258 research outputs found
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Public Policy and Saving for Retirement: The "Autosave" Features of the Pension Protection Act of 2006
Economic
A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro
The human skin barrier, a biological imperative, is impaired in inflammatory skin diseases such as atopic dermatitis (AD). Staphylococcus aureus is associated with AD lesions and contributes to pathological inflammation and further barrier impairment. S. aureus secretes extracellular proteases, such as V8 (or 'SspA'), which cleave extracellular proteins to reduce skin barrier. Previous studies demonstrated that the host defence peptide human beta-defensin 2 (HBD2) prevented V8-mediated damage. Here, the mechanism of HBD2-mediated barrier protection in vitro is examined. Application of exogenous HBD2 provided protection against V8, irrespective of timeline of application or native peptide folding, raising the prospect of simple peptide analogues as therapeutics. HBD2 treatment, in context of V8-mediated damage, modulated the proteomic/secretomic profiles of HaCaT cells, altering levels of specific extracellular matrix proteins, potentially recovering V8 damage. However, HBD2 alone did not substantially modulate cellular proteomic/secretomics profiles in the absence of damage, suggesting possible therapeutic targeting of lesion damage sites only. HBD2 did not show any direct protease inhibition or induce expression of known antiproteases, did not alter keratinocyte migration or proliferation, or form protective nanonet structures. These data validate the barrier-protective properties of HBD2 in vitro and establish key protein datasets for further targeted mechanistic analyses.</p
A mechanistic evaluation of human beta defensin 2 mediated protection of human skin barrier in vitro
Probing quintessence: reconstruction and parameter estimation from supernovae
We explore the prospects for using future supernova observations to probe the
dark energy. We focus on quintessence, an evolving scalar field that has been
suggested as a candidate for the dark energy. After simulating the observations
that would be expected from the proposed SuperNova / Acceleration Probe
satellite (SNAP), we investigate two methods for extracting information about
quintessence from such data. First, by expanding the quintessence equation of
state as w_Q(z) = w_Q(0)-alpha*ln(1+z), to fit the data, it is possible to
reconstruct the quintessence potential for a wide range of smoothly varying
potentials. Second, it will be possible, to test the basic properties of the
dark energy by constraining the parameters Omega_Q, w_Q and alpha. We show that
it may be possible, for example, to distinguish between quintessence and the
cosmological constant in this way. Further, when supernova data are combined
with other planned cosmological observations, the precision of reconstructions
and parameter constraints is significantly improved, allowing a wider range of
dark energy models to be distinguished.Comment: Added references, corrected citations. Final version to appear in
MNRAS. 13 pages, 14 figures. Uses bibTe
Lymphatic clearance of the brain: perivascular, paravascular and significance for neurodegenerative diseases
The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (A?). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimerâs disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that A? is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of A? in the glia limitans in Alzheimerâs disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of A?. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance
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
Letter to the Editor. Phase III randomized controlled trials are essential to properly evaluate the role of radiotherapy in WHO grade II meningioma
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
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