Search

Background: \ud Outcomes for patients with blast-phase chronic myeloid leukaemia are poor. Long-term survival depends on reaching a second chronic phase, followed by allogeneic haematopoietic stem-cell transplantation (HSCT). We investigated whether the novel combination of the tyrosine-kinase inhibitor ponatinib with fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin (FLAG-IDA) could improve response and optimise allogeneic HSCT outcomes in patients with blast-phase chronic myeloid leukaemia. The aim was to identify a dose of ponatinib, which combined with FLAG-IDA, showed clinically meaningful activity and tolerability.\ud \ud Methods: \ud MATCHPOINT was a seamless, phase 1/2, multicentre trial done in eight UK Trials Acceleration Programme-funded centres. Eligible participants were adults (aged ≥16 years) with Philadelphia chromosome-positive or BCR-ABL1-positive blast-phase chronic myeloid leukaemia, suitable for intensive chemotherapy. Participants received up to two cycles of ponatinib with FLAG-IDA. Experimental doses of oral ponatinib (given from day 1 to day 28 of FLAG-IDA) were between 15 mg alternate days and 45 mg once daily and the starting dose was 30 mg once daily. Intravenous fludarabine (30 mg/m2 for 5 days), cytarabine (2 g/m2 for 5 days), and idarubicin (8 mg/m2 for 3 days), and subcutaneous granulocyte colony-stimulating factor (if used), were delivered according to local protocols. We used an innovative EffTox design to investigate the activity and tolerability of ponatinib–FLAG-IDA; the primary endpoints were the optimal ponatinib dose meeting prespecified thresholds of activity (inducement of second chronic phase defined as either haematological or minor cytogenetic response) and tolerability (dose-limiting toxicties). Analyses were planned on an intention-to-treat basis. MATCHPOINT was registered as an International Standard Randomised Controlled Trial, ISRCTN98986889, and has completed recruitment; the final results are presented.\ud \ud Findings: \ud Between March 19, 2015, and April 26, 2018, 17 patients (12 men, five women) were recruited, 16 of whom were evaluable for the coprimary outcomes. Median follow-up was 41 months (IQR 36–48). The EffTox model simultaneously considered clinical responses and dose-limiting toxicities, and determined the optimal ponatinib dose as 30 mg daily, combined with FLAG-IDA. 11 (69%) of 16 patients were in the second chronic phase after one cycle of treatment. Four (25%) patients had a dose-limiting toxicity (comprising cardiomyopathy and grade 4 increased alanine aminotransferase, cerebral venous sinus thrombosis, grade 3 increased amylase, and grade 4 increased alanine aminotransferase), fulfilling the criteria for clinically relevant activity and toxicity. 12 (71%) of 17 patients proceeded to allogeneic HSCT. The most common grade 3–4 non-haematological adverse events were lung infection (n=4 [24%]), fever (n=3 [18%]), and hypocalcaemia (n=3 [18%]). There were 12 serious adverse events in 11 (65%) patients. Three (18%) patients died due to treatment-related events (due to cardiomyopathy, pulmonary haemorrhage, and bone marrow aplasia).\ud \ud Interpretation: \ud Ponatinib–FLAG-IDA can induce second chronic phase in patients with blast-phase chronic myeloid leukaemia, representing an active salvage therapy to bridge to allogeneic HSCT. The number of treatment-related deaths is not in excess of what would be expected in this very high-risk group of patients receiving intensive chemotherapy. The efficient EffTox method is a model for investigating novel therapies in ultra-orphan cancers.\ud \ud Funding: \ud Blood Cancer UK and Incyte.

Photomechanical effects realized in azobenzene-functionalized polyimides have shown large deformation and an exceptional increase in photogenerated force output. Here, we synthesize and characterize the photomechanical output of a series of linear polyimide materials prepared with a bulky substituent, incorporated via the development of a new bis(azobenzene-diamine) monomer containing a 9,9-diphenylfluorene cardo structure (azoCBODA). All six azoCBODA-containing polyimides are amorphous and exhibit high glass transition temperatures (Tg) ranging from 298 to 358 °C, storage moduli ranging from 2.27 to 3.81 GPa (at 30 °C), and good thermal stability. The magnitude of the photoinduced mechanical response of the azobenzene-functionalized polyimide is correlated to the rotational freedom of the polyimide chains (resulting in extensive segmental mobility) and fractional free volume (FFV > 0.1).

