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Background: Most studies of device‐detected atrial fibrillation (AF) have recommended indefinite anticoagulation once a patient crosses a particular threshold for AF duration or burden. However, durations and burdens are known to fluctuate over time, but little is known about the magnitude of spontaneous fluctuations and the potential impact on anticoagulation decisions. Objective: To quantify spontaneous fluctuations in AF duration and burden in patients with implantable loop recorders (ILRs) Methods: We reviewed all ILR interrogations for patients with non‐permanent AF at our institution from 2018 to 2023. We excluded patients treated with rhythm control. The duration of longest AF episode at each interrogation was classified as < 6, 6–24, and > 24 h, and the AF burden reported at each interrogation was classified as < 2%, 2%–11.4%, and > 11.4%. Results: Out of 156 patients, the mean age at ILR implant was 70.9 ± 12.5 years, CHA2DS2‐VASc score was 4.2 ± 1.8, duration of ILR follow‐up was 23.4 ± 11.2 months, and number of ILR interrogations per patient was 18.0 ± 8.9. The duration of longest AF episode at any point during follow‐up was < 6 , 6–24 , and > 24 h in 110, 30, and 16 patients, respectively. Among the 30 patients with a longest AF episode of 6–24 h at some point during follow‐up, out of 594 total ILR interrogations, only 75 (12%) showed a longest episode of 6–24 h. In the remaining 519 interrogations, the longest episode was < 6 h. In patients with a longest episode of > 24 h at any point during follow‐up (n = 16), only 47 out of 320 total ILR interrogations (15%) showed an episode of > 24 h. When evaluating AF burden, 96, 38, and 22 patients had maximum reported AF burdens of < 2%, 2%–11.4%, and > 11.4% at any point during ILR follow‐up. Among those with a maximum burden of 2%–11.4% at some point during follow‐up (n = 38), out of 707 ILR interrogations, only 76 (11%) showed a burden of 2%–11.4%. In the remaining 631 interrogations, the burden was < 2%. In the 22 patients with a burden > 11.4% at some point during follow‐up, only 80 out of 480 interrogations (17%) showed a burden of > 11.4%. In 65% of interrogations, the burden was < 2%. Conclusion: Significant, spontaneous fluctuations in AF burden and duration are common in patients with ILRs. Even in patients with AF episodes of 6–24 h or > 24 h at some point during follow‐up, the vast majority of interrogations show episodes of < 6 h. Similarly, in patients with burdens of 2%–11.4% or > 11.4% at some point during follow‐up, the vast majority of interrogations show burdens of < 2%. More data are needed to determine whether crossing an AF burden or duration threshold once is sufficient to merit lifelong anticoagulation or whether spontaneous fluctuations in AF burden and duration should impact anticoagulation decisions. [ABSTRACT FROM AUTHOR]

Previous studies that intercompared global Level‐4 (L4) sea surface temperature (SST) analyses were centered on the assessment of the accuracy and bias of SST by comparing them with independent near‐surface Argo profile temperature data. This type of assessment is centered on the absolute value of SST rather than on SST spatial properties (gradients), which is more relevant to the study of oceanographic features (e.g., fronts, eddies, etc.) and ocean dynamics. Here, we use, for the first time, the spectrum of singularity exponents to assess the structural and dynamical quality of different L4 gap‐filled products based on the multifractal theory of turbulence. Singularity exponents represent the geometrical projection of the turbulence cascade, and its singular spectrum can be related to the probability density function of the singularity exponents normalized by the scale. Our results reveal that the different schemes used to produce the L4 SST products generate different singularity spectra, which are then used to identify a potential loss of dynamical information or structural coherence. This new diagnostic constitutes a valuable tool to assess the structural quality of SST products and can support data satellite SST producers efforts to improve the interpolation schemes used to generate gap‐filled SST products. Plain Language Summary: Gap‐filled sea surface temperature (SST) gridded products are generated by combining satellite and, in some cases, in situ observations. Previous studies intercomparing the different SST products focused on assessing the differences between the SST products and in situ observations. However, what is relevant for ocean dynamics studies is the local spatial differences of the SST fields. In this work, we propose a new diagnostic that allows us to assess the dynamical quality of SST products. This new diagnostic is based on the multifractal theory of turbulence and enables the identification of the regions where the SST fields do not properly describe ocean dynamics. This diagnostic is a valuable tool that can help the data satellite SST producers to improve the way the different observations are blended in order to build SST fields that are more dynamically coherent. Key Points: We proposed a new diagnostic to assess the structural and dynamical properties of sea surface temperature (SST) productsThis diagnostic is based on multifractal theory of turbulence and consists computing the singularity spectrumThe different schemes used to produce gap‐filled SST products may contribute to the loss of dynamical information or structural coherence [ABSTRACT FROM AUTHOR]

Introduction: The Centers for Medicare & Medicaid Services (CMS) required a shared decision‐making (SDM) interaction, with an "independent" physician, before left atrial appendage closure (LAAC). The purpose of this study is to better understand how this requirement is implemented in clinical practice. Methods: We surveyed LAAC‐performing centers. The characteristics of respondent and nonrespondent hospitals were compared using the CMS Provider of Services File for 2017. Results: We received 86 responses out of 269 surveys mailed (32%). Respondent and nonrespondent hospital affiliations were similar: mean hospital size 525 beds, 15% for‐profit, and 34% teaching hospitals. Thirty‐four respondents (39.5%) stated that the implanting physician conducts some or all of the SDM interactions. The percentage of patients who decide not to undergo LAAC after the SDM interaction was estimated at 8.1%. Out of 72 responses to an open‐ended question about the benefit of the SDM interaction, 44 (61%) described the requirement in negative terms, of which most felt the requirement was burdensome for patients and providers. Only 28 respondents (39%) described the requirement in positive or mixed terms. Conclusion: In violation of the letter of the CMS policy for LAAC, implanting physicians perform the SDM interaction at nearly 40% of responding hospitals. Most respondents felt the SDM requirement was burdensome for patients. More detailed guidance from CMS on how to comply with the policy may result in better alignment between the intent of the policy and how it is implemented. [ABSTRACT FROM AUTHOR]

Objective Design Setting Participants Results Conclusion There is a shortage of nurses, Aboriginal Health Practitioners, GPs and other staff in remote Australian health clinics. There is also high turnover of staff, leading to questions of ‘who’ is appropriate for remote First Nations practice? The aim of this paper was to identify the characteristics of staff who are likely to work well in remote First Nations settings, from the perspectives of remote health practitioners.This is a qualitative study involving content analysis of interviews.The study is conducted in and with 11 Aboriginal Community Controlled Health Services across northern and central Australia.Eighty‐four staff working in these clinics who spoke about staff qualities suited to remote practice.Participants identified a range of qualities desirable in remote practitioners, which were grouped into three topics: (1) professional qualifications and experience, including cultural skills; (2) ways of working, including holisitic approach, resilience, competence, and being a team player, approachable, flexible and hard‐working; and (3) specific community needs, namely the need for local First Nations staff, male practitioners and returning short‐term staff. The combination of experiences, ways of working, and fit to both the team and community were emphasised.Identifying the characteristics of staff who are likely to work well in these settings can inform recruitment strategies. This study found that a combination of professional qualifications, skills and experience as well as ways of working, individual characteristics and needs of communities are desirable for working in remote, First Nations settings. [ABSTRACT FROM AUTHOR]

The article focuses on a study which aims to survey emergency department (ED) patients to determine the proportion that were eligible for unclaimed public benefits. A cross-sectional in-person survey in a convenience sample of ED patients at two large, urban, academic hospitals in Philadelphia, Pennsylvania from May to September 2022 was conducted. Results revealed that ED patients with public or no health insurance were often eligible for unclaimed state or federal benefits.

