Newcastle disease (ND) is a notifiable disease affecting chickens and other avian species caused by virulent strains of Avian paramyxovirus type 1 (APMV-1). While outbreaks of ND can have devastating consequences, avirulent strains of APMV-1 generally cause subclinical infections or mild disease. However, viruses can cause different levels of disease in different species and virulence can evolve following cross-species transmission events. This report describes the detection of three cases of avirulent APMV-1 infection in Great Britain (GB). Case 1 emerged from the ‘testing to exclude’ scheme in chickens in Shropshire while cases 2 and 3 were made directly from notifiable avian disease investigations in chicken broilers in Herefordshire and on premises in Wiltshire containing ducks and mixed species, respectively). Class II/genotype I.1.1 APMV-1 from case 1 shared 99.94% identity to the Queensland V4 strain of APMV-1. Class II/genotype II APMV-1 was detected from case 2 while the class II/genotype I.2 virus from case 3 aligned closely with strains isolated from Anseriformes. Exclusion of ND through rapid detection of avirulent APMV-1 is important where clinical signs caused by avirulent or virulent APMV-1s could be ambiguous. Understanding the diversity of APMV-1s circulating in GB is critical to understanding disease threat from these adaptable viruses.

A semigroup S is said to be right pseudo-finite if the universal right congruence can be generated by a finite set $U\subseteq S\times S$, and there is a bound on the length of derivations for an arbitrary pair $(s,t)\in S\times S$ as a consequence of those in U. This article explores the existence and nature of a minimal ideal in a right pseudo-finite semigroup. Continuing the theme started in an earlier work by Dandan et al., we show that in several natural classes of monoids, right pseudo-finiteness implies the existence of a completely simple minimal ideal. This is the case for orthodox monoids, completely regular monoids, and right reversible monoids, which include all commutative monoids. We also show that certain other conditions imply the existence of a minimal ideal, which need not be completely simple; notably, this is the case for semigroups in which one of the Green’s preorders ${\leq _{\mathcal {L}}}$ or ${\leq _{\mathcal {J}}}$ is left compatible with multiplication. Finally, we establish a number of examples of pseudo-finite monoids without a minimal ideal. We develop an explicit construction that yields such examples with additional desired properties, for instance, regularity or ${\mathcal {J}}$-triviality.

University students have long played an important role in latin american politics. Preceding by several decades the first signs of youthful protest in the United States, student activism in Latin America has been persistent and often decisive. For example, student groups were instrumental in the overthrow of regimes in Cuba (1933, 1959), Guatemala (1944), Venezuela (1958), and Bolivia (1964). At one time or another, virtually every governing strongman in the region has had to contend with varying opposition from student groups. Indeed, as Robert Alexander has noted, “in the past four decades they have constituted one of the most important pressure groups in twenty republics.”

The Hierarchical Taxonomy of Psychopathology (HiTOP) has emerged out of the quantitative approach to psychiatric nosology. This approach identifies psychopathology constructs based on patterns of co-variation among signs and symptoms. The initial HiTOP model, which was published in 2017, is based on a large literature that spans decades of research. HiTOP is a living model that undergoes revision as new data become available. Here we discuss advantages and practical considerations of using this system in psychiatric practice and research. We especially highlight limitations of HiTOP and ongoing efforts to address them. We describe differences and similarities between HiTOP and existing diagnostic systems. Next, we review the types of evidence that informed development of HiTOP, including populations in which it has been studied and data on its validity. The paper also describes how HiTOP can facilitate research on genetic and environmental causes of psychopathology as well as the search for neurobiologic mechanisms and novel treatments. Furthermore, we consider implications for public health programs and prevention of mental disorders. We also review data on clinical utility and illustrate clinical application of HiTOP. Importantly, the model is based on measures and practices that are already used widely in clinical settings. HiTOP offers a way to organize and formalize these techniques. This model already can contribute to progress in psychiatry and complement traditional nosologies. Moreover, HiTOP seeks to facilitate research on linkages between phenotypes and biological processes, which may enable construction of a system that encompasses both biomarkers and precise clinical description.

