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The First Large Absorption Survey in H i (FLASH) is a large-area radio survey for neutral hydrogen in and around galaxies in the intermediate redshift range 0.4 < z < 1.0, using the 21-cm H i absorption line as a probe of cold neutral gas. The survey uses the ASKAP radio telescope and will cover 24,000 deg2 of sky over the next five years. FLASH breaks new ground in two ways – it is the first large H i absorption survey to be carried out without any optical preselection of targets, and we use an automated Bayesian line-finding tool to search through large datasets and assign a statistical significance to potential line detections. Two Pilot Surveys, covering around 3000 deg2 of sky, were carried out in 2019-22 to test and verify the strategy for the full FLASH survey. The processed data products from these Pilot Surveys (spectral-line cubes, continuum images, and catalogues) are public and available online. In this paper, we describe the FLASH spectral-line and continuum data products and discuss the quality of the H i spectra and the completeness of our automated line search. Finally, we present a set of 30 new H i absorption lines that were robustly detected in the Pilot Surveys, almost doubling the number of known H i absorption systems at 0.4 < z < 1. The detected lines span a wide range in H i optical depth, including three lines with a peak optical depth τ > 1, and appear to be a mixture of intervening and associated systems. Interestingly, around two-thirds of the lines found in this untargeted sample are detected against sources with a peaked-spectrum radio continuum, which are only a minor (5-20%) fraction of the overall radio-source population. The detection rate for H i absorption lines in the Pilot Surveys (0.3 to 0.5 lines per 40 deg2 ASKAP field) is a factor of two below the expected value. One possible reason for this is the presence of a range of spectral-line artefacts in the Pilot Survey data that have now been mitigated and are not expected to recur in the full FLASH survey. A future paper in this series will discuss the host galaxies of the H i absorption systems identified here.
The law and corpus linguistics movement shares many of the commitments of experimental jurisprudence. Both are concerned with testing intuitions about legal concepts through the lens of empirical evidence gathered through experimentation. Though often discussed in the context of a given case or legal problem, linguistic evidence from legal corpora can help provide content to otherwise indeterminate concepts in the law.
Using language evidence from linguistic corpora, we can begin to have more meaningful conversations about what concepts like ordinary meaning, ambiguity, and speech community might actually mean and make progress on the boundaries of these concepts and their implications for legal interpretation. And, because corpora are constructed from linguistic utterances made in natural linguistic settings, they can provide an important check and means of triangulation for experimental jurisprudence claims that are often premised on survey data.
Objectives/Goals: The never in mitosis kinase (NEK) family regulates vital processes, namely cell cycle progression, but their potential as therapeutic targets in TNBC has not been fully explored. Our studies aim to develop a toolkit to investigate the functional roles of NEKs in pathologies including carcinogenesis. Methods/Study Population: To assess differential NEK expression in normal and tumor tissues and correlation of gene expression with patient survival, we used Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier Plotter (KMPlot) pan-cancer analysis, respectively. Basal NEK protein levels were determined by immunoblot across a panel of cell lines, including breast cancer, osteosarcoma, hepatocellular carcinoma, and non-cancerous cells, to identify appropriate systems for evaluation of NEK function. Doxycycline-inducible cell lines were generated by transduction with lentiviral stocks of NEK shRNA and overexpression constructs and antibiotic selection. Expression was analyzed by qPCR and immunoblot. Results/Anticipated Results: Expression of NEK2, 4, 5, 6, 8, and 11 was higher in breast tumors compared to normal tissue by GEPIA analysis. Further examination using KMPlot showed a correlation between elevated NEK6 expression and decreased overall survival in patients with aggressive cancers. As an initial proof-of-concept study, we analyzed NEK6 protein expression in breast cancer cells. Levels of NEK6 were elevated in TNBC cells (MDA-MB-231) compared to hormone receptor positive (HR+) breast cancer cells (MCF7). Using complementary approaches to investigate the functional role of NEK6 in breast cancer, we depleted NEK6 expression using shRNAs in TNBC cells and expressed NEK6 in HR+ cells Discussion/Significance of Impact: Because kinase dysregulation promotes oncogenesis and metastasis, targeting kinases is a key strategy in therapeutic development. A NEK-specific molecular toolkit allows researchers to elucidate NEK functions and contributions to carcinogenesis, promoting advancement of novel therapies.
