Draft Genome Sequences of Strains of Pasteurella multocida Isolated from the United Kingdom and the United States

Pasteurella multocida is a major pathogen of farm animals and has worldwide distribution. Here we report the draft genome sequences of four strains that were isolated from animals in the United Kingdom and the United States and represent pathogenic and commensal presentation of the bacterium

Incidence of childhood CNS tumours in Britain and variation in rates by definition of malignant behaviour: population-based study.

BACKGROUND: Intracranial and intraspinal tumours are the most numerous solid tumours in children. Some recently defined subtypes are relatively frequent in childhood. Many cancer registries routinely ascertain CNS tumours of all behaviours, while others only cover malignant neoplasms. Some behaviour codes have changed between revisions of the International Classification of Diseases for Oncology, including pilocytic astrocytoma, downgraded to uncertain behaviour in ICD-O-3. METHODS: We used data from the population-based National Registry of Childhood Tumours, which routinely included non-malignant CNS tumours, to document the occurrence of CNS tumours among children aged < 15 years in Great Britain during 2001-2010 and to document the descriptive epidemiology of childhood CNS tumours over the 40-year period 1971-2010, during which several new entities were accommodated in successive editions of the WHO Classification and revisions of ICD-O. Eligible cases were all those with a diagnosis included in Groups III (CNS tumours) and Xa (CNS germ-cell tumours) of the International Classification of Childhood Cancer, Third Edition. The population at risk was derived from annual mid-year estimates by sex and single year of age compiled by the Office for National Statistics and its predecessors. Incidence rates were calculated for age groups 0, 1-4, 5-9 and 10-14 years, and age-standardised rates were calculated using the weights of the world standard population. RESULTS: Age-standardised incidence in 2001-10 was 40.1 per million. Astrocytomas accounted for 41%, embryonal tumours for 17%, other gliomas for 10%, ependymomas for 7%, rarer subtypes for 20% and unspecified tumours for 5%. Incidence of tumours classified as malignant and non-malignant by ICD-O-3 increased by 30 and 137% respectively between 1971-75 and 2006-10. CONCLUSIONS: Total incidence was similar to that in other large western countries. Deficits of some, predominantly low-grade, tumours or differences in their age distribution compared with the United States and Nordic countries are compatible with delayed diagnosis. Complete registration regardless of tumour behaviour is essential for assessing burden of disease and changes over time. This is particularly important for pilocytic astrocytoma, because of its recent downgrading to non-malignant and time trends in the proportion of astrocytomas with specified subtype

Systems-level discovery of quality attributes and candidate pathways for optimized production of human pluripotent stem cell-derived cardiomyocytes

Numerous protocols exist for differentiation of human pluripotent stem cells (hPSCs) to cardiomyocytes (CMs). Although these methods have improved in efficiency over the past decade, they remain highly variable in their resultant purities, not only among different source hPSC lines but also between batches in the same cell line. This substantial heterogeneity of hPSC-CM product outcomes points to poorly-understood, highly sensitive, and uncontrolled variables present within the overall process. Herein, we have undertaken a multi-omic discovery approach to identify key temporal differences in cell attributes between high- and low-purity hPSC-CM differentiations to provide systems-level insights into underlying mechanisms which drive these populations to divergent endpoints. Specifically, we are combining metabolomic, proteomic, lipidomic, and transcriptomic analyses collected throughout the differentiation process for high- and low-purity (as assessed by %cTnT+ via flow cytometry) differentiation batches. In addition to gaining fundamental insights into the underlying biology of the differentiation process, we are extending our analyses to 1) identify putative critical quality attributes for use in on- or at-line analytics for continuous process monitoring, 2) enhance process robustness through the development of protocols aimed at depressing off-target pathways and enhancing on-target ones, and 3) establish potential feedforward/feedback control schemes based on real-time analytics to respond to in-process intermediate quality attributes through rational adjustment of process parameters. To date we have identified novel putative candidate quality attributes for process monitoring and cellular pathways which may be able to be modulated to augment process robustness in a scaled manufacturing context. Beyond standard single-omic analytical workflows, ongoing work is aimed at integrating these data for deepened insight, including functional integration with systems-scale modeling and high-dimensional machine-learning methodologies to extract dynamic relationships among variables over time

Determination of total IgE by ELISA in tubes and plates compared with PRIST

IgE was measured by ELISA in tubes and in microtiter plates, the results being compared with PRIST data. The recommended readings of the tube contents in a spectrophotometer (SPM) were compared with results using a multi-channel photometer (MCP).Geometric mean values (International Units) and standard deviations of 44 normal sera examined by the 3 different methods were: PRIST 16.2 [plus-or-minus sign] 4.0; SPM 15.6 [plus-or-minus sign] 4.9 and MCP 18.4 [plus-or-minus sign] 4.4. Correlation coefficients were: PRIST-SPM r = 0.98; PRIST-MCP r = 0.98; and SPM-MCP r = 0.97. Intra- and inter-assay coefficients of variation were smaller for MCP than for SPM. In addition, reading in microtiter plates was much faster, while having little effect on sensitivity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/23961/1/0000210.pd

Can biological quantum networks solve NP-hard problems?

