Queen-Worker Conflict over Acceptance of Secondary Queens in Eusocial Insects.

AbstractThe coexistence of multiple reproductives in eusocial insects is widespread, yet the decisions leading to additional queen acceptance are not well understood. Unlike in vertebrates, acceptance decisions are likely controlled by the more numerous helper population rather than the parent reproductive. Yet there are likely to be queen-worker differences in acceptance criteria because workers and queens differ in their relatedness to a secondary queen. We develop a model that examines queen-worker conflict in two scenarios: accepting a queen's sister or daughter. We additionally ask how the mating frequency and split sex ratios affect the outcomes of these conflicts. Our results reveal that conflict over queen acceptance is highest in monandrous mating systems. We identify a "window of conflict" in which a queen is selected to accept her sister but her workers do not. Our result, that polyandry neutralizes conflict over acceptance thresholds, suggests that conflict suppression may be an additional contributor to the maintenance of polyandrous mating systems.

Clinical Outcomes Among High-Risk Primary Care Patients With Diabetic Kidney Disease: Methodological Challenges and Results From the STOP-DKD Study.

BACKGROUND/OBJECTIVE: Slowing the progression of diabetic kidney disease (DKD) is critical. We conducted a randomized controlled trial to target risk factors for DKD progression. METHODS: We evaluated the effect of a pharmacist-led intervention focused on supporting healthy behaviors, medication management, and self-monitoring on decline in estimated glomerular filtration rate (eGFR) for 36 months compared with an educational control. RESULTS: We randomized 138 individuals to the intervention group and 143 to control. At baseline, mean (SD) eGFR was 80.7 (21.7) mL/min/1.73m2, 56% of participants had chronic kidney disease and a history of uncontrolled hypertension with a baseline SBP of 134.3 mm Hg. The mean (SD) decline in eGFR by cystatin C from baseline to 36 months was 5.0 (19.6) and 5.9 (18.6) mL/min/1.73m2 for the control and intervention groups, respectively, with no significant between-group difference (P=0.75). CONCLUSIONS: We did not observe a significant difference in clinical outcomes by study arm. However, we showed that individuals with DKD will engage in a pharmacist-led intervention. The potential explanations for a lack of change in DKD risk factors can be attributed to 5 broad issues, challenges: (1) associated with enrolling patients with low eGFR and poor BP control; (2) implementing the intervention; (3) limited duration during which to observe any clinical benefit from the intervention; (4) potential co-intervention or contamination; and (5) low statistical power.

Suppression of antitumor immune signatures and upregulation of VEGFA as IDH-mutant gliomas progress to higher grade.

OBJECTIVE: Several studies have compared the immune microenvironment of isocitrate dehydrogenase (IDH)-wildtype glioma versus IDH-mutant glioma. The authors sought to determine whether histological tumor progression in a subset of IDH-mutant glioma was associated with concomitant alterations in the intratumoral immune microenvironment. METHODS: The authors performed bulk RNA sequencing on paired and unpaired samples from patients with IDH-mutant glioma who underwent surgery for tumor progression across multiple timepoints. They compared patterns of differential gene expression, overall inflammatory signatures, and transcriptomic measures of relative immune cell proportions. RESULTS: A total of 55 unique IDH-mutant glioma samples were included in the analysis. The authors identified multiple genes associated with progression and higher grade across IDH-mutant oligodendrogliomas and astrocytomas. Compared with lower-grade paired samples, grade 4 IDH-mutant astrocytomas uniquely demonstrated upregulation of VEGFA in addition to counterproductive alterations in inflammatory score reflective of a more hostile immune microenvironment. CONCLUSIONS: Here, the authors have provided a transcriptomic analysis of a progression cohort for IDH-mutant glioma. Compared with lower-grade tumors, grade 4 astrocytomas displayed alterations that may inform the timing of antiangiogenic and immune-based therapy as these tumors progress.

Fate of dimethylsilanediol (DMSD) in soil-plant systems.

