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Both transposition of the great arteries (TGA) previously submitted to a Senning/Mustard procedure and congenitally corrected TGA (cc-TGA) have the systemic circulation supported by the morphological right ventricle, thereby rendering these patients to heart failure events risk. The aim of this study was to evaluate cardiopulmonary exercise test parameters for stratifying the risk of heart failure events in TGA patients.
Retrospective evaluation of adult TGA patients with systemic circulation supported by the morphological right ventricle submitted to cardiopulmonary exercise test in a tertiary centre. Patients were followed up for at least 1 year for the primary endpoint of cardiac death or heart failure hospitalisation. Several cardiopulmonary exercise test parameters were analysed as potential predictors of the combined endpoint and their predictive power were compared (area under the curve).
Cardiopulmonary exercise test was performed in 44 TGA patients (8 cc-TGA), with a mean age of 35.1 ± 8.4 years. The primary endpoint was reached by 10 (22.7%) patients, with a mean follow-up of 36.7 ± 26.8 months. Heart rate at anaerobic threshold had the highest area under the curve value (0.864), followed by peak oxygen consumption (pVO2) (0.838). Heart rate at anaerobic threshold ≤95 bpm and pVO2 ≤20 ml/kg/min had a sensitivity of 87.5 and 80.0% and a specificity of 82.4 and 76.5%, respectively, for the primary outcome.
Heart rate at anaerobic threshold ≤95 bpm had the highest predictive power of all cardiopulmonary exercise test parameters analysed for heart failure events in TGA patients with systemic circulation supported by the morphological right ventricle.
Litter breakdown is an important ecological process at the bottom of food webs in streams. Previous studies have been based only on a temporal interval of a single season, thus ignoring seasonal variation in litter input and community structure. We investigated organic matter input in a Brazilian savanna stream and the influence of its associated hyphomycetes on the invertebrate community. Organic matter input was sampled monthly and the leaves submitted to decomposition experiments. There were lower breakdown rates and higher invertebrate species richness and abundance during the dry season, which reached their maximum in July due to low stream discharge. Invertebrate composition was best explained by hyphomycetes (mainly by Flagellospora curvula and Anguillospora filiformis). Hyphomycetes have the capacity to degrade complex compounds of litter and to rapidly absorb nutrients by growing branched filaments, thus making the leaves more favourable for consumption by invertebrates. Shredder abundance was negatively related to litter richness, indicating possible species-specific relationships. We observed a sequential process with increased leaf litter input promoting an increase in hyphomycetes biomass, which in turn favoured invertebrate density.
Southern crabgrass [Digitaria ciliaris (Retz.) Koeler] is an annual grass weed that commonly infests turfgrass, roadsides, wastelands and cropping systems throughout the southeastern United States. Two biotypes of D. ciliaris (R1 and R2) with known resistance to cyclohexanediones (DIMs) and aryloxyphenoxypropionates (FOPs) previously collected from sod production fields in Georgia were compared to a separate susceptible biotype (S) collected from Alabama for the responses to pinoxaden and to explore the possible mechanisms of resistance. Increasing rates of pinoxaden (0.1 to 23.5 kg ha-1) were evaluated for control of R1, R2 and S. The resistant biotypes, R1 and R2 were resistant to pinoxaden relative to S. The S biotype was completely controlled at rates 11.8 and 23.5 kg ha-1, resulting in no aboveground biomass at 14 DAT. Pinoxaden rates at which tiller length and above-ground biomass would be reduced 50% (I50) and 90% (I90) for R1, R2 and S ranged from 7.2 to 13.2 kg ha-1, 6.9 to 8.6 kg ha-1 and 0.7 to 2.1 kg ha-1, respectively for tiller length and 7.7 to 10.2 kg ha-1, 7.2 to 7.9 kg ha-1 and 1.6 to 2.3 kg ha-1, respectively for above-ground biomass. Prior selection pressure from DIMs and FOPs herbicides could result in the evolution of D. ciliaris cross-resistance to pinoxaden herbicide. Amplification of the carboxyl-transferase domain of the plastidic ACCase by standard PCR identified a point mutation resulting in an Ile-1781-Leu amino acid substitution only for the resistant biotype, R1. Further cloning of PCR product surrounding the 1781 region yielded two distinct ACCase gene sequences such as Ile-1781 and Leu-1781. The amino acid substitution, Ile-1781-Leu in both resistant biotypes (R1 and R2), however, was revealed by next-generation sequencing (NGS) of RNA using Illumina platform. A point mutation in Ile-1781 codon leading to herbicide insensitivity in ACCase enzyme has been previously reported in other grass species. Our research confirms that Ile-1781-Leu is present in pinoxaden-resistant D. ciliaris.