We present the first results from a new backend on the Australian Square Kilometre Array Pathfinder, the Commensal Realtime ASKAP Fast Transient COherent (CRACO) upgrade. CRACO records millisecond time resolution visibility data, and searches for dispersed fast transient signals including fast radio bursts (FRB), pulsars, and ultra-long period objects (ULPO). With the visibility data, CRACO can localise the transient events to arcsecond-level precision after the detection. Here, we describe the CRACO system and report the result from a sky survey carried out by CRACO at 110-ms resolution during its commissioning phase. During the survey, CRACO detected two FRBs (including one discovered solely with CRACO, FRB 20231027A), reported more precise localisations for four pulsars, discovered two new RRATs, and detected one known ULPO, GPM J1839 $-$10, through its sub-pulse structure. We present a sensitivity calibration of CRACO, finding that it achieves the expected sensitivity of 11.6 Jy ms to bursts of 110 ms duration or less. CRACO is currently running at a 13.8 ms time resolution and aims at a 1.7 ms time resolution before the end of 2024. The planned CRACO has an expected sensitivity of 1.5 Jy ms to bursts of 1.7 ms duration or less and can detect $10\times$ more FRBs than the current CRAFT incoherent sum system (i.e. 0.5 $-$2 localised FRBs per day), enabling us to better constrain the models for FRBs and use them as cosmological probes.
North Carolina growers have long struggled to control Italian ryegrass, and recent research has confirmed that some Italian ryegrass biotypes have become resistant to nicosulfuron, glyphosate, clethodim, and paraquat. Integrating alternative management strategies is crucial to effectively control such biotypes. The objectives of this study were to evaluate Italian ryegrass control with cover crops and fall-applied residual herbicides and investigate cover crop injury from residual herbicides. This study was conducted during the fall/winter of 2021–22 in Salisbury, NC, and fall/winter of 2021–22 and 2022–23 in Clayton, NC. The study was designed as a 3 × 5 split-plot in which the main plot consisted of three cover crop treatments (no-cover, cereal rye at 80 kg ha−1, and crimson clover at 18 kg ha−1), and the subplots consisted of five residual herbicide treatments (S-metolachlor, flumioxazin, metribuzin, pyroxasulfone, and nontreated). In the 2021–22 season at Clayton, metribuzin injured cereal rye and crimson clover 65% and 55%, respectively. However, metribuzin injured both cover crops ≤6% in 2022–23. Flumioxazin resulted in unacceptable crimson clover injury of 50% and 38% in 2021–22 and 2022–23 in Clayton and 40% in Salisbury, respectively. Without preemergence herbicides, cereal rye controlled Italian ryegrass by 85% and 61% at 24 wk after planting in 2021–22 and 2022–23 in Clayton and 82% in Salisbury, respectively. In 2021–22, Italian ryegrass seed production was lowest in cereal rye plots at both locations, except when it was treated with metribuzin. For example, in Salisbury, cereal rye plus metribuzin resulted in 39,324 seeds m–2, compared to ≤4,386 seeds m–2 from all other cereal rye treatments. In 2022–23, Italian ryegrass seed production in cereal rye was lower when either metribuzin or pyroxasulfone were used preemergence (2,670 and 1,299 seeds m–2, respectively) compared with cereal rye that did not receive an herbicide treatment (5,600 seeds m–2). cereal rye (Secale cereale L.) and crimson clover (Trifolium incarnatum L.)
