204 research outputs found
Improving Gluten Production: Development of a New Salt-Washing Process
Established and supported under the Australian Government’s Cooperative Research Centre Progra
A Better-response Strategy for Self-interested Planning Agents
[EN] When self-interested agents plan individually, interactions that prevent them from executing their actions as planned may arise. In these coordination problems, game-theoretic planning can be used to enhance the agents¿ strategic behavior considering the interactions as part of the agents¿ utility. In this work, we define a general-sum game in which interactions such as conflicts and congestions are reflected in the agents¿ utility. We propose a better-response planning strategy that guarantees convergence to an equilibrium joint plan by imposing a tax to agents involved in conflicts. We apply our approach to a real-world problem in which agents are Electric Autonomous Vehicles (EAVs). The EAVs intend to find a joint plan that ensures their individual goals are achievable in a transportation scenario where congestion and conflicting situations may arise. Although the task is computationally hard, as we theoretically prove, the experimental results show that our approach outperforms similar approaches in both performance and solution quality.This work is supported by the GLASS project TIN2014-55637-C2-2-R of the Spanish MINECO and the Prometeo project II/2013/019 funded by the Valencian Government.Jordán, J.; Torreño Lerma, A.; De Weerdt, M.; Onaindia De La Rivaherrera, E. (2018). A Better-response Strategy for Self-interested Planning Agents. Applied Intelligence. 48(4):1020-1040. https://doi.org/10.1007/s10489-017-1046-5S10201040484Aghighi M, Bäckström C (2016) A multi-parameter complexity analysis of cost-optimal and net-benefit planning. In: Proceedings of the Twenty-Sixth International Conference on International Conference on Automated Planning and Scheduling. AAAI Press, London, pp 2–10Bercher P, Mattmüller R (2008) A planning graph heuristic for forward-chaining adversarial planning. 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Games and Economic Behavior 13(1):111–124Monderer D, Shapley LS (1996) Potential games. Games and Economic Behavior 14(1):124–143Nigro N, Welch D, Peace J (2015) Strategic planning to implement publicly available ev charching stations: a guide for business and policy makers. Tech rep, Center for Climate and Energy SolutionsNisan N, Ronen A (2007) Computationally feasible vcg mechanisms. J Artif Intell Res 29(1):19–47Nisan N, Roughgarden T, Tardos E, Vazirani VV (2007) Algorithmic game theory. Cambridge University Press, New YorkPapadimitriou CH (1994) On the complexity of the parity argument and other inefficient proofs of existence. J Comput Syst Sci 48(3):498–532Richter S, Westphal M (2010) The LAMA planner: guiding cost-based anytime planning with landmarks. J Artif Intell Res 39(1):127–177Rosenthal RW (1973) A class of games possessing pure-strategy nash equilibria. Int J Game Theory 2(1):65–67Shoham Y, Leyton-Brown K (2009) Multiagent systems: algorithmic, game-theoretic, and logical foundations. Cambridge University PressTorreño A, Onaindia E, Sapena Ó (2014) A flexible coupling approach to multi-agent planning under incomplete information. Knowl Inf Syst 38(1):141–178Torreño A, Onaindia E, Sapena Ó (2014) FMAP: distributed cooperative multi-agent planning. Appl Intell 41(2):606– 626Torreño A, Sapena Ó, Onaindia E (2015) Global heuristics for distributed cooperative multi-agent planning. In: ICAPS 2015. 25th international conference on automated planning and scheduling. AAAI Press, pp 225–233Von Neumann J, Morgenstern O (2007) Theory of games and economic behavior. Princeton University Pressde Weerdt M, Bos A, Tonino H, Witteveen C (2003) A resource logic for multi-agent plan merging. Ann Math Artif Intell 37(1):93–130Wooldridge M, Endriss U, Kraus S, Lang J (2013) Incentive engineering for boolean games. Artif Intell 195:418–43
A functional spleen contributes to afucosylated IgG in humans
As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography–mass spectrometry (LC–MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells
The effectiveness of peer health coaching in improving glycemic control among low-income patients with diabetes: protocol for a randomized controlled trial
<p>Abstract</p> <p>Background</p> <p>Although self-management support improves diabetes outcomes, it is not consistently provided in health care settings strained for time and resources. One proposed solution to personnel and funding shortages is to utilize peer coaches, patients trained to provide diabetes education and support to other patients. Coaches share similar experiences about living with diabetes and are able to reach patients within and beyond the health care setting. Given the limited body of evidence that demonstrates peer coaching significantly improves chronic disease care, this present study examines the impact of peer coaching delivered in a primary care setting on diabetes outcomes.</p> <p>Methods/Design</p> <p>The aim of this multicenter, randomized control trial is to evaluate the effectiveness of utilizing peer coaches to improve clinical outcomes and self-management skills in low-income patients with poorly controlled diabetes. A total of 400 patients from six primary health centers based in San Francisco that serve primarily low-income populations will be randomized to receive peer coaching (n = 200) or usual care (n = 200) over 6 months. Patients in the peer coach group receive coaching from patients with diabetes who are trained and mentored as peer coaches. The primary outcome is change in HbA1c. Secondary outcomes include change in: systolic blood pressure, body mass index (BMI), LDL cholesterol, diabetes self-care activities, medication adherence, diabetes-related quality of life, diabetes self-efficacy, and depression. Clinical values (HbA1c, LDL cholesterol and blood pressure) and self-reported diabetes self-efficacy and self-care activities are measured at baseline and after 6 months for patients and coaches. Peer coaches are also assessed at 12 months.</p> <p>Discussion</p> <p>Patients with diabetes, who are trained as peer health coaches, are uniquely poised to provide diabetes self management support and education to patients. This study is designed to investigate the impact of peer health coaching in patients with poorly controlled diabetes. Additionally, we will assess disease outcomes in patients with well controlled diabetes who are trained and work as peer health coaches.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01040806">NCT01040806</a></p
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Rifampicin resistance conferring mutations among Mycobacterium tuberculosis strains in Rwanda
Background: The World Health Organization-endorsed phenotypic and genotypic drug-susceptibility testing (gDST/pDST) assays for the detection of rifampicin-resistant (RR) tuberculosis (TB), may miss some clinically relevant rpoB mutants, including borderline mutations and mutations outside the gDST-targeted hotspot region. Sequencing of the full rpoB gene is considered the reference standard for rifampicin DST but is rarely available in RR-TB endemic settings and when done indirectly on cultured isolates may not represent the full spectrum of mutations. Hence, in most such settings, the diversity and trends of rpoB mutations remain largely unknown.
Methods: This retrospective study included rpoB sequence data from a longitudinal collection of RR-TB isolates in Rwanda across 30 years (1991–2021).
Results: Of 540 successfully sequenced isolates initially reported as RR-TB, 419 (77.6%) had a confirmed RR conferring mutation. The Ser450 Leu mutation was predominant throughout the study period. The Val170Phe mutation, not covered by rapid gDST assays, was observed in only four patients, three of whom were diagnosed by pDST. Along with the transition from pDST to rapid gDST, borderline RR-associated mutations, particularly Asp435Tyr, were detected more frequently. Borderline mutants were not associated with HIV status but presented lower odds of having rpoA-C compensatory mutations than other resistance-conferring mutations.
Conclusion: Our analysis showed changes in the diversity of RR-TB conferring mutations throughout the study period that coincided with the switch of diagnostic tools to rapid gDST. The study highlights the importance of rapid molecular diagnostics reducing phenotypic bias in the detection of borderline rpoB mutations while vigilance for non-rifampicin resistance determinant region mutations is justified in any setting
A functional spleen contributes to afucosylated IgG in humans
As a lymphoid organ, the spleen hosts a wide range of immune cell populations, which not only remove blood-borne antigens, but also generate and regulate antigen-specific immune responses. In particular, the splenic microenvironment has been demonstrated to play a prominent role in adaptive immune responses to enveloped viral infections and alloantigens. During both types of immunizations, antigen-specific immunoglobulins G (IgGs) have been characterized by the reduced amount of fucose present on N-linked glycans of the fragment crystallizable (Fc) region. These glycans are essential for mediating the induction of immune effector functions. Therefore, we hypothesized that a spleen may modulate humoral responses and serve as a preferential site for afucosylated IgG responses, which potentially play a role in immune thrombocytopenia (ITP) pathogenesis. To determine the role of the spleen in IgG-Fc glycosylation, we performed IgG subclass-specific liquid chromatography-mass spectrometry (LC-MS) analysis of Fc glycosylation in a large cohort of individuals splenectomized due to trauma, due to ITP, or spherocytosis. IgG-Fc fucosylation was consistently increased after splenectomy, while no effects for IgG-Fc galactosylation and sialylation were observed. An increase in IgG1- and IgG2/3-Fc fucosylation level upon splenectomy has been reported here for the first time, suggesting that immune responses occurring in the spleen may be particularly prone to generate afucosylated IgG responses. Surprisingly, the level of total IgG-Fc fucosylation was decreased in ITP patients compared to healthy controls. Overall, our results suggest a yet unrecognized role of the spleen in either the induction or maintenance of afucosylated IgG responses by B cells.Proteomic