Human embryo studies have proposed the use of additional morphological evaluations related to the moment of the first cell divisions as relevant to embryo viability. Nevertheless, there are still not enough data available related to morphokinetic analysis and its relationship with lipid composition in embryos. Therefore, the aim of this study was to address the lipid profile of bovine embryos with different developmental kinetics: fast (four or more cells) and slow (two or three cells) at 40 h post-insemination (hpi), at three time points of in vitro culture (40, 112 and 186 hpi) and compare these to profiles of in vivo embryos. The lipid profiles of embryos were analyzed by matrix-assisted laser desorption ionization mass spectrometry, which mainly detected pools of membrane lipids such as phosphatidylcholine and sphingomyelin. In addition to their structural function, these lipid classes have an important role in cell signalling, particularly regarding events such as stress and pregnancy. Different patterns of lipids in the fast and slow groups were revealed in all the analyzed stages. Also, differences between in vitro embryos were more pronounced at 112 hpi, a critical moment due to embryonic genome activation. At the blastocyst stage, in vitro-produced embryos, despite the kinetics, had a closer lipid profile when compared with in vivo blastocysts. In conclusion, the kinetics of development had a greater effect on the membrane lipid profiles throughout the embryo culture, especially at the 8–16-cell stage. The in vitro environment affects lipid composition and may compromise cell signalling and function in blastocysts.
Dignity therapy (DT) is well established in adult populations, and it is likely that it could benefit younger people. This study aimed to adapt the adult Portuguese DT question framework for adolescents (DT-QF-Adol) (ages 10–18).
Five stages were followed: (1) the Portuguese DT-QF for adults was adapted for adolescents with the original author's collaboration, (2) an expert committee provided feedback on the adapted version, (3) an initial consensus version of the DT-QF-Adol was created, (4) expert committee consult affirmed final consensus, and (5) validation stage with a sample of 17 adolescents followed in ambulatory psychology clinic.
DT's original author endorsed the final Portuguese DT-QF-Adol, reinforcing that it captures the fundamental dimensions of DT. There was 100% agreement on the final consensus version and defined age group (10–18 years old). Twenty adolescents were invited to participate, and 17 were included after informed consent was obtained; 53% were female. The average age was 12.7 years. The interviewed adolescents reported that the DT-QF-Adol was clear, and they did not identify any ambiguity or difficulty in answering any of the questions. They assumed that this information could positively affect the way parents and friends see and cared for them, permitting others to understand their concerns and preferences. Participants felt that the DT-QF-Adol could be a good starting point for a conversation with their loved ones. Although they did not consider vital for health professionals to access their answers, they strongly felt that the DT-QF-Adol might be essential to sick adolescents and they would recommend it to others.
Significance of results
We developed a DT-QF of nine questions for Portuguese adolescents (DT-QF-Adol), coined Protocolo de Perguntas da Terapia da Dignidade para Adolescentes — 10–18 anos. This tool can potentially be considered a good addition for pediatric palliative care.
Timely access to care services is crucial to support people with dementia and their family carers to live well. Carers of people with dementia (N = 390), recruited from eight countries, completed semi-structured interviews about their experiences of either accessing or not using formal care services over a 12-month period in the Access to Timely Formal Care (Actifcare) study. Participant responses were summarised using content analysis, categorised into clusters and frequencies were calculated. Less than half of the participants (42.3%) reported service use. Of those using services, 72.8 per cent reported timely access and of those not using services 67.2 per cent were satisfied with this situation. However, substantial minorities either reported access at the wrong time (27.2%), or feeling dissatisfied or mixed feelings about not accessing services (32.8%). Reasons for not using services included use not necessary yet, the carer provided support or refusal. Reasons given for using services included changes in the condition of the person with dementia, the service's ability to meet individual needs, not coping or the opportunity to access services arose. Facilitators and barriers to service use included whether participants experienced supportive professionals, the speed of the process, whether the general practitioner was helpful, participant's own proactive attitude and the quality of information received. To achieve timely support, simplified pathways to use of formal care services are needed.
Whereas the operation of forgetting has recently seen a considerable amount of attention in the context of Answer Set Programming (ASP), most of it has focused on theoretical aspects, leaving the practical issues largely untouched. Recent studies include results about what sets of properties operators should satisfy, as well as the abstract characterization of several operators and their theoretical limits. However, no concrete operators have been investigated.