Dimethylsilanediol (DMSD) is the degradation product of methylsiloxane polymers and oligomers such as volatile cyclic methylsiloxanes (cVMS). To better understand the environmental fate of this key degradation product, we conducted a three-part study on the movement of DMSD in soil. The objective of this third and final study was to determine the fate of DMSD in soil-plant systems under constant irrigation. Soil columns were constructed using two soils with the upper 20 cm layers spiked with 14C-labeled DMSD. Corn seedlings were transplanted into the soil columns and placed in a field plot underneath a transparent cover that prevented rainwater from reaching the soil columns while allowing soil water to be volatilized freely. The soil-plant columns were regularly irrigated with known amounts of DMSD-free plant growth solution to sustain the plant growth. At pre-determined time intervals (15-67 days), the plant and soil columns were sectioned and the distribution of 14Corganosilicon species in the soil profile and plant parts was determined using a combination of Liquid Scintillation Counting and High-Performance Liquid Chromatography-Flow Scintillation Analysis, while soil water loss was determined gravimetrically. It was found that the majority (>92 %) of DMSD initially spiked into the soil was removed from the soil-plant systems. Although DMSD was transported from the soil to the plant, it was subsequently volatilized from the plant via transpiration, with only a small fraction (∼5%) remaining at the conclusion of the experiments. In addition, little non-extractable DMSD was found in the top layer of soil in the soil-plant systems, suggesting that the air-drying of soil is a necessary pre-condition for the formation of such non-extractable silanol residue on topsoil.

Fate of dimethylsilanediol (DMSD) in outdoor bare surface soil and its relation to soil water loss.

Dimethylsilanediol (DMSD) is a primary degradation product of silicone materials in the environment. Due to its low air/water partition coefficient and low soil/water distribution coefficient, this compound is not expected to undergo sorption and volatilization in wet soil. In an accompanying paper, we confirm that under controlled indoor conditions in test tubes, there is little to no volatilization of DMSD from soil and soil constituents if soil is wet. However, a significant amount of DMSD was volatilized when the soil substrates became air dried. Given the importance of water on the partition and fate of DMSD, we now report a continuation of this study focusing on the relation between DMSD removal and water loss in re-constituted soil columns under outdoor conditions. Consistent with predictions based on its partition properties and reconciling this evidence with previously reported field and laboratory studies, DMSD distribution was found to be largely dependent on water partitioning. The results suggested that DMSD moved upward in soil profile as soil water was evaporated from topmost layers with little DMSD retention by the soil matrix. As soil dried, a fraction of DMSD was sorbed by the soil matrix in the topmost layer, while most of the spiked radio-labeled DMSD was removed from soil through volatilization.

Volatilization of dimethylsilanediol (DMSD) under environmentally relevant conditions: Sampling method and impact of water and soil materials.

Dimethylsilanediol (DMSD) is the common breakdown product of methylsiloxanes such as polydimethylsiloxane (PDMS) and volatile methylsiloxanes (VMS) in soil. In this work, we first present a sorbent selection experiment aiming to identify a sorbent that can trap gas-phase DMSD without causing DMSD condensation and VMS hydrolysis at environmentally relevant humidities. With a proper sorbent (Tenax) identified, the volatilization of DMSD from water and various wet soil and soil materials were measured in a controlled environment. It was demonstrated that DMSD underwent volatilization after soil water was completely evaporated. Various types of soil constituents show drastic differences in preventing DMSD from volatilization. Analysis of the sorbent-captured products provides further insight, most notably that virtually no cyclic methylsiloxanes are formed during the volatilization of DMSD from water or soil materials, except in one extreme case where only traces are detected.

Investigating the transdiagnostic potential of rumination in relation to Cluster B personality disorder symptoms.

This study examined several forms of repetitive negative thinking in relation to measures of Cluster B disorders to identify unique and co-occurring cognitive mechanisms contributing to these symptom presentations. MTurk participants (N = 725; 53% men; 76% White) completed categorical and dimensional trait-based measures of Cluster B disorders alongside six measures of rumination and worry. Oversampling strategies were used during participant recruitment to obtain a sample with clinically relevant personality features. Path analyses examined each form of repetitive negative thinking in relation to Cluster B measures while controlling for shared variance between each construct. Anger rumination demonstrated notable relations across all four Cluster B personality disorders. Similarly, sadness rumination was positively associated with all four Cluster B personality disorders. Self-critical rumination and depressive rumination were uniquely associated with borderline symptoms. Worry demonstrated negative associations with measures of narcissistic, histrionic, and antisocial/psychopathy symptoms. Findings expand previous research by highlighting probable transdiagnostic and distinguishing cognitive process contributing to the presentation of Cluster B personality pathology. However, partialling the influence of overlapping constructs presents notable challenges in identifying and interpreting unique relations between various forms of repetitive negative thinking and Cluster B symptoms. Future research investigating these relations within outpatient and inpatient samples may provide avenues for the development of effective cognitive-based interventions for treating these symptoms. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Oldest old's travel mode choice and new mobility technology acceptance: case in America and China.

