Probing the Distribution and Mobility of Aminopolymers after Multiple Sorption-Regeneration Cycles: Neutron Scattering Studies.

Solid-supported amines are effective CO2 adsorbents capable of capturing CO2 from flue gas streams (10-15 vol % CO2) and from ultradilute streams, such as ambient air (∼400 ppm CO2). Amine sorbents have demonstrated promising performance (e.g., high CO2 uptake and uptake rates) with stable characteristics under repeated, idealized thermal swing conditions, enabling multicycle application. Literature studies suggest that solid-supported amines such as PEI/SBA-15 generally exhibit slowly reducing CO2 uptake rates or capacities over repeated thermal swing capture-regeneration cycles under simulated DAC conditions. While there are experimental reports describing changes in supported amine mass, degradation of amine sites, and changes in support structures over cycling, there is limited knowledge about the structure and mobility of the amine domains in the support pores over extended use. Furthermore, little is known about the effects of H2O on cyclic applications of PEI/SBA-15 despite the inevitable presence of H2O in ambient air. Here, we present a series of neutron scattering studies exploring the distribution and mobility of PEI in mesoporous silica SBA-15 as a function of thermal cycling and cyclic conditions. Small-angle neutron scattering (SANS) and quasielastic neutron scattering (QENS) are used to study the amine and H2O distributions and amine mobility, respectively. Applying repeated thermal swings under dry conditions leads to the thorough removal of water from the sorbent, causing thinner and more rigid wall-coating PEI layers that eventually lead to slower CO2 uptake rates. On the other hand, wet cyclic conditions led to the sorption of atmospheric water at the wall-PEI interfaces. When PEI remains hydrated, the amine distribution (i.e., wall-coating PEI layer thickness) is retained over cycling, while lubrication effects of water yield improved PEI mobility, in turn leading to faster CO2 uptake rates.

Synthesis Route to Single-Walled Zeolite Nanotubes Enabled by Tetrabutylammonium Hydroxide.

Single-walled zeolite nanotubes (ZNT) were recently synthesized in a narrow compositional window. ZNT structural features-thin zeolitic walls and large mesopores-can allow for easy access of small molecules to zeolite micropores, but they also impart processing limitations for these materials, such as challenges with conventional aqueous ion-exchange conditions. Conventional solid- and liquid-phase ion exchange of calcined NaOH-derived ZNT (NaH-ZNT) results in structural degradation to either 2D sheet-like phases, 3D nanocrystals, or amorphous phases, motivating different direct synthesis routes and unconventional ion-exchange procedures of uncalcined ZNT precursors. Here, a modified synthesis route for ZNT synthesis is introduced that facilitates facile ion exchange as well as incorporation of additional non-Al heteroatoms in the zeolite framework. Tetrabutylammonium hydroxide (TBAOH) is used as a hydroxide source and co-OSDA, enabling synthesis of new compositions of ZNT, otherwise unachievable by post-modification of previously reported NaH-ZNT. By varying the gel composition, synthesis temperature, crystallization time, hydroxide source, silicon source, and aluminum source, productive conditions for the new TBAOH synthesis are developed, leading to increased strong acid site density in the ZNT. The collected results demonstrate the sensitivity of the ZNT synthesis to many key parameters and show that the ZNT forms only when Si/(Al + T) ∼ 30 in these synthesis gels and with specific Si and Al sources, and always in the presence of trace Na+. Catalytic testing, via the tandem CO2 hydrogenation to methanol and methanol to aromatics reaction, shows that ZNTs provide adequate catalytic activity (acidity), relative to their conventional 3D counterparts in converting methanol to aromatic compounds.

Effectiveness of an unguided modular online intervention for highly anxious parents in preventing anxiety in their children: a parallel group randomised controlled trial.

