Reducing Postoperative CT Imaging for Children With Complicated Appendicitis: A Pediatric Surgical Quality Collaborative Quality Improvement Project.

BACKGROUND: Despite widespread initiatives to reduce ionizing radiation for appendicitis diagnosis, computed tomography (CT) scanning postoperatively remains common. The Pediatric Surgery Quality Collaborative (PSQC) aimed to identify differences between children's hospitals with high and low postoperative CT usage for complicated appendicitis. METHODS: Using National Surgery Quality Improvement Program Pediatric data from PSQC children's hospitals, we compared postoperative CT imaging for complicated appendicitis (April 2020-March 2021). Key stakeholders from 11 hospitals (5 low CT utilization, 6 high CT utilization) participated in semi-structured interviews regarding postoperative imaging. Qualitative analysis of transcripts was performed deductively and inductively based on the Theoretical Domains Framework (TDF). RESULTS: Five of twelve TDF domains were most prominent in influencing CT use: skills, beliefs about capabilities, intentions/goals, memory and decision processes, and environment. Children's hospitals with lower rates of postoperative CT use tended to: trust and educate the ultrasound technicians; believe US strengths outweigh weaknesses; image no sooner than 7 days postoperatively; have access to sufficient quality improvement resources; maintain trusting relationships between specialties; and prioritize radiation stewardship. CONCLUSION: Hospitals at extremes of postoperative CT use for complicated appendicitis reveal strategies for improvement, which include imaging protocol development and adherence, quality improvement resource availability, interdisciplinary collaboration, and promoting radiation stewardship. LEVEL OF EVIDENCE: Level V.

A Review of Management of Congenital Sublobar Hyperinflation at a Single Institution.

There has been an increased recognition of a subset of congenital lobar emphysema (CLE), termed congenital sublobar hyperinflation (CSLH), which may affect only a segment of lung as opposed to an entire lobe. This is an uncommon variant for which there is a paucity of information in published literature. The majority of CLE are managed surgically. Current literature suggests non-operative management for CSLH. However, there has been slow adoption of non-operative management and there is not a well-established observation pathway. A retrospective review of all pediatric patients diagnosed with CSLH at a single institution was performed from 2017 to 2023 to determine if this variant may be safely managed with observation. A total of 10 patients were identified. Of these, three patients had consolidation on cross-sectional imaging; therefore, operative intervention was undertaken given diagnostic uncertainty. All patients managed observationally remained asymptomatic. This case series validates non-operative management for patients with asymptomatic CSLH.

Computed tomography-guided cannulated lag screw placement for treatment of ununited anconeal process: surgical technique, clinical outcome, and radiographic healing in 7 dogs.

OBJECTIVE: A novel technique and outcomes for correction of ununited anconeal process (UAP) via CT-guided cannulated lag screw placement in 7 canine patients is described. ANIMALS: Cases of canine patients (7 patients/8 elbows) diagnosed with UAP that subsequently underwent CT-guided cannulated lag screw placement were retrospectively evaluated. CLINICAL PRESENTATION: Pre- and postoperative exam findings (lameness and pain on range of motion) are presented. Preoperative radiographs and postoperative radiographs at 2 time points (approximately 8 weeks postoperatively and at the time of the most recent imaging; mean, 221 days; range, 85 to 828 days) were scored for degree of arthrosis and postoperative radiographs were evaluated for radiographic union. Complications were reported and stratified by severity and time postoperatively. RESULTS: Minor perioperative (0 to 3 months postoperatively) complications included seroma formation (n = 1) and major perioperative complications involved development of surgical site infections (2), with 2 patients requiring implant removal in the perioperative period (44 and 82 days postoperatively). All patients achieved radiographic union, defined as partial or complete bridging of the anconeal process to the ulna within the study period (mean radiographic follow-up time 221 days postoperatively; range, 85 to 828 days; 5/8 joints partial bridging, 3/8 joints complete bridging) and pre- versus postoperative elbow arthrosis scores remained static in all patients. CLINICAL RELEVANCE: The case outcomes described support the use of CT-guided cannulated lag screw placement as a feasible option for treatment of UAP.