Two studies were conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to determine the optimal granular ammonium sulfate (AMS) rate and application timing for pyroxasulfone-coated AMS. In the rate study, AMS rates included 161, 214, 267, 321, 374, 428, and 481 kg ha−1, equivalent to 34, 45, 56, 67, 79, 90, and 101 kg N ha−1, respectively. All rates were coated with pyroxasulfone at 118 g ai ha−1 and topdressed onto 5- to 7-leaf cotton. In the timing study, pyroxasulfone (118 g ai ha−1) was coated on AMS and topdressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf, 9- to 11-leaf, and first bloom cotton. In both studies, weed control and cotton tolerance to pyroxasulfone-coated AMS were compared to pyroxasulfone applied POST and POST-directed. The check in both studies received non-herbicide-treated AMS (321 kg ha−1). Before treatment applications, all plots (including the check) were maintained weed-free with glyphosate and glufosinate. In both studies, pyroxasulfone applied POST was most injurious (8% to 16%), while pyroxasulfone-coated AMS resulted in ≤4% injury. Additionally, no differences in cotton lint yield were observed in either study. With the exception of the lowest rate of AMS (161 kg ha−1; 79%), all AMS rates coated with pyroxasulfone controlled Palmer amaranth ≥83%, comparably to pyroxasulfone applied POST (92%) and POST-directed (89%). In the timing study, the application method did not affect Palmer amaranth control; however, applications made at the mid- and late timings outperformed early applications. These results indicate that pyroxasulfone-coated AMS can control Palmer amaranth comparably to pyroxasulfone applied POST and POST-directed, with minimal risk of cotton injury. However, the application timing could warrant additional treatment to achieve adequate late-season weed control.
An experiment was conducted in 2022 and 2023 near Rocky Mount and Clayton, NC, to evaluate residual herbicide-coated fertilizer for cotton tolerance and Palmer amaranth control. Treatments included acetochlor, atrazine, dimethenamid-P, diuron, flumioxazin, fluometuron, fluridone, fomesafen, linuron, metribuzin, pendimethalin, pyroxasulfone, pyroxasulfone + carfentrazone, S-metolachlor, and sulfentrazone. Each herbicide was individually coated on granular ammonium sulfate (AMS) and top-dressed at 321 kg ha−1 (67 kg N ha−1) onto 5- to 7-leaf cotton. The check plots received the equivalent rate of nonherbicide-treated AMS. Before top-dress, all plots (including the check) were treated with glyphosate and glufosinate to control previously emerged weeds. All herbicides except metribuzin resulted in transient cotton injury. Cotton response to metribuzin varied by year and location. In 2022, metribuzin caused 11% to 39% and 8% to 17% injury at the Clayton and Rocky Mount locations, respectively. In 2023, metribuzin caused 13% to 32% injury at Clayton and 73% to 84% injury at Rocky Mount. Pyroxasulfone (91%), pyroxasulfone + carfentrazone (89%), fomesafen (87%), fluridone (86%), flumioxazin (86%), and atrazine (85%) controlled Palmer amaranth ≥85%. Pendimethalin and fluometuron were the least effective treatments, resulting in 58% and 62% control, respectively. As anticipated, early season metribuzin injury translated into yield loss; plots treated with metribuzin yielded 640 kg ha−1 and were comparable to yields after linuron (790 kg ha−1) was used. These findings suggest that with the exception of metribuzin, residual herbicides coated onto AMS may be suitable and effective in cotton production, providing growers with additional modes of action for late-season control of multiple herbicide–resistant Palmer amaranth.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
