430 research outputs found
Adding new experimental arms to randomised clinical trials: Impact on error rates
Background:
Experimental treatments pass through various stages of development. If a treatment passes through early-phase experiments, the investigators may want to assess it in a late-phase randomised controlled trial. An efficient way to do this is adding it as a new research arm to an ongoing trial while the existing research arms continue, a so-called multi-arm platform trial. The familywise type I error rate is often a key quantity of interest in any multi-arm platform trial. We set out to clarify how it should be calculated when new arms are added to a trial some time after it has started.
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Methods:
We show how the familywise type I error rate, any-pair and all-pairs powers can be calculated when a new arm is added to a platform trial. We extend the Dunnett probability and derive analytical formulae for the correlation between the test statistics of the existing pairwise comparison and that of the newly added arm. We also verify our analytical derivation via simulations.
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Results:
Our results indicate that the familywise type I error rate depends on the shared control arm information (i.e. individuals in continuous and binary outcomes and primary outcome events in time-to-event outcomes) from the common control arm patients and the allocation ratio. The familywise type I error rate is driven more by the number of pairwise comparisons and the corresponding (pairwise) type I error rates than by the timing of the addition of the new arms. The familywise type I error rate can be estimated using Ć idĂĄkâs correction if the correlation between the test statistics of pairwise comparisons is less than 0.30.
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Conclusions:
The findings we present in this article can be used to design trials with pre-planned deferred arms or to add new pairwise comparisons within an ongoing platform trial where control of the pairwise error rate or familywise type I error rate (for a subset of pairwise comparisons) is required
Spin and Chirality Effects in Antler-Topology Processes at High Energy Colliders
We perform a model-independent investigation of spin and chirality
correlation effects in the antler-topology processes
at high energy colliders with polarized
beams. Generally the production process
can occur not only through the -channel exchange of vector bosons,
, including the neutral Standard Model (SM) gauge bosons,
and , but also through the - and -channel exchanges of new
neutral states, and , and the -channel
exchange of new doubly-charged states, . The general set of
(non-chiral) three-point couplings of the new particles and leptons allowed in
a renormalizable quantum field theory is considered. The general spin and
chirality analysis is based on the threshold behavior of the excitation curves
for pair production in collisions with
longitudinal and transverse polarized beams, the angular distributions in the
production process and also the production-decay angular correlations. In the
first step, we present the observables in the helicity formalism. Subsequently,
we show how a set of observables can be designed for determining the spins and
chiral structures of the new particles without any model assumptions. Finally,
taking into account a typical set of approximately chiral invariant scenarios,
we demonstrate how the spin and chirality effects can be probed experimentally
at a high energy collider.Comment: 50 pages, 14 figures, 6 tables, matches version published in EPJ
Surveying the agents of galaxy evolution in the tidally stripped, low metallicity small Magellanic cloud (SAGE-SMC), III: young stellar objects
The Spitzer Space Telescope Legacy Program SAGE-SMC allows global studies of resolved stellar populations in the SMC in a different environment than our Galaxy. Using the SAGE-SMC IRAC (3.6-8.0 mu m) and MIPS (24 and 70 mu m) catalogs and images combined with near-infrared (JHK(s)) and optical (UBVI) data, we identified a population of similar to 1000 intermediate-to high-mass young stellar objects (YSOs) in the SMC (three times more than previously known). Our method of identifying YSO candidates builds on the method developed for the Large Magellanic Cloud by Whitney et al. with improvements based on what we learned from our subsequent studies and techniques described in the literature. We perform (1) color-magnitude cuts based on five color-magnitude diagrams (CMDs), (2) visual inspection of multi-wavelength images, and (3) spectral energy distribution (SED) fitting with YSO models. For each YSO candidate, we use its photometry to calculate a measure of our confidence that the source is not a non-YSO contaminant, but rather a true YSO, based on the source's location in the color-magnitude space with respect to non-YSOs. We use this CMD score and the SED fitting results to define two classes of sources: high-reliability YSO candidates and possible YSO candidates. We found that, due to polycyclic aromatic hydrocarbon emission, about half of our sources have [3.6]-[4.5] and [4.5]-[5.8] colors not predicted by previous YSO models. The YSO candidates are spatially correlated with gas tracers
Decaying Dark Matter in the Supersymmetric Standard Model with Freeze-in and Seesaw mechanims
Inspired by the decaying dark matter (DM) which can explain cosmic ray
anomalies naturally, we consider the supersymmetric Standard Model with three
right-handed neutrinos (RHNs) and R-parity, and introduce a TeV-scale DM sector
with two fields \phi_{1,2} and a discrete symmetry. The DM sector only
interacts with the RHNs via a very heavy field exchange and then we can explain
the cosmic ray anomalies. With the second right-handed neutrino N_2 dominant
seesaw mechanism at the low scale around 10^4 GeV, we show that \phi_{1,2} can
obtain the vacuum expectation values around the TeV scale, and then the
lightest state from \phi_{1,2} is the decay DM with lifetime around \sim
10^{26}s. In particular, the DM very long lifetime is related to the tiny
neutrino masses, and the dominant DM decay channels to \mu and \tau are related
to the approximate \mu-\tau symmetry. Furthermore, the correct DM relic density
can be obtained via the freeze-in mechanism, the small-scale problem for power
spectrum can be solved due to the decays of the R-parity odd meta-stable states
in the DM sector, and the baryon asymmetry can be generated via the soft
leptogensis.Comment: 24 pages,3 figure
Hawking emission from quantum gravity black holes
We address the issue of modelling quantum gravity effects in the evaporation
of higher dimensional black holes in order to go beyond the usual
