Switching Rate Research Articles

Proliferation of unstable states and their impact on stochastic out-of-equilibrium dynamics in two coupled Kerr parametric oscillators.

Networks of nonlinear parametric resonators are promising candidates as Ising machines for annealing and optimization. These many-body out-of-equilibrium systems host complex phase diagrams of coexisting stationary states. The plethora of states manifest via a series of bifurcations, including bifurcations that proliferate purely unstable solutions. Here we demonstrate that the latter take a fundamental role in the stochastic dynamics of the system. Specifically, they determine the switching paths and the switching rates between stable solutions. We demonstrate experimentally the impact of the added unstable states on noise-activated switching dynamics in a network of two coupled parametric resonators.

Collagen density regulates tip-stalk cell rearrangement during angiogenesis via cellular bioenergetics.

Tumor vasculature plays a crucial role in tumor progression, affecting nutrition and oxygen transportation as well as the efficiency of drug delivery. While targeting pro-angiogenic growth factors has been a significant focus for treating tumor angiogenesis, recent studies indicate that metabolism also plays a role in regulating endothelial cell behavior. Like cancer cells, tumor endothelial cells undergo metabolic changes that regulate rearrangement for tip cell position during angiogenesis. Our previous studies have shown that altered mechanical properties of the collagen matrix regulate angiogenesis and can promote a tumor vasculature phenotype. Here, we examine the effect of collagen density on endothelial cell tip-stalk cell rearrangement and cellular energetics during angiogenic sprouting. We find that increased collagen density leads to an elevated energy state and an increased rate of tip-stalk cell switching, which is correlated with the energy state of the cells. Tip cells exhibit higher glucose uptake than stalk cells, and inhibition of glucose uptake revealed that invading sprouts rely on glucose to meet elevated energy requirements for invasion in dense matrices. This work helps to elucidate the complex interplay between the mechanical microenvironment and the endothelial cell metabolic status during angiogenesis, which could have important implications for developing new anti-cancer therapies.

Withdrawn: The altered dynamic community structure for adaptive adjustment in stroke patients with multidomain cognitive impairments: A multilayer network analysis

BackgroundInternal capsule strokes can lead to multidomain cognitive impairments, and while the brain showcases adaptability post-stroke, the interplay between this adaptability and multidomain cognitive function remains elusive. In addition, although most studies indicate that adaptive changes after stroke manifest as brain functional network abnormalities, the changes in dynamic topological features, especially dynamic community structure, required for adaptive adjustment in stroke patients are not yet clear. MethodsResting-state fMRI data were acquired from patients with infarct in left-sided (n = 46, CI_L) and right-sided (n = 45, CI_R) internal capsule and 81 healthy controls (HC). Dynamic network matrices were generated using a sliding-window approach. These matrices were partitioned into communities utilizing a multilayer community detection algorithm. The network switching rate were employed as a key metric to characterize the differences of dynamic community structure between stroke and HC groups, and the correlations between these significant intergroup differences and cognitive performance scores was calculated. ResultsCompared to HC, CI_L patients exhibited an increase in network switching rates across all networks in the whole brain. However, these increases were largely unbeneficial for cognitive recovery; CI_R group show a more limited range of increased network switching rates and a more limited negative correlations with cognitive performance. ConclusionsThis study elucidates that following a stroke, the brain continuously adapts its dynamic community structure in an effort to address multidomain cognitive impairments, but this adaptation is often ineffective, unorganized, and disordered. Moreover, these findings elucidate the lateralized effects of stroke lesions on dynamic reorganization.

Modulation of polyaniline memristive device switching voltage by nucleotide-free analogue of vitamin B12

Memristive devices offer essential properties to become a part of the next-generation computing systems based on neuromorphic principles. Organic memristive devices exhibit a unique set of properties which makes them an indispensable choice for specific applications, such as interfacing with biological systems. While the switching rate of organic devices can be easily adjusted over a wide range through various methods, controlling the switching potential is often more challenging, as this parameter is intricately tied to the materials used. Given the limited options in the selection conductive polymers and the complexity of polymer chemical engineering, the most straightforward and accessible approach to modulate switching potentials is by introducing specific molecules into the electrolyte solution. In our study, we show polyaniline (PANI)-based device switching potential control by adding nucleotide-free analogue of vitamin B12, aquacyanocobinamide, to the electrolyte solution. The employed concentrations of this molecule, ranging from 0.2 to 2 mM, enabled organic memristive devices to achieve switching potential decrease for up to 100 mV, thus providing a way to control device properties. This effect is attributed to strong aromatic interactions between PANI phenyl groups and corrin macrocycle of the aquacyanocobinamide molecule, which was supported by ultraviolet-visible spectra analysis.

