Potential Actions Research Articles

Unmet needs in valvular heart disease.

Valvular heart disease (VHD) is the next epidemic in the cardiovascular field, affecting millions of people worldwide and having a major impact on health care systems. With aging of the population, the incidence and prevalence of VHD will continue to increase. However, VHD has not received the attention it deserves from both the public and policymakers. Despite important advances in the pathophysiology, natural history, management, and treatment of VHD including the development of transcatheter therapies, VHD remains underdiagnosed, identified late, and often undertreated with inequality in access to care and treatment options, and there is no medication that can prevent disease progression. The present review article discusses these gaps in the management of VHD and potential actions to undertake to improve the outcome of patients with VHD.

Prognostic and Predictive Value of LIV1 Expression in Early Breast Cancer and by Molecular Subtype.

LIV1 is a transmembrane protein that may become a new therapeutic target through the development of antibody-drug conjugates (ADCs). Few studies are available regarding the assessment of LIV1 expression in clinical breast cancer (BC) samples. We analyzed LIV1 mRNA expression in 8982 primary BC. We searched for correlations between LIV1 expression and clinicopathological data, including disease-free survival (DFS), overall survival (OS), pathological complete response to chemotherapy (pCR), and potential vulnerability and actionability to anti-cancer drugs used or under development in BC. Analyses were performed in the whole population and each molecular subtype separately. LIV1 expression was associated with good-prognosis features and with longer DFS and OS in multivariate analysis. However, patients with high LIV1 expression displayed a lower pCR rate than patients with low expression after anthracycline-based neoadjuvant chemotherapy, including in multivariate analysis adjusted on grade and molecular subtypes. LIV1-high tumors were associated with higher probabilities of sensitivity to hormone therapy and CDK4/6 inhibitors and lower probabilities of sensitivity to immune-checkpoint inhibitors and PARP inhibitors. These observations were different according to the molecular subtypes when analyzed separately. These results may provide novel insights into the clinical development and use of LIV1-targeted ADCs by identifying prognostic and predictive value of LIV1 expression in each molecular subtype and associated vulnerability to other systemic therapies.

Understanding school food systems to support the development and implementation of food based policies and interventions

BackgroundSchools provide opportunities to improve the quality of children's diet, whilst reducing inequalities in childhood diet and health. Evidence supports whole school approaches, including consistency in food quality, eating culture and food education. However, such approaches are often poorly implemented due to the highly complex environments in which schools operate. We aimed to develop a school food systems map using a systems thinking approach to help identify the key factors influencing primary school children’s dietary choice.MethodsEight workshops were conducted with 80 children (from schools from varying locations (region of England/UK; urban/rural), deprivation levels and prioritisation of school food policies)) and 11 workshops were held with 82 adult stakeholders across the UK (principals, teachers, caterers, school governors, parents, and local and voluntary sector organisations) to identify factors that influence food choice in children across a school day and their inter-relationships. Initial exploratory workshops started with a ‘blank canvas’ using a group model building approach. Later workshops consolidated findings and supported a wider discussion of factors, relationships and influences within the systems map. Strengths of the relationship between factors/nodes were agreed by stakeholders and individually depicted on the map. We facilitated an additional eight interactive, in-person workshops with children to map their activities across a whole school day to enable the production of a journey map which was shared with stakeholders in workshops to facilitate discussion.ResultsThe final ‘CONNECTS-Food’ systems map included 202 factors that were grouped into 27 nodes. Thematic analysis identified four key themes: leadership and curriculum; child food preference; home environment; and school food environment. Network analysis highlighted key factors that influence child diet across a school day, which were largely in keeping with the thematic analysis; including: 'available funds/resources', 'awareness of initiatives and resources', 'child food preference and intake', 'eligibility of free school meals', 'family circumstances and eating behaviours', 'peer/social norms', 'priorities of head teachers and senior leaders'.ConclusionsOur systems map demonstrates the need to consider factors external to schools and their food environments. The map supports the identification of potential actions, interventions and policies to facilitate a systems-wide positive impact on children’s diets.

Metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer

The present study aimed to evaluate the effect of metformin pretreatment on the potentiation of antiproliferative action of doxorubicin against breast cancer. Female Wistar rats were administered with 7,12-Dimethylbenz(a)anthracene (DMBA) (35 mg) in 1 ml olive oil subcutaneously beneath the mammary gland. Animals were pretreated with metformin (Met) 200 mg/kg two weeks before DMBA administration. DMBA control groups received doxorubicin (Dox) (4 mg/kg and 2 mg/kg), Met (200 mg/kg) alone and in combination with Dox (4 mg/kg). Met pre-treated DMBA control groups received Dox 4 mg/kg and 2 mg/kg. Met pre-treated groups treated with Dox exhibited a decrease in tumor incidence, tumor volume and increased survival rate than the DMBA group. Organ-to-body weight ratios and histopathology of heart, liver and lungs of Met pre-treated groups treated with Dox showed lesser toxicity than Dox treated DMBA control groups. There was a noteworthy decrease in malondialdehyde levels and a substantial increase in the levels of reduced glutathione together with a significant decrease in the levels of inflammatory markers like IL-6, IL-1β and NF-κB in Met pre-treated groups treated with Dox. Histopathology of breast tumors revealed better control of tumors in Met pre-treated groups treated with Dox than DMBA control group. Immunohistochemistry and real-time PCR data revealed a significant reduction in Ki67 expression in Met pre-treated groups treated with Dox as compared to the DMBA control group. The present study suggests that metformin pretreatment potentiates the antiproliferative action of doxorubicin against breast cancer.

High pH-SCC mechanism investigation of novel Nb/Ce-additional X100 pipeline steel

High pH-SCC introduces great risks to the service safety of X100 pipeline steel. The design of new Nb and RE composite regulated pipeline steel can help to reduce the high pH-SCC. By the addition of Nb and Ce elements into traditional pipeline steel, the toughness of the pipeline steel was enhanced while the sensitivity of high pH-SCC decreased under the action of cathode potential. Mechanism research indicated that the increase of Nb element inhibited the cathodic hydrogen evolution reaction and increased the number of irreversible hydrogen traps in the steel, thus improving the resistance of pipeline steel to high pH-SCC. The addition of Ce element inhibited the anodic dissolution and cathodic hydrogen evolution processes, and reduced the high pH-SCC sensitivity of pipeline steel by changing the solution and precipitation of Nb.

Scaling scrum with a customized nexus framework: A report from a joint industry‐academia research project

AbstractDespite a wide range of scaling frameworks available, large‐scale agile transformations are not straightforward undertakings. Few organizations have structures in place that fit the predefined workflows – while once one applies an off‐the‐shelf framework outside of its prescribed process, guidance quickly runs out. In this paper, we demonstrate how to instantiate a method configuration process using a lightweight experimental approach embedded in Action Research cycles. The proposed approach was developed to assist practitioners working on a multiple‐team project at Intel Technology Poland to find the right practices to continue their Nexus‐based transformation and integrate their in‐house method into the already established company structures, processes, and routines. In particular, it enabled identifying a series of challenges with scaled practices and coping with those. The challenges ranged from logistical problems, through poor availability of the Product Owner, to lackluster knowledge transfer and a wide array of communication/coordination issues at meetings. The study broadens the current body of knowledge within technology management and the scaled agile method‐tailoring domain. It indicates potential corrective actions that may be taken advantage of by entities that are not inclined, due to organizational constraints, to directly implement an off‐the‐shelf framework. Furthermore, our study demonstrates that a gradual transition to large‐scale agile at the project level (1) is possible with the preservation of traditional command‐and‐control management practices; (2) requires neither middle management involvement nor upfront investment; and (3) does not need to disrupt the continuous delivery of the product.

Targeting Post-Translational Modifications to Improve Combinatorial Therapies in Breast Cancer: The Role of Fucosylation

Various tumors rely on post-translational modifications (PTMs) to promote invasiveness and angiogenesis and to reprogram cellular energetics to abate anti-cancer immunity. Among PTMs, fucosylation is a particular type of glycosylation that has been linked to different aspects of immune and hormonal physiological functions as well as hijacked by many types of tumors. Multiple tumors, including breast cancer, have been linked to dismal prognoses and increased metastatic potential due to fucosylation of the glycan core, namely core-fucosylation. Pre-clinical studies have examined the molecular mechanisms regulating core-fucosylation in breast cancer models, its negative prognostic value across multiple disease stages, and the activity of in vivo pharmacological inhibition, instructing combinatorial therapies and translation into clinical practice. Throughout this review, we describe the role of fucosylation in solid tumors, with a particular focus on breast cancer, as well as physiologic conditions on the immune system and hormones, providing a view into its potential as a biomarker for predicating or predicting cancer outcomes, as well as a potential clinical actionability as a biomarker.

