Rethinking constructed action

We aim to demonstrate the importance of defining linguistic phenomena by using constructed action or CA (i.e. a stretch of discourse that represents one role or combination of roles depicting actions, utterances, thought, attitudes and/or feelings of one or more referents) as an example. The problem is that different assumptions about CA have led to some apparent contradictions about the nature of this phenomenon. Based on observations and analyses of the British Sign Language narrative data, we outline criteria and recommendations for defining and analysing CA. We show that, in carefully defining the phenomenon in question and providing criteria for its identification, applying these criteria to usage data leads to emergence of particular types of Constructed Action. We also show how identifying these types can help resolve some of the apparent contradictions in the literature

Predicate structures, gesture, and simultaneity in the representation of action in British Sign Language: evidence from deaf children and adults.

British Sign Language (BSL) signers use a variety of structures, such as constructed action (CA), depicting constructions (DCs), or lexical verbs, to represent action and other verbal meanings. This study examines the use of these verbal predicate structures and their gestural counterparts, both separately and simultaneously, in narratives by deaf children with various levels of exposure to BSL (ages 5;1 to 7;5) and deaf adult native BSL signers. Results reveal that all groups used the same types of predicative structures, including children with minimal BSL exposure. However, adults used CA, DCs, and/or lexical signs simultaneously more frequently than children. These results suggest that simultaneous use of CA with lexical and depicting predicates is more complex than the use of these predicate structures alone and thus may take deaf children more time to master

Propagation Failure in Excitable Media

We study a mechanism of pulse propagation failure in excitable media where stable traveling pulse solutions appear via a subcritical pitchfork bifurcation. The bifurcation plays a key role in that mechanism. Small perturbations, externally applied or from internal instabilities, may cause pulse propagation failure (wave breakup) provided the system is close enough to the bifurcation point. We derive relations showing how the pitchfork bifurcation is unfolded by weak curvature or advective field perturbations and use them to demonstrate wave breakup. We suggest that the recent observations of wave breakup in the Belousov-Zhabotinsky reaction induced either by an electric field or a transverse instability are manifestations of this mechanism.Comment: 8 pages. Aric Hagberg: http://cnls.lanl.gov/~aric; Ehud Meron:http://www.bgu.ac.il/BIDR/research/staff/meron.htm

Beyond the marrow:insights from comprehensive next-generation sequencing of extramedullary multiple myeloma tumors

Extramedullary multiple myeloma (EMM) is an aggressive form of multiple myeloma (MM). This study represents the most comprehensive next-generation sequencing analysis of EMM tumors (N = 14) to date, uncovering key molecular features and describing the tumor microenvironment. We observed the co-occurrence of 1q21 gain/amplification and MAPK pathway mutations in 79% of EMM samples, suggesting that these are crucial mutational events in EMM development. We also demonstrated that patients with mutated KRAS and 1q21 gain/amplification at the time of diagnosis have a significantly higher risk of EMM development (HR = 2.4, p = 0.011) using data from a large CoMMpass dataset. We identified downregulation of CXCR4 and enhanced cell proliferation, along with reduced expression of therapeutic targets (CD38, SLAMF7, GPRC5D, FCRH5), potentially explaining diminished efficacy of immunotherapy. Conversely, we identified significantly upregulated EZH2 and CD70 as potential future therapeutic options. For the first time, we report on the tumor microenvironment of EMM, revealing CD8+ T cells and NK cells as predominant immune effector cells using single-cell sequencing. Finally, this is the first longitudinal study in EMM revealing the molecular changes from the time of diagnosis to EMM relapse.</p

The SsgA-like proteins in actinomycetes: small proteins up to a big task

Several unique protein families have been identified that play a role in the control of developmental cell division in streptomycetes. The SsgA-like proteins or SALPs, of which streptomycetes typically have at least five paralogues, control specific steps of sporulation-specific cell division in streptomycetes, affecting cell wall-related events such as septum localization and synthesis, thickening of the spore wall and autolytic spore separation. The expression level of SsgA, the best studied SALP, has a rather dramatic effect on septation and on hyphal morphology, which is not only of relevance for our understanding of (developmental) cell division but has also been succesfully applied in industrial fermentation, to improve growth and production of filamentous actinomycetes. Recent observations suggest that SsgB most likely is the archetypal SALP, with only SsgB orthologues occurring in all morphologically complex actinomycetes. Here we review 10 years of research on the SsgA-like proteins in actinomycetes and discuss the most interesting regulatory, functional, phylogenetic and applied aspects of this relatively unknown protein family

Receptor Tyrosine Kinases Activate Canonical WNT/β-Catenin Signaling via MAP Kinase/LRP6 Pathway and Direct β-Catenin Phosphorylation

Receptor tyrosine kinase signaling cooperates with WNT/β-catenin signaling in regulating many biological processes, but the mechanisms of their interaction remain poorly defined. We describe a potent activation of WNT/β-catenin by FGFR2, FGFR3, EGFR and TRKA kinases, which is independent of the PI3K/AKT pathway. Instead, this phenotype depends on ERK MAP kinase-mediated phosphorylation of WNT co-receptor LRP6 at Ser1490 and Thr1572 during its Golgi network-based maturation process. This phosphorylation dramatically increases the cellular response to WNT. Moreover, FGFR2, FGFR3, EGFR and TRKA directly phosphorylate β-catenin at Tyr142, which is known to increase cytoplasmic β-catenin concentration via release of β-catenin from membranous cadherin complexes. We conclude that signaling via ERK/LRP6 pathway and direct β-catenin phosphorylation at Tyr142 represent two mechanisms used by various receptor tyrosine kinase systems to activate canonical WNT signaling

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Evaluation of Sub-National Population Projections: a Case Study for London and the Thames Valley

Sub-national population projections help allocate national funding to local areas for planning local services. For example, water utilities prepare plans to meet future water demand over long-term horizons. Future demand depends on projected populations and households and forecasts of per household and per capita domestic water consumption in supply zones. This paper reports on population projections prepared for a water utility, Thames Water, which supplies water to over nine million people in London and the Thames Valley. Thames Water required an evaluation of the accuracy of the delivered projections against alternatives and estimates of uncertainty. The paper reviews how such evaluations have been made by researchers. The factors leading to variation in sub-national projections are identified. The methods, assumptions and results for English sub-national areas, used in five sets of projections, are compared. There is a consensus across projections about the future fertility and mortality but varying views about the future impact of internal and international migration flows. However, the greatest differences were between projections using ethnic populations. and those using homogeneous populations. Areas with high populations of ethnic minorities were projected to grow faster when an ethnic-specific model was used. This result is important for assessing projections for countries housing diverse populations with different demographic profiles. Historic empirical prediction intervals are used to assess the uncertainty of the London and the Thames Valley projections. By 2101 the preferred projection suggests that the population of the Thames Water region will have grown by 85% within an 80% empirical prediction interval between 45 and 125%

Diminishing benefits of urban living for children and adolescents’ growth and development

Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income&nbsp;countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was &lt;1.1 kg m–2 in the vast majority of&nbsp;countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified