Enteric nervous system development in avian and zebrafish models

AbstractOur current understanding of the developmental biology of the enteric nervous system (ENS) and the genesis of ENS diseases is founded almost entirely on studies using model systems. Although genetic studies in the mouse have been at the forefront of this field over the last 20 years or so, historically it was the easy accessibility of the chick embryo for experimental manipulations that allowed the first descriptions of the neural crest origins of the ENS in the 1950s. More recently, studies in the chick and other non-mammalian model systems, notably zebrafish, have continued to advance our understanding of the basic biology of ENS development, with each animal model providing unique experimental advantages. Here we review the basic biology of ENS development in chick and zebrafish, highlighting conserved and unique features, and emphasising novel contributions to our general understanding of ENS development due to technical or biological features

Continuous-wave Raman laser pumped within a semiconductor disk laser cavity

A KGd(WO4)(2) Raman laser was pumped within the cavity of a cw diode-pumped InGaAs semiconductor disk laser (SDL). The Raman laser threshold was reached for 5: 6W of absorbed diode pump power, and output power up to 0.8W at 1143nm, with optical conversion efficiency of 7.5% with respect to the absorbed diode pump power, was demonstrated. Tuning the SDL resulted in tuning of the Raman laser output between 1133 and 1157nm

Identifying features associated with higher-quality hospital care and shorter length of admission for people with dementia : a mixed-methods study

Background: Concerns have repeatedly been expressed about the quality of inpatient care that people with dementia receive. Policies and practices have been introduced that aim to improve this, but their impact is unclear. Aims: To identify which aspects of the organisation and delivery of acute inpatient services for people with dementia are associated with higher-quality care and shorter length of stay. Design: Mixed-methods study combining a secondary analysis of data from the third National Audit of Dementia (2016/17) and a nested qualitative exploration of the context, mechanism and outcomes of acute care for people with dementia. Setting: Quantitative data from 200 general hospitals in England and Wales and qualitative data from six general hospitals in England that were purposively selected based on their performance in the audit. Participants: Quantitative data from clinical records of 10,106 people with dementia who had an admission to hospital lasting ≥ 72 hours and 4688 carers who took part in a cross-sectional survey of carer experience. Qualitative data from interviews with 56 hospital staff and seven carers of people with dementia. Main outcome measures: Length of stay, quality of assessment and carer-rated experience. Results: People with dementia spent less time in hospital when discharge planning was initiated within 24 hours of admission. This is a challenging task when patients have complex needs, and requires named staff to take responsibility for co-ordinating the discharge and effective systems for escalating concerns when obstacles arise. When trust boards review delayed discharges, they can identify recurring problems and work with local stakeholders to try to resolve them. Carers of people with dementia play an important role in helping to ensure that hospital staff are aware of patient needs. When carers are present on the ward, they can reassure patients and help make sure that they eat and drink well, and adhere to treatment and care plans. Clear communication between staff and family carers can help ensure that they have realistic expectations about what the hospital staff can and cannot provide. Dementia-specific training can promote the delivery of person-centred care when it is made available to a wide range of staff and accompanied by ‘hands-on’ support from senior staff. Limitations: The quantitative component of this research relied on audit data of variable quality. We relied on carers of people with dementia to explore aspects of service quality, rather than directly interviewing people with dementia. Conclusions: If effective support is provided by senior managers, appropriately trained staff can work with carers of people with dementia to help ensure that patients receive timely and person-centred treatment, and that the amount of time they spend in hospital is minimised. Future work: Future research could examine new ways to work with carers to co-produce aspects of inpatient care, and to explore the relationship between ethnicity and quality of care in patients with dementia. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 8, No. 22. See the NIHR Journals Library website for further project information

1.6 W continuous-wave Raman laser using low-loss synthetic diamond

Low-birefringence (Δn<2x10−6), low-loss (absorption coefficient <0.006cm−1 at 1064nm), single-crystal, synthetic diamond has been exploited in a CW Raman laser. The diamond Raman laser was intracavity pumped within a Nd:YVO4 laser. At the Raman laser wavelength of 1240nm, CW output powers of 1.6W and a slope efficiency with respect to the absorbed diode-laser pump power (at 808nm) of ~18% were measured. In quasi-CW operation, maximum on-time output powers of 2.8W (slope efficiency ~24%) were observed, resulting in an absorbed diode-laser pump power to the Raman laser output power conversion efficiency of 13%

Identification of a selective G1-phase benzimidazolone inhibitor by a senescence-targeted virtual screen using artificial neural networks

Cellular senescence is a barrier to tumorigenesis in normal cells and tumour cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. 147 virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase (SA-β-gal) assays. Among the found hits a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced SA-β-gal activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1 and CDC25C. Additionally, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long term treatments. Preliminary structure-activity and structure clustering analyses are reported and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells

Case-control study of the association between kava use and pneumonia in eastern Arnhem Land Aboriginal communities (Northern Territory, Australia)

Pneumonia causes significant morbidity and mortality in Aboriginal populations in Australia\u27s Northern Territory (NT). Kava, consumed in Arnhem Land since 1982, may be a risk factor for infectious disease including pneumonia. A case-control study (n=115 cases; n=415 controls) was conducted in 7001 Aboriginal people (4217 over 15 years). Odds ratios (OR) were calculated by conditional logistic regression with substance use and social factors as confounders. Pneumonia, vas not associated with kava use. Crude OR=1.26 (0.74-2.14, P=0.386), increased after controlling for confounders (OR=1.98, 0.63-6.23, P=0.237) but was not significant. Adjusted OR for pneumonia cases involving kava and alcohol users was 1.19 (0.39-3.62, P=0.756). In communities with longer kava-using histories, adjusted OR was 2.19 (0.67-7.14, P=0.187). There was no kava dose-response relationship. Crude ORs for associations between pneumonia and cannabis use (OR=2.27, 1.18-4.37, P=0.014) and alcohol use (OR=1.95, 1.07-3.53, P=0.026) were statistically significant and approached significance for petrol sniffing (OR=1.98, 0.99-3.95, P=0.056)

A second-generation ligand for the enantioselective rhodium-catalyzed addition of arylboronic acids to alkenylazaarenes

A 2,4,6-trialkylanilide-containing chiral diene has been identified as a superior ligand for the enantioselective rhodiumcatalyzed arylation of alkenylazaarenes with arylboronic acids

A timeband framework for modelling real-time systems

Complex real-time systems must integrate physical processes with digital control, human operation and organisational structures. New scientific foundations are required for specifying, designing and implementing these systems. One key challenge is to cope with the wide range of time scales and dynamics inherent in such systems. To exploit the unique properties of time, with the aim of producing more dependable computer-based systems, it is desirable to explicitly identify distinct time bands in which the system is situated. Such a framework enables the temporal properties and associated dynamic behaviour of existing systems to be described and the requirements for new or modified systems to be specified. A system model based on a finite set of distinct time bands is motivated and developed in this paper

The inherent instability of leveed seafloor channels

New analytical models demonstrate that under 2 aggradational flow conditions seafloor channel-levee systems are inherently unstable; both channel area and stability necessarily decrease at long timescales. In time such systems must avulse purely through internal (autogenic) forcing. Although autogenic instabilities likely arise over long enough time for additional allogenic forcing to be expected, channel-levee sensitivity to variations in flow character depends on the prior degree of system evolution. Recalibrated modern Amazon Fan avulsion timings are consistent with this model, challenging accepted interpretations of avulsion triggering