Correction: Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy.

Correction for 'Label free localization of nanoparticles in live cancer cells using spectroscopic microscopy' by Graham L. C. Spicer et al., Nanoscale, 2018, 10, 19125-19130, https://doi.org/10.1039/C8NR07481J.

Thunderstorms, Pollen, and Severe Asthma in a Midwestern, USA, Urban Environment, 2007-2018.

BACKGROUND: Previous research has shown an association between individual thunderstorm events in the presence of high pollen, commonly called thunderstorm asthma, and acute severe asthma events, but little work has studied risk over long periods of time, using detailed measurements of storms and pollen. METHODS: We estimated change in the risk of asthma-related emergency room visits related to thunderstorm asthma events in the Minneapolis-St. Paul metropolitan area over the years 2007-2018. We defined thunderstorm asthma events as daily occurrence of two or more lightning strikes during high pollen periods interpolating weather and pollen monitor data and modeling lightning counts. We acquired daily counts of asthma-related emergency department visits from the Minnesota Hospital Association and used a quasi-Poisson time-series regression to estimate overall relative risk of emergency department visits during thunderstorm asthma events. RESULTS: We observed a 1.047 times higher risk (95% confidence interval = 1.012, 1.083) of asthma-related emergency department visits on the day of thunderstorm asthma event. Our findings are robust to adjustment for temperature, humidity, wind, precipitation, ozone, PM 2.5 , day of week, and seasonal variation in asthma cases. Occurrence of lightning alone or pollen alone showed no association with the risk of severe asthma. A two-stage analysis combining individual zip code-level results shows similar RR, and we see no evidence of spatial correlation or spatial heterogeneity of effect. DISCUSSION: Our results support an association between co-occurrence of lightning and pollen and risk of severe asthma events. Our approach incorporates lightning and pollen data and small-spatial area exposure and outcome counts.

The Rapid Implementation of Ad Hoc Tele-Critical Care Respiratory Therapy (eRT) Service in the Wake of the COVID-19 Surge.

A 24/7 telemedicine respiratory therapist (eRT) service was set up as part of the established University of Pennsylvania teleICU (PENN E-LERT®) service during the COVID-19 pandemic, serving five hospitals and 320 critical care beds to deliver effective remote care in lieu of a unit-based RT. The eRT interventions were components of an evidence-based care bundle and included ventilator liberation protocols, low tidal volume protocols, tube patency, and an extubation checklist. In addition, the proactive rounding of patients, including ventilator checks, was included. A standardized data collection sheet was used to facilitate the review of medical records, direct audio-visual inspection, or direct interactions with staff. In May 2020, a total of 1548 interventions took place, 93.86% of which were coded as "routine" based on established workflows, 4.71% as "urgent", 0.26% "emergent", and 1.17% were missing descriptors. Based on the number of coded interventions, we tracked the number of COVID-19 patients in the system. The average intervention took 6.1 ± 3.79 min. In 16% of all the interactions, no communication with the bedside team took place. The eRT connected with the in-house respiratory therapist (RT) in 66.6% of all the interventions, followed by house staff (9.8%), advanced practice providers (APP; 2.8%), and RN (2.6%). Most of the interaction took place over the telephone (88%), secure text message (16%), or audio-video telemedicine ICU platform (1.7%). A total of 5115 minutes were spent on tasks that a bedside clinician would have otherwise executed, reducing their exposure to COVID-19. The eRT service was instrumental in several emergent and urgent critical interventions. This study shows that an eRT service can support the bedside RT providers, effectively monitor best practice bundles, and carry out patient-ventilator assessments. It was effective in certain emergent situations and reduced the exposure of RTs to COVID-19. We plan to continue the service as part of an integrated RT service and hope to provide a framework for developing similar services in other facilities.

Performance measurement and management in the British higher education sector.

