to a fast metallic electronic relaxation mechanism.

Increased Excited State Metallicity in Neutral Cr2On Clusters (n < 5) upon Sequential Oxidation.

Excited state lifetimes of neutral Cr2On (n < 5) clusters were measured using femtosecond pump-probe spectroscopy. Density functional theory calculations reveal that the excited state dynamics are correlated with changes in the cluster's electronic structure with increasing oxidation. Upon absorption of a UV (400 nm) photon, the clusters exhibit features attributed to three separate relaxation processes. All clusters exhibit similar subpicosecond lifetimes, attributed to vibrational relaxation. However, the ∼30 fs transient signal fraction grows linearly with oxidation, matching the amount of O to Cr charge transfer character of the photoexcitation and highlighting a gradual transition between semiconducting and metallic behavior at the molecular level. A long-lived (>2.5 ps) response is recorded only in clusters with significant d-electron character, suggesting that adiabatic relaxation back to the ground state is efficient in heavily oxidized clusters, due to the presence of terminal O atoms. The simple picture of sequential oxidation of Cr2On reveals a linear variation in the contributions of each relaxation component to the total transient signals, therefore opening possibilities for the design of new molecular spintronic materials.

Travel-Related Economic Burden of Chimeric Antigen Receptor T Cell Therapy Administration by Site of Care.

INTRODUCTION: We previously examined how expanding access to chimeric antigen receptor (CAR) T cell therapy administration sites impacted patient travel distances and time. In the current study, we estimated travel-related economic burden associated with site-of-care options among patients with relapsed/refractory diffuse large B cell lymphoma. METHODS: We used geographic information system methods to quantify travel-related economic burden across three site-of-care scenarios: academic hospitals; academic and community multispecialty hospitals; and academic and community multispecialty hospitals plus nonacademic specialty oncology network centers. Socioeconomic status, administration sites, and county of residence were derived from the US Census Bureau and publicly available sources. Travel costs were based on governmental guidelines, US census wage data, and Bureau of Transportation Statistics. Travel distance and time to the nearest CAR T cell therapy administration sites were estimated from previous research. RESULTS: Total national estimated costs associated with traveling for CAR T cell therapy were $21.1 million if CAR T cell therapy was offered exclusively in academic hospitals, and $14.7 million if expanded to include community hospitals plus nonacademic specialty oncology network centers, representing a $6.5-million reduction associated with expanding access to eligible patients. The largest cost-saving component was lodging/meals. Regional and demographic cost differences were statistically significant between academic hospitals and nonacademic hospitals/specialty oncology centers. In all scenarios, patients living below the federal poverty level (FPL) had higher weighted mean total costs versus patients living above the FPL. White and Native American patients were estimated to have the highest weighted mean total costs across race/ethnicity groups. For all subgroups, costs were reduced by expanding access beyond academic hospitals. CONCLUSION: CAR T cell therapy is currently restricted to academic hospitals; total travel costs could be substantially decreased if access is expanded to nonacademic hospitals and specialty oncology centers. Patients in rural areas and those living below the FPL are particularly disadvantaged by restricted access.

An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples.

MalariaGEN is a data-sharing network that enables groups around the world to work together on the genomic epidemiology of malaria. Here we describe a new release of curated genome variation data on 7,000 Plasmodium falciparum samples from MalariaGEN partner studies in 28 malaria-endemic countries. High-quality genotype calls on 3 million single nucleotide polymorphisms (SNPs) and short indels were produced using a standardised analysis pipeline. Copy number variants associated with drug resistance and structural variants that cause failure of rapid diagnostic tests were also analysed.  Almost all samples showed genetic evidence of resistance to at least one antimalarial drug, and some samples from Southeast Asia carried markers of resistance to six commonly-used drugs. Genes expressed during the mosquito stage of the parasite life-cycle are prominent among loci that show strong geographic differentiation. By continuing to enlarge this open data resource we aim to facilitate research into the evolutionary processes affecting malaria control and to accelerate development of the surveillance toolkit required for malaria elimination.

Indirect Treatment Comparison of Liso-Cel vs. Salvage Chemotherapy in Diffuse Large B-Cell Lymphoma: TRANSCEND vs. SCHOLAR-1.

Most patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have exhausted their treatment options and are deemed palliative. CD19-directed chimeric antigen receptor (CAR) T-cell therapy has recently been introduced as a new option for these patients. Lisocabtagene maraleucel (liso-cel) is an investigational CAR T-cell therapy that has shown promising activity in this setting. We used an unanchored matching-adjusted indirect comparison (MAIC) methodology to compare liso-cel, using individual patient-level data from the TRANSCEND NHL 001 (TRANSCEND; NCT02631044) trial, to salvage chemotherapy, using summary-level data from the SCHOLAR-1 study, for the treatment of patients with R/R LBCL. Standardized mean differences were used to evaluate imbalances between the TRANSCEND and SCHOLAR-1 studies. MAIC was conducted to determine the relative efficacy of liso-cel vs. salvage chemotherapy with regard to overall survival, complete response rate, and objective response rate. For all efficacy outcomes assessed, comparisons of clinical factors before MAIC showed that five of seven baseline characteristics were similar between the TRANSCEND and SCHOLAR-1 studies; however, age and R/R to last therapy status differed between studies, thus requiring matching and adjusting to ensure the validity of this analysis. The base case analyses demonstrated a significantly lower risk of mortality (hazard ratio, 0.5; 95% confidence interval [CI] 0.4-0.6; p < 0.001) with significantly higher rates of complete response (odds ratio, 12.9; 95% CI 8.0-20.7) and objective response (odds ratio, 7.0; 95% CI 4.6-10.5) for patients treated with liso-cel than patients treated with salvage chemotherapy. MAIC comparisons demonstrated favorable efficacy for liso-cel compared with salvage chemotherapy in the treatment of patients with R/R LBCL.Trial Registration ClinicalTrials.gov identifier: NCT02631044.