semi-classical approximation. After reviewing the existing six families of
quantum gravity corrected black hole geometries, we focus our work on
non-commutative geometry inspired black holes, which encode model independent
characteristics, are unaffected by the quantum back reaction and have an
analytical form compact enough for numerical simulations. We consider the
higher dimensional, spherically symmetric case and we proceed with a complete
analysis of the brane/bulk emission for scalar fields. The key feature which
makes the evaporation of non-commutative black holes so peculiar is the
possibility of having a maximum temperature. Contrary to what happens with
classical Schwarzschild black holes, the emission is dominated by low frequency
field modes on the brane. This is a distinctive and potentially testable
signature which might disclose further features about the nature of quantum
gravity.Comment: 36 pages, 18 figures, v2: updated reference list, minor corrections,
version matching that published on JHE
RAMPART: A model for a regulatory-ready academic-led phase III trial in the adjuvant renal cell carcinoma setting
The development of therapeutics in oncology is a highly active research area for the pharmaceutical and biotechnology industries, but also has a strong academic base. Many new agents have been developed in recent years, most with specific biological targets. This has mandated the need to look at different ways to streamline the evaluation of new agents. One solution has been the development of adaptive trial designs that allow the evaluation of multiple agents, concentrating on the most promising agents while screening out those which are unlikely to benefit patients. Another way forward has been the growth of partnerships between academia and industry with the shared goal of designing and conducting high quality clinical trials which answer important clinical questions as efficiently as possible.
The RAMPART trial (NCT03288532) brings together both of these processes in an attempt to improve outcomes for patients with locally advanced renal cell carcinoma (RCC), where no globally acceptable adjuvant strategy after nephrectomy currently exist. RAMPART is led by the MRC CTU at University College London (UCL), in collaboration with other international academic groups and industry. We aim to facilitate the use of data from RAMPART, (dependent on outcomes), for a future regulatory submission that will extend the license of the agents being investigated. We share our experience in order to lay the foundations for an effective trial design and conduct framework and to guide others who may be considering similar collaborations
Hemostasis and ageing
On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characterized by a state of hypercoagulability and possession of several high-risk alleles and well-known atherothrombotic risk markers but this appears to be compatible with longevity and/or health. Parameters considered risk factors for atherosclerotic vascular diseases in young people may lose their biological significance in advanced age and assume a different role
How a Diverse Research Ecosystem Has Generated New Rehabilitation Technologies: Review of NIDILRRâs Rehabilitation Engineering Research Centers
Over 50 million United States citizens (1 in 6 people in the US) have a developmental, acquired, or degenerative disability. The average US citizen can expect to live 20% of his or her life with a disability. Rehabilitation technologies play a major role in improving the quality of life for people with a disability, yet widespread and highly challenging needs remain. Within the US, a major effort aimed at the creation and evaluation of rehabilitation technology has been the Rehabilitation Engineering Research Centers (RERCs) sponsored by the National Institute on Disability, Independent Living, and Rehabilitation Research. As envisioned at their conception by a panel of the National Academy of Science in 1970, these centers were intended to take a âtotal approach to rehabilitationâ, combining medicine, engineering, and related science, to improve the quality of life of individuals with a disability. Here, we review the scope, achievements, and ongoing projects of an unbiased sample of 19 currently active or recently terminated RERCs. Specifically, for each center, we briefly explain the needs it targets, summarize key historical advances, identify emerging innovations, and consider future directions. Our assessment from this review is that the RERC program indeed involves a multidisciplinary approach, with 36 professional fields involved, although 70% of research and development staff are in engineering fields, 23% in clinical fields, and only 7% in basic science fields; significantly, 11% of the professional staff have a disability related to their research. We observe that the RERC program has substantially diversified the scope of its work since the 1970âs, addressing more types of disabilities using more technologies, and, in particular, often now focusing on information technologies. RERC work also now often views users as integrated into an interdependent society through technologies that both people with and without disabilities co-use (such as the internet, wireless communication, and architecture). In addition, RERC research has evolved to view users as able at improving outcomes through learning, exercise, and plasticity (rather than being static), which can be optimally timed. We provide examples of rehabilitation technology innovation produced by the RERCs that illustrate this increasingly diversifying scope and evolving perspective. We conclude by discussing growth opportunities and possible future directions of the RERC program
Spin effects in the antler event topology at hadron colliders
We investigate spin correlation effects in the "antler" event topology pp->
A-> B1, B2 -> l^{-}, C1, l^{+}, C2 at the LHC. We study the shapes of several
kinematic variables, including the relative pseudorapidity, relative azimuthal
angle and the energies of the two leptons, as well as several mass variables
M_{ll}, Meff, \sqrt{s}_{min}, MT2, MCT and MCTx. We focus on the two kinematic
extremes of \sqrt{s} - threshold and infinity - and derive analytical
expressions for the differential distributions of several variables, most
notably the cos{\theta_{ll}}^* variable proposed by Barr in hep-ph/0511115. For
all possible spin assignments of particles A, B and C, we derive the
cos{\theta_{ll}}^* differential distribution at threshold, including the
effects of spin correlations. Our analytical results help identify the
problematic cases for spin discrimination.Comment: 43 pages, 14 figures, Preprint typeset in JHEP styl
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