Background: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes. Methods: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0–53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0–70.0] years, 55.7% female) completed in‐person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form‐36 physical/mental summary scores, social attainment). Results: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%–29.4%) than controls (2.9%, CI 1.4–4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m2 versus none (OR 4.38, CI 1.06–18.08) and etoposide exposure >2036 mg/m2 versus none (OR 12.61, CI 2.19–72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01–1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68–11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10–0.84, Sensory: OR 0.35, CI 0.13–0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22–5.72). Conclusions: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL. [ABSTRACT FROM AUTHOR]

Aims: The potential harm associated with medication errors is widely reported, but data on actual harm are limited. When actual harm has been measured, assessment processes are often poorly described, limiting their ability to be reproduced by other studies. Our aim was to design and implement a new process to assess actual harm resulting from medication errors in paediatric inpatient care. Methods: Prescribing errors were identified through retrospective medical record reviews (n = 26 369 orders) and medication administration errors through direct observation (n = 5137 administrations) in a tertiary paediatric hospital. All errors were assigned potential harm severity ratings on a 5‐point scale. Multidisciplinary panels reviewed case studies for patients assigned the highest three potential severity ratings and determined the following: actual harm occurrence and severity level, plausibility of a link between the error(s) and identified harm(s) and a confidence rating if no harm had occurred. Results: Multidisciplinary harm panels (n = 28) reviewed 566 case studies (173 prescribing related and 393 administration related) and found evidence of actual harm in 89 (prescribing = 22, administration = 67). Eight cases of serious harm cases were found (prescribing = 1, administration = 7) and no cases of severe harm. The panels were very confident in 65% of cases (n = 302) where no harm was found. Potential and actual harm ratings varied. Conclusions: This harm assessment process provides a systematic method for determining actual harm from medication errors. The multidisciplinary nature of the panels was critical in evaluating specific clinical, therapeutic and contextual considerations including care delivery pathways, therapeutic dose ranges and drug–drug and drug–disease interactions. [ABSTRACT FROM AUTHOR]

Summary: Diffuse large B‐cell lymphoma (DLBCL) is the most common subtype of lymphoma worldwide, accounting for up to 40% of new non‐Hodgkin Lymphoma (NHL) globally. People living with HIV are up to 17 times more likely to develop NHL, and as such, DLBCL is the leading cause of cancer death in this high‐risk population. While histologically indistinguishable, HIV‐associated (HIV+) and HIV‐negative (HIV−) DLBCL are molecularly distinct, and biological differences may have implications for the development of future therapeutic interventions. Further, the impact of immunologic differences in people with HIV, including preceding ART, remains largely unknown. Here, we investigate the impact of HIV infection and ART exposure on the clinical features of DLBCL and T‐cell immune response by performing imaging mass cytometry on our unique patient cohort in Malawi. In this cohort, HIV infection is positively prognostic, and HIV+/ART‐naïve patients have the best outcomes. No established biomarkers other than Ki67 are associated with HIV or ART status, and the only tumour‐intrinsic biomarkers that remain prognostic are MYC and MYC/BCL2 protein co‐expression. Finally, TCR clonality is associated with distinct tumour‐T cell interactions by HIV/ART status, indicating differential anti‐tumour immune responses. We demonstrate previously undescribed HIV and ART‐related differences in the DLBCL tumour microenvironment. [ABSTRACT FROM AUTHOR]

In this investigation, a strongly acidic exchange resin was used for the transesterification of methyl acetate with n‐propanol, n‐butanol, and iso‐butanol. Kinetic and equilibrium experiments for the three systems were conducted using a temperature‐controlled batch reactor setup. The effects of the following operating parameters on the transesterification were explored: reaction temperature, catalyst loading, and methyl acetate‐to‐alcohol molar ratio. The conversion of the limiting reactant in the reaction mixture increased with increasing reaction temperature, catalyst loading, and varying reactant proportions from 1:1 to other ratios. It was found that excess methyl acetate would result in higher limiting reactant conversion than using excess alcohol with the same initial molar proportionality between the excess and the limiting reactants. It was found that an increase in the chain length of the alcohol and/or branching suppressed the conversion of the reactants owing to steric hindrance. To mathematically correlate the data, several kinetic models were tested, and the Eley–Rideal model was selected. Accordingly, a reaction mechanism was proposed. [ABSTRACT FROM AUTHOR]

This article reflects on developments in research into Latin American video games two decades after the first studies in the field. In particular, it fills a gap in research by reflecting on the pedagogical uses of video games, focusing both on their value in the undergraduate classroom and on the design of educational games for use by school children, asking to what extent games might afford their players impactful embodied experiences and ways of navigating complex systems of information and power. The case studies centre on the teaching of environmental humanities and digital literacy in a specifically Latin American context. [ABSTRACT FROM AUTHOR]

Background: The expansion of telemedicine (e.g., telephone or video) in the Veterans Health Administration (VA) raises concerns for health care disparities between rural and urban veterans. Factors impeding telemedicine use (e.g., broadband, digital literacy, age) disproportionally affect rural veterans. Purpose: To examine veteran‐reported broadband access, internet use, familiarity with, and preferences for telemedicine stratified by residential rurality. Methods: Three hundred fifty veterans with a VA primary care visit in March 2022 completed a 30‐min computer‐assisted telephone interview. The sampling design stratified veterans by residential rurality (i.e., rural or urban) and how primary care was delivered (i.e., in‐person or by video). Counts and weighted percentages are reported. Findings: After accounting for survey weights, 96.2% of respondents had in‐home internet access and 89.5% reported functional connection speeds. However, rural‐ compared to urban‐residing veterans were less likely to experience a telemedicine visit in the past year (74.1% vs. 85.2%; p = 0.02). When comparing telemedicine to in‐person visits, rural versus urban‐residing veterans rated them not as good (45.3% vs. 36.8%), just as good (51.1% vs. 53.1%), or better (3.5% vs. 10.0%) (p = 0.05). To make telemedicine visits easier, veterans, regardless of where they lived, recommended technology training (46.4%), help accessing the internet (26.1%), or provision of an internet‐enabled device (25.9%). Conclusions: Though rural‐residing veterans were less likely to experience a telemedicine visit, the same actionable facilitators to improve telemedicine access were reported regardless of residential rurality. Importantly, technology training was most often recommended. Policy makers, patient advocates, and other stakeholders should consider novel initiatives to provide training resources. [ABSTRACT FROM AUTHOR]

Background: Early guidance recommended a bolus of intravenous heparin at the beginning of leadless pacemaker (LP) implantation procedures. However, due to concern about bleeding complications, more recent practice has tended toward omitting the bolus and only running a continuous heparin infusion through the introducer sheath. The impact of omitting the heparin bolus on procedural outcomes is not clear. Methods: We reviewed all Medtronic Micra LP implants at our institution from 9/2014 to 9/2022. The decision to bolus with heparin was at operator discretion. Results: Among 621 LP implants, 326 received an intravenous heparin bolus, 243 did not, and 52 patients were excluded because heparin bolus status could not be confirmed. There was a trend toward more frequent omission of the heparin bolus with more recent implants. Median follow‐up after LP implant was 14.3 (interquartile range [IQR]: 8.4–27.9) months. There was no difference between heparin bolus and no bolus groups in the number of device deployments/recaptures (1.42 ± 0.81 vs. 1.31 ± 0.66, p =.15). Implant‐related adverse events were also similar between heparin bolus and no bolus groups: access‐site hematoma requiring intervention (7 vs. 5, p =.99), pseudoaneurysm (1 vs. 1, p =.99), cardiac perforation (1 vs. 1, p =.99), intraprocedural device thrombus formation (2 vs. 4, p =.41), 30‐day rehospitalization (21 vs. 15, p =.98), and 30‐day all‐cause mortality (16 vs. 14, p =.70). There was one additional nonfatal cardiac perforation in a patient who was excluded due to unknown heparin bolus status. Regarding device electrical parameters between heparin bolus and no bolus groups, there were no significant differences at the time of implant: pacing capture threshold 0.5 ± 0.4 vs. 0.5 ± 0.3, p =.10; pacing impedance 739.9 ± 226.4 vs. 719.1 ± 215.4, p =.52; R wave sensing 11.7 ± 5.7 vs. 12.0 ± 5.4, p =.34). Long‐term device performance was also similar between groups. Conclusion: Omission of the systemic heparin bolus at the time of LP implantation appears safe in appropriately selected patients. Heparin bolus may still be considered in long cases requiring multiple device deployments or in patients at high risk for thrombotic complications. [ABSTRACT FROM AUTHOR]