#1325 Patients reporting not “sleeping normally” are more likely to transition to in-center hemodialysis within 90 days of peritoneal dialysis start

Abstract Background and Aims Although there are many advantages to home dialysis therapies such as peritoneal dialysis (PD), many patients drop out of PD and transition to in-center hemodialysis (ICHD). Reasons for this transition are varied and may be multifactorial. The current analysis aims to assess whether self-reported abnormal sleep is associated with transition to ICHD within 90 days of starting automated peritoneal dialysis (APD). Method Patients initiating APD at any Fresenius Kidney Care dialysis clinic between 2017-2019 were eligible for inclusion in this retrospective database analysis (n = 11 668). Monthly, various health-related questions are asked to patients as part of routine care through a home therapy nursing assessment (HTNA). One question asks if the patient is “sleeping normally”. After removing patients without completed HTNA questions on sleep, there were 11 449 patients included. We assessed patients for the first 90 days of PD for transition to ICHD through survival analysis with other reasons for discontinuing PD treated as competing events. Results On average, patients were aged 57 (15) years with BMI of 31 (14.5) and 42% were female. Approximately 5% of patients described their sleep as not normal (553/11449) in their first HTNA. Patients who reported abnormal sleep had 4.4 times the rate of switching to ICHD when compared to patients who reported normal sleep (Hazard Ratio (HR): 4.4; 95% CI: 3.5-5.5, p < 0.0001). After controlling for case mix variables, the HR was 3.7 (95% CI: 2.9-4.7, p < 0.0001). Case mix variables included gender, dialysis vintage, age, race, ethnicity, body size, residual renal function, Charlson Co-morbidity Index, diabetes status, geographic region, size of PD program, insurance primary payor, relationship status, and primary language spoken. Conclusion Among patients dialyzing at home with APD, abnormal sleep may be a risk factor for transitioning from home therapy to ICHD. Identifying root causes of sleep disturbances may help to prevent modality change.

Formation and Manipulation of Diatomic Rotors at the Symmetry-Breaking Surfaces of a Kagome Superconductor.

Construction of diatomic rotors, which is crucial for artificial nanomachines, remains challenging due to surface constraints and limited chemical design. Here we report the construction of diatomic Cr-Cs and Fe-Cs rotors where a Cr or Fe atom switches around a Cs atom at the Sb surface of the newly discovered kagome superconductor CsV3Sb5. The switching rate is controlled by the bias voltage between the rotor and scanning tunneling microscope (STM) tip. The spatial distribution of rates exhibits C2 symmetry, possibly linked to the symmetry-breaking charge orders of CsV3Sb5. We have expanded the rotor construction to include different transition metals (Cr, Fe, V) and alkali metals (Cs, K). Remarkably, designed configurations of rotors are achieved through STM manipulation. Rotor orbits and quantum states are precisely controlled by tuning the inter-rotor distance. Our findings establish a novel platform for the controlled fabrication of atomic motors on symmetry-breaking quantum materials, paving the way for advanced nanoscale devices.

Coupled parametric oscillators: From disorder-induced current to asymmetric Ising model

We study the effects of the interplay of weak disorder and weak coupling in a system of parametric micromechanical oscillators. Each oscillator is bistable, enabling the mapping of its stable states onto spin states. The coupling changes the rate of interstate switching of an oscillator depending on the state of other oscillators. We demonstrate that the change is exponentially strong and therefore manifests even for weak coupling. Difference in the oscillator eigenfrequencies translates into disorder in the system. The analysis and the experiment show that disorder leads to a nontrivial stationary state that displays current. The system provides a well-controlled and fully characterized implementation of the asymmetric Ising model, in which coupled spins affect each other differently. This model plays an important role in physics and biology. Our findings open the possibilities of constructing and exploring asymmetric Ising systems with controlled parameters and connectivity. Published by the American Physical Society 2024

Real-world persistence and adherence to glucagon-like peptide-1 receptor agonists among obese commercially insured adults without diabetes.

