Background: Cerebral venous thrombosis (CVT) is a rare cause of stroke, with 10–15% of patients experiencing dependence or death. The role of endovascular therapy (EVT) in the management of CVT remains controversial and practice patterns are not well-known. Methods: We distributed a comprehensive 53-question survey to neurologists, neuro-interventionalists, neurosurgeons and other relevant clinicians globally from May 2023 to October 2023. The survey asked about practice patterns and perspectives on EVT for CVT and assessed opinions regarding future clinical trials. Results: The overall response rate was 31% (863 respondents from 2744 invited participants) across 61 countries. A majority (74%) supported use of EVT for certain CVT cases. Key considerations for EVT included worsening level of consciousness (86%) and other clinical deficits (76%). Mechanical thrombectomy with aspiration (22%) and stent retriever (19%) were the most utilized techniques, with regional variations. Post-procedurally, low molecular weight heparin was the predominant anticoagulant administered (40%), although North American respondents favored unfractionated heparin. Most respondents supported future trials of EVT (90%). Conclusions: Our survey reveals significant heterogeneity in approaches to EVT for CVT, highlighting the necessity for adequately powered clinical trials to guide standard-of-care practices.

Rodent control tends to involve methods that cause animal suffering, but little attention has been paid to the animal welfare implications of rodent control. The aim of the current study was to gain insight into the opinions and attitudes of clients of Dutch pest controllers, regarding liminal rodents, rodent control, and rodent welfare. A better understanding of their attitudes may contribute to more ethical rodent management programmes. An online survey among 248 clients of Dutch pest controllers was carried out. Respondents, especially those within the agricultural sector, have a relatively negative attitude towards rats and mice. Respondents in the agricultural subgroup do not consider the welfare of liminal rodents important. They also think that the welfare impact of commonly used control methods is limited, and they have low tolerance levels for the presence of rodents. Respondents from other sectors have a far more positive attitude towards rats and mice, consider their welfare to be of greater importance, have a greater estimation of the welfare impact of control methods and show greater tolerance levels towards rodents. The respondents from the latter subgroup have a similar attitude compared to Dutch pest controllers participating in a previous survey. The findings of the current study firstly provide useful information for the further development and practical implementation of preventive control methods. Secondly, they provide input for a more animal-friendly rodent control and for the development of an assessment framework to support ethical decision-making. Finally, they can be helpful for further research and the communication and co-operation between professional pest controllers and their clients.

OBJECTIVES/GOALS: The goal of this study was to develop a clinically applicable technique to increase the precision of in vivo dose monitoring during radiation therapy by mapping the dose deposition and resolving the temporal dose accumulation while the treatment is being delivered in real time. METHODS/STUDY POPULATION: Ironizing radiation acoustic imaging (iRAI) is a novel imaging concept with the potential to map the delivered radiation dose on anatomic structure in real time during external beam radiation therapy without interrupting the clinical workflow. The iRAI system consisted of a custom-designed two-dimensional (2D) matrix transducer array with integrated preamplifier array, driven by a clinic-ready ultrasound imaging platform. The feasibility of iRAI volumetric imaging in mapping dose delivery and real-time monitoring of temporal dose accumulation in a clinical treatment plan were investigated with a phantom, a rabbit model, and a cancer patient. RESULTS/ANTICIPATED RESULTS: The total dose deposition and temporal dose accumulation in 3D space of a clinical C-shape treatment plan in a targeted region were first imaged and optimized in a phantom. Then, semi-quantitative iRAI measurements were achieved in an in vivo rabbit model. Finally, for the first time, real-time visualization of radiation dose delivered deep in a patient with liver metastases was performed with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the radiation dose deposition during treatment. DISCUSSION/SIGNIFICANCE: Described here is the pioneering role of an iRAI system in mapping the 3D radiation dose deposition of a complex clinical radiotherapy treatment plan. iRAI offers a cost-effective and practical solution for real-time visualization of 3D radiation dose delivery, potentially leading to personalized radiotherapy with optimal efficacy and safety.