A multidimensional pan-cancer analysis of DCAF13 and its protumorigenic effect in lung adenocarcinoma.

DCAF13 is a substrate recognition protein in the ubiquitin-proteasome system with oncogenic effects in several malignant tumors. However, it is unclear that the relationship between DCAF13 expression pattern and prognosis across different cancer types. Also unknown is the biological function or effects on the immune microenvironment of DCAF13. In this study, we parsed multiple public databases to explore the potential tumorigenic actions of DCAF13, including correlations with prognosis, microsatellite instability (MSI), tumor mutational burden (TMB), immune checkpoint genes, immune cell infiltration, and immunotherapy response in pan-cancer. Moreover, we validated DCAF13 expression in a tissue microarray by immunohistochemistry and investigate its effects in vitro and in vivo. The results showed that DCAF13 was upregulated in 17 cancer types and correlated with poor prognosis in many cancers. Also, the correlation between DCAF13 and TMB was found in 14 cancers as well as MSI in nine. The expression level of DCAF13 was found to be notably correlated with immune cell infiltration, showing a negative correlation with CD4 T cell infiltration and a positive correlation with neutrophil infiltration. The oncogene DCAF13 expression was shown to have a positive correlation with CD274 or ADORA2A and negative correlation with VSIR, TNFRSF4, or TNFRSF14 across large subsets of human cancers. Finally, we observed that DCAF13 was highly expressed in a tissue microarray of lung cancer. In immunocompromised mouse models, xenograft growth of human lung cancer cells was significantly inhibited by DCAF13 knockdown. Our results highlighted the value of DCAF13 as a promising independent predictor of poor prognosis through numerous biological processes. High DCAF13 expression often predicts suppressive immune microenvironment and immunotherapy resistance in a pan-cancer context.

Changes in Dog Behaviour Associated with the COVID-19 Lockdown, Pre-Existing Separation-Related Problems and Alterations in Owner Behaviour.

During the COVID-19 pandemic, lockdowns provided an opportunity to assess what factors, including changes in an owner's routine and time spent at home, were associated with changes in dog behaviour. We undertook a longitudinal survey over a period of 8 months during which we asked about people's work patterns, dog management, and their dogs' behaviour. Generalized linear models revealed that the pre-existence of signs of potential separation-related problems, and especially vocalisation, self-injury, and chewing to escape confinement, was associated with an increase in a range of separation issues. Dogs showing separation-related signs prior to COVID were also more likely to develop more problems during lockdown. Management changes tended to result in increased physical and social stress, with a range of potential compensatory actions taken by the dog, however these signs of stress did not generally appear to be connected to separation-related issues. Survival analysis was used to investigate the emergence of specific issues over time. This indicated that a change to working from home was related initially to a decreased risk of aggression towards the owner, but over time, those who continued to work from the home were at an increased risk of this problem. No other significant time-related relationships were found.

On a Class of Semi-Regular Gyrostat Precessions with Variable Gyrostatic Moment

The article considers the problem of the motion of a gyrostat under the action of potential and gyroscopic forces in the case of a variable gyrostatic moment. The conditions for the existence of semi-regular precessions characterized by the constancy of their own rotation rate are studied. A new solution of the equations of the Kirchhoff–Poisson class is constructed, based on a special type of three invariant relations with respect to the main variables of these equations.

On a Class of Semi-Regular Gyrostat Precessions with Variable Gyrostatic Moment

The article considers the problem of the motion of a gyrostat under the action of potential and gyroscopic forces in the case of a variable gyrostatic moment. The conditions for the existence of semi-regular precessions characterized by the constancy of their own rotation rate are studied. A new solution of the equations of the Kirchhoff–Poisson class is constructed, based on a special type of three invariant relations with respect to the main variables of these equations.