Background: This phase 1b study (ClinicalTrials.gov identifier NCT03695380) evaluated regimens combining PARP and MEK inhibition, with or without PD‐L1 inhibition, for BRCA wild‐type, platinum‐sensitive, recurrent ovarian cancer (PSROC). Methods: Patients with PSROC who had received one or two prior treatment lines were treated with 28‐day cycles of cobimetinib 60 mg daily (days 1–21) plus niraparib 200 mg daily (days 1–28) with or without atezolizumab 840 mg (days 1 and 15). Stage 1 assessed safety before expansion to stage 2, which randomized patients who had BRCA wild‐type PSROC to receive either doublet or triplet therapy, stratified by genome‐wide loss of heterozygosity status (<16% vs. ≥16%; FoundationOne CDx assay) and platinum‐free interval (≥6 to <12 vs. ≥12 months). Coprimary end points were safety and the investigator‐determined objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Potential associations between genetic parameters and efficacy were explored, and biomarker profiles of super‐responders (complete response or those with progression‐free survival [PFS] >15 months) and progressors (disease progression as the best response) were characterized. Results: The ORR in patients who had BRCA wild‐type PSROC was 35% (95% confidence interval, 20%–53%) with the doublet regimen (n = 37) and 27% (95% confidence interval, 14%–44%) with the triplet regimen (n = 37), and the median PFS was 6.0 and 7.4 months, respectively. Post‐hoc analyses indicated more favorable ORR and PFS in the homologous recombination‐deficiency‐signature (HRDsig)‐positive subgroup than in the HRDsig‐negative subgroup. Tolerability was consistent with the known profiles of individual agents. NF1 and MKNK1 mutations were associated with sustained benefit from the doublet and triplet regimens, respectively. Conclusions: Chemotherapy‐free doublet and triplet therapy demonstrated encouraging activity, including among patients who had BRCA wild‐type, HRDsig‐positive or HRDsig‐negative PSROC harboring NF1 or MKNK1 mutations. In this phase 1b study evaluating the efficacy and safety of a cobimetinib–niraparib doublet regimen and a cobimetinib–niraparib–atezolizumab triplet regimen as treatment for BRCA wild‐type, platinum‐sensitive, recurrent ovarian cancer, clinical outcomes were more favorable in the subgroup with homologous recombination‐deficiency signature–positive tumors than in the subgroup with homologous recombination‐deficiency signature–negative tumors. In exploratory analyses within the doublet arm, NF1 mutations showed a trend toward sustained benefit, whereas FGFR1 and WHSC1L1 alterations tended to be associated with resistance; with the triplet regimen, MKNK1 mutations showed a trend toward sustained benefit and PIK3CA alterations with resistance. [ABSTRACT FROM AUTHOR]

Introduction: Transvenous leads have been implicated in tricuspid valve (TV) dysfunction, but limited data are available regarding the effect of extracting leads across the TV on valve regurgitation. The aim of this study is to quantify tricuspid regurgitation (TR) before and after lead extraction and identify predictors of worsening TR. Methods: We studied 321 patients who had echocardiographic data before and after lead extraction. TR was graded on a scale (0 = none/trivial, 1 = mild, 2 = moderate, 3 = severe). A change of >1 grade following extraction was considered significant. Results: A total of 321 patients underwent extraction of a total of 338 leads across the TV (1.05 ± 0.31 leads across the TV per patient). There was no significant difference on average TR grade pre‐ and postextraction (1.18 ± 0.91 vs. 1.15 ± 0.87; p = 0.79). TR severity increased after extraction in 84 patients, but was classified as significantly worse (i.e., >1 grade change in severity) in only 8 patients (2.5%). Use of laser lead extraction was associated with a higher rate of worsening TR postextraction (44.0% vs. 31.6%, p = 0.04). Conclusion: In our single‐center analysis, extraction of leads across the TV did not significantly affect the extent of TR in most patients. Laser lead extraction was associated with a higher rate of worsening TR after extraction. [ABSTRACT FROM AUTHOR]

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N‐doped CDs (N‐CDs) were synthesized through a single‐step hydrothermal process, using citric acid and urea as precursor materials. The prepared N‐CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N‐CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV–vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N‐CDs and AZEL, leading to fluorescence quenching of N‐CDs as a result of ground‐state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10–200 μg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL. [ABSTRACT FROM AUTHOR]

Morphological adaptation is the change in the form of an organism that benefits the individual in its current habitat. Mole‐rats (family Bathyergidae), despite being subterranean, are impacted by both local and broad‐scale environmental conditions that occur above ground. Common mole‐rats (Cryptomys hottentotus hottentotus) present an ideal mammalian model system for the study of morphological variation in response to ecology, as this species is found along an aridity gradient and thus can be sampled from geographically non‐overlapping populations of the same species along an environmental longitudinal cline. Using the mass of five internal organs, ten skeletal measurements and 3D morphometric analyses of skulls, we assessed the morphology of wild non‐breeding individuals from five common mole‐rat populations in South Africa. We found that the body mass and mean relative mass of the spleen and kidneys in arid populations was larger, and individuals from arid regions possessed shorter legs and larger inter‐shoulder widths compared to individuals from mesic regions. Additionally, arid populations demonstrated greater skull depth, and shape change of features such as angular processes of the lower jaw than mesic individuals, indicating that these distinct geographic populations show differences corresponding to the aridity gradient, potentially in response to environmental factors such as the variation in food sources found between different habitats, in addition to different soil compositions found in the different regions. Arid populations potentially require a stronger jaw and neck musculature associated with mastication to chew xeric‐adapted plants and to dig through hard soil types, whereas mesic populations excavate through soft, looser soil and may make use of their front limbs to aid the movement of soils when digging. Aridity influences the morphology of this species and could indicate the impact of environmental changes on speciation and mammalian skull morphology. [ABSTRACT FROM AUTHOR]

Objective: Lead time to treatment (clinical onset of epileptic spasms [ES] to initiation of appropriate treatment) is known to predict outcomes in infantile epileptic spasms syndrome (IESS). Timing the clinical onset of ES is crucial to establish lead time. We investigated how often ES onset could be established to the nearest week. We aimed to (1) ascertain the exact date or estimate the nearest week of ES onset and (2) compare clinical/demographic factors between patients where date of ES onset was determined or estimated to the nearest week and patients whose date of ES onset could not be estimated to the nearest week. Reasons for difficulties in estimating date of ES onset were explored. Methods: Retrospective chart review of new onset IESS patients (January 2019–May 2022) extracted the date or week of the clinical onset of ES. Predictors of difficulty in date of ES onset estimation to the nearest week were examined by regression analysis. Sources contributing to difficulties determining date of ES onset were assessed after grouping into categories (provider‐, caregiver‐, disease‐related). Results: Among 100 patients, date of ES onset was estimated to the nearest week in 47%. On univariable analysis, age at diagnosis (p =.021), development delay (p =.007), developmental regression/stagnation (p =.021), ES intermixed with other seizures (p =.011), and nonclustered ES at onset (p =.005) were associated with difficulties estimating date of ES onset. On multivariable analysis, failure to establish date of ES onset was related to ES intermixed with other seizures (p =.004) and nonclustered ES at onset (p =.003). Sources contributing to difficulties determining date of ES onset included disease‐related factors (ES characteristics, challenges interpreting electroencephalograms) and provider/caregiver‐related factors (delayed diagnosis). Significance: Difficulties with estimation of lead time (due to difficulties timing ES onset) can impact clinical care (prognostication), as even small increments in lead time duration can have adverse developmental consequences. [ABSTRACT FROM AUTHOR]