This review aims to highlight the bioprocessing strategies behind one of the most commercially produced enzymes in the biotechnological market, pectinase. Significant steps in the upstream processing of this enzyme include its source, the selection of the substrate, the reaction conditions and the overall reactor design, all of which will be discussed in great detail. Past literature which has contributed to the viability of this design will be highlighted with the intention of generating a comparative review that accounts not only for the contributions of previous research but also for what needs to be done in the future to further increase the productivity of this vital industrial process. There is an incredibly wide net of application based research and industry which currently depends on the bioprocessing of pectinase, these will thereby benefit greatly from the concepts of process intensification and optimisation which are at the forefront of this review and will likely be inspired by the outlined steps that need to be taken to further improve this process.

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level

In patients with peripheral artery disease (PAD), plaque is accumulating in arteries which leads to a reduction in blood supply to the extremities. In advanced stages, surgical intervention is required to reopen the arteries and restore limb perfusion. During this procedure, it is important to correctly identify which areas of the foot lack perfusion. The standard procedure to obtain this information is X-ray angiography, which is performed repeatedly during the intervention. The disadvantage of this procedure is the relatively high radiation dose and extensive use of contrast agents. To reduce this problem, we evaluate in this pilot study (involving 4 patients) the ability of vascular optical spectroscopy (VOS) to detect the X-ray contrast agent permeating the angiosomes in the foot. We show that the contrast agent can be detected by optical measurements as it temporarily replaces the blood in the different angiosomes, which leads to a 1% to 5% change in the signal amplitude. In addition, measurements of the blood pooling in the foot were performed before the intervention. We observed a strong correlation between the angiosomes that showed a worsen state in the measurement done before the intervention and the absence of angiographic contrast agent signals during the intervention itself. Among the 4 patients monitored, 2 showed a response to the contrast agent in their angiosomes and they corresponded to the patients with a relatively better perfusion in the pre-intervention measurements.

The objective of this study was to take a multi-domain approach to predict feelings of anxiety among graduate allied health students. Participants (n=77) from a small university in upstate New York completed a series of questionnaires [International Physical Activity Questionnaire-short form (IPAQ-SF), Rapid Eating Assessment of Participants-Short Form (REAP-S), Pittsburgh Sleep Quality Inventory (PSQI), Profile of Mood Survey-Short Form (POMS-SF), Trait and State Mental and Physical Energy and Fatigue Survey], and their resting metabolic rate, fat free mass and muscle oxygen saturation levels were measured. A backwards linear regression was used to identify predictors of anxiety. Our model predicted 28.1% of variance with women reporting greater feelings of anxiety. Poor sleep quality, increased sedentary behavior, and low trait physical energy were all significant predictors of increased feelings anxiety. Our results suggest that educators should attempt to reduce in class sitting time and promote better sleep hygiene. Additionally, researchers should examine barriers and burdens female students face that increase feelings of anxiety.

The problem of a lack of qualified teachers is acute in the Global South, where countries often struggle with limited resources and significant rural–urban, regional, and gender gaps in the provision of quality education. The shortage of qualified teachers affects student learning engagement, reducing the effectiveness of schooling. There is a need for countries in the Global South to provide high-quality teacher professional development to all teachers, from pre-service to induction to in-service. Initiated in 2018, the TPD@Scale Coalition for the Global South seeks to address this need for inclusive, quality, and cost-effective teacher professional development programs through collaboration, research, and implementation support. The coalition works with governments to design and develop their respective TPD@Scale systems while addressing critical issues of learner differentiation or personalization, learner support, and assessment. Depending on their contexts, such systems harness ICT to reach teachers remotely, face-to-face, or both, to provide accessible, sustainable, and quality teachers’ professional learning.