In 2014, the US Food and Drug Administration approved the first glucagon-like peptide-1 (GLP-1) receptor agonist product, liraglutide injection, for obesity treatment. Many GLP-1 obesity treatment clinical trials report significant weight loss and medication adherence at more than 85%. Little is known about the real-world GLP-1 obesity treatment adherence, persistence, and switch rates. To measure GLP-1 therapy persistence, adherence, and switch rates in a real-world cohort of members without diabetes using these drugs for obesity treatment. Integrated pharmacy and medical claims data from 16.5 million average monthly commercially insured membership were used to identify obese members without diabetes newly initiating GLP-1 therapy between January 1, 2021, and December 31, 2021. Members were required to be continuously enrolled 1-year before and after the GLP-1 therapy start date and aged 19 years of age or older. Persistence was measured as no greater than or equal to 60-day gap with allowance for GLP-1 switching. Adherence was measured as the proportion of days covered (PDC) and members with a PDC greater than or equal to 80% were considered adherent. GLP-1 product switching was also assessed descriptively. 4,066 commercially insured obese members without diabetes that newly initiated GLP-1 therapy met all study criteria. The mean age was 46 years, and 81% were female. Overall, GLP-1 persistence was 46.3% at 180 days and 32.3% at 1 year. The highest and lowest persistence rates at 1 year were observed for semaglutide (Ozempic) at 47.1% and liraglutide (Saxenda) 19.2%, respectively. Average PDC during the 1-year assessment was 51.0% with 27.2% adherent to therapy and 11.1% switched GLP-1 drugs. This GLP-1 weight loss treatment real-world analysis, among obese individuals without diabetes, found poor 1-year persistence and adherence and low rates of switching between products. These findings will aid in assessing products cost-effectiveness, understanding obesity care management program needs, forecasting future GLP-1 use and cost trends, and negotiating GLP-1 pharmaceutical manufacturer value-based purchasing agreements.

Faster bi-stable visual switching in psychosis

Bi-stable stimuli evoke two distinct perceptual interpretations that alternate and compete for dominance. Bi-stable perception is thought to be driven at least in part by mutual suppression between distinct neural populations that represent each percept. Abnormal visual perception has been observed among people with psychotic psychopathology (PwPP), and there is evidence to suggest that these visual deficits may depend on impaired neural suppression in the visual cortex. However, it is not yet clear whether bi-stable visual perception is abnormal among PwPP. Here, we examined bi-stable perception in a visual structure-from-motion task using a rotating cylinder illusion in a group of 65 PwPP, 44 first-degree biological relatives, and 43 healthy controls. Data from a ‘real switch’ task, in which physical depth cues signaled real switches in rotation direction were used to exclude individuals who did not show adequate task performance. In addition, we measured concentrations of neurochemicals, including glutamate, glutamine, and γ-amino butyric acid (GABA), involved in excitatory and inhibitory neurotransmission. These neurochemicals were measured non-invasively in the visual cortex using 7 tesla MR spectroscopy. We found that PwPP and their relatives showed faster bi-stable switch rates than healthy controls. Faster switch rates also correlated with significantly higher psychiatric symptom levels, specifically disorganization, across all participants. However, we did not observe any significant relationships across individuals between neurochemical concentrations and SFM switch rates. Our results are consistent with a reduction in suppressive neural processes during structure-from-motion perception in PwPP, and suggest that genetic liability for psychosis is associated with disrupted bi-stable perception.

Electronically Controlled Dual‐Wavelength Switchable SRS Fiber Amplifier in the NIR‐II Region for Multispectral Photoacoustic Microscopy

AbstractPhotoacoustic microscopy (PAM) is a high‐resolution and non‐invasive imaging modality that provides optical absorption contrast. By employing dual‐ or multiple‐wavelength excitation, PAM extends its capabilities to offer valuable spectroscopic information. To achieve efficient multispectral PAM imaging, an essential requirement is a light source characterized by a high repetition rate and switching rate, a ≈microjoule pulse energy, and a ≈nanosecond pulse duration. However, there exists a notable deficiency in suitable light sources, particularly in the near‐infrared‐II window. In this study, a custom‐built all‐fiber‐based light source is reported that provides >3 µJ, 2 ns pulses with a repetition rate of 200 kHz. Digitally addressed semiconductor seed lasers, followed by stimulated Raman scattering amplification, enabled arbitrary sequences of pulses having wavelengths of either 1168.4 or 1202.1 nm. In a switching mode of operation, a 100 kHz switching rate is used to alternate between these wavelengths in even/odd pulses. Furthermore, a high‐resolution multispectral photoacoustic microscopy of three polymer samples is demonstrated with the proposed light source.