Background: Children whose parents have anxiety problems are at increased risk of developing anxiety themselves. Parenting behaviors are a contributing factor to intergenerational transmission. Interventions which seek to limit anxiogenic parenting behaviors have shown potential in reducing anxiety in offspring but are not widely accessible. This prevention trial aimed to establish the effectiveness of an unguided modular online intervention for highly anxious parents in preventing anxiety in their children. Methods: A parallel group, block-randomised controlled trial of unblinded participants in a 1:1 ratio was conducted to compare efficacy of the online course compared to a no-intervention control. The intervention comprised 8 modules, of approximately 20 min each, and participants progressed through the course at their own pace. The study was conducted entirely online with a self-referred UK-based community sample of parents (child 2-11 years) with substantial anxiety. The primary outcome measure was change in parent-reported child anxiety, as measured by the Spence Children's Anxiety Scale-Parent Report (SCAS-P) or Spence Pre-School Anxiety Scale-Parent Report (Preschool SCAS). Secondary outcomes were child internalising, externalising, and attentional symptoms (Pediatric Symptom Checklist), and parent anxiety (SCARED-Adult). Analyses using complete case analysis following intention to treat principles investigated intervention effects at 6 months (primary analysis) and additionally at 9 to 25-months' follow-up. Trial registration: ClinicalTrials.GovNCT04755933, https://clinicaltrials.gov/ct2/show/NCT04755933. Findings: 1811 participants (intervention = 900; control = 911; 92.7% (1677/1810) female; 85.3% (1535/1800) White-British; 66.8% (1201/1799) university educated). Participant retention (based on primary outcome completion) at T2 (6-months post consent) was 67.6% overall (n = 1224) and substantially lower in the intervention arm 57.3% ((516/900) control = 77.8% (708/910)). Child anxiety was lower in the intervention group compared to control at 6-month follow-up (adjusted effect size estimate -0.15 (95% CI: -0.23 to -0.08, p < 0.001). There was very strong evidence that those in the intervention arm had lowered child anxiety (standardised SCAS score) compared to the control arm, with an effect size (Cohen's d) of -0.16 (95% CI: -0.23 to -0.08, p < 0.001). The difference in standardised Spence Child Anxiety Scale score between the arms was -0.15 standard deviations. On the original scales for SCAS-P (0-114) and Preschool SCAS (0-112), this corresponds to a reduction of -2.38 (95% CI: -3.59 to -1.16) and -2.68 (95% CI: -4.05 to -1.31), respectively. No reported harms. Interpretation: A clinically unsupported online intervention designed for parents with high levels of anxiety is effective in reducing anxiety and internalising symptoms in their children, and also anxiety in parents. Given the low resource intensity of this intervention, and the positive effects reported here, these findings suggest it has promise in limiting the intergenerational transmission of severe anxiety. Funding: This work was supported by Kavli Trust (grant 38/19).

Comparing Knowledge and Perceptions of Palliative Care Among Neuro-Oncology Patients, Caregivers, and Providers to a Representative U.S. Sample.

BACKGROUND: Primary brain tumors (PBTs) pose a significant health challenge, affecting patients and their caregivers. While early integration of palliative care (PC) has shown benefits in advanced cancer, its integration for PBT patients, particularly glioblastoma (GBM) patients, remains complex. We hypothesized that our previous PC integration efforts may have failed due to knowledge-gaps and misconceptions among patients, caregivers, and providers. OBJECTIVE: This study aimed to identify knowledge gaps and misconceptions about PC among patients with primary brain tumors (PBTs), their caregivers, and their medical providers. METHOD: An electronic survey was distributed to PBT patients, caregivers, and medical providers, that included questions regarding PC from the Health Information National Trends Survey (HINTS). Survey responses were analyzed; comparisons were made between the 3 groups as well as the general population. RESULTS: Of 141 respondents (59 patients, 57 caregivers, and 25 providers), each group held perspectives on PC differing from the general population. While all groups had an improved understanding of PC's role in symptom management, uncertainty persisted among patients and caregivers regarding life-prolonging treatment and certain PC goals like caregiver support or end-of-life care. CONCLUSION: Understanding gaps in knowledge and perceptions of PC among PBT patients and caregivers is crucial for effective intervention, with caregivers playing a vital role in advocating for PC. Future research should explore factors influencing these perceptions and development of targeted education to improve early PC referrals for patients with PBTs.