This study aimed to evaluate the effect of an extended voluntary waiting period (VWP) on SCC, SCC elevations and clinical mastitis incidence during the complete lactation and the first 6 weeks of the next lactation. Holstein-Friesian dairy cows (N = 154) were blocked for parity, expected milk yield, calving season and breeding value for persistency and were randomly distributed across 3 VWP (50, 125, or 200 d: VWP-50, VWP-125, VWP-200). Cows were monitored from calving until 6 weeks into the next lactation, or until culling. An elevation of SCC in milk was defined as SCC in milk ≥200 000 cells/ml after two previous weeks with SCC < 200 000 cells/ml. Over the complete lactation, extending the VWP did not affect SCC elevations and the occurrence of clinical mastitis per lactation or per cow per year. There was no clear effect of VWP length on SCC in the complete lactation, except that multiparous cows in VWP-125 had a higher SCC compared with multiparous cows in VWP-50. Dry-off antibiotic usage per cow per year was lower in VWP-200 compared with VWP-50 for multiparous cows. In the first 6 weeks of the next lactation, cows in VWP-200 had a higher SCC compared with cows in VWP-50, with no effect of VWP on the number of elevations of SCC or the occurrence of clinical mastitis. Extending the VWP may therefore be used to reduce the frequency of transition periods and the associated use of dry-cow antibiotics, with limited impact on udder health, and a similar occurrence of SCC elevations and clinical mastitis per year.

This study compares the δ15N values and the trophic position of two seabird species throughout the late Holocene in three regions in the southwestern Atlantic Ocean to assess the hypothesis that the decimation of megafauna led to changes in the trophic position of mesopredators. Modern and ancient mollusk shells were also analyzed to account for changes in the isotopic baseline through time. Results revealed that modern Magellanic penguins have higher δ15N values than their ancient conspecifics in the three regions, after controlling for changes in the isotopic baseline. This was also true for modern Imperial shags compared with ancient unidentified cormorants/shags from the two areas where ancient specimens were recovered (southern Patagonia and the Beagle Channel). Such temporal variability might be caused by three non–mutually exclusive processes: decreased availability of pelagic squat lobster resulting from decreasing primary productivity through the late Holocene, increased availability of small fishes resulting from the sequential depletion of other piscivores (South American fur seal and sea lion and Argentine hake) since the late eighteenth century, and modification of the migratory patterns of Magellanic penguins. Although disentangling the relative contribution of all those processes is impossible at this time, the results reported here demonstrate that the ecology of Magellanic penguins and Imperial shags has undergone major changes since the late Holocene.

To generate aerodynamic forces required for flight, two-winged insects (Diptera) move their wings back and forth at high wing-beat frequencies. This results in exceptionally high wing-stroke accelerations, and consequently relatively high acceleration-dependent fluid forces. Quasi-steady fluid force models have reasonable success in relating the generated aerodynamic forces to the instantaneous wing motion kinematics. However, existing approaches model the stroke-rate and stroke-acceleration effects independently from each other, which might be too simplified for capturing the complex unsteady aerodynamics of accelerating wings. Here, we use computational-fluid-dynamics simulations to systematically explore how aerodynamic forces and flow dynamics depend on wing-stroke rate, wing-stroke acceleration and wing-planform geometry. Based on this, we developed and calibrated a novel unsteady aerodynamic force model for insect wings with stroke accelerations. This includes improved versions of the translational-force model and the added-mass force model, and we identify a third novel component generated by the interaction of the two. This term reflects the delay in bound-circulation build-up as the wing accelerates. The physical interpretation of this effect is analogous to the Wagner effect experienced by a wing starting from rest. Here, we show that this effect can be modelled in the context of flapping wings as a stroke-acceleration-dependent correction on the translational-force model. Our revised added-mass model includes a viscous force component, which is relatively small but not negligible. We subsequently applied our new model to realistic wing-beat kinematics of hovering Dipteran insects, in a quasi-steady approach. This revealed that stroke-acceleration-related aerodynamic forces contribute substantially to lift and drag production, particularly for high-frequency flapping mosquito wings.

Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.

Background: Medulloblastoma (MB) is the most common solid malignant pediatric brain neoplasm. Group 3 (G3) MB, particularly MYC amplified G3 MB, is the most aggressive subgroup with the highest frequency of children presenting with metastatic disease, and is associated with a poor prognosis. To further our understanding of the role of MSI1 in MYC amplified G3 MB, we performed an unbiased integrative analysis of eCLIP binding sites, with changes observed at the transcriptome, the translatome, and the proteome after shMSI1 inhibition. Methods: Primary human pediatric MBs, SU_MB002 and HD-MB03 were kind gifts from Dr. Yoon-Jae Cho (Harvard, MS) and Dr. Till Milde (Heidelberg) and cultured for in vitro and in vivo experiments. eCLIP, RNA-seq, Polysome-seq, and TMT-MS were completed as previously described. Results:MSI1 is overexpressed in G3 MB. shRNA Msi1 interference resulted in a reduction in tumour burden conferring a survival advantage to mice injected with shMSI1 G3MB cells. Robust ranked multiomic analysis (RRA) identified an unconventional gene set directly perturbed by MSI1 in G3 MB. Conclusions: Our robust unbiased integrative analysis revealed a distinct role for MSI1 in the maintenance of the stem cell state in G3 MB through post-transcriptional modification of multiple pathways including identification of unconventional targets such as HIPK1.

