304 research outputs found
Reversible adsorption on a random site surface
We examine the reversible adsorption of hard spheres on a random site surface
in which the adsorption sites are uniformly and randomly distributed on a
plane. Each site can be occupied by one solute provided that the nearest
occupied site is at least one diameter away. We use a numerical method to
obtain the adsorption isotherm, i.e. the number of adsorbed particles as a
function of the bulk activity. The maximum coverage is obtained in the limit of
infinite activity and is known exactly in the limits of low and high site
density. An approximate theory for the adsorption isotherms, valid at low site
density, is developed by using a cluster expansion of the grand canonical
partition function. This requires as input the number of clusters of adsorption
site of a given size. The theory is accurate for the entire range of activity
as long as the site density is less than about 0.3 sites per particle area. We
also discuss a connection between this model and the vertex cover problem.Comment: 16 pages, 10 figure
Transient, unsettling and creative space: Experiences of liminality through the accounts of Chinese students on a UK-based MBA
This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ The Author(s) 2009.This article explores the experiences of liminality through the accounts of Chinese students on a UK-based MBA programme. The transient nature of the MBA experience, as well as the international status of the Chinese student, is resonant with conceptualizations of liminality as ‘in between’ space. Based on semi-structured interviews with 20 MBA graduates who had subsequently returned to China with their qualification, we explored their perceptions of outcomes from the course and their experiences as international students on a programme imbued with western norms and values. Results support the unsettling yet creative implications of liminality, as well as the fragmented insecure nature of identities, as individuals pass through the MBA ‘rite of passage’ in terms of ‘becoming’ a manager and entering a new phase of career. Accounts suggest the creation of hierarchical structures within liminal space whereby Chinese students, through their positioning at the margin, have uncomfortable yet illuminating encounters with alterity. At the same time, they experience levels of ambiguity and uncertainty in the post-liminal phase of China-located employments, as new western-based managerial identities collide with dominant discourses of Chinese organization
Concomitant CIS on TURBT does not impact oncological outcomes in patients treated with neoadjuvant or induction chemotherapy followed by radical cystectomy
© Springer-Verlag GmbH Germany, part of Springer Nature 2018Background: Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle invasive bladder cancer improves all-cause and cancer specific survival. We aimed to evaluate whether the detection of carcinoma in situ (CIS) at the time of initial transurethral resection of bladder tumor (TURBT) has an oncological impact on the response to NAC prior to radical cystectomy. Patients and methods: Patients were identified retrospectively from 19 centers who received at least three cycles of NAC or induction chemotherapy for cT2-T4aN0-3M0 urothelial carcinoma of the bladder followed by radical cystectomy between 2000 and 2013. The primary and secondary outcomes were pathological response and overall survival, respectively. Multivariable analysis was performed to determine the independent predictive value of CIS on these outcomes. Results: Of 1213 patients included in the analysis, 21.8% had concomitant CIS. Baseline clinical and pathologic characteristics of the ‘CIS’ versus ‘no-CIS’ groups were similar. The pathological response did not differ between the two arms when response was defined as pT0N0 (17.9% with CIS vs 21.9% without CIS; p = 0.16) which may indicate that patients with CIS may be less sensitive to NAC or ≤ pT1N0 (42.8% with CIS vs 37.8% without CIS; p = 0.15). On Cox regression model for overall survival for the cN0 cohort, the presence of CIS was not associated with survival (HR 0.86 (95% CI 0.63–1.18; p = 0.35). The presence of LVI (HR 1.41, 95% CI 1.01–1.96; p = 0.04), hydronephrosis (HR 1.63, 95% CI 1.23–2.16; p = 0.001) and use of chemotherapy other than ddMVAC (HR 0.57, 95% CI 0.34–0.94; p = 0.03) were associated with shorter overall survival. For the whole cohort, the presence of CIS was also not associated with survival (HR 1.05 (95% CI 0.82–1.35; p = 0.70). Conclusion: In this multicenter, real-world cohort, CIS status at TURBT did not affect pathologic response to neoadjuvant or induction chemotherapy. This study is limited by its retrospective nature as well as variability in chemotherapy regimens and surveillance regimens.Peer reviewedFinal Accepted Versio
Evaluation of live attenuated Streptococcus pneumoniae vaccine strains on the epithelial response to colonisation using a human challenge model
Background: Streptococcus pneumoniae frequently colonises
the human nasopharynx but causes over 500,000 deaths each year
from Pneumonia, Sepsis and Meningitis. Nasopharyngeal carriage
is required for transmission and is a pre-requisite for disease.
The conjugate polysaccharide vaccines have proven effective in
decreasing disease. However, replacement of vaccine serotypes
with non-vaccine types in carriage threatens the future of the vaccines’
efficiency.
Using an Experimental Human Pneumococcal Challenge model
(EHPC) and epithelial cell culture models, we have previously
shown that pneumococcal colonisation involves both direct epithelial
association and micro-invasion, inducing innate immunity and
clearance without overt disease. Repeated challenge in the EHPC
with the same strain decreases subsequent carriage efficiency and
diminishes transmission potential and/or progression to disease,
suggesting active mucosal immunity in the nasopharynx.