CO2 Uptake and Stability Enhancement in Vinyltrimethoxysilane-Treated SBA-15 Solid Amine-Based Sorbents.

Silica-supported amine absorbents, including materials produced by tethering aminosilanes or infusion of poly(ethyleneimine), represent a promising class of materials for CO2 capture applications, including direct air and point source capture. Various silica surface treatments and functionalization strategies are explored to enhance stability and CO2 uptake in amine-based solid sorbent systems. Here, the synthesis and characterization of novel vinyltrimethoxysilane-treated Santa Barbara Amorphous-15 (SBA-15) supports and the corresponding enhancement in CO2 uptake compared to various SBA-15-based control supports are presented. The relationship between CO2 diffusion and amine efficiency in these systems is explored using a previously reported kinetic model. The synthesized materials are characterized with CO2 and H2O isotherms, diffuse reflectance infrared Fourier transform spectroscopy, 1H T1-T2 relaxation correlation NMR, and rapid thermal cycling experiments. The novel support materials are shown to enable high amine efficiencies, approaching a fourfold improvement over standard SBA-15-supported amines, while simultaneously exhibiting excellent stability when cycled rapidly under humid conditions. As the poly(ethyleneimine) loadings are held constant across the various samples, enhancements in CO2 uptake are attributed to differences in the way the poly(ethyleneimine) interacts with the support surface.

Affinity purification mass spectrometry characterisation of the interactome of receptor tyrosine kinase proline-rich motifs in cancer.

Receptor tyrosine kinase (RTK) overexpression is linked to the development and progression of multiple cancers. RTKs are classically considered to initiate cytoplasmic signalling pathways via ligand-induced tyrosine phosphorylation, however recent evidence points to a second tier of signalling contingent on interactions mediated by the proline-rich motif (PRM) regions of non-activated RTKs. The presence of PRMs on the C-termini of >40 % of all RTKs and the abundance of PRM-binding proteins encoded by the human genome suggests that there is likely to be a large number of previously unexplored interactions which add to the RTK intracellular interactome. Here, we explore the RTK PRM interactome and its potential significance using affinity purification mass spectrometry and in silico enrichment analyses. Peptides comprising PRM-containing C-terminal tail regions of EGFR, FGFR2 and HER2 were used as bait to affinity purify bound proteins from different cancer cell line lysates. 490 unique interactors were identified, amongst which proteins with metabolic, homeostatic and migratory functions were overrepresented. This suggests that PRMs from RTKs may sustain a diverse interactome in cancer cells. Since RTK overexpression is common in cancer, RTK PRM-derived signalling may be an important, but as yet underexplored, contributor to negative cancer outcomes including resistance to kinase inhibitors.

An App Platform-Facilitated Collaborative Palliative Care Intervention for Outpatients With Interstitial Lung Disease: A Pilot Randomized Trial.

Rationale: Outpatients with interstitial lung disease often experience serious symptoms, yet infrequently receive palliative care. Objective: To determine the feasibility and clinical impact of a mobile application (PCplanner) in an outpatient setting. Methods: We conducted a pilot randomized controlled trial among adults with interstitial lung disease in a single-center academic clinic. Clinical outcomes included change in Needs at the End-of-Life Screening Tool (NEST) scale between baseline and 3 months as well as frequency of advance care planning discussions and referrals to palliative care services. Results: Observed feasibility outcomes were similar to targeted benchmarks including randomization rates (82.1% vs 80%) and retention (84.8% vs 80%). Mean NEST scores between the intervention and control group were 38.9 (SD, 18.9) vs 41.5 (SD, 20.5) at baseline, 34.6 (SD, 18.9) vs 33.6 (SD, 19.4) at 1 month after clinic visit, 40.5 (SD, 21.6) vs 35.3 (SD, 25.0) at 3 months after clinic visit. Changes in NEST scores between baseline and 3 months showed no difference in the primary outcome (P = 0.481, 95% CI [-8.45, 17.62]). Conclusion: Among patients with interstitial lung disease, a mobile app designed to focus patients and clinicians on palliative care principles demonstrated evidence of feasibility. Although changes in self-reported needs were similar between intervention and control groups, more patients in the intervention group updated their advance directives and code status compared to the control group. Clinical Trial Registration: Palliative Care Planner (PCplanner) NCT05095363. https://www.clinicaltrials.gov/study/NCT05095363.

