830 research outputs found
The Emergence of Precision Urologic Oncology: A Collaborative Review on Biomarker-driven Therapeutics
CONTEXT:
Biomarker-driven cancer therapy, also referred to as precision oncology, has received increasing attention for its promise of improving patient outcomes by defining subsets of patients more likely to respond to various therapies.
OBJECTIVES:
In this collaborative review article, we examine recent literature regarding biomarker-driven therapeutics in urologic oncology, to better define the state of the field, explore the current evidence supporting utility of this approach, and gauge potential for the future.
EVIDENCE ACQUISITION:
We reviewed relevant literature, with a particular focus on recent studies about targeted therapy, predictors of response, and biomarker development.
EVIDENCE SYNTHESIS:
The recent advances in molecular profiling have led to a rapid expansion of potential biomarkers and predictive information for patients with urologic malignancies. Across disease states, distinct molecular subtypes of cancers have been identified, with the potential to inform choices of management strategy. Biomarkers predicting response to standard therapies (such as platinum-based chemotherapy) are emerging. In several malignancies (particularly renal cell carcinoma and castration-resistant prostate cancer), targeted therapy against commonly altered signaling pathways has emerged as standard of care. Finally, targeted therapy against alterations present in rare patients (less than 2%) across diseases has the potential to drastically alter patterns of care and choices of therapeutic options.
CONCLUSIONS:
Precision medicine has the highest potential to impact the care of patients. Prospective studies in the setting of clinical trials and standard of care therapy will help define reliable predictive biomarkers and new therapeutic targets leading to real improvement in patient outcomes.
PATIENT SUMMARY:
Precision oncology uses molecular information (DNA and RNA) from the individual and the tumor to match the right patient with the right treatment. Tremendous strides have been made in defining the molecular underpinnings of urologic malignancies and understanding how these predict response to treatment—this represents the future of urologic oncology
Impact of the COVID-19 pandemic on the Emergency Department of a tertiary children's hospital
Composite GUTs: models and expectations at the LHC
We investigate grand unified theories (GUTs) in scenarios where electroweak
(EW) symmetry breaking is triggered by a light composite Higgs, arising as a
Nambu-Goldstone boson from a strongly interacting sector. The evolution of the
standard model (SM) gauge couplings can be predicted at leading order, if the
global symmetry of the composite sector is a simple group G that contains the
SM gauge group. It was noticed that, if the right-handed top quark is also
composite, precision gauge unification can be achieved. We build minimal
consistent models for a composite sector with these properties, thus
demonstrating how composite GUTs may represent an alternative to supersymmetric
GUTs. Taking into account the new contributions to the EW precision parameters,
we compute the Higgs effective potential and prove that it realizes
consistently EW symmetry breaking with little fine-tuning. The G group
structure and the requirement of proton stability determine the nature of the
light composite states accompanying the Higgs and the top quark: a coloured
triplet scalar and several vector-like fermions with exotic quantum numbers. We
analyse the signatures of these composite partners at hadron colliders:
distinctive final states contain multiple top and bottom quarks, either alone
or accompanied by a heavy stable charged particle, or by missing transverse
energy.Comment: 55 pages, 13 figures, final version to be published in JHE
A slice of AdS_5 as the large N limit of Seiberg duality
A slice of AdS_5 is used to provide a 5D gravitational description of 4D
strongly-coupled Seiberg dual gauge theories. An (electric) SU(N) gauge theory
in the conformal window at large N is described by the 5D bulk, while its
weakly coupled (magnetic) dual is confined to the IR brane. This framework can
be used to construct an N = 1 MSSM on the IR brane, reminiscent of the original
Randall-Sundrum model. In addition, we use our framework to study
strongly-coupled scenarios of supersymmetry breaking mediated by gauge forces.
This leads to a unified scenario that connects the extra-ordinary gauge
mediation limit to the gaugino mediation limit in warped space.Comment: 47 Pages, axodraw4j.st
Loop Quantum Gravity a la Aharonov-Bohm
The state space of Loop Quantum Gravity admits a decomposition into
orthogonal subspaces associated to diffeomorphism equivalence classes of
spin-network graphs. In this paper I investigate the possibility of obtaining
this state space from the quantization of a topological field theory with many
degrees of freedom. The starting point is a 3-manifold with a network of
defect-lines. A locally-flat connection on this manifold can have non-trivial
holonomy around non-contractible loops. This is in fact the mathematical origin
of the Aharonov-Bohm effect. I quantize this theory using standard field
theoretical methods. The functional integral defining the scalar product is
shown to reduce to a finite dimensional integral over moduli space. A
non-trivial measure given by the Faddeev-Popov determinant is derived. I argue
that the scalar product obtained coincides with the one used in Loop Quantum
Gravity. I provide an explicit derivation in the case of a single defect-line,
corresponding to a single loop in Loop Quantum Gravity. Moreover, I discuss the
relation with spin-networks as used in the context of spin foam models.Comment: 19 pages, 1 figure; v2: corrected typos, section 4 expanded
Results from PAMELA, ATIC and FERMI : Pulsars or Dark Matter ?
It is well known that the dark matter dominates the dynamics of galaxies and
clusters of galaxies. Its constituents remain a mystery despite an assiduous
search for them over the past three decades. Recent results from the
satellite-based PAMELA experiment detect an excess in the positron fraction at
energies between 10-100 GeV in the secondary cosmic ray spectrum. Other
experiments namely ATIC, HESS and FERMI show an excess in the total electron
(\ps + \el) spectrum for energies greater 100 GeV. These excesses in the
positron fraction as well as the electron spectrum could arise in local
astrophysical processes like pulsars, or can be attributed to the annihilation
of the dark matter particles. The second possibility gives clues to the
possible candidates for the dark matter in galaxies and other astrophysical
systems. In this article, we give a report of these exciting developments.Comment: 27 Pages, extensively revised and significantly extended, to appear
in Pramana as topical revie
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