Defined benefit pension funds invest in illiquid asset classes for return, diversification or liability hedging reasons. So far, little is known about factors influencing how much they invest in illiquid assets. We conjecture that liquidity and capital requirements are pivotal in this decision. Short-term pension payments and margining on derivative contracts generate liquidity requirements, while regulations impose capital requirements. Consistent with our model we empirically find that these requirements create a hump-shaped impact of liability duration on the fraction of risky assets invested in illiquid assets. Further, we report that pension fund size, type, and funding ratio impact illiquid assets allocations.

In this paper, we consider the risk–return trade-off for variable annuities in a Black–Scholes setting. Our analysis is based on a novel explicit allocation of initial wealth over the payments at various horizons. We investigate the relationship between the optimal consumption problem and the design of variable annuities by deriving the optimal so-called assumed interest rate for an investor with constant relative risk aversion preferences. We investigate the utility loss due to deviations from this. Finally, we show analytically how habit-formation-type smoothing of financial market shocks over the remaining lifetime leads to smaller year-to-year volatility in pension payouts, but to increases in the longer-term volatility.

Knowing the burden of influenza is helpful for policy decisions. Here we estimated the contribution of influenza-like illness (ILI) visits associated with laboratory-confirmed influenza among all clinic visits in a Senegal sentinel network. ILI data from ten sentinel sites were collected from January 2013 to December 2015. ILI was defined as an axillary measured fever of more than 37.5 °C with a cough or a sore throat. Collected nasopharyngeal swabs were tested for influenza viruses by rRT-PCR. Influenza-associated ILI was defined as ILI with laboratory-confirmed influenza. For the influenza disease burden estimation, we used all-case outpatient visits during the study period who sought care at selected sites. Of 4030 ILI outpatients tested, 1022 were influenza positive. The estimated proportional contribution of influenza-associated ILI was, per 100 outpatients, 1.2 (95% CI 1.1–1.3), 0.32 (95% CI 0.28–0.35), 1.11 (95% CI 1.05–1.16) during 2013, 2014, 2015, respectively. The age-specific outpatient visits proportions of influenza-associated ILI were higher among children under 5 years (0.68%, 95% CI: 0.62–0.70). The predominant virus during years 2013 and 2015 was influenza B while A/H3N2 subtype was predominant during 2014. Influenza viruses cause a substantial burden of outpatient visits particularly among children under 5 of age in Senegal and highlight the need of vaccination in risk groups.

Hydatigera (Cestoda: Taeniidae) is a recently resurrected genus including species seldom investigated in sub-Saharan Africa. We surveyed wild small mammal populations in the areas of Richard Toll and Lake Guiers, Senegal, with the objective to evaluate their potential role as intermediate hosts of larval taeniid stages (i.e. metacestodes). Based on genetic sequences of a segment of the mitochondrial DNA gene cytochrome c oxidase subunit 1 (COI), we identified Hydatigera parva metacestodes in 19 out of 172 (11.0%) Hubert's multimammate mice (Mastomys huberti) and one out of six (16.7%) gerbils (Taterillus sp.) and Hydatigera taeniaeformis sensu stricto metacestodes in one out of 215 (0.5%) Nile rats (Arvicanthis niloticus). This study reports epidemiological and molecular information on H. parva and H. taeniaeformis in West African rodents, further supporting the phylogeographic hypothesis on the African origin of H. parva. Our findings may indicate significant trophic interactions contributing to the local transmission of Hydatigera spp. and other parasites with similar life-cycle mechanisms. We therefore propose that further field investigations of rodent population dynamics and rodent-borne infectious organisms are necessary to improve our understanding of host–parasite associations driving the transmission risks of rodent parasites in West Africa.