A bispecific T cell engager recruits both type 1 NKT and Vy9V52-T cells for the treatment of CD1d-expressing hematological malignancies
Bispecific T cell engagers (bsTCEs) hold great promise for cancer treatment but face challenges due to the induction of cytokine release syndrome (CRS), on-target off-tumor toxicity, and the engagement of immuno-suppressive regulatory T cells that limit efficacy. The development of Vy9V52-T cell engagers may overcome these challenges by combining high therapeutic efficacy with limited toxicity. By linking a CD1d-specific single-domain antibody (VHH) to a V52-TCR-specific VHH, we create a bsTCE with trispecific properties, which engages not only Vy9V52-T cells but also type 1 NKT cells to CD1d+ tumors and triggers robust proin-flammatory cytokine production, effector cell expansion, and target cell lysis in vitro. We show that CD1d is expressed by the majority of patient MM, (myelo)monocytic AML, and CLL cells and that the bsTCE triggers type 1 NKT and Vy9V52-T cell-mediated antitumor activity against these patient tumor cells and improves survival in in vivo AML, MM, and T-ALL mouse models. Evaluation of a surrogate CD1d-y5 bsTCE in NHPs shows Vy9V52-T cell engagement and excellent tolerability. Based on these results, CD1d-V52 bsTCE (LAVA-051) is now evaluated in a phase 1/2a study in patients with therapy refractory CLL, MM, or AML.Transplantation and autoimmunit
Cost-effectiveness of a structured progressive task-oriented circuit class training programme to enhance walking competency after stroke: The protocol of the FIT-Stroke trial
<p>Abstract</p> <p>Background</p> <p>Most patients who suffer a stroke experience reduced walking competency and health-related quality of life (HRQoL). A key factor in effective stroke rehabilitation is intensive, task-specific training. Recent studies suggest that intensive, patient-tailored training can be organized as a circuit with a series of task-oriented workstations.</p> <p>Primary aim of the FIT-Stroke trial is to evaluate the effects and cost-effectiveness of a structured, progressive task-oriented circuit class training (CCT) programme, compared to usual physiotherapeutic care during outpatient rehabilitation in a rehabilitation centre. The task-oriented CCT will be applied in groups of 4 to 6 patients. Outcome will be defined in terms of gait and gait-related ADLs after stroke. The trial will also investigate the generalizability of treatment effects of task-oriented CCT in terms of perceived fatigue, anxiety, depression and perceived HRQoL.</p> <p>Methods/design</p> <p>The multicentre single-blinded randomized trial will include 220 stroke patients discharged to the community from inpatient rehabilitation, who are able to communicate and walk at least 10 m without physical, hands-on assistance. After discharge from inpatient rehabilitation, patients in the experimental group will receive task-oriented CCT two times a week for 12 weeks at the physiotherapy department of the rehabilitation centre. Control group patients will receive usual individual, face-to-face, physiotherapy. Costs will be evaluated by having each patient keep a cost diary for the first 24 weeks after randomisation. Primary outcomes are the mobility part of the Stroke Impact Scale (SIS-3.0) and the EuroQol. Secondary outcomes are the other domains of SIS-3.0, lower limb muscle strength, walking endurance, gait speed, balance, confidence not to fall, instrumental ADL, fatigue, anxiety, depression and HRQoL.</p> <p>Discussion</p> <p>Based on assumptions about the effect of intensity of practice and specificity of treatment effects, FIT-Stroke will address two key aims. The first aim is to investigate the effects of task-oriented CCT on walking competency and HRQoL compared to usual face-to-face physiotherapy. The second aim is to reveal the cost-effectiveness of task-oriented CCT in the first 6 months post stroke. Both aims were recently recommended as priorities by the American Hearth Association and Stroke Council.</p> <p>Trial registration</p> <p>This study is registered in the Dutch Trial Register as NTR1534.</p
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