97 research outputs found
Challenges to adaptation: a fundamental concept for the shared socio-economic pathways and beyond
The framework for the new scenarios being developed for climate research calls
for the development of a set of Shared Socioeconomic Pathways (SSPs), which are meant to
differ in terms of their challenges to mitigation and challenges to adaptation. In order for the
scenario process to fulfill its goals, the research and policy communities need to develop a
shared understanding of these concepts. This paper focuses on challenges to adaptation. We
begin by situating this new concept in the context of the rich literatures related to inter alia
adaptation, vulnerability, and resilience. We argue that a proper characterization of challenges to adaptation requires a rich, exploration of the concept, which goes beyond mere
description. This has a number of implications for the operationalization of the concept in
the basic and extended versions of the SSPs. First, the elements comprising challenges to
adaptation must include a wide range of socioeconomic and even some (non-climatic)
biophysical factors. Second, careful consideration must be given to differences in these
factors across scales, as well as cross-scale interactions. Third, any representation of the
concept will require both quantitative and qualitative elements. The scenario framework
offers the opportunity for the SSPs and full scenarios to be of greater value than has been the
case in past exercises to both Integrated Assessment Modeling (IAM) and Impacts,Adaptation, and Vulnerability (IAV) researchers, but this will require a renegotiation of the
traditional, primarily unidirectional relationship between the two communities
Inflammation Triggers Emergency Granulopoiesis through a Density-Dependent Feedback Mechanism
Normally, neutrophil pools are maintained by homeostatic mechanisms that require
the transcription factor C/EBPα. Inflammation, however, induces neutrophilia
through a distinct pathway of âemergencyâ granulopoiesis that is
dependent on C/EBPÎČ. Here, we show in mice that alum triggers emergency
granulopoiesis through the IL-1RI-dependent induction of G-CSF. G-CSF/G-CSF-R
neutralization impairs proliferative responses of hematopoietic stem and
progenitor cells (HSPC) to alum, but also abrogates the acute mobilization of BM
neutrophils, raising the possibility that HSPC responses to inflammation are an
indirect result of the exhaustion of BM neutrophil stores. The induction of
neutropenia, via depletion with Gr-1 mAb or myeloid-specific ablation of Mcl-1,
elicits G-CSF via an IL-1RI-independent pathway, stimulating granulopoietic
responses indistinguishable from those induced by adjuvant. Notably, C/EBPÎČ,
thought to be necessary for enhanced generative capacity of BM, is dispensable
for increased proliferation of HSPC to alum or neutropenia, but plays a role in
terminal neutrophil differentiation during granulopoietic recovery. We conclude
that alum elicits a transient increase in G-CSF production via IL-1RI for the
mobilization of BM neutrophils, but density-dependent feedback sustains G-CSF
for accelerated granulopoiesis
Prophylaxis of chemotherapy-induced febrile neutropenia with granulocyte colony-stimulating factors: where are we now?
Updated international guidelines published in 2006 have broadened the scope for the use of granulocyte colony-stimulating factor (G-CSF) in supporting delivery of myelosuppressive chemotherapy. G-CSF prophylaxis is now recommended when the overall risk of febrile neutropenia (FN) due to regimen and individual patient factors is â„20%, for supporting dose-dense and dose-intense chemotherapy and to help maintain dose density where dose reductions have been shown to compromise outcomes. Indeed, there is now a large body of evidence for the efficacy of G-CSFs in supporting dose-dense chemotherapy. Predictive tools that can help target those patients who are most at risk of FN are now becoming available. Recent analyses have shown that, by reducing the risk of FN and chemotherapy dose delays and reductions, G-CSF prophylaxis can potentially enhance survival benefits in patients receiving chemotherapy in curative settings. Accumulating data from âreal-worldâ clinical practice settings indicate that patients often receive abbreviated courses of daily G-CSF and consequently obtain a reduced level of FN protection. A single dose of PEGylated G-CSF (pegfilgrastim) may provide a more effective, as well as a more convenient, alternative to daily G-CSF. Prospective studies are needed to validate the importance of delivering the full dose intensity of standard chemotherapy regimens, with G-CSF support where appropriate, across a range of settings. These studies should also incorporate prospective evaluation of risk stratification for neutropenia and its complications
Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases
The production of peroxide and superoxide is an inevitable consequence of
aerobic metabolism, and while these particular "reactive oxygen species" (ROSs)
can exhibit a number of biological effects, they are not of themselves
excessively reactive and thus they are not especially damaging at physiological
concentrations. However, their reactions with poorly liganded iron species can
lead to the catalytic production of the very reactive and dangerous hydroxyl
radical, which is exceptionally damaging, and a major cause of chronic
inflammation. We review the considerable and wide-ranging evidence for the
involvement of this combination of (su)peroxide and poorly liganded iron in a
large number of physiological and indeed pathological processes and
inflammatory disorders, especially those involving the progressive degradation
of cellular and organismal performance. These diseases share a great many
similarities and thus might be considered to have a common cause (i.e.
iron-catalysed free radical and especially hydroxyl radical generation). The
studies reviewed include those focused on a series of cardiovascular, metabolic
and neurological diseases, where iron can be found at the sites of plaques and
lesions, as well as studies showing the significance of iron to aging and
longevity. The effective chelation of iron by natural or synthetic ligands is
thus of major physiological (and potentially therapeutic) importance. As
systems properties, we need to recognise that physiological observables have
multiple molecular causes, and studying them in isolation leads to inconsistent
patterns of apparent causality when it is the simultaneous combination of
multiple factors that is responsible. This explains, for instance, the
decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference
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Search for anomalous production of photonic events with missing energy in e(+)e(-) collisions at root s=130-172 GeV
Tests of the standard model and constraints on new physics from measurements of fermion-pair production at 130-172GeV at LEP
Production of events with hadronic and leptonic final states has been measured in e(+)e(-) collisions at centre-of-mass energies of 130-172 GeV, using the OPAL detector at LEP. Cross-sections and leptonic forward-backward asymmetries are presented, both including and excluding the dominant production of radiative Z gamma events, and compared to Standard Model expectations. The ratio R-b of the cross-section for production to the hadronic cross-section has been measured. In a model-independent fit to the Z lineshape, the data have been used to obtain an improved precision on the measurement of gamma-Z interference. The energy dependence of alpha(em) has been investigated. The measurements have also been used to obtain limits on extensions of the Standard Model described by effective four-fermion contact interactions, to search for t-channel contributions from new massive particles and to place limits on gaugino pair production with subsequent decay of the gaugino into a light gluino and a quark pair
Search for anomalous production of di-lepton events with missing transverse momentum in e(+)e(-) collisions at root s = 161 and 172 GeV
Events containing a pair of charged leptons and significant missing transverse momentum are selected from a data sample corresponding to a total integrated luminosity of 20.6 pb^-1 at centre-of-mass energies of 161 GeV and 172 GeV. The observed number of events, four at 161 GeV and nine at 172 GeV, is consistent with the number expected from Standard Model processes, predominantly arising from W+W- production with each W decaying leptonically. This topology is also an experimental signature for the pair production of new particles that decay to a charged lepton accompanied by one or more invisible particles. Further event selection criteria are described that optimise the sensitivity to particular new physics channels. No evidence for new phenomena is observed and limits on the production of scalar charged lepton pairs and other new particles are presented
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