We present the Pilot Survey Phase 2 data release for the Wide-field ASKAP L-band Legacy All-sky Blind surveY (WALLABY), carried-out using the Australian SKA Pathfinder (ASKAP). We present 1760 H i detections (with a default spatial resolution of 30′′) from three pilot fields including the NGC 5044 and NGC 4808 groups as well as the Vela field, covering a total of $\sim 180$ deg$^2$ of the sky and spanning a redshift up to $z \simeq 0.09$. This release also includes kinematic models for over 126 spatially resolved galaxies. The observed median rms noise in the image cubes is 1.7 mJy per 30′′ beam and 18.5 kHz channel. This corresponds to a 5$\sigma$ H i column density sensitivity of $\sim 9.1\times10^{19}(1 + z)^4$ cm$^{-2}$ per 30′′ beam and $\sim 20$ km s$^{-1}$ channel and a 5$\sigma$ H i mass sensitivity of $\sim 5.5\times10^8 (D/100$ Mpc)$^{2}$ M$_{\odot}$ for point sources. Furthermore, we also present for the first time 12′′ high-resolution images (“cut-outs”) and catalogues for a sub-sample of 80 sources from the Pilot Survey Phase 2 fields. While we are able to recover sources with lower signal-to-noise ratio compared to sources in the Public Data Release 1, we do note that some data quality issues still persist, notably, flux discrepancies that are linked to the impact of side lobes associated with the dirty beams due to inadequate deconvolution. However, in spite of these limitations, the WALLABY Pilot Survey Phase 2 has already produced roughly a third of the number of HIPASS sources, making this the largest spatially resolved H i sample from a single survey to date.
The Vela pulsar (J0835$-$4510) is known to exhibit variations in Faraday rotation and dispersion on multi-decade timescales due to the changing sightline through the surrounding Vela supernova remnant and the Gum Nebula. Until now, variations in Faraday rotation towards Vela have not been studied on timescales less than around a decade. We present the results of a high-cadence observing campaign carried out with the Aperture Array Verification System 2 (AAVS2), a prototype SKA-Low station, which received a significant bandwidth upgrade in 2022. We collected observations of the Vela pulsar and PSR J0630$-$2834 (a nearby pulsar located outside the Gum Nebula), spanning $\sim$1 and $\sim$0.3 yr, respectively, and searched for linear trends in the rotation measure (RM) as a function of time. We do not detect any significant trends on this timescale ($\sim$months) for either pulsar, but the constraints could be greatly improved with more accurate ionospheric models. For the Vela pulsar, the combination of our data and historical data from the published literature have enabled us to model long-term correlated trends in RM and dispersion measure (DM) over the past two decades. We detect a change in DM of $\sim$0.3 $\mathrm{cm}^{-3}\,\mathrm{pc}$ which corresponds to a change in electron density of $\sim$$10^5\,\mathrm{cm}^{-3}$ on a transverse length scale of $\sim$1–2 au. The apparent magnetic field strength in the time-varying region changes from $240^{+30}_{-20}\,\mu\mathrm{G}$ to $-6.2^{+0.7}_{-0.9}\,\mu\mathrm{G}$ over the time span of the dataset. As well as providing an important validation of polarimetry, this work highlights the pulsar monitoring capabilities of SKA-Low stations, and the niche science opportunities they offer for high-precision polarimetry and probing the microstructure of the magneto-ionic interstellar medium.
New drugs to target different pathways in pulmonary hypertension has resulted in increased combination therapy, but details of this use in infants are not well described. In this large multicenter database study, we describe the pharmacoepidemiology of combination pulmonary vasodilator therapy in critically ill infants.
Methods:
We identified inborn infants discharged home from a Pediatrix neonatal ICU from 1997 to 2020 exposed to inhaled nitric oxide, sildenafil, epoprostenol, or bosentan for greater than two consecutive days. We compared clinical variables and drug utilisation between infants receiving simultaneous combination and monotherapy. We reported each combination’s frequency, timing, and duration and graphically represented drug use over time.