In this paper, we address this issue by presenting the first concrete operator that satisfies strong persistence – a property that seems to best capture the essence of forgetting in the context of ASP – whenever this is possible, and many other important properties. The operator is syntactic, limiting the computation of the forgetting result to manipulating the rules in which the atoms to be forgotten occur, naturally yielding a forgetting result that is close to the original program.
The current drugs for Chagas disease treatment present several limitations
The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.
The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.
GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.
Considering a potential exercise-drug interaction, we investigated whether exercise training could improve the efficacy of specific antiparasitic chemotherapy in a rodent model of Chagas disease. Wistar rats were randomized into five groups: sedentary and uninfected (CT); sedentary and infected (SI); sedentary, infected and treated (SIT); trained and infected (TI); trained, infected and treated (TIT). After 9-weeks running training, the animals were infected with T. cruzi and followed up for 4 weeks, receiving 100 mg kg−1 day−1 benznidazole. No evidence of myocarditis was observed in CT animals. TI animals exhibited reduced parasitemia, myocarditis, and reactive tissue damage compared to SI animals, in addition to increased IFN-γ, IL-4, IL-10, heart non-protein antioxidant (NPA) levels and glutathione-s transferase activity (P < 0.05). The CT, SIT and TIT groups presented similar reductions in parasitemia, cytokines (IFN-γ, TNF-α, IL-4, IL-10, IL-17 and MCP-1), inflammatory infiltrate, oxidative heart damage and antioxidant enzymes activity compared to SI and TI animals, as well as reduced heart microstructural remodeling (P < 0.05). By modulating heart inflammation and redox metabolism, exercise training exerts a protective effect against T. cruzi infection in rats. However, the antiparasitic and cardioprotective effects of benznidazole chemotherapy are more pronounced, determining similar endpoints in sedentary and trained T. cruzi-infected rats.
We evaluated the effects of high-Ca fat-free milk v. low-Ca control diet on adiposity and on glycaemic control. Fourteen subjects with type 2 diabetes (aged 49·5 (sd 8·6) years, BMI 29·4 (sd 4·5) kg/m2, low habitual Ca consumption (<600 mg/d)) were included in this randomised, crossover clinical trial. Subjects participated in two 12-week experimental sessions (high-Ca fat-free milk (HC) or low-Ca control (LC)) separated by 8-week washout. Subjects daily consumed in the laboratory a breakfast shake containing 700 mg (HC) or 6·4 mg (LC) of Ca. Energy-restricted diets containing 800 mg of dietary Ca/d were prescribed. Dietary records data indicated the consumption of 1200 mg of Ca/d during HC and of 525 mg of Ca/d during LC. There was a greater reduction in body weight, body fat mass, waist circumference and waist:hip ratio after HC. Serum 25-hydoxyvitamin D and homeostatic model assessment-2 β-cell function (HOMA2-%B) increased, and serum uric acid, parathormone (PTH) and glycated Hb (HbA1c) concentrations reduced after HC. In addition, changes from baseline in terms of serum uric acid, glucose, HbA1c and PTH concentrations were lower, and those of HOMA2-%B, serum Ca and 25-hydoxyvitamin D were higher after the HC than after LC. The consumption of approximately three servings of fat-free milk and 1200 mg of dietary Ca/d enhanced weight loss, improved body composition and promoted glycaemic control in subjects with type 2 diabetes and low habitual Ca consumption (<600 mg/d).
Multidisciplinary agile teams working in fast paced, delivery-oriented sprint cycles of two weeks can experience moments of stuckness. Typically, these moments can be characterised by the inability to continue, which can be quite detrimental in agile settings, where time is pressured. This paper aims to explore these moments of stuckness, to understand when and why they occur and to understand the different strategies Scrum teams use to overcome them, both on a personal as well as team level. A combination of interviews and observations were conducted with six Scrum team members and two experts to understand their process and experiences while working in an agile set up. We have identified five strategies, which strongly rely on agile values of collaboration, communication, and creativity. These are: looking for expert guidance, open communication, creating spike stories, visual communication and incubation. The findings from this study provide both practice and academia with a deeper understanding into how can creativity be supported in agile settings.
In their early years of education, design students may experience difficulties in reframing design problems. Since reframing is linked to creativity, this may be problematic. While there are some models available to describe the reframing process, it is yet unclear how they are supporting design students. This study concerned the development and test of a framing model based on co-evolution transitions, through a two-part study: interviews with expert designers and workshops followed by group interviews with novices. The resulting model offers a way of thinking and a way of working, based on the fluidity of the design process. This study yielded two major insights. Firstly, students tend to perceive the problem space to be fixed once they defined it, even if they discovered disparate information along the way. Secondly, the developed model provides students with guidance and confidence in dealing with complex problems. Our results have a considerable impact on design education, as it is important to reinforce to design students that both the problem and solution understanding are fluid, and this model provides initial steps to help designers structuring their process.
