798 research outputs found
Effects of dietary fibre and the provision of a foraging substrate on the welfare of sows in different grouping systems
End of project reportThere are no clear guidelines on how best to meet the EU legislative requirement (Council Directive 2001/88/EC) that pregnant sows and gilts should be provided with sufficient amounts of bulky or high fibre diets and high energy food to satisfy hunger and the motivation to chew. Therefore the aim of this project was to investigate the effect of increasing dietary fibre levels and providing access to a foraging substrate on the welfare of sows housed in dynamic and static groups. To achieve this a review paper was compiled and three experiments were conducted.
The aim of the review paper was to assess the effectiveness of increasing dietary fibre levels on the welfare of pregnant sows. Previous research found that increasing dietary fibre levels decrease activity levels and the performance of stereotypic behaviour, and increase resting behaviour. However, high fibre diets do not appear to reduce aggression between group-housed pregnant sows. The research clearly showed that the effectiveness of high fibre diets is influenced by the source of fibre, with soluble fibres being more effective in reducing stereotypic behaviours than insoluble fibres. However the optimum fibrous ingredient, or combination of ingredients, and the optimum dietary inclusion rate for these ingredients remains unclear
Does visual perceptual testing correlate with caregiver and teacher reported functional visual skill difficulties in school-aged children? Considerations for practice
Purpose - As occupational therapists embrace evidence-informed and occupation-centred practice, the use of standardised visual perceptual tests remains a strong feature of typical paediatric practice. Yet, the research evidence for the use of such tools is inconclusive at best. This study compared the results of the Test of Visual Perceptual Skills (TVPS) with a checklist of reported functional difficulties in 30 children attending occupational therapy. The purpose of this paper was to determine the usefulness of visual perceptual testing in relation to occupation-centred practice. Design/methodology/approach - A descriptive correlational study design was used. Participants were 30 primary school-age children who were on a paediatric occupational therapy caseload. An additional 30 typically developing children participated in the development of the checklist. Findings - Correlations were found between reported functional visual skill difficulties and two subtests of the TVPS (visual memory and visual discrimination). No correlation was found between the reported functional difficulties and any of the other five subtests of the TVPS or the total score. Originality/value - Results highlight the weak relationship that existed in this study between standardised measures of visual perception, as measured by the TVPS, and functional difficulties. Therapists are cautioned to explore both the evidence base for continued use of standardised visual perceptual measures to inform occupation-centred practice and the need to embrace a more comprehensive person-centred approach to visual perceptual assessment
Influence of water models on water movement through AQP1
Water diffusion through membrane proteins is a key aspect of cellular
function. Essential processes of cellular metabolism are driven by osmotic
pressure, which depends on water channels. Membrane proteins such as aquaporins
(AQPs) are responsible for enabling water transport through the cell membrane.
AQPs are highly selective, allowing only water and relatively small polar
molecules to cross the membrane. Experimentally, estimation of water flux
through membrane proteins is still a challenge, and hence accurate simulations
of water transport are of particular importance. We present a numerical study
of water diffusion through AQP1 comparing three water models: TIP3P, OPC and
TIP4P/2005. Bulk diffusion, diffusion permeability and osmotic permeability are
computed and compared among all models. The results show that there are
significant differences between TIP3P (a particularly widespread model for
simulations of biological systems), and the more recently developed TIP4P/2005
and OPC models. We demonstrate that OPC and TIP4P/2005 reproduce protein-water
interactions and dynamics in excellent agreement with experimental data. From
this study, we find that the choice of the water model has a significant effect
on the computed water dynamics as well as its molecular behaviour within a
biological nanopore
Effect of water models on transmembrane self-assembled cyclic peptide nanotubes