Results:
Of the 7681 infants that met inclusion criteria, 664 (9%) received combination therapy. These infants had a lower median gestational age and birth weight, were more likely to have cardiac and pulmonary anomalies, receive cardiorespiratory support, and had higher in-hospital mortality than those receiving monotherapy. Inhaled nitric oxide and sildenafil were most frequently used, and utilisation of combination and monotherapy for all drugs increased over time. Inhaled nitric oxide and epoprostenol were used in infants with a higher gestational age, earlier postnatal age, and shorter duration than sildenafil and bosentan. Dual therapy with inhaled nitric oxide and sildenafil was the most common combination therapy.
Conclusion:
Our study revealed an increased use of combination pulmonary vasodilator therapy, favouring inhaled nitric oxide and sildenafil, yet with considerable practice variation. Further research is needed to determine the optimal combination, sequence, dosing, and disease-specific indications for combination therapy.
The primary objective was to grade the potential impact of antimicrobial stewardship program (ASP) interventions on patient safety at a single center using a newly developed scoring tool, the Antimicrobial Stewardship Impact Scoring Tool (ASIST).
Design:
Retrospective descriptive study.
Setting:
A 367-bed free-standing, pediatric academic medical center.
Methods:
The ASP team developed the ASIST which scored each intervention on an impact level (low, moderate, high) based on patient harm avoidance and degree of antibiotic optimization. Intervention frequency and characteristics were collected between May 1, 2022 and October 31, 2023. Intervention rates per impact level were calculated monthly.
Results:
The ASP team made 1024 interventions further classified as low (45.1%), moderate (47%), and high impact (7.9%). The interventions for general pediatrics (53.9%) and those to modify formulation (62.2%), dose/frequency (58.1%), and duration (57.5%) were frequently low impact. Hematology/oncology (12.5%), sub-specialty (11.7%), and surgical services (11.3%) had the greatest rate of high-impact interventions. Interventions to broaden antibiotics (40.8%) and those associated with antibiotics used to treat bacteremia (20.6%) were frequently classified as high-impact.
Conclusion:
The ASIST is an effective tool to link ASP interventions to prevention of antimicrobial-associated patient harm. For our ASP team, it provided meaningful data to present to hospital leadership and identified opportunities to prevent future harm and reduce ASP team workload.
Background: Hyperacute stroke care demands rapid, coordinated care. Traditional metrics like Door-to-Needle time are pivotal but insufficient for capturing the complexity of endovascular stroke interventions. The SMILES collaboration aims to standardize and optimize protocols for door-to-intervention times, incorporating Crew Resource Management (CRM). Methods: The multidisciplinary initiative integrates both hospitals, ED, neurology, and QI teams. We employed a comprehensive approach: stakeholder engagement, simulation-based learning, process mapping, and literature review. Emphasis was placed on enhancing situational awareness, triage and prioritization, cognitive load management, role clarity, effective communication, and debriefing. Results: The collaboration led to PDSA cycles and development of refined stroke protocols. Interventions included: 1) A ’zero point survey’ for team pre-arrival briefings, enhancing situational awareness and role clarity; 2) Streamlined patient registration to reduce cognitive load and improve triage efficiency; 3) Direct transfer of patients to imaging. Additionally, digital tools were implemented to facilitate communication. Simulation sessions reinforced CRM principles, leading to improved team cohesion and operational performance. Conclusions: The SMILES initiative is grounded in CRM principles by standardizing protocols and emphasizing non-technical skills crucial for high-stakes environments. This improves outcomes but also fosters a culture of safety and efficiency. Future directions include an evaluation of these protocols’ impact on patient factors.
Understanding characteristics of healthcare personnel (HCP) with SARS-CoV-2 infection supports the development and prioritization of interventions to protect this important workforce. We report detailed characteristics of HCP who tested positive for SARS-CoV-2 from April 20, 2020 through December 31, 2021.