Migration, movements, and survival in a partially migratory elk (Cervus canadensis) population

AbstractMigration provides an adaptive strategy to improve fitness by allowing individuals to exploit gradients of resources and changes in predation risk. In recent decades, the extent and prevalence of migration has declined in numerous ungulate species including many populations of elk (Cervus canadensis). Resident elk are often more closely associated with human activity, are more readily involved in agricultural conflicts and may contribute to overgrazing on some ranges. We evaluated migratory trends, survival rates, and causes of mortality in a partially migratory elk population in southeastern British Columbia, Canada, and compared these parameters with data from a 1982–1996 study from the same area. Analysis of 201 animal‐years (n = 78 collared cow elk) between 2016 and 2022 showed a ratio of 52% migratory to 48% resident elk, similar to what was found during the 1982–1996 study (55% migratory to 45% resident; n = 40 cows). Among the migrants, 55% were standard migrants (traveling moderate to longer distances and changing little in elevation), 35% elevational, and 10% mixed/atypical. We detected a 14% yearly switching rate between migratory and resident strategies. We recorded 30 mortalities: 47% from human causes, predominantly elk‐vehicle/train collisions (33% of mortalities), apparent starvation/old age (17%), and predation (17%). Notably, while mortality from natural causes was similar between strategies, human‐caused mortality was nearly twice as high in resident elk. Signs of nutritional stress and lower pregnancy rates indicated potential forage limitations. Migrants had higher average survival rates (0.90) compared to residents (0.83), a shift from the 1982–1996 study that recorded higher resident survival rates (0.98), the same migrant survival rate (0.90), and fewer elk‐vehicle/train collisions. Cow elk in our study made fewer and shorter movements into upper mountain tributaries and greater use of mine properties than observed during the 1982–1996 study. Wildlife managers should consider opportunities to enhance elk forage within traditional high‐elevation summer ranges and mitigations to reduce elk‐vehicle/train collisions. Further research is needed to quantify reproductive success, monitor calf survival, and determine relative forage quality among summering areas between migratory strategies, and determine winter ranges of long‐distant migrants.

Abstract PO5-24-09: Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model

Abstract Despite rapid advancements in treatments and technology, breast cancer remains the second leading cause of cancer related morbidity in women in the US. As a heterogeneous disease, the unique genetic and phenotypic profile of each tumor complicates the prediction of treatment responses and optimized treatment strategies. One primary manifestation of phenotypic plasticity and concomitant intra-tumoral heterogeneity is the Epithelial-Mesenchymal Transition (EMT). The acquisition of migratory and invasive properties through EMT facilitates tumor metastasis and results in worse patient outcomes. As a result, the EMT and its reverse process (MET) often influence treatment response. However, the different mechanisms through which these therapeutic drugs affect the EMT-related phenotypic switching rates as well as each phenotype’s replication rates are unclear, and further investigation is required for better understanding their precise effect for directing optimal treatment strategies and improved patient outcomes. Here, we compile an atlas of publicly available metastatic and non-metastatic RNA sequencing data of breast cancer cell lines treated with therapeutic and chemotherapeutic drugs and propose a dual data-driven theoretical framework for understanding the effects of each drug on breast cancer treatment response. We infer the cell fractions, EMT phenotypic transition rates and phenotypic replication rates of each case through an extension of our previously developed hybrid data-driven and theoretical model, COMET. We infer single-cell RNA sequencing-derived EMT-related trajectories and apply a continuous time Markov chain model to infer inter-state transition rates. By analyzing the atlas of RNA sequencing data and integration with our framework, we gain novel insights into the context-specific mechanisms by which therapeutic drugs affect the phenotypic transition rates. This comprehensive understanding will contribute to optimizing breast cancer therapy and ultimately improving patient outcomes. Citation Format: A. Najafi. Optimizing the Therapeutic Treatment of Breast Cancer Through a Dual Data-driven Theoretical Model [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-24-09.

Reviving Bistable Perception in Patients With Depression by Decreasing the Overestimation of Prior Precision.