Progress in high‐resolution numerical weather prediction (NWP) for urban areas will require new modelling approaches and extensive evaluation. Here, we exploit land surface temperature (LST) data from Landsat‐8 to assess 100 m resolution NWP for London (UK) on four cloud‐free days. The LST observations are directional radiometric temperatures with non‐negligible uncertainties. We consider the challenges of informative comparison between the Landsat LST and the NWP scheme's internal characterisation of the complete surface temperature. The LST spatial coverage allows large‐scale observation–model differences to be explored. In one case, obvious spatial artifacts in the NWP surface temperature are observed relative to the Landsat LST. These are found to be related to the NWP's initial method of downscaling of soil moisture using soil properties. Updated model runs have higher spatial correlation between model and Landsat LST. In cases where meteorological conditions favour the formation of horizontal convective rolls, warmer air temperatures associated with updraughts in the mixed layer extend inappropriately to the urban surface. This manifests as warm stripes in the model surface temperature that are not present in the Landsat LST. NWP–Landsat LST differences are larger in more built‐up areas on days nearer summer solstice. This is largely attributed to urban thermal anisotropy, as Landsat preferentially views warmer urban surfaces, whereas the model LST represents all surfaces. We evaluate two approaches to quantify this sampling effect, but further work is needed to fully constrain it and facilitate more informative model evaluation. [ABSTRACT FROM AUTHOR]

Background: Clinical neurophysiology (CNP) involves the use of neurophysiological techniques to make an accurate clinical diagnosis, to quantify the severity, and to measure the treatment response. Despite several studies showing CNP to be a useful diagnostic tool in Movement Disorders (MD), its more widespread utilization in clinical practice has been limited. Objectives: To better understand the current availability, global perceptions, and challenges for implementation of diagnostic CNP in the clinical practice of MD. Methods: The International Parkinson and Movement Disorders Society (IPMDS) formed a Task Force on CNP. The Task Force distributed an online survey via email to all the members of the IPMDS between August 5 and 30, 2021. Descriptive statistics were used for analysis of the survey results. Some results are presented by IPMDS geographical sections namely PanAmerican (PAS), European (ES), African (AFR), Asian and Oceanian (AOS). Results: Four hundred and ninety‐one IPMDS members (52% males), from 196 countries, responded. The majority of responders from the AFR (65%) and PAS (63%) sections had no formal training in diagnostic CNP (40% for AOS and 37% for ES). The most commonly used techniques are electroencephalography (EEG) (72%) followed by surface EMG (71%). The majority of responders think that CNP is somewhat valuable or very valuable in the assessment of MD. All the sections identified "lack of training" as one of the biggest challenges for diagnostic CNP studies in MD. Conclusions: CNP is perceived to be a useful diagnostic tool in MD. Several challenges were identified that prevent widespread utilization of CNP in MD. [ABSTRACT FROM AUTHOR]

Hyper‐allometry, whereby an anatomical unit increases in size at a faster rate than other structures of the same organism, is considered to be an important feature of many sexually selected structures, with large 'high‐quality' animals carrying a feature that is proportionally larger than smaller, 'low‐quality' animals. When these structures are bilaterally symmetrical, it has been suggested that the degree of fluctuating asymmetry (deviation from perfect symmetry) acts as an indicator of the quality of the bearer. Bovids are useful models for testing sexual selection hypotheses due to their large horns and variety of reproductive systems. Here we use male and female specimens of the southern African blue wildebeest (Connochaetes taurinus) to assess the levels of allometry and fluctuating asymmetry in morphological features of the horns and skull. Males were found to be significantly larger than females for overall horn size, horn length and horn circumference and the horns were found to be isometric in both sexes. Directional asymmetry was found for horn length and horn circumference with the right being longer than the left side. These findings suggest that in C. taurinus the horns follow predicted patterns of variation for sexually selected traits, but that here fluctuating asymmetry may not be as important in sexual selection as previously suggested. Additionally, females did not differ greatly from males in variation and asymmetry and allometry, indicating their horns could be under sexual selection as a result of male choice, or that like males, they also engage in intraspecific combat as well. [ABSTRACT FROM AUTHOR]

Gastroenteropancreatic neuroendocrine tumors (GEP‐NETs) are heterogeneous malignancies that arise from complex cellular interactions within the tissue microenvironment. Here, we sought to decipher tumor‐derived signals from the surrounding microenvironment by applying digital spatial profiling (DSP) to hormone‐secreting and non‐functional GEP‐NETs. By combining this approach with in vitro studies of human‐derived organoids, we demonstrated the convergence of cell autonomous immune and pro‐inflammatory proteins that suggests their role in neuroendocrine differentiation and tumorigenesis. DSP was used to evaluate the expression of 40 neural‐ and immune‐related proteins in surgically resected duodenal and pancreatic NETs (n = 20) primarily consisting of gastrinomas (18/20). A total of 279 regions of interest were examined between tumors, adjacent normal and abnormal‐appearing epithelium, and the surrounding stroma. The results were stratified by tissue type and multiple endocrine neoplasia I (MEN1) status, whereas protein expression was validated by immunohistochemistry (IHC). A tumor immune cell autonomous inflammatory signature was further evaluated by IHC and RNAscope, while functional pro‐inflammatory signaling was confirmed using patient‐derived duodenal organoids. Gastrin‐secreting and non‐functional pancreatic NETs showed a higher abundance of immune cell markers and immune infiltrate compared with duodenal gastrinomas. Compared with non‐MEN1 tumors, MEN1 gastrinomas and preneoplastic lesions showed strong immune exclusion and upregulated expression of neuropathological proteins. Despite a paucity of immune cells, duodenal gastrinomas expressed the pro‐inflammatory and pro‐neural factor IL‐17B. Treatment of human duodenal organoids with IL‐17B activated NF‐κB and STAT3 signaling and induced the expression of neuroendocrine markers. In conclusion, multiplexed spatial protein analysis identified tissue‐specific neuro‐immune signatures in GEP‐NETs. Duodenal gastrinomas are characterized by an immunologically cold microenvironment that permits cellular reprogramming and neoplastic transformation of the preneoplastic epithelium. Moreover, duodenal gastrinomas cell autonomously express immune and pro‐inflammatory factors, including tumor‐derived IL‐17B, that stimulate the neuroendocrine phenotype. © 2024 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Alzheimer disease (AD) has been linked with periodontal microorganisms such as Porphyromonas gingivalis in observational and mechanistic studies. IgG antibodies against periodontal microorganisms which are markers of past and current periodontal infection have been correlated with cognitive impairment. We examined associations between empirically derived groups of 19 IgG antibodies against periodontal microorganisms and AD mortality. Methods: Individuals participating in the Third National Health and Nutrition Examination Survey (NHANES III) with complete data on IgG titers were followed up between 1988 and December 31, 2019. The outcome was AD mortality, and the main exposures were IgG antibodies against periodontal microorganisms classified into four mutually exclusive groups using cluster analysis. Survey‐weighted Cox proportional hazard models were used to evaluate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for the relationship between clusters and AD mortality. Results: With up to 21 years of follow‐up, 160 AD‐related deaths were documented. In the multivariable‐adjusted model, AD mortality overall was not associated with the Red‐Green (aHR 1.18; 95% CI, 0.46–3.07), Yellow‐Orange (aHR 1.36; 95% CI, 0.58–3.19), Orange‐Blue (aHR 0.63; 95%, CI, 0.33–1.21), and the Orange‐Red (aHR 0.79; 95% CI, 0.37–1.70) when the upper tertiles were compared to the bottom tertiles. However, the subgroup of middle‐aged individuals in the highest tertile of the Red‐Green cluster, but not older individuals, had a 13% higher risk of AD mortality (aHR 1.13; 95% CI, 1.02–1.26) compared with those in the bottom tertile. Conclusion: Clusters of IgG antibodies against periodontal microorganisms did not predict AD mortality in this study. [ABSTRACT FROM AUTHOR]