Background: Gemtuzumab (GO) is an antibody drug conjugate that links a CD33 antibody to calicheamicin, a potent DNA-damaging agent. GO has been studied in combination with standard chemotherapy in multiple randomized clinical trials, though the doses and schedules of GO in these studies varied significantly. In a meta-analysis, 1 the addition of GO was found to improve relapse-free (RFS) and overall survival (OS), particularly in patients with favorable cytogenetics. It is now approved for use in combination with 7+3 in newly diagnosed CD33-positive AML. The studies that supported its approval were heterogenous and, in clinical practice, the uptake and utilization patterns for GO have been wide-ranging. At Johns Hopkins Sidney Kimmel Cancer Center, a single dose of GO at a dose of 3 mg/m2 has been incorporated into standard 7+3 induction for patients with core binding factor (CBF) AML since . Herein, we report the impact of this practice change on clinical outcomes for patients with CBF AML. Methods: 72 patients with newly-diagnosed, previously untreated CBF AML from 2008-2020 were identified. Electronic medical records were reviewed for initial CBF AML presentation, management, and outcomes. Patient, disease, and transplant characteristics were summarized by treatment groups using descriptive statistics. Group differences were tested via Wilcoxon rank-sum test, chi-square test of independence, and Fisher's exact disease. Kaplan-Meier estimates were reported for OS and RFS. Group differences were tested via log-rank test. All analyses were carried out with R version 4.0.2 using the "survival" and "cmprsk" packages (R Foundation for Statistical Computing, Vienna, Austria). Results: There were 28 (40%) patients who received GO and 43 (60%) who did not (non-GO) (Table 1). The percentage of patients in the GO group who had favorable ELN risk was similar to the non-GO group (p>0.9). The proportion of patients with inv(16) was lower in the GO group (p=0.018) while the proportion of patients with t(8;21) was greater in the GO group (p=0.018). At presentation, the GO group had a significantly lower mean WBC compared to the non-GO group (p = .007). The rates of complete response (CR) after induction were similar between the GO and non-GO groups (p = 0.6). The GO group took longer to achieve neutrophil count (0.5 K/cu mm) recovery (p=0.13) whereas the non-GO group took longer to achieve a platelet count of 100K/cu mm (p=0.005). The rates of post-induction measurable residual disease (MRD) by flow cytometry were similar between the GO and non-GO groups (p=0.6). 7 (24%) patients in the GO group and 13 (30%) of patients in the non-GO group underwent allogeneic bone marrow transplant in first remission. The only non-hematologic adverse effects noted in the GO group were rapid weight gain in 2 patients (7%) and grade I/II elevated liver enzymes in 5 patients (18%). No grade III-IV liver enzyme abnormalities. There were no therapy-related deaths in the GO group and no episodes of vaso-occlusive disease in those who went on to transplant. There was a trend towards improved RFS (p=0.05, Figure C-D) and significantly improved OS (p=0.04, Figure B) favoring patients who received a one-time dose of GO. Conclusions: Patients who received GO had a trend towards improved RFS and significantly improved OS compared to patients who did not. This real-world study suggests that there may be a benefit, with little detriment, to the addition of a single dose of GO. The study, however, is limited by differences between the two groups including WBC at presentation, distribution of inv(16) vs. t(8;21), the eras in which patients were diagnosed and treated, and shorter median follow-up time for the GO group. Our study was further limited by missing data for a significant proportion of patients with regards to C-KIT and rates of post-induction MRD by PCR. It is important to note that this study compared GO and any regimen (not limited to 7+3) to any regimen without GO. Treatment protocols evolved during GO utilization and these changes in practice patterns could have impacted clinical outcomes. Lastly, this study highlights the fact that patients with CBF AML can expect to have favorable outcomes. References: 1. Hills RK, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: A meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15(9):986-996. Figure 1 Figure 1. Disclosures DeZern: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Taiho: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Thresholds for belowground decomposition rates based on nearness to groundwater were identified on a Virginia barrier island. Negative exponential decay rates (k = 0.310–0.915 yr.−1) varied according to average distance to the freshwater free surface, with lowest decay occurring in low elevations (marsh and deeper soils of a wooded swale), and highest decay occurring at mid to high elevations (surface soils in wooded swales and all dune sites). The majority of decay rate variances were explained by mean annual depth to the freshwater free surface (r2 = 0.78). Locations with mean annual groundwater depths greater than 0.95 m were substantially less affected by fluctuations in groundwater levels (r2 = 0.09) than where groundwater was near the soil surface (r2 = 0.83). Two vegetation-based decay thresholds were identified at mean annual groundwater depths of −0.041 m and 0.538 m, separating belowground decay into three groups (low, moderate, and high decay). These groups tended to correspond to the three interior barrier island plant communities (marsh, wooded swale, and dune), but with overlap. The groundwater free surface provides a useful metric that can be used in geospatial models to predict process rates and vegetation patterns in the dynamic barrier island landscape.