Slower perceptual alternations, a notable perceptual effect observed in psychiatric disorders, can be alleviated by antidepressant therapies that affect serotonin levels in the brain. While these phenomena have been well documented, the underlying neurocognitive mechanisms remain to be elucidated. Our study bridges this gap by employing a computational cognitive approach within a Bayesian predictive coding framework to explore these mechanisms in depression. We fitted a prediction error (PE) model to behavioral data from a binocular rivalry task, uncovering that significantly higher initial prior precision and lower PE led to a slower switch rate in patients with depression. Furthermore, serotonin-targeting antidepressant treatments significantly decreased the prior precision and increased PE, both of which were predictive of improvements in the perceptual alternation rate of depression patients. These findings indicated that the substantially slower perception switch rate in patients with depression was caused by the greater reliance on top-down priors and that serotonin treatment's efficacy was in its recalibration of these priors and enhancement of PE. Our study not only elucidates the cognitive underpinnings of depression, but also suggests computational modeling as a potent tool for integrating cognitive science with clinical psychology, advancing our understanding and treatment of cognitive impairments in depression.

A Novel Leg-Integrated Switched Capacitor Inverter Topology for Three-Phase Induction Motor Drives

This paper presents an optimized leg-integrated switched capacitor inverter (LISCI) topology for 3-φ induction motor driven home appliance applications where a switched capacitor (SC) network, used for voltage boosting, is integrated with one of the inverter legs (phase-A leg). This results in a reduced semiconductor requirement as the voltage ratings of the phase-A switches are reduced by half. Moreover, due to the unique structure of the proposed topology, it can produce 3-level pole voltage corresponding to phase-A, even though the pole voltages of phases B and C remain 2-level. This kind of performance, referred to as quasi 3-level performance, results in an unusual space vector (SV) hexagon with 12 SVs, which is implemented by using a novel PWM method. A comparison study of the proposed topology with the existing SC based 3-φ inverter topologies reveals that the former has the lowest semiconductor requirement, highly improved harmonic performance and very low losses. All the claims are supported by experimental validations performed on a 3φ induction motor (3φIM) drive.

Heterogeneous Responses to Job Mobility Shocks in a HANK Model with a Frictional Labor Market

We use a heterogeneous agent New Keynesian model with a frictional labor market featuring on-the-job-search to study how job switching affects consumption decisions for individuals with different wealth levels. We find that an increased job switching rate, driven by an exogenous shift in employed individuals' job search efficiency—acting as a positive future income shock—results in a larger decline in current demand for the wealth rich relative to the wealth poor. This larger consumption reduction for the wealth rich is due to the equilibrium decline in their financial wealth.

The Switchmaze: an open-design device for measuring motivation and drive switching in mice.

Animals need to switch between motivated behaviours, like drinking, feeding or social interaction, to meet environmental availability, internal needs and more complex ethological needs such as hiding future actions from competitors. Inflexible, repetitive behaviours are a hallmark of many neuropsychiatric disorders. However, how the brain orchestrates switching between the neural mechanisms controlling motivated behaviours, or drives, is unknown. This is partly due to a lack of appropriate measurement systems. We designed an automated extended home-cage, the Switchmaze, using open-source hardware and software. In this study, we use it to establish a behavioural assay of motivational switching in mice. Individual animals access the Switchmaze from the home-cage and choose between entering one of two chambers containing different goal objects or returning to the home-cage. Motivational switching is measured as a ratio of switching between chambers and continuous exploitation of one chamber. Behavioural transition analysis is used to further dissect altered motivational switching. As proof-of-concept, we show environmental manipulation, and targeted brain manipulation experiments which altered motivational switching without effect on traditional behavioural parameters. Chemogenetic inhibition of the prefrontal-hypothalamic axis increased the rate of motivation switching, highlighting the involvement of this pathway in drive switching. This work demonstrates the utility of open-design in understanding animal behaviour and its neural correlates.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. Multicenter, international, BRVO database study. Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. Mean adjusted VA change was+11 letters (95% confidence interval 9-13), mean adjusted change in CST was-176 μm (-193,-159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n= 677) and as a monotherapy in 71% (n= 538). Few eyes were switched to steroids (11%, n= 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs.-128 vs.-114 μm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Climate warming promotes collateral antibiotic resistance development in cyanobacteria

