1,688 research outputs found
Estrogens and aspects of prostate disease
Estrogens have long been associated with the processes involved in prostate carcinogenesis, particularly in cancer suppression. However, the synergistic influence of low concentrations of estrogens, together with androgens, in promoting aberrant growth of the gland has also been recognized. As new insights into the complex molecular events implicated in growth regulation of the prostate are revealed, the role of the estrogens has become clearer. The present review considers this role in relation to the pathogenesis of prostate cancer and the potential cancer-repressive influence of the dietary estrogens
New first trimester crown-rump length's equations optimized by structured data collection from a French general population
--- Objectives --- Prior to foetal karyotyping, the likelihood of Down's
syndrome is often determined combining maternal age, serum free beta-HCG,
PAPP-A levels and embryonic measurements of crown-rump length and nuchal
translucency for gestational ages between 11 and 13 weeks. It appeared
important to get a precise knowledge of these scan parameters' normal values
during the first trimester. This paper focused on crown-rump length. ---
METHODS --- 402 pregnancies from in-vitro fertilization allowing a precise
estimation of foetal ages (FA) were used to determine the best model that
describes crown-rump length (CRL) as a function of FA. Scan measures by a
single operator from 3846 spontaneous pregnancies representative of the general
population from Northern France were used to build a mathematical model linking
FA and CRL in a context as close as possible to normal scan screening used in
Down's syndrome likelihood determination. We modeled both CRL as a function of
FA and FA as a function of CRL. For this, we used a clear methodology and
performed regressions with heteroskedastic corrections and robust regressions.
The results were compared by cross-validation to retain the equations with the
best predictive power. We also studied the errors between observed and
predicted values. --- Results --- Data from 513 spontaneous pregnancies allowed
to model CRL as a function of age of foetal age. The best model was a
polynomial of degree 2. Datation with our equation that models spontaneous
pregnancies from a general population was in quite agreement with objective
datations obtained from 402 IVF pregnancies and thus support the validity of
our model. The most precise measure of CRL was when the SD was minimal
(1.83mm), for a CRL of 23.6 mm where our model predicted a 49.4 days of foetal
age. Our study allowed to model the SD from 30 to 90 days of foetal age and
offers the opportunity of using Zscores in the future to detect growth
abnormalities. --- Conclusion --- With powerful statistical tools we report a
good modeling of the first trimester embryonic growth in the general population
allowing a better knowledge of the date of fertilization useful in the
ultrasound screening of Down's syndrome. The optimal period to measure CRL and
predict foetal age was 49.4 days (9 weeks of gestational age). Our results open
the way to the detection of foetal growth abnormalities using CRL Zscores
throughout the first trimester
Population mixing and leukaemia in young people around the La Hague nuclear waste reprocessing plant
In order to investigate for an association between population mixing and the occurrence of leukaemia in young people (less than 25 years), a geographical study was conducted, for the years 1979 to 1998, in Nord Cotentin (France). This area experienced between the years 1978 and 1992 a major influx of workers for the construction of a nuclear power station and a new nuclear waste reprocessing unit. A population mixing index was defined on the basis of the number of workers born outside the French department of ‘La Manche’ and living in each ‘commune’, the basic geographical unit under study. The analyses were done with indirect standardisation and Poisson regression model allowing or not for extra-Poisson variation. Urban ‘communes’ were considered as the reference population. The Incidence Rate Ratio was 2.7 in rural ‘communes’ belonging to the highest tertile of population mixing (95% Bayesian credible interval, 95%BCI=1.2–5.9). A positive trend was observed among rural strata with increasing population mixing index (IRR for trend=1.4, 95%BCI=1.1–1.8). The risk became stronger for Acute Lymphoblastic Leukaemia in children 1–6 years old in the highest tertile of population mixing (IRR=5.5, 95%BCI=1.4–23.3). These findings provide further support for a possible infective basis of childhood leukaemia
Transannular Photocyclization of (E)-3B-Acetoxy-5,10-seco-1(10)-cholesten-5-one*
UV irradiation of the (E)-5,10-seco-steroidal ketone 1 in acetone
solution results, in addition to the previously describedE/Z isomerization and intramolecular Paterno-Buchi reaction(leading to the la,5:x-oxetane 4 in about 42% yield and 1~,5~-oxetane5 in 2-3% yield), in atransannular cyclization (accompaniedby acetic acid elimination) producing the anthrasteroidal enone 3 (in about 7% yield). The structureof 3 was deduced from spectral data and confirmed by X-ray analysis
Theoretical and Phenomenological Constraints on Form Factors for Radiative and Semi-Leptonic B-Meson Decays
We study transition form factors for radiative and rare semi-leptonic B-meson
decays into light pseudoscalar or vector mesons, combining theoretical
constraints and phenomenological information from Lattice QCD, light-cone sum
rules, and dispersive bounds. We pay particular attention to form factor
parameterisations which are based on the so-called series expansion, and study
the related systematic uncertainties on a quantitative level. In this context,
we also provide the NLO corrections to the correlation function between two
flavour-changing tensor currents, which enters the unitarity constraints for
the coefficients in the series expansion.Comment: 52 pages; v2: normalization error in (29ff.) corrected, conclusion
about relevance of unitarity bounds modified; form factor fits unaffected;
references added; v3: discussion on truncation of series expansion added,
matches version to be published in JHEP; v4: corrected typos in Tables 5 and