Theoretical enquiry and empirical studies demonstrate the significance of performance management (PM) in the higher education sector and it is a fulcrum for developing a strategic role for people management within universities. In spite of the perceived weaknesses of people management in the higher education sector, in general, the current period of rapid and substantial contextual change may necessitate greater formalisation of HR practices across the British higher education sector. In addition to the changing role of the HR function and line managers, these developments may result in an increasingly stringent performance regime across the sector, especially in more hard-pressed institutions. Through a literature review and a pilot study, this paper attempts to address two main research questions: (i) what are the current performance management practices in the British Higher Education sector? and (ii) what needs to be done to strategically align these practices within HEIs in the UK? This paper discusses the wider literature related to performance management in general and to academic institutions in particular. We also undertook a small-scale qualitative study to explore the views of HR professionals on the need for, and the current performance measurement systems in their universities in the UK. The preliminary findings confirmed that PM is a key issue in the respondents' institutions, with substantial and recent changes in policy. This underscores the need for a large-scale research agenda to capture the current dynamics of change the sector is undergoing. The paper concludes by stimulating a policy debate and placing a number of research calls, along with suggestions on how these research questions may be investigated.

Nanoscale chromatin imaging and analysis platform bridges 4D chromatin organization with molecular function.

Extending across multiple length scales, dynamic chromatin structure is linked to transcription through the regulation of genome organization. However, no individual technique can fully elucidate this structure and its relation to molecular function at all length and time scales at both a single-cell level and a population level. Here, we present a multitechnique nanoscale chromatin imaging and analysis (nano-ChIA) platform that consolidates electron tomography of the primary chromatin fiber, optical super-resolution imaging of transcription processes, and label-free nano-sensing of chromatin packing and its dynamics in live cells. Using nano-ChIA, we observed that chromatin is localized into spatially separable packing domains, with an average diameter of around 200 nanometers, sub-megabase genomic size, and an internal fractal structure. The chromatin packing behavior of these domains exhibits a complex bidirectional relationship with active gene transcription. Furthermore, we found that properties of PDs are correlated among progenitor and progeny cells across cell division.

Clonal sector analysis and cell ablation confirm a function for DORNROESCHEN-LIKE in founder cells and the vasculature in Arabidopsis.

MAIN CONCLUSION: Inducible lineage analysis and cell ablation via conditional toxin expression in cells expressing the DORNRÖSCHEN-LIKE transcription factor represent an effective and complementary adjunct to conventional methods of functional gene analysis. Classical methods of functional gene analysis via mutational and expression studies possess inherent limitations, and therefore, the function of a large proportion of transcription factors remains unknown. We have employed two complementary, indirect methods to obtain functional information for the AP2/ERF transcription factor DORNRÖSCHEN-LIKE (DRNL), which is dynamically expressed in flowers and marks lateral organ founder cells. An inducible, two-component Cre-Lox system was used to express beta-glucuronidase GUS in cells expressing DRNL, to perform a sector analysis that reveals lineages of cells that transiently expressed DRNL throughout plant development. In a complementary approach, an inducible system was used to ablate cells expressing DRNL using diphtheria toxin A chain, to visualise the phenotypic consequences. These complementary analyses demonstrate that DRNL functionally marks founder cells of leaves and floral organs. Clonal sectors also included the vasculature of the leaves and petals, implicating a previously unidentified role for DRNL in provasculature development, which was confirmed in cotyledons by closer analysis of drnl mutants. Our findings demonstrate that inducible gene-specific lineage analysis and cell ablation via conditional toxin expression represent an effective and informative adjunct to conventional methods of functional gene analysis.