Both cyanobacterial blooms and antibiotic resistance have aggravated worldwide and posed a great threat to public health in recent years. As a significant source and reservoir of water environmental resistome, cyanobacteria exhibit confusing discrepancy between their reduced susceptibility and their chronic exposure to antibiotic mixtures at sub-inhibitory concentrations. How the increasing temperature affects the adaptive evolution of cyanobacteria-associated antibiotic resistance in response to low-level antibiotic combinations under climate change remains unclear. Here we profiled the antibiotic interaction and collateral susceptibility networks among 33 commonly detected antibiotics in 600 cyanobacterial strains isolated from 50 sites across four eutrophicated lakes in China. Cyanobacteria-associated antibiotic resistance level was found positively correlated to antibiotic heterogeneity across all sites. Among 528 antibiotic combinations, antagonism was observed for 62 % interactions and highly conserved within cyanobacterial species. Collateral resistance was detected in 78.5 % of pairwise antibiotic interaction, leading to a widened or shifted upwards mutant selection window for increased opportunity of acquiring second-step mutations. We quantified the interactive promoting effect of collateral resistance and increasing temperature on the evolution of both phenotypic and genotypic cyanobacteria-associated resistance under chronic exposure to environmental level of antibiotic combinations. With temperature increasing from 16 °C to 36 °C, the evolvability index and genotypic resistance level increased by 1.25 – 2.5 folds and 3 – 295 folds in the collateral-resistance-informed lineages, respectively. Emergence of resistance mutation pioneered by tolerance, which was jointly driven by mutation rate and persister fraction, was found to be accelerated by increased temperature and antibiotic switching rate. Our findings provided mechanic insights into the boosting effect of climate warming on the emergence and development of cyanobacteria-associated resistance against collateral antibiotic phenotypes.

Learned switch readiness via concurrent activation of task sets: Evidence from task specificity and memory load.

Cognitive flexibility increases when switch demands increase. In task switching experiments, repeated pairing of flexibility-demanding situations with specific contexts leads subjects to become more prepared to adapt to changing task demands in those contexts. One form of such upregulated cognitive flexibility has been demonstrated with a list-wide switch probability (LWSP) effect, where switch costs are smaller in lists with frequent switches than in lists with rare switches. According to a recent proposal, the LWSP effect is supported by a concurrent activation mechanism whereby both task rules are kept available simultaneously in working memory. We conducted four experiments to test two key features in this concurrent activation account of LWSP effects. First, we asked whether the LWSP effects are limited to only the trained tasks, and second, we asked whether concurrent working memory load would reduce the LWSP effects. In Experiment 1, we replicated and extended previous findings that the LWSP manipulation modulates both performance (switch costs) and voluntary switch rates, indicating that context-driven increases in flexibility are generalizable so long as the task-sets remain the same. Results of Experiments 2 and 3 showed that novel tasks do not benefit from the concurrent activation of the two other tasks, suggesting that the LWSP effect is task specific. Experiment 4 showed that holding additional information in working memory reduces the LWSP effect. While these findings support the hypothesis of concurrent activation underlying the increased flexibility in the LWSP effect, caveats remain; additional research is needed to further test this account.

Real-world evidence of treatment patterns and survival of metastatic gastric cancer patients in Germany

BackgroundPatients with metastatic gastric cancer (mGC) have poor prognosis. This real-world study aimed to describe treatment regimens and survival of mGC patients.MethodsA retrospective analysis was conducted using anonymized German claims data (AOK PLUS) covering a period from 2010 to 2021. The study population included newly diagnosed mGC cases identified from 2011 to 2020. The index date was defined as the first diagnosis of metastasis on or after gastric cancer diagnosis. Therapy regimens were identified based on inpatient and outpatient data, and subsequently stratified by line of treatment. Survival analyses were conducted using the Kaplan–Meier method.ResultsThe cohort consisted of 5,278 mGC incident cases (mean age: 72.7 years; male: 61.9%). Nearly half of the incident cases received mGC-related treatment (49.8%). Treated patients were more often male, younger, and had fewer comorbidities compared to untreated patients. Of the 2,629 mGC patients who started the first line of treatment (1LOT), 32.8% switched to 2LOT, and 10.2% reached 3LOT. Longer survival time was observed among disease-specific treated cases compared with untreated cases (median real-world overall survival (rwOS): 12.7 months [95%CI 12.1 – 13.3 months] vs. 3.7 months [95%CI 3.4 – 4.0 months]).ConclusionSystemic therapy was not received in almost half of the mGC patients. In those patients, a very short median rwOS was observed. Treatment patterns were generally in line with the guideline recommendations, however, therapy switching rates and poor prognosis indicate high unmet needs also in the treated population.