Methods:
CDC collaborated with Emerging Infections Program sites in 10 states to interview HCP with SARS-CoV-2 infection (case-HCP) about their demographics, underlying medical conditions, healthcare roles, exposures, personal protective equipment (PPE) use, and COVID-19 vaccination status. We grouped case-HCP by healthcare role. To describe residential social vulnerability, we merged geocoded HCP residential addresses with CDC/ATSDR Social Vulnerability Index (SVI) values at the census tract level. We defined highest and lowest SVI quartiles as high and low social vulnerability, respectively.
Results:
Our analysis included 7,531 case-HCP. Most case-HCP with roles as certified nursing assistant (CNA) (444, 61.3%), medical assistant (252, 65.3%), or home healthcare worker (HHW) (225, 59.5%) reported their race and ethnicity as either non-Hispanic Black or Hispanic. More than one third of HHWs (166, 45.2%), CNAs (283, 41.7%), and medical assistants (138, 37.9%) reported a residential address in the high social vulnerability category. The proportion of case-HCP who reported using recommended PPE at all times when caring for patients with COVID-19 was lowest among HHWs compared with other roles.
Conclusions:
To mitigate SARS-CoV-2 infection risk in healthcare settings, infection prevention, and control interventions should be specific to HCP roles and educational backgrounds. Additional interventions are needed to address high social vulnerability among HHWs, CNAs, and medical assistants.
Observing stars and satellites in optical wavelengths during the day (optical daytime astronomy) has begun a resurgence of interest. The recent dramatic dimming event of Betelgeuse has spurred interest in continuous monitoring of the brightest variable stars, even when an object is only visible during the day due to their proximity to the Sun. In addition, an exponential increase in the number of satellites being launched into low Earth orbit in recent years has driven an interest in optical daytime astronomy for the detection and monitoring of satellites in space situational awareness (SSA) networks. In this paper we explore the use of the Huntsman Telescope as an optical daytime astronomy facility, by conducting an exploratory survey using a pathfinder instrument. We find that an absolute photometric accuracy between 1–10% can be achieved during the day, with a detection limit of V band 4.6 mag at midday in sloan $g,$ and $r,$ wavelengths. In addition, we characterise the daytime sky brightness, colour, and observing conditions in order to achieve the most reliable and highest signal-to-noise observations within the limitations of the bright sky background. We undertake a 7-month survey of the brightness of Betelgeuse during the day and demonstrate that our results are in agreement with measurements from other observatories. Finally we present our preliminary results that demonstrate obtaining absolute photometric measurements of the International Space Station during the day.
Both impulsivity and compulsivity have been identified as risk factors for problematic use of the internet (PUI). Yet little is known about the relationship between impulsivity, compulsivity and individual PUI symptoms, limiting a more precise understanding of mechanisms underlying PUI.
Aims
The current study is the first to use network analysis to (a) examine the unique association among impulsivity, compulsivity and PUI symptoms, and (b) identify the most influential drivers in relation to the PUI symptom community.
Method
We estimated a Gaussian graphical model consisting of five facets of impulsivity, compulsivity and individual PUI symptoms among 370 Australian adults (51.1% female, mean age = 29.8, s.d. = 11.1). Network structure and bridge expected influence were examined to elucidate differential associations among impulsivity, compulsivity and PUI symptoms, as well as identify influential nodes bridging impulsivity, compulsivity and PUI symptoms.
Results
Results revealed that four facets of impulsivity (i.e. negative urgency, positive urgency, lack of premeditation and lack of perseverance) and compulsivity were related to different PUI symptoms. Further, compulsivity and negative urgency were the most influential nodes in relation to the PUI symptom community due to their highest bridge expected influence.
Conclusions
The current findings delineate distinct relationships across impulsivity, compulsivity and PUI, which offer insights into potential mechanistic pathways and targets for future interventions in this space. To realise this potential, future studies are needed to replicate the identified network structure in different populations and determine the directionality of the relationships among impulsivity, compulsivity and PUI symptoms.