Global aspects of the space of 6D N = 1 supergravities
We perform a global analysis of the space of consistent 6D quantum gravity
theories with N = 1 supersymmetry, including models with multiple tensor
multiplets. We prove that for theories with fewer than T = 9 tensor multiplets,
a finite number of distinct gauge groups and matter content are possible. We
find infinite families of field combinations satisfying anomaly cancellation
and admitting physical gauge kinetic terms for T > 8. We find an integral
lattice associated with each apparently-consistent supergravity theory; this
lattice is determined by the form of the anomaly polynomial. For models which
can be realized in F-theory, this anomaly lattice is related to the
intersection form on the base of the F-theory elliptic fibration. The condition
that a supergravity model have an F-theory realization imposes constraints
which can be expressed in terms of this lattice. The analysis of models which
satisfy known low-energy consistency conditions and yet violate F-theory
constraints suggests possible novel constraints on low-energy supergravity
theories.Comment: 41 pages, 1 figur
Holmium-166 radioembolization for the treatment of patients with liver metastases: design of the phase I HEPAR trial
<p>Abstract</p> <p>Background</p> <p>Intra-arterial radioembolization with yttrium-90 microspheres ( <sup>90</sup>Y-RE) is an increasingly used therapy for patients with unresectable liver malignancies. Over the last decade, radioactive holmium-166 poly(L-lactic acid) microspheres ( <sup>166</sup>Ho-PLLA-MS) have been developed as a possible alternative to <sup>90</sup>Y-RE. Next to high-energy beta-radiation, <sup>166</sup>Ho also emits gamma-radiation, which allows for imaging by gamma scintigraphy. In addition, Ho is a highly paramagnetic element and can therefore be visualized by MRI. These imaging modalities are useful for assessment of the biodistribution, and allow dosimetry through quantitative analysis of the scintigraphic and MR images. Previous studies have demonstrated the safety of <sup>166</sup>Ho-PLLA-MS radioembolization ( <sup>166</sup>Ho-RE) in animals. The aim of this phase I trial is to assess the safety and toxicity profile of <sup>166</sup>Ho-RE in patients with liver metastases.</p> <p>Methods</p> <p>The HEPAR study (Holmium Embolization Particles for Arterial Radiotherapy) is a non-randomized, open label, safety study. We aim to include 15 to 24 patients with liver metastases of any origin, who have chemotherapy-refractory disease and who are not amenable to surgical resection. Prior to treatment, in addition to the standard technetium-99m labelled macroaggregated albumin ( <sup>99m</sup>Tc-MAA) dose, a low radioactive safety dose of 60-mg <sup>166</sup>Ho-PLLA-MS will be administered. Patients are treated in 4 cohorts of 3-6 patients, according to a standard dose escalation protocol (20 Gy, 40 Gy, 60 Gy, and 80 Gy, respectively). The primary objective will be to establish the maximum tolerated radiation dose of <sup>166</sup>Ho-PLLA-MS. Secondary objectives are to assess tumour response, biodistribution, performance status, quality of life, and to compare the <sup>166</sup>Ho-PLLA-MS safety dose and the <sup>99m</sup>Tc-MAA dose distributions with respect to the ability to accurately predict microsphere distribution.</p> <p>Discussion</p> <p>This will be the first clinical study on <sup>166</sup>Ho-RE. Based on preclinical studies, it is expected that <sup>166</sup>Ho-RE has a safety and toxicity profile comparable to that of <sup>90</sup>Y-RE. The biochemical and radionuclide characteristics of <sup>166</sup>Ho-PLLA-MS that enable accurate dosimetry calculations and biodistribution assessment may however improve the overall safety of the procedure.</p> <p>Trial registration</p> <p>ClinicalTrials.gov NCT01031784</p
The decay Bs -> mu+ mu-: updated SUSY constraints and prospects
We perform a study of the impact of the recently released limits on BR(Bs ->
mu+ mu-) by LHCb and CMS on several SUSY models. We show that the obtained
constraints can be superior to those which are derived from direct searches for
SUSY particles in some scenarios, and the use of a double ratio of purely
leptonic decays involving Bs -> mu+ mu- can further strengthen such
constraints. We also discuss the experimental sensitivity and prospects for
observation of Bs -> mu+ mu- during the sqrt(s)=7 TeV run of the LHC, and its
potential implications.Comment: 30 pages, 21 figures. v2: Improved discussion of constraints from B
-> tau nu, references adde
Thyrotropin-releasing hormone (TRH) promotes wound re-epithelialisation in frog and human skin
There remains a critical need for new therapeutics that promote wound healing in patients suffering from chronic skin wounds. This is, in part, due to a shortage of simple, physiologically and clinically relevant test systems for investigating candidate agents. The skin of amphibians possesses a remarkable regenerative capacity, which remains insufficiently explored for clinical purposes. Combining comparative biology with a translational medicine approach, we report the development and application of a simple ex vivo frog (Xenopus tropicalis) skin organ culture system that permits exploration of the effects of amphibian skin-derived agents on re-epithelialisation in both frog and human skin. Using this amphibian model, we identify thyrotropin-releasing hormone (TRH) as a novel stimulant of epidermal regeneration. Moving to a complementary human ex vivo wounded skin assay, we demonstrate that the effects of TRH are conserved across the amphibian-mammalian divide: TRH stimulates wound closure and formation of neo-epidermis in organ-cultured human skin, accompanied by increased keratinocyte proliferation and wound healing-associated differentiation (cytokeratin 6 expression). Thus, TRH represents a novel, clinically relevant neuroendocrine wound repair promoter that deserves further exploration. These complementary frog and human skin ex vivo assays encourage a comparative biology approach in future wound healing research so as to facilitate the rapid identification and preclinical testing of novel, evolutionarily conserved, and clinically relevant wound healing promoters
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