Background: Mutations in the isocitrate dehydrogenase (IDH) 1 and 2 genes are found in approximately 20% of patients with acute myeloid leukemia (AML). Although independent prognostic data are lacking, our program often moves patients with IDH-mutated AML (mIDH) towards allogeneic bone marrow transplant (BMT). Reports on the impact of mIDH on BMT outcomes are conflicting. One study (Quek L, et al. Blood Adv. 2016; 1(3):19320) found improved rates of relapse (RR), relapse free survival (RFS) and overall survival (OS) for patients with mIDH1, whereas another study (Salhotra A, et al. Clin Lymphoma, Myeloma Leuk. 2019 Jul 1;19(7):e400-5) reported higher RR, but no differences in RFS or OS for patients with mIDH1/2. In light of the approved IDH1/2 inhibitors, the role of early BMT for such patients requires additional study. We examined the BMT outcomes of patients with mIDH AML compared to wildtype (wt)-IDH AML. Patients and methods: Patients with AML who underwent a first allo-BMT at Johns Hopkins between 2014 and 2020 and had molecular testing for IDH mutation status were included. Patients were grouped according to IDH mutation status (mIDH versus wt-IDH). Patient demographics, molecular genetics, initial treatment response, and BMT characteristics were compared. Post-BMT RR, RFS and OS were then compared between groups. Multivariate models were used to assess the prognostic significance of mIDH after controlling for co-variates. We also examined the relationship between peri-BMT IDH inhibitor use and IDH mutation status at the time of post-BMT relapse. Results: We identified 109 patients with mIDH AML, 70 (64%) of whom underwent BMT. 210 BMT patients with wt-IDH AML were used as a comparison. Outcomes between patients with mIDH1 and mIDH2 AML were similar and they were combined for all further analyses. Patients with mIDH were generally older (mean age at diagnosis 61 (range 28-75) vs. 54 (range 19-76), p < .001), less likely to have poor-risk cytogenetics, more likely to have a haploidentical donor, and more likely to receive non-myeloablative conditioning (Table 1). mIDH AML was associated with co-mutations in SRSF2 and DNMT3A mutations and less likely to have TET2 and KRAS co-mutations. Patients with mIDH had significantly improved post-BMT RR, RFS and OS compared to patients with wt-IDH (log rank p = 0.04, .01, and .01 respectively, Figure 1). In a multivariate model controlling for ELN risk classification, mIDH was associated with improved OS with a trend towards significance (HR 0.51, 95% CI 0.24 - 1.10, p = 0.085). Recognizing that significant heterogeneity exists within ELN risk groups, we examined the specific components of poor ELN risk classification in each group and found that poor risk in the wt-IDH group was primarily driven by complex karyotypes and TP53 mutations, whereas the ELN poor risk was driven by RUNX1 or ASXL1 co-mutation in the mIDH group. In a model controlling for specific genetic abnormalities (complex karyotype, TP53 mutation, and KRAS mutation) IDH mutation status was not an independent prognostic factor (HR 0.66, 0.34 - 1.28, p = 0.2, Table 2). We also assessed whether improved outcomes might be associated with use of IDH inhibitors in the pre or post-BMT setting. 22 (31%) of the 70 patients with mIDH AML received pre-BMT IDH inhibitors and an additional 4 patients received post-BMT maintenance. Of the 15 patients with mIDH who relapsed post-BMT, 13 had mIDH at the time of relapse. 11 of the 11 patients who had never received an IDH inhibitor had mIDH at relapse compared to 2 of 4 (50%) patients who had received IDH inhibitors (p = .057). Conclusion: In our cohort, patients with mIDH AML had significantly better OS, RFS, and RR following BMT compared to patients with wt-IDH. However, our analyses suggest that IDH mutations are associated with favorable genetic abnormalities and that the differences in BMT outcome are likely attributable to these differing genetic profiles as opposed to the presence of the mIDH. Differences in outcome were specifically driven by a lower prevalence of complex cytogenetics, TP53 mutations, and KRAS mutations amongst mIDH AML and were incompletely captured by ELN risk classification. In addition, the frequency with which post-BMT relapsed AML bears the IDH-mutant clone suggests that incorporation of IDH inhibitors into the peri-BMT setting, as is currently being studied in large randomized trials (NCT03564821, NCT03515512), may further improve outcomes. Disclosures DeZern: Celgene: Consultancy, Honoraria; Astex: Research Funding; Abbvie: Consultancy; MEI: Consultancy. Levis:Astellas: Honoraria, Research Funding; Daiichi-Sankyo: Honoraria; FujiFilm: Honoraria, Research Funding; Amgen: Honoraria; Menarini: Honoraria. Smith:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Directly transducing light into work is attractive for remotely powering soft mechanisms designed from photoresponsive polymers, but presents challenges for achieving reliable actuation within a control framework. Here, we utilize azobenzene-functionalized polyimides to fabricate actuators characterized by mechanically discrete states. Irradiation initiates the photochemically induced, quasistatic deformation to advance the actuator to the edge of instability. Following this latency, ultrafast snap through actuation (∼10 ms-scale) ensues. Restricting the role of control to the attainment of the edge of instability, strategies for achieving repetitive actuation via multiplexed irradiation are demonstrated. Approaches are examined for modulating the latency of the actuator using an all-optical strategy as well as mechanical design of the actuator. Prototypical assemblies of these actuators in arrays are used to fabricate morphable surfaces and structures, which is aided by the realization that the ultrafast actuation is characterized by a high power-density on the order of ∼kW/m3.

Quantum information science aims to revolutionize existing methods for manipulating data by utilizing the unique features of nonclassical physical phenomena. This control is realized over several platforms, one particular being photonics which employs state of the art fabrication techniques that achieve integrated nanocircuit components. The Hong-Ou-Mandel effect underlies the basic entangling mechanism of linear optical quantum computing, and is a critical feature in the design of nanophotonic circuits used for quantum information processing. We will present some results from an on-chip Hong-Ou-Mandel (HOM) experiment that replaces the conventional beam splitter with a more compact and highly versatile ring resonator allowing greater functionality with an expanded parameter space dubbed Hong-Ou-Mandel Manifold (HOMM). The overarching goal of this work is to demonstrate on-chip, scalable, dynamically configurable quantum-optical interconnects for integration into photonic quantum information processing devices.

This chapter examines the potential of digital learning to achieve the goals of education equity, quality, and efficiency in developing Asian countries. Drawing on a comprehensive review of literature, it reports that digital learning innovations, such as massive open online courses (MOOCs), intelligent tutoring systems (ITS), digital game-based learning (DGBL), and learning analytics (LA), are a relatively new phenomenon in developing Asian countries. The corresponding research literature is therefore understandably scant but growing. Yet, the review underscores that if these technologies are implemented in an evidence-informed manner, digital learning could contribute significantly to advancing the Sustainable Development Goal (SDG) 4 of inclusive and equitable quality education and lifelong learning opportunities for all. Future research could focus on understanding how factors such as localization/customization, equity, quality, efficiency, sustainability, and scalability interplay with digital learning in developing Asian countries. In particular, recognizing that digital learning holds significant potential, there is a need to explore how to effectively realize this potential across diverse and often constrained contexts. The chapter concludes that effectiveness, sustainability, and scalability factors are the most crucial considerations in bringing about the intended benefits of digital learning for all to turn the SDG4 vision into reality.

Literature Reviews (LR) are particularly useful for demonstrating the coherence and cumulativeness (or lack thereof) of MIS research and for developing avenues for further research. Most top-tier journals now publish LRs, and many have even begun devoting specific sections to them. Our starting point is that LRs are not epistemologically neutral, and three approaches commonly underlie literature reviews: positivism (identifying the concepts, theories and models closest to the phenomenon that is being explained); interpretivism (identifying the various concepts and theories expressed by various actors and grouping them into multiple perspectives); and critical approaches (identifying both the underlying assumptions and conditions of the production of theories and their effects). We suggest a fourth approach to LRs underpinned by the philosophy of critical realism (CR) and argue that it can enable the (re)interpretation of existing literature through the identification of underlying generative mechanisms. These generative mechanisms provide a common denominator to enable the synthesis of concepts and theories in new ways, helping to bridge previously thought to be incompatible theories, and contributing to a more cumulative view of academic knowledge. We illustrate the value of a CR-based literature through its application to the topic of IT Strategic Value in the MIS and strategic management literature; we show how the identification of four generative mechanisms and three core agencies can support a more integrated view of IT Strategic Value. We then discuss the implications of the use of generative mechanisms and propose guidelines from a CR perspective for carrying out literature reviews.