ABSTRACT IMPACT: This work will help to understand a novel therapeutic approach to a common type of acute myeloid leukemia. OBJECTIVES/GOALS: FMS-like tyrosine kinase 3 (or FLT3) mutations occur in ˜30% of acute myeloid leukemia (AML) cases. FLT3 tyrosine kinase domain (TKD) mutations are particularly important in relapsed/refractory FLT3 mutant AML, which portends poor prognosis. This study describes a therapeutic approach to overcoming resistance conferred by FLT3-TKD mutations. METHODS/STUDY POPULATION: To understand the efficacy of a novel type 1 FLT3 inhibitor (NCGC1481), as a monotherapy and combination therapy, several assays were utilized to interrogate functionality of these therapies. Cell lines and patient samples containing aspartate 835 to tyrosine mutations (D835Y, the most common TKD alteration) and phenylalanine 691 to leucine (F691L) were utilized to examine the effects of NCGC1481 with and without other targeted therapies like MEK inhibitors. Specifically, assays measuring viability, cell death using flow cytometry, in vitro clonogenicity, cellular signaling, and xenograft survival were examined in these FLT3-TKD AML models. Synergy was also measured using well described methods, which also allowed for appropriate dose finding for drug combination experiments. RESULTS/ANTICIPATED RESULTS: Our novel type 1 FLT3 inhibitor (NCGC1481) was particularly effective in the most common FLT3 TKD mutant, D835Y. NCGC1481 reduced viability and cell signaling, while also inducing cell death and prolonging xenograft survival in the FLT3-D835Y model system. In contrast, clinically approved FLT3 inhibitors were less effective at suppressing AML cells expressing FLT3-D835Y. In the case of FLT3-F691L, most of the FLT3 inhibitors tested, including NCGC1481, suppressed canonical FLT3 signaling, but did not significantly reduce viability or leukemic clonogenicity. However, when NCGC1481 was combined with other targeted agents like MEK inhibitors, at synergistic doses, eradication of the FLT3-F691L AML clone was substantially increased. DISCUSSION/SIGNIFICANCE OF FINDINGS: In AML, response to FLT3 inhibitor therapy is often short-lived, with resistance sometimes occurring via FLT3-TKD mutations. Given the dismal prognosis of relapsed FLT3 mutant AML, novel therapies are necessary. This study describes efficacy of a novel FLT3 inhibitor, along with its synergistic activity when combined with other targeted agents.

Mass asymptomatic SARS-CoV-2 nucleic acid amplified testing of healthcare personnel (HCP) was performed at a large tertiary health system. A low period-prevalence of positive HCP was observed. Of those who tested positive, half had mild symptoms in retrospect. HCP with even mild symptoms should be isolated and tested.

Exercise has many health benefits for individuals with Type 1 Diabetes (T1D), however it carries the risk of hypoglycaemia. Research has indicated that intermittent high intensity exercise reduces this risk compared to steady state exercise, potentially via a greater anaerobic component inducing increased lactate and catecholamine response.Six physically active males aged 23 ± 5 years, BMI 24.9 ± 1.8 kg•m-2, Vo2 max 47.9 ± 10.1 ml•kg-1•min-1 diagnosed with Type 1 Diabetes for 9 ± 3 years and a HbA1c concentration of 8.6 ± 0.3% participated in a randomised counterbalanced trial. Participants exercised for 60 min on a cycle ergometer on two occasions separated by 7 days, which consisted of a moderate continuous steady state exercise session at 40% o2 max (CONT), or the same exercise intensity interspersed with 7 s high intensity sprints at 100% Vo2 max every 2 min (INT). Blood glucose concentration was assessed via capillary blood sampling every 10 min during exercise and at regular intervals in the 60 min post exercise (Accu-Chek Aviva, Roche, UK). Additional metabolic measures such as blood lactate concentration and carbohydrate oxidation rates were assessed during exercise. Participants ingested small quantities of a carbohydrate drink, if required, to avoid hypoglycaemia during exercise. Magnitude based inferences were used to compare the two exercise trials and Effect Sizes (ES) calculated using Cohen's d and results presented as mean ± SD.Average blood glucose concentration was lower on the INT trial compared to CONT during both the exercise phase (8.9 ± 1.7 mmol•l-1 vs 7.1 ± 1.1 mmol•l-1; ES 0.55) and the 60 min post-exercise recovery phase (8.1 ± 1.9 mmol•l-1 vs 7.0 ± 1.8 mmol•l-1; ES 0.56). Carbohydrate oxidation was greater on the INT trial compared to CONT (1.9 ± 1.4 g•min-1 vs 1.5 ± 0.6 g•min-1; ES 0.35). Capillary blood lactate concentration was markedly elevated on INT when compared to CONT (5.0 ± 1.4 mmol•l-1 vs 2.4 ± 1.1 mmol•l-1; ES 2.48). Carbohydrate ingestion during exercise was 13 ± 11 g and differed little between trials (ES 0.18).Despite greater anaerobic metabolic response, the addition of intermittent high intensity sprints to 60 min steady-state cycle exercise resulted in greater declines in blood glucose concentration during the exercise and post-exercise period, potentially by inhibition of the counter regulatory hormone response expected on the INT trial. These results would indicate that additional exogenous carbohydrate ingestion may be required for individuals with T1D when intermittent sprints are added to prolonged continuous exercise.

In the 2015 review paper ‘Petawatt Class Lasers Worldwide’ a comprehensive overview of the current status of high-power facilities of ${>}200~\text{TW}$ was presented. This was largely based on facility specifications, with some description of their uses, for instance in fundamental ultra-high-intensity interactions, secondary source generation, and inertial confinement fusion (ICF). With the 2018 Nobel Prize in Physics being awarded to Professors Donna Strickland and Gerard Mourou for the development of the technique of chirped pulse amplification (CPA), which made these lasers possible, we celebrate by providing a comprehensive update of the current status of ultra-high-power lasers and demonstrate how the technology has developed. We are now in the era of multi-petawatt facilities coming online, with 100 PW lasers being proposed and even under construction. In addition to this there is a pull towards development of industrial and multi-disciplinary applications, which demands much higher repetition rates, delivering high-average powers with higher efficiencies and the use of alternative wavelengths: mid-IR facilities. So apart from a comprehensive update of the current global status, we want to look at what technologies are to be deployed to get to these new regimes, and some of the critical issues facing their development.