Introduction: The oldest olds (aged 85 and over) are the fastest-growing age segment. However, our understanding of their mobility is limited. To address this gap, we invited 19 U.S. and 30 Chinese "oldest old" to take part in focus groups and complete a mobility questionnaire. We focus on travel mode choice, which includes changes in travel modes, frequency of usage, and perceptions of comfort. Methods: Older adults' familiarity and acceptance of new mobility technologies (e.g., ridesharing, carsharing, and autonomous vehicles) were measured by questionnaire and focus group. Word clouds were also used to illustrate people's reasons for choosing their primary mode of transportation. Results and discussion: The results show that both panels of older adults similarly feel some extent of travel limitations. But the responses among the two groups differ: 18 American participants chose "drive myself" as their primary option a decade ago, while 11 chose it now; no Chinese participants selected it either a decade ago or now. Both currently and 10 years ago, there was a significant difference in mode choice between participants in China and the United States. However, this gap has narrowed over the past decade. Participants in China have significantly changed their transportation preferences compared to 10 years ago, while participants in the US have remained nearly unchanged. American respondents consider "ease" as an important factor, while Chinese respondents pay more attention to "safety" and "no other option to get around" when making travel mode choices. Compared to Chinese participants, American participants were more comfortable with driving an autonomous vehicle. These differences may result from the various developmental stages and transportation policies of the two countries. This study supports the development of new mobility technologies for the oldest old to improve their quality of life.

Successful Intravascular Lithotripsy Use for Acute Stent Underexpansion in Saphenous Vein Grafts.

Experience with intravascular lithotripsy (IVL) following stent deployment in saphenous vein graft (SVG) lesions is limited. We present 2 cases of percutaneous intervention in SVG in which acute stent underexpansion was successfully managed with IVL. In the first case, recalcitrant plaque required prestent deployment IVL, with intracoronary imaging showing persistent calcification. Additional poststent deployment IVL facilitated full expansion and successful stent delivery. In the second case, predilation with semicompliant balloons appeared angiographically effective, but stent deployment showed acute underexpansion. Postdilation with noncompliant balloons and ultimately IVL allowed full expansion and successful stent delivery. These are the first reported cases of IVL use immediately after stent deployment in SVG to treat underexpansion due to recalcitrant calcification.

"This Is Going To Be Different, But It's Not Impossible": Adapting To Telehealth Occupational Therapy For Autistic Children.

This qualitative study examined participants' experiences of transitioning to telehealth-delivered pediatric occupational therapy for autistic children during the COVID-19 pandemic. We interviewed three clinic administrators, four occupational therapists, and six parents of autistic children (n=13) from three Los Angeles area clinics over a 7-month period. Our narrative and thematic analyses yielded three overarching themes: Transformative Experiences, Reimagining Therapy, and Going Forward. Overall, we found that the transition to telehealth shifted participants' preconceptions about themselves, their relationships, and the nature of occupational therapy. Many deepened their relationships; adapted interventions; uncovered surprising capabilities; and challenged the occupational therapy status quo to advocate for ongoing virtual delivery. Our findings bear relevance to the body of current literature debating the post-pandemic viability of telehealth-delivered occupational therapy.

Implementation of a Multidimensional Strategy to Reduce Post-PCI Bleeding Risk.