Abstract P1-14-05: Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients with Chest Wall Breast Cancer (PERICLES): an immune-biomarker analysis of tumor infiltrating lymphocytes (TILs) and programmed cell death ligand protein 1 (PD-L1)

Abstract Background: Breast cancer (BC) with lymphangitic spread to the chest wall is a rare clinical entity affecting about 2% of pts, with poorer survival outcomes. A brisk immune infiltrate is typically reported, with up-regulation of inflammation and immune-tolerogenic genes. PERICLES clinical trial is testing the administration of pembrolizumab 200 mg Q3w plus cyclophosphamide 50 mg daily for BC with chest wall disease. In this exploratory biomarker analysis, we assessed the prevalence of the TILs score and the PD-L1 combined positive score (CPS) obtained from skin biopsies performed at screening. Methods: PERICLES (NCT03971045) is a single-center, single-arm, interventional phase 2 trial. Main inclusion criteria: histologically confirmed, inoperable, locally recurrent and/or metastatic BC with lymphangitic spread to the chest wall (including and not limited to inflammatory BC); PD-L1 positive (CPS≥1; 22C3 pharmDx®) and/or TILs positive (≥1% of CD3 or CD20-positive cells) disease on skin biopsy obtained at screening; progression to at least one prior cytotoxic treatment; no prior immune checkpoint inhibitors. The primary endpoint is objective response rate as per immune-related RECIST criteria. 46 pts will be required for the study to power for the primary hypothesis. In this analysis, we describe the baseline immune-biomarker status, in the overall population enrolled based on hormone receptor status and HER2. Correlative analyses were provided (significance at p-value< 0.05). Results: 37 pts were screened with skin biopsy of the chest wall disease (June 2020-June 2022). Biopsy and biomarker analysis were successful in 35 pts. Median age was 58 years (range: 35-79). Among the 35 pts included in the biomarker analysis, 25 (71%) pts had visceral disease and 20 (57%) had skin metastases at the diagnosis of metastatic disease; median number of previous lines of therapies was 4 (range: 1-12) and of chemotherapies was 4 (range: 1-10). 2 (6%) pts had HER2-positive disease, 13 (37%) HR-positive/HER2-negative disease, and 20 (20%) had triple-negative breast cancer (TNBC). TILs and PD-L1 CPS were < 1 in 15 (43%) pts; 20 pts (57%) were eligible for CPS and/or TILs criteria: 16 (43%) were both PD-L1 positive and TILs positive, 4 only PD-L1 positive. Median PD-L1 CPS score was 5 (range: 0-80%) in the overall population and 17 (range: 2-80%) in eligible patients; 16/35 pts (43%) had CPS≥10. Median TILs score was 0% (range: 0-55%) in the overall population, 0% (range: 0-40%) in the HER2-negative (n=16), 0% (range 0-20%) in the HER2-low (n=18), and 37.5% (range 20-55%) in the HER2-positive (n=2). No significant differences in baseline characteristics were found between positive and negative biopsies (Table). Considering only the TILs, a statistically significant correlation between HER2-positive status and TILs score was demonstrated (p< 0.001); no other correlations between receptor status (estrogen receptor, progesterone receptor, HER2) and PD-L1 CPS or TILs emerged. Conclusions: 57% of patients with chest wall BC have skin metastases positive for PD-L1 CPS and/or TILs score ≥1%. To our knowledge, these are the first prospective data on the prevalence of PD-L1 and TILs in metastatic BC with lymphangitic spread to the chest wall, highlighting potential actionability through therapeutic strategies with new immune-oncology agents in this setting. Table: Characteristics of patients included in the biomarker analysis (n=35) *Calculated with T test or Fisher’s exact test, as appropriate. Keys: BC, breast cancer; CPS, combined positive score; CT, chemotherapy; HR; hormone receptor; n, number; NA; not available; PD-L1, Programmed cell death ligand protein 1; TILs, tumor infiltrating lymphocytes; TNBC, triple negative breast cancer. Citation Format: Carmine Valenza, Pier Paolo Maria Berton Giachetti, Paola Zagami, Eleonora Nicolò, Dario Trapani, Laura Boldrini, Beatrice Taurelli Salimbeni, Liliana Ascione, Gabriele Antonarelli, Chiara Corti, Angela Esposito, Carmen Criscitiello, Nicola Fusco, Giuseppe Curigliano. Pembrolizumab and Oral Metronomic Cyclophosphamide in Patients with Chest Wall Breast Cancer (PERICLES): an immune-biomarker analysis of tumor infiltrating lymphocytes (TILs) and programmed cell death ligand protein 1 (PD-L1) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-14-05.