Graduate education in the healthcare professions can be stressful and mentally taxing. The objective of this study was to identify differences in health and health-related behaviors among graduate allied health students based on sex and curriculum stage (i.e., didactic or clinical education).Participants (n=77) were assessed for body fat, BMI, resting metabolic rate (RMR), and peripheral arterial-venous O2 (AVO2), as well as a series of cognitive tasks and self-reported health and health-related behaviors. Independent sample t-tests and tests of proportions were used to assess differences between groups.There was no evidence that the didactic and clinical students were meaningfully different upon entering their programs. Didactic students reported significantly higher tension/anxiety, depression, anger, confusion, fatigue, total mood disturbance, trait mental fatigue, total intensity of mental work performed, and time spent sitting (p0.05). Didactic students also reported significantly lower RMR (p=0.033), but not after normalizing for fat-free mass. Males reported lower intensity of mental work performed on non-work days compared to females (p=0.009).Findings indicate students in didactic stages have worse mood and decreased health relative to their counterparts in clinical stages. Opportunities exist to integrate physical and mental health-related education, resources, and self-management programming into graduate allied health curricula to improve wellness among students.

Since the early 2000s, there has been an explosion in the usage of the term open, arguably stemming from the advent of networked technologies — including the Internet and mobile technologies. ‘Openness’ seems to be everywhere, and takes many forms: from open knowledge, open education, open data and open science, to open Internet, open medical records systems and open innovation. These applications of openness are having a profound, and sometimes transformative, effect on social, political and economic life.This explosion of the use of the term has led to multiple interpretations, ambiguities, and even misunderstandings, not to mention countless debates and disagreements over precise definitions. The paper “Fifty shades of open” by Pomerantz and Peek (2016) highlighted the increasing ambiguity and even confusion surrounding this term. This article builds on Pomerantz and Peek’s attempt to disambiguate the term by offering an alternative understanding to openness — that of social praxis. More specifically, our framing can be broken down into three social processes: open production, open distribution, and open consumption. Each process shares two traits that make them open: you don’t have to pay (free price), and anyone can participate (non-discrimination) in these processes.We argue that conceptualizing openness as social praxis offers several benefits. First, it provides a way out of a variety of problems that result from ambiguities and misunderstandings that emerge from the current multitude of uses of openness. Second, it provides a contextually sensitive understanding of openness that allows space for the many different ways openness is experienced — often very different from the way that more formal definitions conceptualize it. Third, it points us towards an approach to developing practice-specific theory that we believe helps us build generalizable knowledge on what works (or not), for whom, and in what contexts.

Critical technologies from medicine to defense are highly dependent on advanced composite materials. Increasingly there is a greater demand for materials with expanded functionality. The state of the art includes a wide range of responsive composites capable of impressive structural feats such as externally triggered shape morphing. Here a different composite concept is presented, one in which a portion of the constituent materials feed off of ambient energy and dynamically couple to convert it to mechanical motion in a cooperative, biomimetic fashion. Using a recently developed self-oscillating gel based on gelatin and the oscillating Belousov–Zhabotinsky (BZ) reaction, a technique is demonstrated for producing continuous patterned heterogeneous BZ hydrogel composites capable of sustained autonomic function. The coupling between two adjacent reactive patches is demonstrated in an autonomic cantilever actuator which converts chemical energy into amplified mechanical motion. The design of heterogeneous BZ gels for motion using a basic finite element model is discussed. This work represents notable progress toward developing internally responsive, bio-inspired composite materials for constructing modular autonomic morphing structures and devices.

Autonomic systems in biology, such as the circulatory system, function independently without an external stimulus. Materials that mimic this behavior hold promise for energy and medical technologies in the form of sensors, energy conversion units, and versatile micrometer scale machinery. Self-oscillating hydrogels driven by the Belousov–Zhabotinsky (BZ) reaction are one class of autonomic materials that convert chemical energy to mechanical swell–deswell motion. Effective feedback control techniques, as well as materials and processing options, are key challenges in making these materials technologically relevant. To address these challenges we have expanded BZ hydrogel materials options, by utilizing a flexible water-based succinimide–amine coupling reaction for functionalizing bio- and synthetic polymers containing primary amines for use in BZ devices. Herein we characterize the chemomechanical behavior of homogeneous BZ gelatin gels and determine the range of periods and strains attainable. We highlig...