BACKGROUND: The American College of Cardiology Reduce the Risk: PCI Bleed Campaign was a hospital-based quality improvement campaign designed to reduce post-percutaneous coronary intervention (PCI) bleeding events. The aim of the campaign was to provide actionable evidence-based tools for participants to review, adapt, and adopt, depending upon hospital resources and engagement. METHODS: We used data from 8 757 737 procedures in the National Cardiovascular Data Registry between 2015 and 2021 to compare patient and hospital characteristics and bleeding outcomes among campaign participants (n=195 hospitals) and noncampaign participants (n=1384). Post-PCI bleeding risk was compared before and after campaign participation. Multivariable hierarchical logistic regression was used to determine the adjusted association between campaign participation and post-PCI bleeding events. Prespecified subgroups were examined. RESULTS: Campaign hospitals were more often higher volume teaching facilities located in urban or suburban locations. After adjustment, campaign participation was associated with a significant reduction in the rate of bleeding (bleeding: adjusted odds ratio, 0.61 [95% CI, 0.53-0.71]). Campaign hospitals had a greater decrease in bleeding events than noncampaign hospitals. In a subgroup analysis, the reduction in bleeding was noted in non-ST-segment-elevation acute coronary syndrome and ST-segment-elevation myocardial infarction patients, but no significant reduction was seen in patients without acute coronary syndrome. CONCLUSIONS: Participation in the American College of Cardiology Reduce the Risk: PCI Bleed Campaign was associated with a significant reduction in post-PCI bleeding. Our results underscore that national quality improvement efforts can be associated with a significant impact on PCI outcomes.

The impact of delayed diagnosis and treatment due to COVID-19 on Australian thyroid cancer patients: a qualitative interview study.

OBJECTIVES: The study aims to investigate the perceptions of patients with thyroid cancer on the potential impact of diagnosis and treatment delays during the COVID-19 pandemic. DESIGN: This study involved qualitative semi-structured telephone interviews. The interviews were transcribed verbatim, analysed using the thematic framework analysis method and reported using the Consolidated Criteria for Reporting Qualitative Research. SETTING: Participants in the study were treated and/or managed at hospital sites across New South Wales and Victoria, Australia. PARTICIPANTS: 17 patients with thyroid cancer were interviewed and included in the analysis (14 females and 3 males). RESULTS: The delays experienced by patients ranged from <3 months to >12 months. The patients reported about delays to diagnostic tests, delays to surgery and radioactive iodine treatment, perceived disease progression and, for some, the financial burden of choosing to go through private treatment to minimise the delay. Most patients also reported not wanting to experience delays any longer than they did, due to unease and anxiety. CONCLUSIONS: This study highlights an increased psychological burden in patients with thyroid cancer who experienced delayed diagnosis and/or treatment during COVID-19. The impacts experienced by patients during this time may be similar in the case of other unexpected delays and highlight the need for regular clinical review during delays to diagnosis or treatment.

CDKN2A/B Homozygous Deletion Sensitizes IDH-Mutant Glioma to CDK4/6 Inhibition.

PURPOSE: Treatment paradigms for isocitrate dehydrogenase (IDH)-mutant gliomas are rapidly evolving. Although typically indolent and responsive to initial treatment, these tumors invariably recur at a higher grade and require salvage treatment. Homozygous deletion of the tumor suppressor gene CDKN2A/B frequently emerges at recurrence in these tumors, driving poor patient outcomes. We investigated the effect of CDK-Rb pathway blockade on IDH-mutant glioma growth in vitro and in vivo using CDK4/6 inhibitors (CDKi). EXPERIMENTAL DESIGN: Cell viability, proliferation assays, and flow cytometry were used to examine the pharmacologic effect of two distinct CDKi, palbociclib and abemaciclib, in multiple patient-derived IDH-mutant glioma lines. Isogenic models were used to directly investigate the influence of CDKN2A/B status on CDKi sensitivity. Orthotopic xenograft tumor models were used to examine the efficacy and tolerability of CDKi in vivo. RESULTS: CDKi treatment leads to decreased cell viability and proliferative capacity in patient-derived IDH-mutant glioma lines, coupled with enrichment of cells in the G1 phase. CDKN2A inactivation sensitizes IDH-mutant glioma to CDKi in both endogenous and isogenic models with engineered CDKN2A deletion. CDK4/6 inhibitor administration improves survival in orthotopically implanted IDH-mutant glioma models. CONCLUSIONS: IDH-mutant gliomas with deletion of CDKN2A/B are sensitized to CDK4/6 inhibitors. These results support the investigation of the use of these agents in a clinical setting.

Factors influencing support for the implementation of community-based out-of-hospital cardiac arrest interventions in high- and low-performing counties.