Exploring the prevalence of childhood adversity among university students in the United Kingdom: A systematic review and meta-analysis.

OBJECTIVES: The focus of this review was to systematically review and meta-analyse the prevalence of ACEs among university students in the UK. METHOD: The systematic searching of six electronic databases (conducted February 2024) identified ten relevant articles (peer-reviewed articles of a quantitative nature that included ACE prevalence). PROSPERO reference: CRD42022364799. RESULTS: Pooled prevalence for number of ACEs endured was 55.4% (95% CI: 32.4% - 78.4%; I2 > 99.5%) for one or more, and 31.6% (7.5% - 55.6%; I2 > 99.5%) for three or more. Pooled prevalence was: 15.9% (7.0% - 24.7%; I2 > 94.5%) for physical abuse; 27.0% (18.1% - 35.9%; I2 > 94.5%) for emotional abuse; 12.1% (5.2% - 19.0%; I2 > 94.5%) for sexual abuse; 8.4% (1.7% - 15.1%; I2 > 95.4%) for physical neglect, and 30.0% (21.5% - 38.5%; I2 > 95.4%) for emotional neglect. Pooled prevalence for household dysfunction categories were: 34.4% (22.8% - 46.0%) for parental separation; 18.4% (10.1% - 26.8%) for domestic violence; 35.2% (23.6% - 46.8%) for mental health difficulties; 21.4% (12.9% - 29.9%) for substance use; and 5.7% (2.3% - 9.1%) for incarceration (I2 > 88.8% for all household dysfunction items). Significant heterogeneity was observed between studies for most categories of adversity, and it was not possible to explain/reduce this variance by removing small numbers of influential/discrepant studies. Further analyses suggested potential influences of measurement tool used, country of data collection, and age and sex of participants. CONCLUSION: Results demonstrate considerable, largely unaccounted-for, heterogeneity in estimates of the prevalence of ACEs, impeding confidence in any summary statistics. Conclusions must be tentative due to analyses being underpowered given small numbers of papers, as well as potential confounds, meaning results may not be truly representative. However, results do suggest high prevalence rates which warrant further investigation, with appropriate support offered to students.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Patients with Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are a group of rare chronic progressive blood cancers that vary widely in clinical presentation, yet all patients have a risk of disease progression and thrombotic complications. Diseases include primary myelofibrosis, polycythemia vera, and essential thrombocythemia. With current treatment approaches, most patients live a prolonged life, but many experience a complex of symptoms that negatively influence their functional status and quality of life. Although significant advances have been made in preventing arterial and venous complications while mitigating inflammatory processes, comprehensive palliative care can help address unmet complex physical and psychosocial needs on a long-term basis. This article, created by a multidisciplinary group of providers, offers an overview of MPNs so palliative care clinicians can better support patients with these hematologic cancers.

The link between anxiety and theory of mind in children: A meta-analysis.

BACKGROUND: The ability to reason about someone else's mental states, an ability known as theory of mind, is essential to help children navigate social life. However, not all children are socially skilled. Given socialisation is key for healthy development in children, finding what might exacerbate these difficulties is important. Emerging research suggests a potential link between anxiety and theory of mind abilities in children. This meta-analysis aims to characterise that link. METHOD: Four electronic databases were systematically searched to identify relevant studies. Search terms included variations of terms for theory of mind, anxiety, and children. Studies were screened with inclusion and exclusion criteria for eligibility and identified papers were appraised on quality. RESULTS: The search returned 3674 papers of which 20 were included in the analysis. These included a total of 3110 participants, aged 4-19. Overall, it was found that anxiety had a negative relationship with theory of mind and this appeared to be more pronounced in theory of mind processes related to affective states. There were no differences in the negative relationship between subtypes of anxiety or between studies with autistic and neurotypical children. CONCLUSION: The findings suggest that anxious children may have difficulties using theory of mind abilities. Heterogeneity was substantial in the data, which limits the confidence in conclusions. Quality appraisal identified that the quality of theory of mind and anxiety measures varied between studies.