Objective: Non‐Hispanic (NH) Black children are less likely to receive a standard treatment course for infantile epileptic spasms syndrome (IESS) than White/NH children at pediatric tertiary care epilepsy centers in the United States. However, if inequities exist in time to diagnosis is unknown. Diagnostic delays as little as 1 week can be associated with worse developmental outcomes. Methods: Diagnostic delays were evaluated in a retrospective cohort of 100 children with new onset IESS between January 2019 and May 2022. Results: Children with Black, Indigenous, and People of Color (BIPOC) caregivers were more likely to experience clinically significant delays in referral from first provider to neurologist, when compared to White/NH children, even after controlling for other demographic and clinical variables (odds ratio = 4.98, confidence interval = 1.24–19.94, p =.023). Significance: Disproportionate diagnostic delays place BIPOC children at risk of adverse developmental and epilepsy outcomes. Further interventional prospective and qualitative studies are needed to address inequities in care. [ABSTRACT FROM AUTHOR]

Stomata are the gatekeepers of plant water use and must quickly respond to changes in plant water status to ensure plant survival under fluctuating environmental conditions. The mechanism for their closure is highly sensitive to disturbances in leaf water status, which makes isolating their response to declining water content difficult to characterise and to compare responses among species. Using a small‐scale non‐destructive nuclear magnetic resonance spectrometer as a leaf water content sensor, we measure the stomatal response to rapid induction of water deficit in the leaves of nine species of eucalypt from contrasting climates. We found a strong linear correlation between relative water content at 50% stomatal conductance (RWCgs50) and mean annual temperature at the climate of origin of each species. We also show evidence for stomata to maintain control over water loss well below turgor loss point in species adapted to warmer climates and secondary increases in stomatal conductance despite declining water content. We propose that RWCgs50 is a promising trait to guide future investigations comparing stomatal responses to water deficit. It may provide a useful phenotyping trait to delineate tolerance and adaption to hot temperatures and high leaf‐to‐air vapour pressure deficits. SUMMARY STATEMENT: Nine species of eucalypt from contrasting climates and grown in a common climate (Angophora crassifolia, Corymbia tessellaris, Eucalyptus atrata, Eucalyptus caesia, Eucalyptus grandis, Eucalyptus laevopinea, Eucalyptus longifolia, Eucalyptus macrandra and Eucalyptus tereticornis) demonstrated a strong linear correlation between relative water content at 50% stomatal conductance (RWCgs50) and mean annual temperature at the climate of origin. [ABSTRACT FROM AUTHOR]

Activation and transdifferentiation of hepatic stellate cells (HSC) into migratory myofibroblasts is a key process in liver fibrogenesis. Cell migration requires an active remodeling of the cytoskeleton, which is a tightly regulated process coordinated by Rho‐specific guanine nucleotide exchange factors (GEFs) and the Rho family of small GTPases. Rho‐associated kinase (ROCK) promotes assembly of focal adhesions and actin stress fibers by regulating cytoskeleton organization. GEF exchange protein directly activated by cAMP 1 (EPAC1) has been implicated in modulating TGFβ1 and Rho signaling; however, its role in HSC migration has never been examined. The aim of this study was to evaluate the role of cAMP‐degrading phosphodiesterase 4 (PDE4) enzymes in regulating EPAC1 signaling, HSC migration, and fibrogenesis. We show that PDE4 protein expression is increased in activated HSCs expressing alpha smooth muscle actin and active myosin light chain (MLC) in fibrotic tissues of human nonalcoholic steatohepatitis cirrhosis livers and mouse livers exposed to carbon tetrachloride. In human livers, TGFβ1 levels were highly correlated with PDE4 expression. TGFβ1 treatment of LX2 HSCs decreased levels of cAMP and EPAC1 and increased PDE4D expression. PDE4 specific inhibitor, rolipram, and an EPAC‐specific agonist decreased TGFβ1‐mediated cell migration in vitro. In vivo, targeted delivery of rolipram to the liver prevented fibrogenesis and collagen deposition and decreased the expression of several fibrosis‐related genes, and HSC activation. Proteomic analysis of mouse liver tissues identified the regulation of actin cytoskeleton by the kinase effectors of Rho GTPases as a major pathway impacted by rolipram. Western blot analyses confirmed that PDE4 inhibition decreased active MLC and endothelin 1 levels, key proteins involved in cytoskeleton remodeling and contractility. The current study, for the first time, demonstrates that PDE4 enzymes are expressed in hepatic myofibroblasts and promote cytoskeleton remodeling and HSC migration. © 2023 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Introduction: Permanent pacing indications are common after cardiac surgery and transcatheter structural valve interventions. Leadless pacemakers (LPs) have emerged as a useful alternative to transvenous pacemakers. However, current commercially available LPs are unable to provide atrial pacing or cardiac resynchronization and relatively little is known about LP outcomes after cardiac surgery and transcatheter valve interventions. Methods: This retrospective study included patients who received a Micra VR (MicraTM MC1VR01) or Micra AV (MicraTM MC1AVR1) (Medtronic) leadless pacemaker following cardiac surgery or transcatheter structural valve intervention between September 2014 and September 2022. Device performance and clinical outcomes, including ventricular pacing burden, ejection fraction, and need for conversion to transvenous pacing systems, were evaluated during follow‐up. Results: A total of 78 patients were included, of whom 40 received a Micra VR LP implant, and 38 received a Micra AV LP implant. The mean age of the cohort was 65.9 ± 17.9 years, and 48.1% were females. The follow‐up duration for the entire cohort was 1.3 ± 1.1 years: 1.6 ± 1.3 years for the Micra VR group and 0.8 ± 0.5 years for the Micra AV group. Among the cohort, 50 patients had undergone cardiac surgery and 28 underwent transcatheter structural valve interventions. Device electrical performance was excellent during follow‐up, with a small but clinically insignificant increase in ventricular pacing threshold and a slight decrease in pacing impedance. The mean right ventricle pacing (RVP) burden significantly decreased over time in the entire cohort (74.3% ± 37.2% postprocedure vs. 47.7% ± 40.6% at last follow‐up, p <.001), and left ventricle ejection fraction (LVEF) showed a modest but significant downward trend during follow‐up (55.0% ± 10.6% vs. 51.5% ± 11.2% p <.001). Patients with Micra VR implants had significantly reduced LVEF during follow‐up (54.1% ± 11.9% vs. 48.8% ± 11.9%, p =.003), whereas LVEF appeared stable in the Micra AV group during follow‐up (56.1% ± 9.0% vs. 54.6% ± 9.7%, p =.06). Six patients (7.7%) required conversion to transvenous pacing systems, four who required cardiac resynchronization for drop in LVEF with high RVP burden and two who required dual‐chamber pacemakers for symptomatic sinus node dysfunction. Conclusion: Leadless pacemakers provide a useful alternative to transvenous pacemakers in appropriately selected patients after cardiac surgery and transcatheter structural valve interventions. Device performance is excellent over medium‐term follow‐up. However, a significant minority of patients require conversion to transvenous pacing systems for cardiac resynchronization or atrial pacing support, demonstrating the need for close electrophysiologic follow‐up in this cohort. [ABSTRACT FROM AUTHOR]