The problems of today are increasingly complex in nature. Yet, most support provided by design agencies and innovation consultancies is based on unstructured approaches, guided by the facilitators own intuition. This article presents the Teckel canvas, an approach to guide problem reframing in facilitation to both tackle solution and problem understanding. After synthesising the main insights from prominent reframing methods and models, a meta-process of reframing was created, which was translated into a practical canvas. Two Dutch case studies are examined in which the proposed reframing canvas is tested. When this canvas was used in facilitation, we found out that the medium and message can be reframed separately or together and that the canvas can be used as a tool for overview on the subject. Our findings indicate that an explicit and tangible use of reframing can improve solving complex problems to be more clear, visual and reflective.
In this paper on designing organizational processes, we combine insight on reflection-in-action with the role of reflection and experimenting from the organizational routine dynamics literature. Illustrated through a case at a strategy consultancy, we show how a prototyped workshop can elicit reflection-in- action when designing organizational processes. The artifacts used in the prototyped workshop made previous implicit assumptions about the work more explicit. This led to on the spot reflection-in-action of how to improve the prototype. This shows how collective reflection-action can be created by creating a space for reflection, that simultaneously allows for experimentation. Future research between design science and organizational science would thus be fruitful when studying the role of collective reflection- in-action when prototyping organizational processes.
Framing is a crucial skill for connecting problem and solution spaces in the creative design process, both for individuals and teams. Frames are implicit in individuals’ cognitive thinking, but the creation of shared frames plays a vital role in collaborative design. Many studies have attempted to describe the framing process, but little is still known about how to support designers in framing, specifically in teams. This paper addresses this gap, by exploring the connection between sketching and framing within interdisciplinary teams. Following a qualitative and explorative approach, we have investigated the process and outcome of five interdisciplinary teams. We identified that sketching assists in the creation and elaboration of frames. Furthermore, in tandem with discussion and reflection, sketching helps increase the chance of a frame to survive within the design process. Our findings have practical and educational implications for improving the creative design process in interdisciplinary teams.
There is no suitable vaccine against human visceral leishmaniasis (VL) and available drugs are toxic and/or present high cost. In this context, diagnostic tools should be improved for clinical management and epidemiological evaluation of disease. However, the variable sensitivity and/or specificity of the used antigens are limitations, showing the necessity to identify new molecules to be tested in a more sensitive and specific serology. In the present study, an immunoproteomics approach was performed in Leishmania infantum promastigotes and amastigotes employing sera samples from VL patients. Aiming to avoid undesired cross-reactivity in the serological assays, sera from Chagas disease patients and healthy subjects living in the endemic region of disease were also used in immunoblottings. The most reactive spots for VL samples were selected, and 29 and 21 proteins were identified in the promastigote and amastigote extracts, respectively. Two of them, endonuclease III and GTP-binding protein, were cloned, expressed, purified and tested in ELISA experiments against a large serological panel, and results showed high sensitivity and specificity values for the diagnosis of disease. In conclusion, the identified proteins could be considered in future studies as candidate antigens for the serodiagnosis of human VL.
For parasites in natural systems, the most common pattern of spatial distribution is aggregation among hosts. The main causes of such aggregation are variable exposure of hosts to parasites and heterogeneity in host susceptibility. The objective of this study was to determine if there are differences in the aggregation pattern of two species of ectoparasitic flies between the Pantanal and Cerrado regions of Brazil on the bat Artibeus planirostris. We collected the ectoparasites from bats captured between 2002 and 2017 with mist nets in 21 sites in the Pantanal and 15 sites in the surrounding plateaus. The results showed that the aggregation of ectoparasitic flies in Pantanal was more pronounced than in Cerrado. The discrepancy aggregation index (D) of the bat fly Megistopoda aranea was 0.877 in Pantanal and 0.724 in Cerrado. The D values of Aspidoptera phyllostomatis was even higher, with 0.916 and 0.848 in the Pantanal and Cerrado, respectively. Differences in the shelters used may be the main factor shaping variation in aggregation, since the Pantanal does not have rock formations, with only foliage, crowns and hollow tree trunks. These differences likely affect host exposure to the parasites, leading to an increase in parasite aggregation.