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. In: ECAI, vol 8, pp 921–922Brafman RI, Domshlak C, Engel Y, Tennenholtz M (2009) Planning games. In: IJCAI 2009, Proceedings of the 21st international joint conference on artificial intelligence, pp 73–78Bylander T (1994) The computational complexity of propositional strips planning. Artif Intell 69(1):165–204Chen X, Deng X (2006) Settling the complexity of two-player nash equilibrium. In: 47th annual IEEE symposium on foundations of computer science, 2006. FOCS’06. IEEE, pp 261–272Chien S, Sinclair A (2011) Convergence to approximate nash equilibria in congestion games. Games and Economic Behavior 71(2):315–327de Cote EM, Chapman A, Sykulski AM, Jennings N (2010) Automated planning in repeated adversarial games. In: 26th conference on uncertainty in artificial intelligence (UAI 2010), pp 376–383Dunne PE, Kraus S, Manisterski E, Wooldridge M (2010) Solving coalitional resource games. Artif Intell 174(1):20–50Fabrikant A, Papadimitriou C, Talwar K (2004) The complexity of pure nash equilibria. In: Proceedings of the thirty-sixth annual ACM symposium on theory of computing, STOC ’04, pp 604–612Friedman JW, Mezzetti C (2001) Learning in games by random sampling. J Econ Theory 98(1):55–84Ghallab M, Nau D, Traverso P (2004) Automated planning: theory & practice. ElsevierGoemans M, Mirrokni V, Vetta A (2005) Sink equilibria and convergence. In: Proceedings of the 46th annual IEEE symposium on foundations of computer science, FOCS ’05, pp 142–154Hadad M, Kraus S, Hartman IBA, Rosenfeld A (2013) Group planning with time constraints. Ann Math Artif Intell 69(3):243–291Hart S, Mansour Y (2010) How long to equilibrium? the communication complexity of uncoupled equilibrium procedures. Games and Economic Behavior 69(1):107–126Helmert M (2003) Complexity results for standard benchmark domains in planning. Artif Intell 143(2):219–262Helmert M (2006) The fast downward planning system. J Artif Intell Res 26(1):191–246Jennings N, Faratin P, Lomuscio A, Parsons S, Wooldrige M, Sierra C (2001) Automated negotiation: prospects, methods and challenges. Group Decis Negot 10(2):199–215Johnson DS, Papadimtriou CH, Yannakakis M (1988) How easy is local search? J Comput Syst Sci 37 (1):79–100Jonsson A, Rovatsos M (2011) Scaling up multiagent planning: a best-response approach. In: Proceedings of the 21st international conference on automated planning and scheduling, ICAPSJordán J, Onaindía E (2015) Game-theoretic approach for non-cooperative planning. In: 29th AAAI conference on artificial intelligence (AAAI-15), pp 1357–1363McDermott D, Ghallab M, Howe A, Knoblock C, Ram A, Veloso M, Weld D, Wilkins D (1998) PDDL: the planning domain definition language. Yale Center for Computational Vision and Control, New HavenMilchtaich I (1996) Congestion games with player-specific payoff functions. 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. 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Chronic lymphocytic leukaemia: the role of T cells in a B cell disease

Chronic lymphocytic leukaemia (CLL) has long been thought to be an immunosuppressive disease and abnormalities in T‐cell subset distribution and function have been observed in many studies. However, the role of T cells (if any) in disease progression remains unclear and has not been directly studied. This has changed with the advent of new therapies, such as chimeric antigen receptor‐T cells, which actively use retargeted patient‐derived T cells as “living drugs” for CLL. However complete responses are relatively low (~26%) and recent studies have suggested the differentiation status of patient T cells before therapy may influence efficacy. Non‐chemotherapeutic drugs, such as idelalisib and ibrutinib, also have an impact on T cell populations in CLL patients. This review will highlight what is known about T cells in CLL during disease progression and after treatment, and discuss the prospects of using T cells as predictive biomarkers for immune status and response to therapy

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

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 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

Risk Stratification in Older Intensively Treated Patients With AML

\ua9 2024 by American Society of Clinical Oncology.PURPOSE AML is a genetically heterogeneous disease, particularly in older patients. In patients older than 60 years, survival rates are variable after the most important curative approach, intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HCT). Thus, there is an urgent need in clinical practice for a prognostic model to identify older patients with AML who benefit from curative treatment. METHODS We studied 1,910 intensively treated patients older than 60 years with AML and high-risk myelodysplastic syndrome (HR-MDS) from two cohorts (NCRIAML18 and HOVON-SAKK). The median patient age was 67 years. Using a random survival forest, clinical, molecular, and cytogenetic variables were evaluated in an AML development cohort (n = 1,204) for association with overall survival (OS). Relative weights of selected variables determined the prognostic model, which was validated in AML (n = 491) and HR-MDS cohorts (n = 215). RESULTS The complete cohort had a high frequency of poor-risk features, including 2022 European LeukemiaNet adverse-risk (57.3%), mutated TP53 (14.4%), and myelodysplasia-related genetic features (65.1%). Nine variables were used to construct four groups with highly distinct 4-year OS in the (1) AML development, (2) AML validation, and (3) HR-MDS test cohorts ([1] favorable: 54% \ub1 4%, intermediate: 38% \ub1 2%, poor: 21% \ub1 2%, very poor: 4% \ub1 1%; [2] 54% \ub1 9%, 43% \ub1 4%, 27% \ub1 4%, 4% \ub1 3%; and [3] 54% \ub1 10%, 33% \ub1 6%, 14% \ub1 5%, 0% \ub1 3%, respectively). This new AML60+ classification improves current prognostic classifications. Importantly, patients within the AML60+ intermediate- and very poor-risk group significantly benefited from allo-HCT, whereas the poor-risk patients showed an indication, albeit nonsignificant, for improved outcome after allo-HCT. CONCLUSION The new AML60+ classification provides prognostic information for intensively treated patients 60 years and older with AML and HR-MDS and identifies patients who benefit from intensive chemotherapy and allo-HCT