Introduction: The need for pacemaker is a common complication after transcatheter aortic valve replacement (TAVR). We previously described the Emory Risk Score (ERS) to predict the need for new pacemaker implant (PPM) after TAVR. Metrics included in the score are a history of syncope, pre‐existing RBBB, QRS duration ≥140 ms, and prosthesis oversizing ≥16%. To prospectively validate the previously described risk score. Methods: We prospectively evaluated all patients without pre‐existing pacemakers, ICD, or pre‐existing indications for pacing undergoing TAVR with the Edwards SAPIEN 3 prosthesis at our institution from March 2019 to December 2020 (n = 661). Patients were scored prospectively; however, results were blinded from clinical decision‐making. The primary endpoint was PPM at 30 days after TAVR. Performance of the ERS was evaluated using logistic regression, a calibration curve to prior performance, and receiver operating characteristic (ROC) analysis. Results: A total of 48 patients (7.3%) had PPM after TAVR. A higher ERS predicted an increased likelihood of PPM (OR 2.61, 95% CI: 2.05–3.25 per point, p < 0.001). There was good correlation between observed and expected values on the calibration curve (slope = 1.04, calibration at large = 0.001). The area under the ROC curve was 0.81 (95% CI [0.74–0.88], p < 0.001). Conclusions: The ERS prospectively predicted the need for PPM in a serial, real‐world cohort of patients undergoing TAVR with a balloon‐expandable prosthesis, confirming findings previously described in retrospective cohorts. Notably, the prospective performance of the score was comparable with that of the initial cohorts. The risk score could serve as a framework for preprocedural risk stratification for PPM after TAVR. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus disease 2019 (COVID‐19) pandemic presented patients with numerous barriers to accessing health care, including access to reproductive health services. The goal of this study was to assess the prevalence of abortion prior to versus during the COVID‐19 pandemic within a large health care system to better understand if patients were able to access abortion care. Methods: This was a retrospective, data‐only cohort study examining the prevalence of abortion among patients aged 15 to 44 within Kaiser Permanente Northern California (KPNC) in the first 6 months of the COVID‐19 stay‐at‐home order (April 1 to September 30, 2020) compared with a 6‐month period in the year prior to the COVID‐19 pandemic (April 1 to September 30, 2019). Analyses were conducted using χ2 and t tests, with a P value <.05 considered statistically significant. Results: The prevalence of abortion among patients at risk of pregnancy in 2019 and 2020 was identical, at 0.04% (P =.93). Baseline characteristics were similar between the 2 periods. The prevalence of smoking among patients who had an abortion in 2019 was 11.24%, compared with 9.04% in 2020 (P =.0009). Additionally, 85.80% of patients had KPNC insurance 6 months after the abortion in 2019, compared with 89.53% in 2020 (P <.0001). Discussion: The prevalence of abortion remained similar prior to and during the first 6 months of the COVID‐19 pandemic within KPNC. Patients seeking abortion were less likely to smoke and were more likely to have consistent insurance 6 months after their abortion in 2020 versus 2019, potentially suggesting the COVID‐19 pandemic resulted in healthier behaviors and more consistent access to health care. Despite stay‐at‐home orders and canceling of in‐person clinic visits, abortion services remained accessible to a diverse population within a large health care system. [ABSTRACT FROM AUTHOR]

Background: Haloxyfop‐P‐methyl, an acetyl‐CoA carboxylase (ACCase)‐inhibiting herbicide, has been extensively used to control grass weeds. Widespread use of haloxyfop‐P‐methyl in cotton fields in China has led to the development of glutathione transferase (GST)‐mediated resistance in Digitaria sanguinalis. An RNA‐seq analysis identified DsGSTU1, a tau class glutathione transferase from the D. sanguinalis transcriptome as a potential candidate. Here, we cloned DsGSTU1 from D. sanguinalis young leaf tissues and subsequently characterized DsGSTU1 by a combination of sequence analysis, as well as functional heterologous expression in rice. RESULTS: The full‐length coding DNA sequence (CDS) of DsGSTU1 is 717 bp in length. Higher DsGSTU1 expression was observed in haloxyfop‐P‐methyl‐resistant (HR) D. sanguinalis than in haloxyfop‐P‐methyl‐susceptible (HS) plants. Overexpression of the DsGSTU1 gene was confirmed by transformation into the wild‐type (WT) Nipponbare rice with pBWA(V)HS, a recombinant expression vector. GST activity in transgenic rice seedlings was 1.18–1.40‐fold higher than the WT rice seedlings before and after haloxyfop‐P‐methyl treatment, respectively. Additionally, transgenic rice seedlings overexpressing DsGSTU1 were less sensitive to haloxyfop‐P‐methyl. CONCLUSION: Our combined findings suggest that DsGSTU1 is involved in metabolic resistance to haloxyfop‐P‐methyl in D. sanguinalis. A better understanding of the major genes contributing to herbicide‐resistant D. sanguinalis facilitates the development of resistance management strategies for this global invasive grass weed. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Background: Survivors of pediatric central nervous system (CNS) tumors are at risk for neurocognitive and social difficulties throughout childhood. This study characterized social cognition (perception and reasoning from social cues) and adjustment in adulthood. Methods: A total of 81 adult survivors of pediatric CNS tumors (51% female; mean [SD] age, 28.0 [5.8] years), were recruited across four groups: (1) no radiation therapy (RT) [n = 21], (2) infratentorial (IT) tumors + focal RT [n = 20], (3) IT tumors + craniospinal irradiation [n = 20], and (4) supratentorial tumors + focal RT [n = 20]. Prevalence of social cognitive and adjustment impairments was compared to test norms. Multivariable models examined clinical and neurocognitive predictors of social cognition and its impact on functional outcomes. Results: Survivors demonstrated elevated risk of severe social cognitive impairments (social perception Morbidity Ratio [95% CI] 5.70 [3.46–9.20]), but self‐reported few social adjustment problems. Survivors of IT tumors treated with craniospinal irradiation performed nearly 1 SD worse than survivors treated without RT on multiple measures of social cognition (e.g., social perception: β = −0.89, p =.004). Impaired executive functioning and nonverbal reasoning were associated with worse social cognitive performance (e.g., social perception: β = −0.75, p <.001; β = –0.84, p <.001, respectively). Better social perception was associated with higher odds of attaining full‐time employment (odds ratio, 1.52 [1.17–1.97]) and at least some college education (odds ratio, 1.39 [1.11–1.74]). Conclusions: Adult survivors of CNS tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Better understanding of potential mechanisms underlying social cognitive deficits may inform intervention targets to promote better functional outcomes for at‐risk survivors. Adult survivors of childhood central nervous system tumors are at elevated risk of severely impaired social cognition, but do not perceive social adjustment difficulties. Infratentorial tumor survivors treated with craniospinal radiation demonstrated worse social cognition, which was in turn associated with reduced social attainment. [ABSTRACT FROM AUTHOR]

Objective: This study aims to estimate the rate of postoperative meningitis (both immediate and long‐term) in patients following cochlear implants (CIs). It aims to do so through a systematic review and meta‐analysis of published studies tracking complications after CIs. Data Sources: MEDLINE, Embase, and Cochrane Library. Review Methods: This review was performed in line with Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines. Studies tracking complications following CIs in patients were included. Exclusion criteria included non‐English language studies and case series reporting <10 patients. Bias risk was evaluated using the Newcastle‐Ottawa Scale. Meta‐analysis was performed through DerSimonian and Laird random‐effects models. Results: A total of 116/1931 studies met the inclusion criteria and were included in the meta‐analysis. Overall, there were 112 cases of meningitis in 58,940 patients after CIs. Meta‐analysis estimated an overall rate of postoperative meningitis of 0.07% (95% confidence interval [CIs], 0.03%‐0.1%; I2 = 55%). Subgroup meta‐analysis showed this rate had 95% CIs crossing 0% in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, those with postoperative acute otitis media (AOM), and those implanted less than 5 years. Conclusion: Meningitis is a rare complication following CIs. Our estimated rates of meningitis after CIs appear lower than prior estimates based on epidemiological studies in the early 2000s. However, the rate still appears higher than the baseline rate in the general population. The risk was very low in implanted patients who received the pneumococcal vaccine, antibiotic prophylaxis, received unilateral or bilateral implantations, developed AOM, those implanted with a round window or cochleostomy techniques, and those under 5 years. [ABSTRACT FROM AUTHOR]