OBJECTIVES/GOALS: In this study, we aim to report the role of porins and blaCTX-M β-lactamases among Escherichia coli and Klebsiella pneumoniae, focusing on emerging carbapenem resistant Enterobacterales (CRE) subtypes, including non-carbapenemase producing Enterobacterales (NCPE) and ertapenem-resistant but meropenem-susceptible (ErMs) strains. METHODS/STUDY POPULATION: Whole genome sequencing was conducted on 76 carbapenem-resistant isolates across 5 hospitals in San Antonio, U.S. Among these, NCP isolates accounted for the majority of CRE (41/76). Identification and antimicrobial susceptibility testing (AST) results were collected from the clinical charts. Repeat speciation was determined through whole genome sequencing (WGS) analysis and repeat AST, performed with microdilution or ETEST®. Minimum inhibitory concentrations (MIC) were consistent with Clinical and Laboratory Standards Institute (CLSI M100, ED33). WGS and qPCR were used to characterize the resistome of all clinical CRE subtypes, while western blotting and liquid chromatography with tandem mass spectrometry (LC-MS-MS) were used to determine porin expression and carbapenem hydrolysis, respectively. RESULTS/ANTICIPATED RESULTS: blaCTX-Mwas found to be most prevalent among NCP isolates (p = 0.02). LC-MS/MS analysis of carbapenem hydrolysis revealed that blaCTX-M-mediated carbapenem hydrolysis, indicating the need to reappraise the term, “non-carbapenemase (NCP)®” for quantitatively uncharacterized CRE strains harboring blaCTX-M. Susceptibility results showed that 56% of all NCPE isolates had an ErMs phenotype (NCPE vs. CPE, p < 0.001), with E. coli driving the phenotype (E. coli vs. K. pneumoniae, p < 0.001). ErMs strains carrying blaCTX-M, had 4-fold more copies of blaCTX-M than ceftriaxone-resistant but ertapenem-susceptible isolates (3.7 v. 0.9, p < 0.001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage ofompC. DISCUSSION/SIGNIFICANCE: Overall, this work provides evidence of a collaborative effort between blaCTX-M and OmpC in NCP strains that confer resistance to ertapenem but not meropenem. Clinically, CRE subtypes are not readily appreciated, potentially leading to mismanagement of CRE infected patients. A greater focus on optimal treatments for CRE subtypes is needed.
Clinical outcomes of repetitive transcranial magnetic stimulation (rTMS) for treatment of treatment-resistant depression (TRD) vary widely and there is no mood rating scale that is standard for assessing rTMS outcome. It remains unclear whether TMS is as efficacious in older adults with late-life depression (LLD) compared to younger adults with major depressive disorder (MDD). This study examined the effect of age on outcomes of rTMS treatment of adults with TRD. Self-report and observer mood ratings were measured weekly in 687 subjects ages 16–100 years undergoing rTMS treatment using the Inventory of Depressive Symptomatology 30-item Self-Report (IDS-SR), Patient Health Questionnaire 9-item (PHQ), Profile of Mood States 30-item, and Hamilton Depression Rating Scale 17-item (HDRS). All rating scales detected significant improvement with treatment; response and remission rates varied by scale but not by age (response/remission ≥ 60: 38%–57%/25%–33%; <60: 32%–49%/18%–25%). Proportional hazards models showed early improvement predicted later improvement across ages, though early improvements in PHQ and HDRS were more predictive of remission in those < 60 years (relative to those ≥ 60) and greater baseline IDS burden was more predictive of non-remission in those ≥ 60 years (relative to those < 60). These results indicate there is no significant effect of age on treatment outcomes in rTMS for TRD, though rating instruments may differ in assessment of symptom burden between younger and older adults during treatment.
We argue that editorial independence, through robust practice of publication ethics and research integrity, promotes good science and prevents bad science. We elucidate the concept of research integrity, and then discuss the dimensions of editorial independence. Best practice guidelines exist, but compliance with these guidelines varies. Therefore, we make recommendations for protecting and strengthening editorial independence.