Self-assembling cyclic peptide nanotubes can form nanopores when they are inserted in lipid bilayers, acting as ion and/or water permeable channels. In order to improve the versatility of these systems, it is possible to specifically design cyclic peptides with a combination of natural and non-natural amino acids, enabling the control of the nature of the inner cavity of the channels. Here, the behavior of two types of self-assembling peptide motifs, alternating Îą-amino acids with Îł- or δ-aminocycloalkanecarboxylic acids, is studied via molecular dynamics (MD) simulations. The behavior of water molecules in nanopores is expected to affect the properties of these channels and therefore merits detailed examination. A number of water models commonly used in MD simulations have been validated by how well they reproduce bulk water properties. However, it is less clear how these water models behave in the nanoconfined condition inside a channel. The behavior of four different water modelsâTIP3P, TIP4P, TIP4P/2005, and OPCâare evaluated in MD simulations of self-assembled cyclic peptide nanotubes of distinct composition and diameter. The dynamic behavior of the water molecules and ions in these designed artificial channels depends subtly on the water model used. TIP3P water molecules move faster than those of TIP4P, TIP4P/2005, and OPC. This demeanor is clearly observed in the filling of the nanotube, in water diffusion within the pore, and in the number and stability of hydrogen bonds of the peptides with water. It was also shown that the water model influences the simulated ion flux through the nanotubes, with TIP3P producing the greatest ion flux. Additionally, the two more recent models, TIP4P/2005 and OPC, which are known to reproduce the experimental self-diffusion coefficient of bulk water quite well, exhibit very similar results under the nanoconfined conditions studied here. Because none of these models have been parametrized specifically for waters confined in peptide nanotubes, this study provides a point of reference for further validationThis work was supported by the Spanish Agencia Estatal de InvestigaciĂłn (AEI) and the ERDF (CTQ2016-78423-R, PID2019-111126RB-100, and RTI2018-098795-A-I00) and by the Xunta de Galicia and the ERDF (ED431F 2020/05, ED431C 2017/25, and Centro singular de investigaciĂłn de Galicia accreditation 2016-2019, ED431G/09). M.C. thanks Xunta de Galicia for a predoctoral fellowship (ED481A-2017/068). R.G.-F. thanks Ministerio de Ciencia, InnovaciĂłn y Universidades for a RamĂłn y Cajal contract (RYC-2016- 20335). Research in MSPSâs group is supported by EPSRC (EP/R004722/1; EP/V010948/1) BBSRC (BB/R00126X/1) and Wellcome Trust (208361/Z/17/Z)S
Prediction of pyrazinamide resistance in Mycobacterium tuberculosis using structure-based machine learning approaches
Background
Pyrazinamide is one of four first-line antibiotics used to treat tuberculosis; however, antibiotic susceptibility testing for pyrazinamide is challenging. Resistance to pyrazinamide is primarily driven by genetic variation in pncA, encoding an enzyme that converts pyrazinamide into its active form.
Methods
We curated a dataset of 664 non-redundant, missense amino acid mutations in PncA with associated high-confidence phenotypes from published studies and then trained three different machine-learning models to predict pyrazinamide resistance. All models had access to a range of protein structural-, chemical- and sequence-based features.
Results
The best model, a gradient-boosted decision tree, achieved a sensitivity of 80.2% and a specificity of 76.9% on the hold-out test dataset. The clinical performance of the models was then estimated by predicting the binary pyrazinamide resistance phenotype of 4027 samples harbouring 367 unique missense mutations in pncA derived from 24â231 clinical isolates.
Conclusions
This work demonstrates how machine learning can enhance the sensitivity/specificity of pyrazinamide resistance prediction in genetics-based clinical microbiology workflows, highlights novel mutations for future biochemical investigation, and is a proof of concept for using this approach in other drugs
A double ovulation protocol for Xenopus laevis produces doubled fertilisation yield and moderately transiently elevated corticosterone levels without loss of egg quality
The African claw-toed frog, Xenopus laevis, is a well-established laboratory model for the biology of vertebrate oogenesis, fertilisation, and development at embryonic, larval, and metamorphic stages. For ovulation, X. laevis females are usually injected with chorionic gonadotropin, whereupon they lay typically hundreds to thousands of eggs in a day. After being rested for a minimum of three months, animals are re-used. The literature suggests that adult females can lay much larger numbers of eggs in a short period. Here, we compared the standard âsingle ovulationâ protocol with a âdouble ovulationâ protocol, in which females were ovulated, then re-ovulated after seven days and then rested for three months before re-use. We quantified egg number, fertilisation rate (development to cleavage stage), and corticosterone secretion rate as a measure of stress response for the two protocol groups over seven 3-month cycles. We found no differences in egg number-per-ovulation or egg quality between the groups and no long-term changes in any measures over the 21-month trial period. Corticosterone secretion was elevated by ovulation, similarly for the single ovulation as for the first ovulation in the double-ovulation protocol, but more highly for the second ovulation (to a level comparable to that seen following shipment) in the latter. However, both groups exhibited the same baseline secretion rates by the time of the subsequent cycle. Double ovulation is thus transiently more stressful/demanding than single ovulation but within the levels routinely experienced by laboratory X. laevis. Noting that âstress hormoneâ corticosterone/cortisol secretion is linked to physiological processes, such as ovulation, that are not necessarily harmful to the individual, we suggest that the benefits of a doubling in egg yield-per-cycle per animal without loss of egg quality or signs of acute or long-term harm may outweigh the relatively modest and transient corticosterone elevation we observed. The double ovulation protocol therefore represents a potential new standard practice for promoting the â3Rsâ (animal use reduction, refinement and replacement) mission for Xenopus research