There is a widespread view that the human brain is so complex that it cannot be efficiently simulated by universal Turing machines. During the last decades the question has therefore been raised whether we need to consider quantum effects to explain the imagined cognitive power of a conscious mind. This paper presents a personal view of several fields of philosophy and computational neurobiology in an attempt to suggest a realistic picture of how the brain might work as a basis for perception, consciousness and cognition. The purpose is to be able to identify and evaluate instances where quantum effects might play a significant role in cognitive processes. Not surprisingly, the conclusion is that quantum-enhanced cognition and intelligence are very unlikely to be found in biological brains. Quantum effects may certainly influence the functionality of various components and signalling pathways at the molecular level in the brain network, like ion ports, synapses, sensors, and enzymes. This might evidently influence the functionality of some nodes and perhaps even the overall intelligence of the brain network, but hardly give it any dramatically enhanced functionality. So, the conclusion is that biological quantum networks can only approximately solve small instances of NP-hard problems. On the other hand, artificial intelligence and machine learning implemented in complex dynamical systems based on genuine quantum networks can certainly be expected to show enhanced performance and quantum advantage compared with classical networks. Nevertheless, even quantum networks can only be expected to efficiently solve NP-hard problems approximately. In the end it is a question of precision - Nature is approximate.Comment: 38 page

Ontological transparency, (in)visibility, and hidden curricula:Critical pedagogy and contentious edtech

AbstractThe steady migration of higher education online has accelerated in the wake of Covid-19. The implications of this migration on critical praxis—the theory-in-practice of pedagogy—deserve further scrutiny. This paper explores how teacher and student-led educational technology research and development can help rethink online critical praxis. The paper is based on a recent research project at the University of Edinburgh that speculatively explored the potential for automation in teaching, which generated insights into current and future pedagogical practice among both teachers and students. From this project emerged a series of pedagogical positions that were centred around visions of the future of teaching in response to automation: the pedagogical potential of visibility and invisibility online, transparency, and interrogating the hidden curricula of both higher education and educational technology itself. Through the surfacing of these pedagogical positions, this paper explores how critical pedagogy can be built into the broader teacher function and begins to identify the institutional structures that could potentially impede or accelerate that process.</jats:p

In Defence of Modest Doxasticism About Delusions

Here I reply to the main points raised by the commentators on the arguments put forward in my Delusions and Other Irrational Beliefs (OUP, 2009). My response is aimed at defending a modest doxastic account of clinical delusions, and is articulated in three sections. First, I consider the view that delusions are in-between perceptual and doxastic states, defended by Jacob Hohwy and Vivek Rajan, and the view that delusions are failed attempts at believing or not-quite-beliefs, proposed by Eric Schwitzgebel and Maura Tumulty. Then, I address the relationship between the doxastic account of delusions and the role, nature, and prospects of folk psychology, which is discussed by Dominic Murphy, Keith Frankish, and Maura Tumulty in their contributions. In the final remarks, I turn to the continuity thesis and suggest that, although there are important differences between clinical delusions and non-pathological beliefs, these differences cannot be characterised satisfactorily in epistemic terms. \u

Response to novel objects and foraging tasks by common marmoset (Callithrix Jacchus) female Pairs

Many studies have shown that environmental enrichment can significantly improve the psychological well-being of captive primates, increasing the occurrence of explorative behavior and thus reducing boredom. The response of primates to enrichment devices may be affected by many factors such as species, sex, age, personality and social context. Environmental enrichment is particularly important for social primates living in unnatural social groupings (i.e. same-sex pairs or singly housed animals), who have very few, or no, benefits from the presence of social companions in addition to all the problems related to captivity (e.g. increased inactivity). This study analyses the effects of enrichment devices (i.e. novel objects and foraging tasks) on the behavior of common marmoset (Callithrix jacchus) female pairs, a species that usually lives in family groups. It aims to determine which aspects of an enrichment device are more likely to elicit explorative behaviors, and how aggressive and stress-related behaviors are affected by its presence. Overall, the marmosets explored foraging tasks significantly longer than novel objects. The type of object, which varied in size, shape and aural responsiveness (i.e. they made a noise when the monkey touched them), did not affect the response of the monkeys, but they explored objects that were placed higher in the enclosure more than those placed lower down.Younger monkeys were more attracted to the enrichment devices than the older ones. Finally, stress-related behavior (i.e. scratching) significantly decreased when the monkeys were presented with the objects; aggressive behavior as unaffected. This study supports the importance of environmental enrichment for captive primates and shows that in marmosets its effectiveness strongly depends upon the height of the device in the enclosure and the presence of hidden food. The findings can be explained ifone considers the foraging behavior of wild common marmosets. Broader applications for the research findings are suggested in relation to enrichment

The Challenge for Innovation in Direct Restorative Materials

During the past 50 years, a series of key UN conferences have established a framework to minimize human health risks from environmental exposures to key chemicals. In January 2013, more than 140 countries agreed to the text of new treaty to minimize Hg effects on the environment (the Minamata Convention). Dental caries is omnipresent around the globe, affecting 60% to 90% of school children and most adults, and producing discomfort that affects quality of life. Dental amalgam is frequently used to treat carious lesions and its use releases mercury into the environment. The best way to avoid the use of dental amalgam is to emphasize caries prevention. Alternatives to amalgam are suitable in some applications, but no replacement for amalgam has been found for large posterior restorations. For any restorative material, safety and environmental impacts are part of clinical risk assessment. Safety is freedom from unacceptable risks. Risk is a combination of probability of exposure and severity of harm. Best management practices are crucial to manage dental amalgam, but these impose additional that are disproportionately more for developing countries. The Minamata Convention seeks a phase-out of all mercury-based products except dental amalgam, where a phase-down is the present goal. For dentistry, the most important focus is the promotion of caries prevention and research on new materials