Background: Brain tumors present unique challenges to patient and family quality of life (QOL). Cognitive dysfunction is common and functionally limiting, with no established treatments. These studies evaluate feasibility and preliminary efficacy of behavioral interventions developed for neuro-oncology patients. Study 1: A randomized controlled trial (N=25 primary brain tumor patients) compared an adapted version of Goal Management Training (GMT, a neuroscience-based integration of mindfulness and strategy training) and a newly-designed supportive psychoeducational intervention (Brain Health Program, BHP) to standard of care. Each intervention comprised 8 individual sessions and at-home practice between sessions. GMT patients’ executive functions improved immediately (p=.077, d=1.13), with maintenance at 4-month follow-up (p=.046, d=1.09). Both intervention groups reported improvements in everyday cognitive functioning immediately (p=.049; d’s GMT=0.43, BHP=0.79) and at follow-up (p=.001; d’s GMT=0.22, BHP=1.01). BHP patients also reported improved mood (p’s=.026 & .012, d’s=0.61 & 0.62). Study 2: Following a needs assessment about cognitive concerns and QOL in brain metastases patients (N=109) and caregivers (N=31), we developed a novel, brief (3 sessions + homework) Cognitive Support Program to provide education and strategy-training in key areas of concern: executive functions, memory, and communication. Options include caregiver co-training, and in-person or web-based delivery. Preliminary data from a pilot trial in progress demonstrate objective and subjective improvements. Conclusions: Cognitive rehabilitation may be a feasible and effective option for primary or metastatic brain tumor patients, addressing a need that is largely unmet in standard cancer care. Further development and larger trials appear warranted, with capacity for remote delivery recommended.

The ∽16 Ma Rangwa Caldera Complex, part of the large Kisingiri nephelinite-carbonatite volcano, Homa Bay District, western Kenya (0º34’S; 34º09’E) contains carbonatitic lapilli and ash tuffs, agglomerate and tuffisite, and a number of intrusive calcite carbonatites. A detailed petrographic and electron microprobe study has been performed on 20 fresh samples from the collection at The Natural History Museum, London.

Most of the juvenile lapilli and ash particles are either predominantly composed of devitrified silicate glass (now biotite/phlogopite but probably also originally potassic silicate) or calcite carbonatite, which suggests that two molten liquids were erupted simultaneously. Some 10 mm-diameter lapilli contain quench-textured calcite crystals set in devitrified glass. They are interpreted as having crystallized from a molten silicate-carbonate melt at, or very near, the surface.

The extrusive carbonate is mostly composed of calcite, consistent with intrusive calcite compositions at Rangwa. Other key minerals are magnetite, two types of mica (magnesian-biotite phenocrysts and phlogopite xenocrysts) and fluorapatite.

The pyroclastic rocks contain many calcite carbonatite clasts, and fragments of calcite, aegirine and diopside, fluorapatite, magnetite, plus some phlogopite, titanite, K-feldspar, fenite and glimmerite; ijolite lithics are rare. Thus, there is no evidence for a cognate nephelinitic (ijolitic) or melilitic magma nor evidence for a direct relationship with the nephelinites of the Kisingiri volcano.

Two hypotheses are discussed. A rising silicate and K-rich carbonatite liquid may have evolved towards a carbonate-rich K-silicate liquid after crystallization of calcite, phlogopite, apatite and magnetite. Preservation of the the potassic component may be rare, with a more usual scenario being that potassic component separates as fenitizing fluids. The alternative is that the silicate component is remobilized fenite, formed from country rock that was mobilized by supercritical K-rich, fenitizing fluids associated with the carbonatite. Both scenarios require generation of a K-rich carbonatite magma, probably from a carbonated phlogopite-rich metasomatized mantle.

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes over 2 years (y) versus SC IFNB-1a (CARE-MS II [NCT00548405]), with durable efficacy over a 4-y extension (NCT00930553). We present 6-y efficacy (2-y core study plus 4-y extension) in patients with relapse (relapsers) between Courses (C) 1 and 2. Methods: Annualized relapse rate (ARR); 6-month confirmed disability worsening (CDW); MRI disease activity (Gd-enhancing lesions; new/enlarging T2 hyperintense lesions); brain volume loss (BVL; derived by relative change in brain parenchymal fraction). Results: 105/435 (24%) patients relapsed between C1 and C2; 33% (relapsers) versus 55% without relapse (non-relapsers) received neither alemtuzumab retreatment nor another disease-modifying therapy through Y6. ARR (Y1: 1.2) declined post-C2 (0.5), remaining low through Y6 (0.2 [0.1, non-relapsers]; 10/105 [10%] relapsed). Through Y6, patients remained CDW-free (60% [relapsers]; 75% [non-relapsers]), Gd-enhancing lesion-free (94% [relapsers]; 90% [non-relapsers]), new/enlarging T2 hyperintense lesion-free (68% [relapsers]; 69% [non-relapsers]), and MRI disease activity-free (68% [relapsers]; 69% [non-relapsers]). Alemtuzumab slowed median percent yearly BVL (Y6: -0.13% [relapsers]; -0.10% [non-relapsers]). Conclusions: Patients relapsing between C1 and C2 improved post-C2 through Y6. These findings support administering 2 alemtuzumab courses to achieve optimal and durable benefit.

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).