Coral reefs are facing severe threats and are at risk of accelerated decline due to climate change‐induced changes in their environment. Ongoing efforts to understand the mechanisms of coral response to warming rely on multiple sources of temperature data. Yet, it remains uncertain whether the Sea Surface Temperature (SST) data used for coral reef studies are consistent among different data products, despite potential implications for conservation. A better understanding of the consistency among the different SST data applied to coral reefs may facilitate the fusion of data into a standard product. This will improve monitoring and understanding of the impact of global warming on coral reefs. Four types of SST data across North‐Western and South‐Western Australia are compared to assess their differences and ability to observe high thermal stress during historical coral bleaching events. The four SST data sources included those derived from Global Circulation Models, NOAA CoralTemp SST product, ESA CCI SST product, and coral core derived SST. Coral bleaching risk indicators, Degree Heating Week (DHW), and Degree Heating Month (DHM) were calculated using these sources and compared for consistency. DHW and DHM were inconsistent among data sets and did not accurately reflect high thermal stress metrics during moderate and severe bleaching events. Some reefs did not experience bleaching in spite of high DHWs and DHMs, suggesting a mismatch in data scales, or perhaps other oceanographic factors and coral adaptation. By exploring the differences and similarities among these four data sources, this study highlights the need to compare existing indicators of thermal stress from different data sets. Plain Language Summary: Climate change and warming have resulted in global coral bleaching events, severely compromising our environment's health. Monitoring the changes in ocean temperatures around them is essential to maximizing our efforts to protect them. Different ocean temperature data products exist and are being used without understanding their differences. To highlight these differences, the present study compares historical warming from climate models and remote and in situ sensors and known bleaching events on five reefs across Western Australia. Key Points: Temperature data sources did not provide consistent risk indicators for coral bleachingAcross five reefs, coral bleaching risk indicators differed in their ability to predict the observed coral bleaching eventsTemperature data in daily and monthly temporal resolutions differed in the accuracy of coral bleaching risk indicators [ABSTRACT FROM AUTHOR]

Purpose/Objective(s): To describe a log file–based patient‐specific quality assurance (QA) method and develop an in‐house tool for system performance tracking and dose reconstruction in pencil‐beam scanning proton therapy that can be used for pre‐treatment plan review. Materials/Methods: The software extracts beam‐specific information from the treatment delivery log file and automatically compares the monitor units (MU), lateral position, and size of each spot against the intended values in the treatment plan to identify any discrepancies in the beam delivery. The software has been used to analyze 992 patients, 2004 plans, 4865 fields, and more than 32 million proton spots from 2016 to 2021. The composite doses of 10 craniospinal irradiation (CSI) plans were reconstructed based on the delivered spots and compared with the original plans as an offline plan review method. Results: Over the course of 6 years, the proton delivery system has proved stable in delivering patient QA fields with proton energies of 69.4–221.3 MeV and an MU range of 0.003–1.473 MU per spot. The planned mean and standard deviation (SD) of the energy and spot MU were 114.4 ± 26.4 MeV and 0.010 ± 0.009 MU, respectively. The mean and SD of the differences in MU and position between the delivered and planned spots were 9.56 × 10−8 ± 2.0 × 10−4 MU and 0.029/−0.007 ± 0.049/0.044 mm on the X/Y‐axis for random differences and 0.005/0.125 ± 0.189/0.175 mm on the X/Y‐axis for systematic differences. The mean and SD of the difference between the commissioning and delivered spot sizes were 0.086/0.089 ± 0.131/0.166 mm on the X/Y‐axis. Conclusion: A tool has been developed to extract crucial information about the performance of the proton delivery and monitor system and provide a dose reconstruction based on delivered spots for quality improvement. Each patient's plan was verified before treatment to ensure accurate and safe delivery within the delivery tolerance of the machine. [ABSTRACT FROM AUTHOR]

Objectives: To identify biopsy rates and indications for BI‐RADS 3 lesions in a large cohort of patients and compare with follow‐up compliance and malignancy outcomes. Methods: We retrospectively reviewed all BI‐RADS category‐3 lesions seen on mammography and/or ultrasound between 2013 and 2015. Patient age, lesion size, follow‐up rates at 6‐, 12‐, and 24‐months were collected. Biopsy timing, indication, and outcomes (malignant vs benign) were recorded using at least 2‐year follow‐up or biopsy pathology as endpoint. Results: Of 2319 BI‐RADS 3 lesions in 2075 women analyzed, biopsy was performed in 173 (7.5%). Most biopsies were performed upfront (99, 57.2%), followed by at 6 (44, 25.4%), 12 (21, 12.1%), and 24‐month follow‐up (9, 5.2%; P <.001). Palpable (P <.001) and larger (median 1.4 vs 1.0 cm, P <.001) lesions in women <40 years (15.2% vs 4.8%, P <.001) were more likely to undergo biopsy. Most biopsies were prompted by patient/physician desire (64.5%, P <.001). Of 783 lesions with available endpoint, 5 (0.6%) were cancer. All cancers were identified either at presentation (in 0–5 months, n = 1) or 6‐month follow‐up (in 5–9 months, n = 4) with biopsy prompted by either morphology change (n = 3) or lesion growth (n = 2). Of the 1855 lesions which were expected for follow up, only 310 (16.7%) underwent all follow‐ups, while 482 (26.1%) had two, 489 (26.5%) one, and 565 (30.6%) had no follow‐up. Conclusions: In our cohort, BI‐RADS category 3 lesions had significantly higher biopsy rates compared with the small malignancy rate, all of which were identified at baseline or first follow‐up. Overall patient follow‐up compliance low. Imaging follow‐up, especially at first 6‐month time point, should be encouraged in BI‐RADS 3 lesions, instead of upfront biopsies. [ABSTRACT FROM AUTHOR]

Background: Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD). Objectives: We used data from a multi‐site, international, prospective cohort study to explore the impact of dopamine system‐related biomarkers on CI in PD. Methods: PD participants were assessed annually from disease onset out to 7 years, and CI determined by applying cut‐offs to four measures: (1) Montreal Cognitive Assessment; (2) detailed neuropsychological test battery; (3) Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) cognition score; and (4) site investigator diagnosis of CI (mild cognitive impairment or dementia). The dopamine system was assessed by serial Iodine‐123 Ioflupane dopamine transporter (DAT) imaging, genotyping, and levodopa equivalent daily dose (LEDD) recorded at each assessment. Multivariate longitudinal analyses, with adjustment for multiple comparisons, determined the association between dopamine system‐related biomarkers and CI, including persistent impairment. Results: Demographic and clinical variables associated with CI were higher age, male sex, lower education, non‐White race, higher depression and anxiety scores and higher MDS‐UPDRS motor score. For the dopamine system, lower baseline mean striatum dopamine transporter values (P range 0.003–0.005) and higher LEDD over time (P range <0.001–0.01) were significantly associated with increased risk for CI. Conclusions: Our results provide preliminary evidence that alterations in the dopamine system predict development of clinically‐relevant, cognitive impairment in Parkinson's disease. If replicated and determined to be causative, they demonstrate that the dopamine system is instrumental to cognitive health status throughout the disease course. TRIAL REGISTRATION: Parkinson's Progression Markers Initiative is registered with ClinicalTrials.gov (NCT01141023). [ABSTRACT FROM AUTHOR]