Effects of endocrine disruptors on the electrical activity of leptin receptor neurons in the dorsomedial hypothalamus and anxiety-like behavior in male mice

There is increasing concern about the effects of endocrine disrupting chemicals (EDCs) on human health. Recently, some EDCs are suggested to affect energy metabolism leading to increased risk of obesity. Obesogenic effects of some EDCs on adipogenesis have been reported, however, there is no study examining their potential actions on the brain circuits controlling feeding and metabolism. We have investigated effects of tributyltin (TBT) and dichlorodiphenyltrichloroethane (p,p'-DDT) on electrical activity on dorsomedial hypothalamic leptin receptor neurons (DMHLepR), morphological adaptations in neuronal anatomy of DMHLepR, locomotion, and anxiety-like behaviors in mice. Twenty-three Lep-Cre transgenic mice were intracranially injected with GFP virus. Control animals received intraperitoneal corn oil alone while group 2 and 3 received TBT (25 μg/kg) and p,p'-DDT (2 mg/kg) for one month. Locomotor activity and anxiety-like behavior of the animals were determined by open field test. Electrophysiological effects of TBT and p,p'-DDT on DMHLepR neurons were determined by patch clamp method. Neuronal anatomy was determined by confocal microscopy. Spontaneous firing frequency of DMHLepR neurons of TBT group of mice was significantly higher than both p,p'-DDT and control groups (p < 0.01). TBT and p,p'-DDT significantly decreased frequency of the spontaneous inhibitory post-synaptic currents to DMHLepR neurons compared to the control group (p < 0.05). The time spent in the center and the number of entrances to the center by the TBT-administered mice were significantly lower than other groups (p < 0.01). The total distance traveled and mean speed of the control group of mice were significantly higher than the p,p'-DDT- and TBT-administered animals (p < 0.0001). c-Fos activity of the p,p'-DDT- and TBT-administered animals were significantly elevated compared to the control group (p < 0.001), while no change in the number of dendritic spines were observed. In conclusion, this study demonstrates that exposure to TBT and p,p'-DDT alters electrical activity in DMHLepR neurons and behavioral state in mice.

Identifying correlates of coral‐reef fish biomass on Florida’s Coral Reef to assess potential management actions

Abstract Coral reef fish assemblages are threatened globally, underscoring the need for data‐driven management to reduce threats and restore populations. Comparing fishery management approaches is aided by a detailed understanding of the key factors controlling species’ abundances. The aims of this study were to assess the importance of biophysical factors compared with fishing impacts on the biomass of reef fishes on Florida’s Coral Reef and to evaluate the potential effects of common management interventions on fish biomass. Fishing impact was estimated using a fishery‐independent modelling approach and the biomass of the snapper–grouper complex as a proxy for the effects of fishing. Using a separate subset of data from underwater fish surveys, estimated fishing impact was then combined with 18 biophysical variables to model the current biomass of all reef fish species, the snapper–grouper complex, grazing species and species collected for aquaria. Models explained between 51 and 64% of the variance in fish biomass for the fish groups. The strongest predictor of biomass in the snapper–grouper complex was fishing impact (accounting for 25.2% of the explained variance), whereas reef complexity was the strongest predictor for all other groups. High‐resolution maps were produced from the statistical models, including maps of current fish biomass and maps of potential biomass under several management scenarios: a no‐take marine reserve, moderate and extensive coral restoration and the addition of artificial benthic structure. Adding structure had the largest single impact on predicted fish biomass (23–72% increase from current estimated levels). However, beneficial synergies emerged when combining habitat‐based management and fishing closures, with some combinations resulting in a reef‐wide averaged 89% increase in biomass relative to current estimated levels. The results suggest that conservation strategies aimed at protecting and increasing structural reef complexity should be an important part of fishery management discussions.