Methods and materials: We have generated live attenuated
strains of 6B S. pneumoniae (AS1 and AS2) that have double virulence
deletions and cannot revert to cause disease. Here, we have
explored the hypothesis that despite their attenuation in a mouse
model of disease, these attenuated strains retain their ability to
invade the epithelium and induce epithelial-derived innate immunity
in humans.
Colonisation were measured by confocal microscopy and microbiology
density by CFU counts. Epithelial activation was measured
by flow cytometry, ELISA and RNAseq.
Results: We found that both mutants colonised the human
nasopharynx and formed epithelial associations with microinvasion
in the EHPC model. In vitro, both mutants adhered, invaded
and transmigrated across the epithelium 4-fold less than wild type.
However, both mutants still resulted in secretion of IL-8, IL-6 and
ICAM-1 secretion and barrier integrity was maintained. PCA analyses
revealed that epithelial transcriptomic responses between wild
type and the mutants generally overlapped, indicating overall similar
stimulation of signaling pathways following exposure.
Conclusion: The results reveal that attenuation of these pneumococcal
strains has not led to loss of their ability to elicit amucosal
immune/inflammatory response. This approach provides an exciting
new pipeline for the development and testing of novel vaccines.
The application of these attenuated strains in the EHPC also has the
potential to provide important new knowledge on the mechanisms
behind bacterial clearance, transmission and disease progression
during colonisation
An exploratory cluster randomised controlled trial of knowledge translation strategies to support evidence-informed decision-making in local governments (The KT4LG study)
Background: Childhood overweight and obesity is the most prevalent and, arguably, politically complex child health problem internationally. Governments, communities and industry have important roles to play, and are increasingly expected to deliver an evidence-informed system-wide prevention program. However, efforts are impeded by a lack of organisational access to and use of research evidence. This study aims to identify feasible, acceptable and ideally, effective knowledge translation (KT) strategies to increase evidence-informed decision making in local governments, within the context of childhood obesity prevention as a national policy priority.Methods/Design: This paper describes the methods for KT4LG, a cluster randomised controlled trial which is exploratory in nature, given the limited evidence base and methodological advances. KT4LG aims to examine a program of KT strategies to increase the use of research evidence in informing public health decisions in local governments. KT4LG will also assess the feasibility and acceptability of the intervention. The intervention program comprises a facilitated program of evidence awareness, access to tailored research evidence, critical appraisal skills development, networking and evidence summaries and will be compared to provision of evidence summaries alone in the control program. 28 local governments were randomised to intervention or control, using computer generated numbers, stratified by budget tertile (high, medium or low). Questionnaires will be used to measure impact, costs, and outcomes, and key informant interviews will be used to examine processes, feasibility, and experiences. Policy tracer studies will be included to examine impact of intervention on policies within relevant government policy documents.Discussion: Knowledge translation intervention studies with a focus on public health and prevention are very few in number. Thus, this study will provide essential data on the experience of program implementation and evaluation of a system-integrated intervention program employed within the local government public health context. Standardised programs of system, organisational and individual KT strategies have not been described or rigorously evaluated. As such, the findings will make a significant contribution to understanding whether a facilitated program of KT strategies hold promise for facilitating evidence-informed public health decision making within complex multisectoral government organisations.<br /
Infrared Properties of Cataclysmic Variables from 2MASS: Results from the 2nd Incremental Data Release
Because accretion-generated luminosity dominates the radiated energy of most
cataclysmic variables, they have been ``traditionally'' observed primarily at
short wavelengths. Infrared observations of cataclysmic variables contribute to
the understanding of key system components that are expected to radiate at
these wavelengths, such as the cool outer disk, accretion stream, and secondary
star. We have compiled the J, H, and Ks photometry of all cataclysmic variables
located in the sky coverage of the 2 Micron All Sky Survey (2MASS) 2nd
Incremental Data Release. This data comprises 251 systems with reliably
identified near-IR counterparts and S/N > 10 photometry in one or more of the
three near-IR bands.Comment: 2 pages, including 1 figure. To appear in the proceedings of The
Physics of Cataclysmic Variables and Related Objects, Goettingen, Germany.
For our followup ApJ paper (in press), also see
http://www.ctio.noao.edu/~hoard/research/2mass/index.htm
Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface
Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance
Cryptic Variation between Species and the Basis of Hybrid Performance
Studies on natural variation in gene expression and its phenotypic effects provide fresh insights into the origins of vigour and sterility in species hybrids
Dietary Supplements and Sports Performance: Introduction and Vitamins
Sports success is dependent primarily on genetic endowment in athletes with morphologic, psychologic, physiologic and metabolic traits specific to performance characteristics vital to their sport. Such genetically-endowed athletes must also receive optimal training to increase physical power, enhance mental strength, and provide a mechanical advantage. However, athletes often attempt to go beyond training and use substances and techniques, often referred to as ergogenics, in attempts to gain a competitive advantage. Pharmacological agents, such as anabolic steroids and amphetamines, have been used in the past, but such practices by athletes have led to the establishment of anti-doping legislation and effective testing protocols to help deter their use. Thus, many athletes have turned to various dietary strategies, including the use of various dietary supplements (sports supplements), which they presume to be effective, safe and legal
- …