Background: Patient navigation (P.N.) is designed to eliminate barriers to care. The objective of this study was to evaluate the impact of a novel P.N. program on timeliness of care in patients with esophageal cancer. Methods: This retrospective study compared the timeliness of care for esophageal cancer patients before (January 2014-March 2018) and after the implementation of a novel P.N. program (April 2018-March 2020), called EDAP, at a tertiary care center. The primary outcome was time from biopsy to first treatment; secondary outcomes included time from biopsy to complete staging, biopsy to complete preoperative workup, and referral to the first point of contact. The outcomes were evaluated in the entire cohort and then in a subgroup of patients undergoing curative multimodality therapy. Results: There were 96 patients in the pre-EDAP group and 98 patients in the post-EDAP group. There was no significant difference between pre-and post-EDAP in the time from biopsy to first treatment and time from biopsy to staging in the overall cohort. In the subgroup of patients undergoing curative multimodality therapy, there was a significant decrease in time from biopsy to first treatment postnavigation (60-51 days, p = 0.02), in addition to a significant decrease in time from biopsy to preoperative workup and time from biopsy to staging. Conclusions: This is the first study demonstrating that a novel P.N. program for patients with esophageal cancer improved timeliness of care. The group of patients who benefited most were those undergoing curative multimodality therapy, likely given the extensive coordination of services required by this group. [ABSTRACT FROM AUTHOR]

Background: Chronic inducible urticaria (CIndU) is characterized by mast cell (MC)‐mediated wheals in response to triggers: cold in cold urticaria (ColdU) and friction in symptomatic dermographism (SD). KIT receptor activation by stem cell factor (SCF) is essential for MC function. Barzolvolimab (CDX‐0159) is a humanized antibody that inhibits KIT activation by SCF and was well tolerated in healthy volunteers with dose‐dependent plasma tryptase suppression indicative of systemic mast cell ablation. Methods: This is an open‐label, trial in patients with antihistamine refractory ColdU or SD, receiving one IV dose of barzolvolimab (3 mg/kg), with a 12‐week follow‐up. Primary endpoint was safety/tolerability; pharmacodynamic (PD)/clinical endpoints included serum tryptase, plasma SCF, skin MC histology, provocation tests, urticaria control test (UCT), and dermatology life quality index (DLQI). Results: Analysis populations were safety (n = 21) and pharmacodynamics/clinical activity (n = 20). Barzolvolimab was well tolerated; most adverse events were mild and resolved. Treatment resulted in significant depletion of skin MCs, decreased tryptase (

Introduction: Hemodynamic decompensation during catheter ablation occurs due to prolonged procedure time and irrigant delivery directly into the cardiac chambers. Real‐time hemodynamic monitoring of patients undergoing catheter ablation procedures may identify patients at risk of decompensation; we set out to assess the feasibility of a novel, real‐time, intracardiac pressure monitoring system using a standard irrigated ablation catheter. Methods: We studied 13 consecutive who underwent pressure measurement of the left atrium (LA) and left ventricle (LV) via transeptal access with a Swan Ganz (SG) catheter followed by two commercially available irrigated ablation catheters. Pressure waveform data was extracted to compare LA peak pressure, LV peak systolic pressure, LV end‐diastolic pressure, and waveform analysis. Results: Comparison between the SG and ablation catheters (AblA; AblB) demonstrated that LV systolic pressure (0.61–16.8 mmHg; 1.32–18.2 mmHg), and LV end‐diastolic pressure (−3.4 to 2.8 mmHg; −3.0 to 3.35 mmHg) were well correlated and had accepted repeatability. Ablation waveforms demonstrated an 89.9 ± 6.4% correlation compared to SG waveforms. Conclusion: Pressure measurements derived from an irrigated ablation catheter are accurate and reliable when compared to an SG catheter. Further studies are needed to determine how real‐time pressure monitoring can improve outcomes during ablation procedures. [ABSTRACT FROM AUTHOR]

Within the psychoanalytic school there has been substantial and ongoing debate about the efficacy of teleanalysis. However, as a result of the current COVID‐19 pandemic and the online work with which the Jungian analytic community has now had to engage, this paper initially focuses on analysts' actual experiences of working by teleanalysis. These experiences highlight a range of issues like "Zoom fatigue", "online disinhibition", dissonance, confidentiality, the frame and working with new patients. Alongside these issues, there were ample experiences by analysts of both productive psychotherapy apace with analytic work involving transference and countertransference phenomena, all indicating that a genuine and good enough analytic process can occur with teleanalysis. An overview of the research and literature both prior to the pandemic and as a result of it, confirms the validity of these experiences so long as analysts are cognizant of the specifics of such an online modality. Conclusions to do with the question, "what have we learned?", alongside training, ethics and supervision issues are subsequently discussed. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (Hp) is among the most common bacterial infections in the world and one of the most common infectious agents linked to malignancy, gastric cancer (GC). Within the US there is high disparity in the rates of Hp infection and associated diseases. Hp infection is treatable, and knowledge may influence screening and treatment seeking behaviors. Materials and Methods: In this cross‐sectional study of 1042 respondents recruited from the Online Amazon MTurk platform, we sought to assess baseline knowledge of Hp and to gain insight into barriers related to Hp care. Results: Just over half (52.3%) reported some prior knowledge of Hp with 11.7% (n = 122) reporting being treated for Hp themselves and 21.4% reporting family members diagnosed with Hp. Of respondents reporting prior treatment, 95 (78%) reported GI upset and 27 (21%) reported not completing medications. Specific to Hp and GC, 70% indicated that a belief that the treatment was worse than the symptoms would affect their willingness to seek care, while 81% indicated knowing Hp can cause GC would affect their treatment decisions and knowing their gastric symptoms were caused by Hp would affect their willingness to receive care. Conclusions: Knowledge of Hp in this US sample of online respondents is low and self‐reported difficulties with treatment compliance is high. Increasing awareness of this infection and addressing the challenges to treatment compliance could potentially reduce rates of Hp antibiotic resistance and progression to GC or other complications of Hp infection. [ABSTRACT FROM AUTHOR]

Background: Cancer patients are often malnourished pre‐operatively. The present study aimed to establish whether current screening was appropriate for use in prehabilitation and investigate any association between nutritional risk, functionality and quality of life (QoL). Methods: This cohort study used routinely collected data from September 2020 to August 2021 from patients in a Prehab4cancer programme. Included patients were aged ≥ 18 years, had colorectal, lung or oesophago‐gastric cancer and were scheduled for surgery. Nutritional assessment included Patient‐Generated Subjective Global Assessment (PG‐SGA) Short‐Form and QoL with a sit‐to‐stand test. Association between nutritional risk and outcomes was analysed using adjusted logistic regression. Results: From 928 patients referred to Prehab4Cancer service over 12 months, data on nutritional risk were collected from 526 patients. Pre‐operatively, 233 out of 526 (44%) patients were at nutritional risk (score ≥ 2). During prehabilitation, 31% of patients improved their PG‐SGA and 74% of patients maintained or improved their weight. Odds ratios (OR) with confidence intervals (CI) showed that patients with better QoL using EuroQol‐5 Dimensions (OR = 0.05, 95% CI = 0.01, 0.45, p = 0.01), EuroQol Visual Analogue Scale (OR = 0.96, 95% CI = 0.93, 1.00, p = 0.04) or sit‐to‐stand (OR = 0.96, 95% 0.93, 1.00, p = 0.04) were less likely to be nutritional at risk. Conclusions: Almost half of patients in Prehab4Cancer programme assessed using PG‐SGA were at risk of malnutrition. However, almost half of the sample did not have their risk assessed. Patients at risk of malnutrition were more likely to have a poorer QoL and sit‐to‐stand test than those who were not at risk. Key points: Colorectal, lung or oesopho‐gastric cancer patients referred to the Prehab4Cancer service underwent a nutritional assessment. Almost half of patients assessed using the Patient‐Generated Subjective Global Assessment (i.e., PG‐SGA) were at risk of malnutrition. Patients at risk of malnutrition were more likely to have a worse quality of life and sit‐to‐stand test indicating reduced physical function than those who were not at risk of malnutrition. This indicates that optimising the nutritional status of cancer patients in the prehabilitation period can maximise the nutritional status, functionality and quality of life of patients. [ABSTRACT FROM AUTHOR]