Household Compositions and Substance Use among Young Adults in the U.S.

BACKGROUND: Adults aged 21-29 have the highest past-month prevalence of tobacco, alcohol, and illicit drug use in the U.S. Currently, young adults often delay traditional adulthood milestones (e.g., marriage and childbearing), which may impact their household composition and substance use. METHODS: We examined how the past-month prevalence of eight mutually exclusive substance use outcomes varied by household composition among young adults using the 2016-2019 National Surveys on Drug Use and Health (NSDUH) data. Bivariable and multivariable multinomial logistic regression analyses were applied. RESULTS: Among young adults residing with their children, the most common household composition was residing with children and a spouse/partner (16.6%, 95% CI = 16.5-16.8%). Among those residing without children, common household compositions included residing with parents (22.8%, 95% CI = 22.2-23.4%) and residing only with a spouse/partner (17.9%, 95% CI = 17.6-18.3%). Past-month prevalence of binge alcohol, tobacco, and illicit drug use varied by household composition. Residing only with children and a spouse/partner was associated with a low prevalence of most examined substance use patterns. Across household compositions, those residing solely with unrelated individuals had the highest adjusted prevalence of tobacco, drug, and binge alcohol use (13.8%, 95% CI = 12.5-15.1%). CONCLUSIONS: The prevalence of substance use patterns among U.S. young adults varies by household composition. Those residing solely with unrelated individuals had the highest prevalence of tobacco, binge alcohol, and drug use. The presence of a young adult's own children and a spouse/partner is associated with a lower prevalence of most examined substance use patterns. As household compositions continue to diversify, targeted substance use prevention/treatment strategies may be needed.

Competing Kinetic Consequences of CO2 on the Oxidative Degradation of Branched Poly(ethylenimine).

Amine-functionalized porous solid materials are effective sorbents for direct air capture (DAC) of CO2. However, they are prone to oxidative degradation in service, increasing the materials cost for widespread implementation. While the identification of oxidation products has given insights into degradation pathways, the roles of some species, like CO2 itself, remain unresolved, with conflicting information in the literature. Here, we investigate the impact of CO2 on the oxidative degradation of poly(ethylenimine)-alumina (PEI/Al2O3) sorbents under conditions encompassing a wide range of CO2-air mixture compositions and temperatures relevant to DAC conditions, thereby reconciling the conflicting data in the literature. Degradation profiles characterized by thermogravimetric analysis, in situ ATR-FTIR, and CO2 capacity measurements reveal nonmonotonic effects of CO2 concentrations and temperatures on oxidation kinetics. Specifically, 0.04% CO2 accelerates PEI/Al2O3 oxidation more at low temperatures (<90 °C) compared to 1% and 5% CO2, but this trend reverses at high temperatures (>90 °C). First-principles metadynamics, machine learning accelerated molecular dynamics simulations, and 1H relaxometry experiments show that chemisorbed CO2 acid-catalyzes critical oxidation reactions, while extensive CO2 uptake reduces PEI branch mobility, slowing radical propagation. These contrasting kinetic effects of CO2 explain the complex degradation profiles observed in this work and in prior literature. Collectively, this work highlights the importance of considering atmospheric components in the design of DAC sorbents and processes. Additionally, it identifies the unconstrained branch mobility and local acid environment as two of the major culprits in the oxidation of amine-based sorbents, suggesting potential strategies to mitigate sorbent degradation.

Association between echocardiographic features, troponin levels, and survival time in hospitalized COVID-19 patients with cardiovascular events.