Arithmetic Expression Construction
When can given numbers be combined using arithmetic operators from a
given subset of to obtain a given target number? We
study three variations of this problem of Arithmetic Expression Construction:
when the expression (1) is unconstrained; (2) has a specified pattern of
parentheses and operators (and only the numbers need to be assigned to blanks);
or (3) must match a specified ordering of the numbers (but the operators and
parenthesization are free). For each of these variants, and many of the subsets
of , we prove the problem NP-complete, sometimes in the
weak sense and sometimes in the strong sense. Most of these proofs make use of
a "rational function framework" which proves equivalence of these problems for
values in rational functions with values in positive integers.Comment: 36 pages, 5 figures. Full version of paper accepted to 31st
International Symposium on Algorithms and Computation (ISAAC 2020
Variation in suspected cancer referral pathways in primary care: comparative analysis across the International Benchmarking Cancer Partnership
Background
International variations in cancer outcomes
persist and may be influenced by differences
in the accessibility and organisation of cancer
patient pathways. More evidence is needed
to understand to what extent variations in the
structure of primary care referral pathways for
cancer investigation contribute to differences in
the timeliness of diagnoses and cancer outcomes
in different countries.
Aim
To explore the variation in primary care referral
pathways for the management of suspected
cancer across different countries.
Design and setting
Descriptive comparative analysis using mixed
methods across the International Cancer
Benchmarking Partnership (ICBP) countries.
Method
Schematics of primary care referral pathways
were developed across 10 ICBP jurisdictions. The
schematics were initially developed using the
Aarhus statement (a resource providing greater
insight and precision into early cancer diagnosis
research) and were further supplemented with
expert insights through consulting leading experts
in primary care and cancer, existing ICBP data,
a focused review of existing evidence on the
management of suspected cancer, published
primary care cancer guidelines, and evaluations of
referral tools and initiatives in primary care.
Results
Referral pathway schematics for 10 ICBP
jurisdictions were presented alongside a
descriptive comparison of the organisation
of primary care management of suspected
cancer. Several key areas of variation across
countries were identified: inflexibility of
referral pathways, lack of a managed route for
non-âspecific symptoms, primary care practitioner
decision-âmaking autonomy, direct access to
investigations, and use of emergency routes.
Conclusion
Analysing the differences in referral processes can
prompt further research to better understand the
impact of variation on the timeliness of diagnoses
and cancer outcomes. Studying these schematics
in local contexts may help to identify opportunities
to improve care and facilitate discussions on what
may constitute best referral practice
Variation in suspected cancer referral pathways in primary care:comparative analysis across the International Benchmarking Cancer Partnership
BACKGROUND: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries. AIM: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries. DESIGN AND SETTING: Descriptive comparative analysis using mixed methods across the International Cancer Benchmarking Partnership (ICBP) countries. METHOD: Schematics of primary care referral pathways were developed across 10 ICBP jurisdictions. The schematics were initially developed using the Aarhus statement (a resource providing greater insight and precision into early cancer diagnosis research) and were further supplemented with expert insights through consulting leading experts in primary care and cancer, existing ICBP data, a focused review of existing evidence on the management of suspected cancer, published primary care cancer guidelines, and evaluations of referral tools and initiatives in primary care. RESULTS: Referral pathway schematics for 10 ICBP jurisdictions were presented alongside a descriptive comparison of the organisation of primary care management of suspected cancer. Several key areas of variation across countries were identified: inflexibility of referral pathways, lack of a managed route for non-specific symptoms, primary care practitioner decision-making autonomy, direct access to investigations, and use of emergency routes. CONCLUSION: Analysing the differences in referral processes can prompt further research to better understand the impact of variation on the timeliness of diagnoses and cancer outcomes. Studying these schematics in local contexts may help to identify opportunities to improve care and facilitate discussions on what may constitute best referral practice
- âŚ