Characteristics, Outcomes, and Trends of Patients With COVID-19-Related Critical Illness at a Learning Health System in the United States.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to surge in the United States and globally. OBJECTIVE: To describe the epidemiology of COVID-19-related critical illness, including trends in outcomes and care delivery. DESIGN: Single-health system, multihospital retrospective cohort study. SETTING: 5 hospitals within the University of Pennsylvania Health System. PATIENTS: Adults with COVID-19-related critical illness who were admitted to an intensive care unit (ICU) with acute respiratory failure or shock during the initial surge of the pandemic. MEASUREMENTS: The primary exposure for outcomes and care delivery trend analyses was longitudinal time during the pandemic. The primary outcome was all-cause 28-day in-hospital mortality. Secondary outcomes were all-cause death at any time, receipt of mechanical ventilation (MV), and readmissions. RESULTS: Among 468 patients with COVID-19-related critical illness, 319 (68.2%) were treated with MV and 121 (25.9%) with vasopressors. Outcomes were notable for an all-cause 28-day in-hospital mortality rate of 29.9%, a median ICU stay of 8 days (interquartile range [IQR], 3 to 17 days), a median hospital stay of 13 days (IQR, 7 to 25 days), and an all-cause 30-day readmission rate (among nonhospice survivors) of 10.8%. Mortality decreased over time, from 43.5% (95% CI, 31.3% to 53.8%) to 19.2% (CI, 11.6% to 26.7%) between the first and last 15-day periods in the core adjusted model, whereas patient acuity and other factors did not change. LIMITATIONS: Single-health system study; use of, or highly dynamic trends in, other clinical interventions were not evaluated, nor were complications. CONCLUSION: Among patients with COVID-19-related critical illness admitted to ICUs of a learning health system in the United States, mortality seemed to decrease over time despite stable patient characteristics. Further studies are necessary to confirm this result and to investigate causal mechanisms. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

Developing the eMedical Student (eMS)-A Pilot Project Integrating Medical Students into the Tele-ICU during the COVID-19 Pandemic and beyond.

The COVID-19 pandemic has accelerated the demand for virtual healthcare delivery and highlighted the scarcity of telehealth medical student curricula, particularly tele-critical care. In partnership with the Penn E-lert program and the Department of Anesthesiology and Critical Care, the Perelman School of Medicine (PSOM) established a tele-ICU rotation to support the care of patients diagnosed with COVID-19 in the Intensive Care Unit (ICU). The four-week course had seven elements: (1) 60 h of clinical engagement; (2) multiple-choice pretest; (3) faculty-supervised, student-led case and topic presentations; (4) faculty-led debriefing sessions; (5) evidence-based-medicine discussion forum; (6) multiple-choice post-test; and (7) final reflection. Five third- and fourth-year medical students completed 300 h of supervised clinical engagement, following 16 patients over three weeks and documenting 70 clinical interventions. Knowledge of critical care and telehealth was demonstrated through improvement between pre-test and post-test scores. Professional development was demonstrated through post-course preceptor and learner feedback. This tele-ICU rotation allowed students to gain telemedicine exposure and participate in the care of COVID patients in a safe environment.

Gene regulatory networks controlled by FLOWERING LOCUS C that confer variation in seasonal flowering and life history.

Responses to environmental cues synchronize reproduction of higher plants to the changing seasons. The genetic basis of these responses has been intensively studied in the Brassicaceae. The MADS-domain transcription factor FLOWERING LOCUS C (FLC) plays a central role in the regulatory network that controls flowering of Arabidopsis thaliana in response to seasonal cues. FLC blocks flowering until its transcription is stably repressed by extended exposure to low temperatures in autumn or winter and, therefore, FLC activity is assumed to limit flowering to spring. Recent reviews describe the complex epigenetic mechanisms responsible for FLC repression in cold. We focus on the gene regulatory networks controlled by FLC and how they influence floral transition. Genome-wide approaches determined the in vivo target genes of FLC and identified those whose transcription changes during vernalization or in flc mutants. We describe how studying FLC targets such as FLOWERING LOCUS T, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE 15, and TARGET OF FLC AND SVP 1 can explain different flowering behaviours in response to vernalization and other environmental cues, and help define mechanisms by which FLC represses gene transcription. Elucidating the gene regulatory networks controlled by FLC provides access to the developmental and physiological mechanisms that regulate floral transition.

Auxin and Flower Development: A Blossoming Field.