Introduction: This study aims to explore the predictive roles of echocardiographic parameters and biomarkers in determining outcomes among hospitalized COVID-19 patients experiencing cardiovascular events. Methods: A retrospective cohort study was conducted involving 49 COVID-19 patients who encountered cardiovascular events during hospitalization and underwent echocardiography. Our findings revealed notable associations between echocardiographic parameters and survival time. Results: A decrease in left ventricular ejection fraction (LVEF) of 10% was linked to a 20% reduction in survival time (TR: 0.80, 95% CI: 0.67 - 0.96, p = .017). Similarly, an increase in left ventricular (LV) volume by 10 mL was associated with a 9% decrease in survival time (TR: 0.91, 95% CI: 0.84 - 0.98, p = .011). Moreover, an increase in left atrial (LA) volume by 10 mL corresponded to an 8% decrease in survival time (TR: 0.92, 95% CI: 0.86 - 0.99, p = .026). Additionally, each 1 cm increase in right ventricular (RV) diameter was linked to a 22% reduction in survival time (TR: 0.78, 95% CI: 0.61 - 0.99, p = .043). Furthermore, a 10 mL increase in right atrial (RA) volume was associated with a 12% decrease in survival time (TR: 0.88, 95% CI: 0.78 - 0.98, p = .017). Notably, a tenfold rise in troponin levels was linked to a 33% decrease in survival time (TR: 0.67, 95% CI: 0.48 - 0.93, p = .014). Conclusions: Our study emphasizes the significant associations between various echocardiographic parameters and troponin levels with reduced survival time among COVID-19 patients experiencing cardiovascular events. These findings highlight the potential utility of echocardiography and troponin assessment in predicting outcomes and guiding management strategies in this patient population.

A Geometrically Flexible Three-Dimensional Nanocarbon.

The development of architecturally unique molecular nanocarbons by bottom-up organic synthesis is essential for accessing functional organic materials awaiting technological developments in fields such as energy, electronics, and biomedicine. Herein, we describe the design and synthesis of a triptycene-based three-dimensional (3D) nanocarbon, GFN-1, with geometrical flexibility on account of its three peripheral π-panels being capable of interconverting between two curved conformations. An effective through-space electronic communication among the three π-panels of GFN-1 has been observed in its monocationic radical form, which exhibits an extensively delocalized spin density over the entire 3D π-system as revealed by electron paramagnetic resonance and UV-vis-NIR spectroscopies. The flexible 3D molecular architecture of GFN-1, along with its densely packed superstructures in the presence of fullerenes, is revealed by microcrystal electron diffraction and single-crystal X-ray diffraction, which establish the coexistence of both propeller and tweezer conformations in the solid state. GFN-1 exhibits strong binding affinities for fullerenes, leading to host-guest complexes that display rapid photoinduced electron transfer within a picosecond. The outcomes of this research could pave the way for the utilization of shape and electronically complementary nanocarbons in the construction of functional coassemblies.

Top Ten Tips Palliative Care Clinicians Should Know About Diagnosing, Categorizing, and Addressing Fatigue.

Fatigue is a multifactorial symptom that is commonly faced by patients with cancer, chronic disease, and other serious illnesses. Fatigue causes suffering across biopsychosocial domains and affects patients and their loved ones. In this article, a consortium of professionals across cancer care, physical therapy, exercise, pharmacy, psychiatry, and palliative medicine offers tips and insights on evaluating, categorizing, and addressing fatigue in the setting of serious illness. The comprehensive approach to managing fatigue underscores the importance of collaborative efforts characteristic of interdisciplinary palliative care. Prioritizing screening, diagnosing, and treating fatigue is crucial for enhancing patients' and families' overall quality of life.

Baseline total brain volume predicts changes in quality of life and overall survival after cranial radiotherapy in older patients with glioblastoma: Results from the prospective BRITER study.