Acute myeloid leukaemia (AML) is one of the most common haematological malignancies and is increasing in frequency due to an ageing population. Whilst remission will be achieved in up to 80% of those receiving intensive chemotherapy, the main variables precluding cure are the treatment-related mortality and relapse rates. Decisions on intensification, de-escalation and allografting rely on the ability to divide an apparently homogeneous group according to risk. A wide range of clinical, cytogenetic and molecular variables may be used to inform this task. Cytogenetic and molecular characterisation has already identified subgroups, such as acute promyelocytic leukaemia (APL) with t(15;17)/PML-RARA and AML with FLT3 mutation for which targeted therapies are available, and further molecularly defined groups who may be potential candidates for this approach are likely to be identified in the future. This review examines the range of established clinical and diagnostic parameters that should be used in assessing prognosis for a patient with AML and looks ahead to an expanding repertoire of potential variables that are currently under evaluation.

While Sen has written extensively on the social factors of capabilities, the exact nature of these social factors and how they interact to form and influence capabilities is contested and unclear. Consequently, how to coherently integrate social components into capability research remains a concern for those attempting to put the capability approach to practical use. This paper proposes one approach to understanding and integrating the social nature of capabilities. Building upon two recent contributions by Martins, we argue that underpinning Sen’s notion of capabilities is an ontological conception of a relational society. In this perspective, an individual’s capabilities emerge from the combination and interaction of individual‐level capacities and the individual’s relative position vis‐a‐vis social structures that provide reasons and resources for particular behaviors. Crucially, this conception of society is predicated upon a contextual notion of causality that is flexible enough to incorpora...

Elastic rod models provide a means to interpret single molecule DNA experiments as well as predict DNA behavior under physiological conditions. Here we use an elastic rod model to predict the stability boundary (critical torque vs. applied tension) for single molecule DNA experiments in which the molecule is subjected to applied tension and twist. We discuss the shortcomings of the usual isotropic rod model. We then derive a consistent non-linear material law from the general representation for a hemitropic (chiral) rod. Finally, we present results of a standard bifurcation analysis predicting the stability boundary. We find results from the non-linear hemitropic rod to match the data closely.

Health is a serious development issue. The perceived link between health and development has been articulated in much of the policy and academic literature resulting in many initiatives to introduce integrated health information systems at the local level. Despite huge investments made in this direction, these systems have not made any radical impact on the delivery of healthcare for local communities. Drawing on empirical work in Tanzania, we argue that this has been because of the adoption of a narrow, managerialist perspective of “integration”. We propose instead an interpretation of integration from a variety of standpoints; development studies, management, and sociology. According to this approach, it is not just data that is integrated, but ways of working and the social relations which support the health information systems at global, national and local levels. In our discussion section, we broaden the scope of integrated health information systems to consider the integration of not just management information but also epidemiological data.

Fisetin (3,3',4',7-tetrahydroxyflavone), a flavonoid found in a number of fruits and vegetables, has diverse biological activities, including cytotoxic effects on cancer cells. In this study, we investigated the effect of fisetin on triple-negative breast cancer (TNBC) cells. TNBC has a poorer prognosis than other types of breast cancer and treatment options for this disease are limited. Fisetin inhibited the growth of MDA-MB-468 and MDA-MB-231 TNBC cells, as well as their ability to form colonies, without substantially affecting the growth of non-malignant cells. In addition, fisetin inhibited the growth of estrogen receptor-bearing MCF-7 breast cancer cells and human epidermal growth factor receptor 2-overexpressing SK-BR-3 breast cancer cells. Fisetin inhibited TNBC cell division and induced apoptosis, which was associated with mitochondrial membrane permeabilization and the activation of caspase-9 and caspase-8, as well as the cleavage of poly(ADP-ribose) polymerase-1. Induction of caspase-dependent apoptosis by fisetin was confirmed by reduced killing of TNBC cells in the presence of the pan-caspase inhibitors Z-VAD-FMK and BOC-D-FMK. Decreased phosphorylation of histone H3 at serine 10 in fisetin-treated TNBC cells at G2/M phase of the cell cycle suggested that fisetin-induced apoptosis was the result of Aurora B kinase inhibition. Interestingly, the cytotoxic effect of cisplatin, 5-fluorouracil, and 4-hydroxycyclophosphamide metabolite of cyclophosphamide on TNBC cells was increased in the presence of fisetin. These findings suggest that further investigation of fisetin is warranted for possible use in the management of TNBC. J. Cell. Biochem. 117: 1913-1925, 2016. © 2016 Wiley Periodicals, Inc.