Effect of lisocabtagene maraleucel on HRQoL and symptom severity in relapsed/refractory large B-cell lymphoma.

CD19-directed chimeric antigen receptor (CAR) T-cell therapy has shown efficacy as a third-line or later treatment in patients with relapsed/refractory large B-cell lymphoma (LBCL). Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire, we evaluated the impact of CAR T-cell treatment with lisocabtagene maraleucel (liso-cel) on health-related quality of life (HRQoL) and symptoms in patients with relapsed/refractory LBCL in the ongoing, open-label, nonrandomized TRANSCEND NHL 001 trial. Clinically meaningful improvement was observed in EORTC QLQ-C30 scores for global health status/QoL, based on a minimally important difference of 10 points at 2 to 18 months after liso-cel infusion. There were no clinically meaningful changes in physical functioning and pain, whereas clinically meaningful improvements were observed in fatigue at 2, 12, and 18 months. The proportion of patients with clinically meaningful improvement in global health status/QoL was generally higher for treatment responders than for nonresponders. A trend toward decreased mean EQ-5D-5L index scores was observed at 1 month after liso-cel infusion, followed by subsequent increases through 18 months. Mean EQ-5D-5L visual analog scale scores increased from 2 through 18 months. In summary, patients with relapsed/refractory LBCL treated with liso-cel had early, sustained, and clinically meaningful improvements in HRQoL and symptoms that correlated with antitumor activity. This study was registered at www.clinicaltrials.gov as #NCT02631044.

Oscillation in Excited State Lifetimes with Size of Sub-nanometer Neutral (TiO2)n Clusters Observed with Ultrafast Pump-Probe Spectroscopy.

Neutral titanium oxide clusters of up to 1 nm in diameter (TiO2)n, with n < 10, are produced in a laser vaporization source and subsequently ionized by a sequence of femtosecond laser pulses. Using a 400 nm pump and 800 nm probe lasers, the excited state lifetimes of neutral (TiO2)n clusters are measured. All clusters exhibit a rapid relaxation lifetime of ∼35 fs, followed by a sub-picosecond lifetime that we attribute to carrier recombination. The excited state lifetimes oscillate with size, with even-numbered clusters possessing longer lifetimes. Density functional theory calculations show the excited state lifetimes are correlated with charge carrier localization or polaron-like formation in the excited states of neutral clusters. Thus, structural rigidity is suggested as a feature for extending excited state lifetimes in titania materials.

Cytokine release syndrome and neurological event costs in lisocabtagene maraleucel-treated patients in the TRANSCEND NHL 001 trial.

Chimeric antigen receptor (CAR) T-cell therapies have demonstrated high response rates in patients with relapsed/refractory large B-cell lymphoma (LBCL); however, these therapies are associated with 2 CAR T cell-specific potentially severe adverse events (AEs): cytokine release syndrome (CRS) and neurological events (NEs). This study estimated the management costs associated with CRS/NEs among patients with relapsed/refractory LBCL using data from the pivotal TRANSCEND NHL 001 trial of lisocabtagene maraleucel, an investigational CD19-directed defined composition CAR T-cell product with a 4-1BB costimulation domain administered at equal target doses of CD8+ and CD4+ CAR+ T cells. This retrospective analysis of patients from TRANSCEND with prospectively identified CRS and/or NE episodes examined relevant trial-observed health care resource utilization (HCRU) associated with toxicity management based on the severity of the event from the health care system perspective. Cost estimates for this analysis were taken from publicly available databases and published literature. Of 268 treated patients as of April 2019, 127 (47.4%) experienced all-grade CRS and/or NEs, which were predominantly grade ≤2 (77.2%). Median total AE management costs ranged from $1930 (grade 1 NE) to $177 343 (concurrent grade ≥3 CRS and NE). Key drivers of cost were facility expenses, including intensive care unit and other inpatient hospitalization lengths of stay. HCRU and costs were significantly greater among patients with grade ≥3 AEs (22.8%). Therefore, CAR T-cell therapies with a low incidence of severe CRS/NEs will likely reduce HCRU and costs associated with managing patients receiving CAR T-cell therapy. This clinical trial was registered at www.clinicaltrials.gov as #NCT02631044.

Ultrafast pump-probe spectroscopy of neutral FenOm clusters (n, m < 16).

Neutral iron oxide clusters (FenOm, n, m ≤ 16) are produced in a laser vaporization source using O2 gas seeded in He. The neutral clusters are ionized with a sequence of femtosecond laser pulses and detected using time-of-flight mass spectrometry. Small clusters are confirmed to be most prominent in the stoichiometric (n = m) distribution, with m = n + 1 clusters observed above n = 4. Pump-probe spectroscopy is employed to study the dynamics of an electron transfer from an oxygen orbital to an iron nonbonding orbital of iron oxide clusters that is driven by absorption of a 400 nm photon. A bifurcation of the initial wavepacket occurs, where a femtosecond component is attributed to electron relaxation assisted through internuclear vibrational relaxation and high density of states, and a slow relaxation shows the formation of a bound excited state. The lifetime and relative ratio of the two pathways depend on both the cluster size and iron oxidation state. The femtosecond lifetime decreases with increased cluster size until a saturation timescale is achieved at n > 5. The relative population of the long-lived excited state decreases with cluster size and suggests that the excited electron remains on the Fe atom for >20 ps.