Background: Short-course partial brain radiotherapy ± chemotherapy for older patients with GBM extends survival but there is no validated evidence for prediction of individual risk of acute radiotherapy-related side effects. Methods: This prospective multicentre observational trial recruited patients with newly diagnosed GBM aged ≥65 planned for cranial radiotherapy. Baseline MRI scans were analyzed for markers of brain resilience including relative total brain volume (ratio of cerebrospinal fluid (CSF) volume to total intracranial volume (TIV)) and their relationship to change in quality of life (QoL). Results: 126 patients enrolled: mean age 72 years (range 65-83). 77% had debulking surgery. 79% received radiotherapy with concurrent TMZ, and 21% received palliative radiotherapy alone. The median OS was 10.7 months. After accounting for age, sex, treatment, and baseline MoCA score, there was a relationship between baseline CSF:TIV and change in QoL score at 8 weeks post treatment. For each unit point of increase in CSF:TIV, there was a corresponding decrease in QoL score of 1.72 (95% CI -3.24 to -0.19 P = .027). 35 participants were too unwell to complete questionnaires or had died by the 8 week follow-up visit. In this subgroup, post hoc logistic regression showed baseline CSF:TIV was related to the risk of non-attendance (OR 1.35, 95% CI 1.01 to 1.80, P = .042). Cox regression models showed baseline CSF:TIV was associated with worsened OS (HR 1.41, 95% CI 1.19 to 1.66, P < .001). Conclusions: This study provides evidence to support the use of an imaging biomarker to help assess the risk:benefit ratio for radiotherapy.

Standard or high dose chemoradiotherapy, with or without the protease inhibitor nelfinavir, in patients with locally advanced pancreatic cancer: The phase 1/randomised phase 2 SCALOP-2 trial.

BACKGROUND: The multi-centre two-stage SCALOP-2 trial (ISRCTN50083238) assessed whether dose escalation of consolidative chemoradiotherapy (CRT) or concurrent sensitization using the protease inhibitor nelfinavir improve outcomes in locally advanced pancreatic cancer (LAPC) following four cycles of gemcitabine/nab-paclitaxel. METHODS: In stage 1, the maximum tolerated dose (MTD) of nelfinavir concurrent with standard-dose CRT (50.4 Gy in 28 fractions) was identified from a cohort of 27 patients. In stage 2, 159 patients were enrolled in an open-label randomized controlled comparison of standard versus high dose (60 Gy in 30 fractions) CRT, with or without nelfinavir at MTD. Primary outcomes following dose escalation and nelfinavir use were respectively overall survival (OS) and progression free survival (PFS). Secondary endpoints included health-related quality of life (HRQoL). RESULTS: High dose CRT did not improve OS (16.9 (60 % confidence interval, CI 16.2-17.7) vs. 15.6 (60 %CI 14.3-18.2) months; adjusted hazard ratio, HR 1.13 (60 %CI 0.91-1.40; p = 0.68)). Similarly, median PFS was not improved by nelfinavir (10.0 (60 %CI 9.9-10.2) vs. 11.1 (60 %CI 10.3-12.8) months; adjusted HR 1.71 (60 %CI 1.38-2.12; p = 0.98)). Local progression at 12 months was numerically lower with high-dose CRT than with standard dose CRT (n = 11/46 (23.9 %) vs. n = 15/45 (33.3 %)). Neither nelfinavir nor radiotherapy dose escalation impacted on treatment compliance or grade 3/4 adverse event rate. There were no sustained differences in HRQoL scores between treatment groups over 28 weeks post-treatment. CONCLUSIONS: Dose-escalated CRT may improve local tumour control and is well tolerated when used as consolidative treatment in LAPC but does not impact OS. Nelfinavir use does not improve PFS.

Prescription Opioid Use Disorder Among Adults Reporting Prescription Opioid Use With or Without Misuse in the United States.