The establishment of the species-specific floral organ body plan involves many coordinated spatiotemporal processes, which include the perception of positional information that specifies floral meristem and floral organ founder cells, coordinated organ outgrowth coupled with the generation and maintenance of inter-organ and inter-whorl boundaries, and the termination of meristem activity. Auxin is integrated within the gene regulatory networks that control these processes and plays instructive roles at the level of tissue-specific biosynthesis and polar transport to generate local maxima, perception, and signaling. Key features of auxin function in several floral contexts include cell nonautonomy, interaction with cytokinin gradients, and the central role of MONOPTEROS and ETTIN to regulate canonical and noncanonical auxin response pathways, respectively. Arabidopsis flowers are not representative of the enormous angiosperm floral diversity; therefore, comparative studies are required to understand how auxin underlies these developmental differences. It will be of great interest to compare the conservation of auxin pathways among flowering plants and to discuss the evolutionary role of auxin in floral development.

Caregiver's Recall of Stroke Discharge Education Exceeds Patients and Is Associated With Greater Satisfaction.

Stroke survivors and their caregivers report not receiving enough information at discharge. To identify strengths and weaknesses of stroke discharge education, we delivered questionnaires that assessed patient and caregiver recall, perceived utility, and satisfaction at discharge as well as 1- and 3-month follow-up. Categorical data of responses were compared between time periods using Fischer exact test. Recall significantly differed between discharge (86%) and 1-month follow-up (54%, P < .05), but not discharge and 3-month follow-up (69%). Patient perceived utility at both 1 month (69%) and 3 months (64%) was lower than at discharge (92%, P < .05). Patient satisfaction was lower at 1 month (69%) and 3 months (54%) than discharge (92%, P < .05). Caregiver recall declined from discharge (81%) to 1 month (65%) but improved from 1 to 3 months (82%, P < .05). Caregiver satisfaction and perceived utility remained positive through the study. The results suggest stroke patients and their caregivers suffer from education recall failure over time that is associated with worse satisfaction and perceived utility by patients. Reinforcement at 1 month may improve caregiver recall. We conclude that education for caregivers may be more reliably reinforced, suggesting a role in continued patient education.

Functional dissection of the DORNRÖSCHEN-LIKE enhancer 2 during embryonic and phyllotactic patterning.

MAIN CONCLUSION: The Arabidopsis DORNRÖSCHEN-LIKE enhancer 2 comprises a high-occupancy target region in the IM periphery that integrates signals for the spiral phyllotactic pattern and cruciferous arrangement of sepals. Transcription of the DORNRÖSCHEN-LIKE (DRNL) gene marks lateral organ founder cells (LOFCs) in the peripheral zone of the inflorescence meristem (IM) and enhancer 2 (En2) in the DRNL promoter upstream region essentially contributes to this phyllotactic transcription pattern. Further analysis focused on the phylogenetically highly conserved 100-bp En2core element, which was sufficient to promote the phyllotactic pattern, but was recalcitrant to further shortening. Here, we show that En2core functions independent of orientation and create a series of mutations to study consequences on the transcription pattern. Their analysis shows that, first, in addition to in the inflorescence apex, En2core acts in the embryo; second, cis-regulatory target sequences are distributed throughout the 100-bp element, although substantial differences exist in their function between embryo and IM. Third, putative core auxin response elements (AuxREs) spatially activate or restrict DRNL expression, and fourth, according to chromatin configuration data, En2core enhancer activity in LOFCs correlates with an open chromatin structure at the DRNL transcription start. In combination, mutational and chromatin analyses imply that En2core comprises a high-occupancy target (HOT) region for transcription factors, which implements phyllotactic information for the spiral LOFC pattern in the IM periphery and coordinates the cruciferous array of floral sepals. Our data disfavor a contribution of activating auxin response factors (ARFs) but do not exclude auxin as a morphogenetic signal.

Antidepressant Use for Improving Functional Ischemic Stroke Outcomes.