Adapting wastewater management systems in California for water conservation and climate change

ABSTRACT In California, wastewater systems have adapted to water conservation and drought for decades. Yet, few studies have investigated how past design assumptions influence potential mitigation and adaptation actions. This paper evaluates adaptation pathways for wastewater management in California and addresses two questions. First, are wastewater facilities experiencing challenges from mismatches in design flow values and current rates of influent flow? Second, what, if any, adaptation actions are underway or planned? To answer these questions, we compiled historical literature and conducted surveys and interviews with wastewater system managers. Approximately half of respondents indicated that they are experiencing challenges associated with changing water use rates. Aging systems have implemented many types of mitigation and adaptation actions, including operational changes, chemical additions, and facility rebuilds. California’s wastewater industry is largely pursuing an incremental adaptation pathway to manage drought and climate change. The paper demonstrates an engaged approach to research on climate change adaptation.

Public Support for Nutrition-Related Actions by Food Companies in Australia: A Cross-Sectional Analysis of Findings from the 2020 International Food Policy Study.

Unhealthy food environments contribute to unhealthy population diets. In Australia, the government currently relies on voluntary food company actions (e.g., related to front-of-pack labelling, restricting promotion of unhealthy foods, and product formulation) as part of their efforts to improve population diets, despite evidence that such voluntary approaches are less effective than mandatory policies. This study aimed to understand public perceptions of potential food industry nutrition-related actions in Australia. An online survey was completed by 4289 Australians in 2020 as part of the International Food Policy Study. The level of public support was assessed for six different nutrition-related actions related to food labelling, food promotion, and product formulation. High levels of support were observed for all six company actions, with the highest support observed for displaying the Health Star Rating on all products (80.4%) and restricting children's exposure to online promotion of unhealthy food (76.8%). Findings suggest the Australian public is strongly supportive of food companies taking action to improve nutrition and the healthiness of food environments. However, given the limitations of the voluntary action from food companies, mandatory policy action by the Australian government is likely to be needed to ensure company practices align with public expectations.

Consensus on Prioritisation of Actions for Reducing the Environmental Impact of a Large Tertiary Hospital: Application of the Nominal Group Technique

Hospitals are the largest greenhouse gas producers within the Australian healthcare sector due to the large amounts of energy, resource utilization, equipment and pharmaceuticals required to deliver care. In order to reduce healthcare emissions, healthcare services must take multiple actions to address the broad range of emissions produced when delivering patient care. The goal of this study was to seek consensus on the priority actions needed to reduce the environmental impact of a tertiary Australian hospital. A nominal group technique was utilized within a multidisciplinary, executive-led environmental sustainability committee to find consensus on the 62 proposed actions to reduce the environmental impact of a tertiary Australian hospital. Thirteen participants joined an online workshop during which an educational presentation was delivered, 62 potential actions were privately ranked according to two domains of 'amenability to change' and 'scale of climate impact' and a moderated group discussion ensued. The group achieved verbal consensus on 16 actions that span staff education, procurement, pharmaceuticals, waste, transport and advocacy on all-electric capital works upgrades. In addition, the individual ratings of potential actions according to each domain were ranked and shared with the group. Despite a large number of actions and varied perspectives within the group, the nominal group technique can be used to focus a hospital leadership group on priority actions to improve environmental sustainability.

Abrupt, but not gradual, motor adaptation biases saccadic target selection.