Aim of the study: Survival to hospital discharge from out-of-hospital cardiac arrest (OHCA) after receiving treatment from emergency medical services (EMS) is less than 10% in the United States. Community-focused interventions improve survival rates, but there is limited information on how to gain support for new interventions or program activities within these populations. Using data from the RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial, we aimed to identify the factors influencing emergency response agencies' support in implementing an OHCA intervention. Methods: North Carolina counties were stratified into high-performing or low-performing counties based on the county's cardiac arrest volume, percent of bystander-cardiopulmonary resuscitation (CPR) performed, patient survival to hospital discharge, cerebral performance in patients after cardiac arrest, and perceived engagement in the RACE-CARS project. We randomly selected 4 high-performing and 3 low-performing counties and conducted semi-structured qualitative interviews with emergency response stakeholders in each county. Results: From 10/2021 to 02/2022, we completed 29 interviews across the 7 counties (EMS (n = 9), telecommunications (n = 7), fire/first responders (n = 7), and hospital representatives (n = 6)). We identified three themes salient to community support for OHCA intervention: (1) initiating support at emergency response agencies; (2) obtaining support from emergency response agency staff (senior leadership and emergency response teams); and (3) and maintaining support. For each theme, we described similarities and differences by high- and low-performing county. Conclusions: We identified techniques for supporting effective engagement of emergency response agencies in community-based interventions for OHCA improving survival rates. This work may inform future programs and initiatives around implementation of community-based interventions for OHCA.

Clinical utility of a blood based assay for the detection of IDH1.R132H-mutant gliomas.

Glioma represents the most common central nervous system neoplasm in adults. Current classification scheme utilizes molecular alterations, particularly IDH1.R132H, to stratify lesions into distinct prognostic groups. Identification of the single nucleotide variant through traditional tissue biopsy assessment poses procedural risks and does not fully reflect the heterogeneous and evolving tumor landscape. Here, we introduce a liquid biopsy assay, mt-IDH1dx. The blood-based test allows minimally invasive detection of tumor-derived extracellular vesicle RNA using only 2 ml plasma volume. We perform rigorous, blinded validation testing across the study population (n = 133), comprising of IDH1.R132H patients (n = 80), IDH1 wild-type gliomas (n = 44), and age matched healthy controls (n = 9). Results from our plasma testing demonstrate an overall sensitivity of 75.0% (95% CI: 64.1%-84.0%), specificity 88.7% (95% CI: 77.0%-95.7%), positive predictive value 90.9%, and negative predictive value 70.1% compared to the tissue gold standard. In addition to fundamental diagnostic applications, the study also highlights the utility of mt-IDH1dx platform for blood-based monitoring and surveillance, offering valuable prognostic information. Finally, the optimized workflow enables rapid and efficient completion of both tumor tissue and plasma testing in under 4 hours from the time of sampling.

Mutant IDH modulates suppressive myeloid populations in malignant glioma.

PURPOSE: Mutations in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 have critical diagnostic and prognostic significance in diffuse gliomas. Neomorphic mutant IDH activity has been previously implicated in T-cell suppression; however, the effects of IDH mutations on intratumoral myeloid populations remain underexplored. Here, we investigate the influence of IDH status on the myeloid compartment using human glioma specimens and preclinical models. EXPERIMENTAL DESIGN: We performed RNA-sequencing and quantitative immunofluorescence on newly diagnosed, treatment-naive IDH-mutant grade 4 astrocytoma and IDH-wildtype glioblastoma (GBM) specimens. We also generated a syngeneic murine model, comparing transcriptomic and cell-level changes in paired isogenic glioma lines that differ only in IDH mutational status. RESULTS: Among patient samples, IDH-mutant tumors displayed underrepresentation of suppressive myeloid transcriptional signatures, which was confirmed at the cellular level with decreased numbers of intratumoral M2-like macrophages and MDSCs. Introduction of the IDH-mutant enzyme into murine glioma was sufficient to recapitulate the transcriptomic and cellular shifts observed in patient samples. CONCLUSIONS: We provide transcriptomic and cellular evidence that mutant IDH is associated with a quantitative reduction of suppressive myeloid cells in gliomas and that introduction of the mutant enzyme is sufficient to result in corresponding cellular changes using an in vivo preclinical model. These data advance our understanding of high-grade gliomas by identifying key myeloid cell populations that are reprogrammed by mutant-IDH and may be targetable through therapeutic approaches.

Mutant IDH inhibitors induce lineage differentiation in IDH-mutant oligodendroglioma.

A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation toward the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.