Objective To assess the effect of antidepressants on functional post-stroke recovery, we conducted a retrospective analysis among acute ischemic stroke patients with a subgroup analysis of severe stroke cases, assessing outcomes through 18 months. Methods A retrospectively gathered ischemic stroke population was obtained from an institutional database. Grouping was via intention-to-treat with antidepressant use post-stroke or lack thereof. Patients with severe stroke (NIHSS ≥ 21) were further analyzed independently. The primary and secondary outcomes were modified Rankin scale (mRS) and survival over 18 months, respectively. Patient demographics and NIHSS were obtained. Data were analyzed in R using adjusted logarithmic-multivariate models. Adjusted Cox proportional hazards models were used to estimate associations between survival and antidepressants. Results Eight-hundred six patients (52 severe strokes) received antidepressants post-stroke while 948 (56 severe) did not. The antidepressant group was more female (56% to 43.5%) and had significantly better survival rates (88% vs. 79%, HR 0.62, p < 0.01) but not mRS scores (2.13 vs 2.24, p = 0.262) by the end of the study period. Among severe stroke cases, those receiving antidepressants showed better survival rates (79% vs. 60%, HR 0.36, p=0.026) and most recent mRS score (3.9 vs 5, p < 0.01). The analysis controlling for demographics variables retained significance. Conclusion Antidepressant use post-stroke may improve functional outcomes in patients suffering from severe stroke and may decrease all-cause mortality for strokes of any severity.

Multimodal interference-based imaging of nanoscale structure and macromolecular motion uncovers UV induced cellular paroxysm.

Understanding the relationship between intracellular motion and macromolecular structure remains a challenge in biology. Macromolecular structures are assembled from numerous molecules, some of which cannot be labeled. Most techniques to study motion require potentially cytotoxic dyes or transfection, which can alter cellular behavior and are susceptible to photobleaching. Here we present a multimodal label-free imaging platform for measuring intracellular structure and macromolecular dynamics in living cells with a sensitivity to macromolecular structure as small as 20 nm and millisecond temporal resolution. We develop and validate a theory for temporal measurements of light interference. In vitro, we study how higher-order chromatin structure and dynamics change during cell differentiation and ultraviolet (UV) light irradiation. Finally, we discover cellular paroxysms, a near-instantaneous burst of macromolecular motion that occurs during UV induced cell death. With nanoscale sensitive, millisecond resolved capabilities, this platform could address critical questions about macromolecular behavior in live cells.

Histology versus phylogeny: Viewing plant embryogenesis from an evo-devo perspective.

The goal of evolutionary developmental (evo-devo) biology compares inter-organism developmental processes to infer ancestral relationships and evolutionary adaptations. Frameworks to address macroevolutionary traits such as plant embryogenesis commonly involve two complementary approaches. Historically, focus has been placed on comparative morphology and histology, but more recently, accumulating genome data from diverse taxa have elicited the construction of molecular phylogenies, which aid the identification of gene homologies and orthologies that have been adaptive and that underlie differences in form. Distinguishing between ancestral or derived traits in phyletic or cladistic-driven approaches is challenging, but relates to the broader applicability of existing developmental models such as Arabidopsis thaliana.

Sub-10-nm imaging of nucleic acids using spectroscopic intrinsic-contrast photon-localization optical nanoscopy (SICLON).

Elucidating chromatin structure in vitro requires resolution below 10 nm to visualize the mononucleosome has been an ongoing challenge. In this work, we achieve sub-10-nm imaging of nucleic acids via spectroscopic intrinsic-contrast photon-localization optical nanoscopy (SICLON) without the use of external labels. SICLON leverages two key innovations: using endogenous nucleotides as the emission source and a custom-made imaging system that can simultaneously record the position and optical spectra of emitting molecules. With a novel spectral regression algorithm that identifies the spectroscopic fingerprints of neighboring molecules that were previously indistinguishable, we demonstrate the utility of SICLON by visualizing unlabeled poly-nucleotides and linear single-stranded DNA fibers with a resolution of 6.2 nm.