Motor costs influence movement selection. These costs could change when movements are adapted in response to errors. When the motor system attributes the encountered errors to an external cause, appropriate movement selection requires an update of the movement goal, which prompts the selection of a different control policy. However, when errors are attributed to an internal cause, the initially selected control policy could remain unchanged, but the internal forward model of the body needs to be updated, resulting in an online correction of the movement. We hypothesized that external attribution of errors leads to the selection of a different control policy, and thus to a change in the expected cost of movements. This should also affect subsequent motor decisions. Conversely, internal attribution of errors may (initially) only evoke online corrections, and thus is expected to leave the motor decision process unchanged. We tested this hypothesis using a saccadic adaptation paradigm, designed to change the relative motor cost of two targets. Motor decisions were measured using a target selection task between the two saccadic targets before and after adaptation. Adaptation was induced by either abrupt or gradual perturbation schedules, which are thought to induce more external or internal attribution of errors, respectively. By taking individual variability into account, our results show that saccadic decisions shift toward the least costly target after adaptation, but only when the perturbation is abruptly, and not gradually, introduced. We suggest that credit assignment of errors not only influences motor adaptation but also subsequent motor decisions.NEW & NOTEWORTHY Decisions between potential motor actions are influenced by their costs, but costs change when movements are adapted. Using a saccadic target selection task, we show that target preference shifts after abrupt, but not after gradual adaptation. We suggest that this difference emerges because abrupt adaptation results in target remapping, and thus directly influences cost calculations, whereas gradual adaptation is mainly driven by corrections to a forward model that is not involved in cost calculations.

Barriers to and strategies for early implementation of pharmacy-delivered HIV PrEP services in Kenya: An analysis of routine data.

For individuals who face challenges accessing clinic-based HIV pre-exposure prophylaxis (PrEP), differentiated service delivery models are needed to expand access and reach. During a pilot study testing a novel pharmacy-delivered oral PrEP model in Kenya, we used routine programmatic data to identify early implementation barriers and actions that providers and study staff took in response to the barriers. We trained pharmacy providers at five private pharmacies in Kisumu and Kiambu Counties to initiate and continue clients at risk of HIV acquisition on PrEP for a fee of 300 KES per visit (∼$3 USD) using a prescribing checklist with remote clinician oversight. Research assistants stationed at the pharmacies completed weekly observation reports of pharmacy-delivered PrEP services using a structured template. We analyzed reports from the first 6 month of implementation using content analysis and identified multi-level early implementation barriers and actions taken to address these. We then organized the identified barriers and actions according to the Consolidated Framework for Implementation Research (CFIR). From November 2020 to May 2021, research assistants completed 74 observation reports (∼18/pharmacy). During this period, pharmacy providers screened 496 potential PrEP clients, identified 425 as eligible for pharmacy-delivered PrEP services, and initiated 230 (54%) on PrEP; 125 of 197 (63%) clients eligible for PrEP continuation refilled PrEP. We identified the following early implementation barriers to pharmacy-delivered PrEP services (by CFIR domain): high costs to clients (intervention characteristics), client discomfort discussing sexual behaviors and HIV testing with providers (outer setting), provider frustrations that PrEP delivery was time-consuming and disruptive to their workflow (inner setting), and provider hesitancy to deliver PrEP due to concerns about encouraging sexual promiscuity (characteristics of individuals). To help address these, pharmacy providers implemented a self-screening option for behavioral HIV risk assessment for prospective PrEP clients, allowed flexible appointment scheduling, and conducted pharmacy PrEP trainings for newly hired staff. Our study provides insight into early barriers to implementing pharmacy-delivered PrEP services in Kenya and potential actions to mitigate these barriers. It also demonstrates how routine programmatic data can be used to understand the early implementation process.

Controlled nonautonomous matter–wave solitons in spinor Bose–Einstein condensates with spatiotemporal modulation

To study controlled evolution of nonautonomous matter–wave solitons in spinor Bose–Einstein condensates with spatiotemporal modulation, we focus on a system of three coupled Gross–Pitaevskii (GP) equations with space–time-dependent external potentials and temporally modulated gain/loss distributions. An integrability condition and a nonisospectral Lax pair for the coupled GP equations are obtained. Using it, we derive an infinite set of dynamical invariants, the first two of which are the mass and momentum. The Darboux transform is used to generate one- and two-soliton solutions. Under the action of different external potentials and gain/loss distributions, various solutions for controlled nonautonomous matter–wave solitons of both ferromagnetic and polar types are obtained, such as self-compressed, snake-like and stepwise solitons, and as well as breathers. In particular, the formation of states resembling rogue waves, under the action of a sign-reversible gain–loss distribution, is demonstrated too. Shape-preserving and changing interactions between two nonautonomous matter–wave solitons and bound states of solitons are addressed too. In this context, spin switching arises in the polar-ferromagnetic interaction. Stability of the nonautonomous matter–wave solitons is verified by means of systematic simulations of their perturbed evolution.