Objective: We examined prescription related opioid use disorder (POUD) prevalence, individual symptoms, severity, characteristics, and treatment by prescription opioid misuse status among adults with prescription opioid use.Methods: Cross-sectional study using nationally representative data from 47,291 adults aged ≥18 years who participated in the 2021 National Survey on Drug Use and Health. Past-year POUD used DSM-5 criteria.Results: Among US adults with past-year prescription opioid use, 12.1% (95% CI, 11.1%-13.1%) misused prescription opioids, and 7.0% (95% CI, 6.2%-8.9%) had POUD. Among adults with POUD, 62.0% (95% CI, 56.7%-67.2%) reported no prescription opioid misuse, including 49.1% (95% CI, 43.5%-54.7%) with mild POUD, 11.0% (95% CI, 6.5%-15.4%) with moderate POUD, and 1.9% (95% CI, 0.6%-3.2%) with severe POUD. Prevalence of POUD was 4.5 times higher (prevalence ratio = 4.5, 95% CI, 3.6-5.6) among those reporting prescription opioid misuse (22.0%, 95% CI, 18.6%-25.8%) than those reporting use without misuse (4.9%, 95% CI, 4.2%-5.7%). Among adults reporting prescription opioid use without misuse, high POUD prevalence was found for those with ≥3 emergency department visits (16.4%, 95% CI, 11.5%-23.0%), heroin use/use disorder (17.1%, 95% CI, 5.2%-43.8%), prescription sedative/ tranquilizer use disorder (36.2%, 95% CI, 23.6%-51.1%), and prescription stimulant use disorder (21.8%, 95% CI, 11.0%-38.7%).Conclusions: Moderate-to-severe POUD is more frequent among adults who report misusing prescription opioids. However, 62% of adults with POUD do not report prescription opioid misuse, suggesting that adults who are treated with prescription opioids and report no misuse could be at risk for developing POUD. Results highlight the need to screen for and treat POUD among adults taking prescription opioids regardless of whether they report prescription opioid misuse.

Small dams drive Anopheles abundance during the dry season in a high malaria burden area of Malawi.

This study explores the influence of small dams on the exposure to malaria vectors during the dry season in Kasungu district, Malawi, an area recently identified as high priority for malaria interventions by the National Malaria Control Programme. Small dam impoundments provide communities with a continuous supply of water for domestic and agricultural activities across sub-Saharan Africa and are considered vital to food security and climate change resilience. However, these permanent water bodies also create ideal breeding sites for mosquitoes in typically arid landscapes. The study focuses on a specific dam impoundment and its vicinity, aiming to assess its spatial and temporal influence on indoor vector densities. From May to August 2021, CDC light traps were used to measure indoor mosquito densities for two consecutive nights per month in three communities located at increasing distances from the dam (0, ~1 and ~2 km). Simultaneously, drone imagery was captured for each community, enabling the identification of additional standing water within approximately 400 m of selected households. Larval sampling was carried out within the impoundment periphery and in additional water bodies identified in the drone imagery. Generalised linear mixed models (GLMMs) were employed to analyse the indoor Anopheles abundance data, estimating the effects of household structure (open/closed eaves), month, temperature and water proximity on malaria vector exposure. Throughout 685 trapping nights, a total of 1256 mosquitoes were captured, with 33% (412) being female Anopheles. Among these, 91% were morphologically identified as Anopheles funestus s.l., and 5% as Anopheles gambiae s.l. Catches progressively decline in each consecutive trapping month as the environment became drier. This decline was much slower in Malangano, the community next to the dam, with abundance being notably higher in June and July. Further, the majority of An. gambiae s.l. were caught in May, with none identified in July and August. Anopheles larvae were found both in the impoundment and other smaller water bodies such as irrigation wells in each survey month; however, the presence of these smaller water bodies did not have a significant impact on adult female mosquito catches in the GLMM. The study concludes that proximity to the dam impoundment was the primary driver of differences between survey communities with the abundance in Chikhombwe (~1 km away) and Chiponde (~2 km away) being 0.35 (95% confidence interval [CI], 0.19-0.66) and 0.28 (95% CI, 0.16-0.47) lower than Malangano, respectively, after adjusting for other factors. These findings underscore the importance of targeted interventions, such as larval source management or housing improvements, near small dams to mitigate malaria transmission risks during the dry season. Further research is needed to develop cost-effective strategies for vector control within and around these impoundments.