Fertility and early pregnancy outcomes after treatment for cervical intraepithelial neoplasia: systematic review and meta-analysis

OBJECTIVE: To determine the impact of cervical excision for cervical intraepithelial neoplasia on fertility and early pregnancy outcomes. DESIGN: Systematic review and meta-analysis of cohort studies. DATA SOURCES: Medline and Embase. ELIGIBILITY CRITERIA: Studies assessing fertility and early pregnancy outcomes in women with a history of treatment for cervical intraepithelial neoplasia versus untreated women. We classified the included studies according to treatment type and fertility or early pregnancy endpoint. ANALYSIS: Pooled relative risks and 95% confidence intervals using a random effect model, and interstudy heterogeneity with I(2) statistics. RESULTS: 15 studies fulfilled the inclusion criteria and were included. The meta-analysis did not provide any evidence that treatment for cervical intraepithelial neoplasia adversely affected the chances of conception. The overall pregnancy rate was higher for treated women than for untreated women (four studies; 43% v 38%, pooled relative risk 1.29, 95% confidence interval 1.02 to 1.64), although the heterogeneity between studies was high (P<0.0001). Pregnancy rates did not differ between women with an intention to conceive (two studies; 88% v 95%, 0.93, 0.80 to 1.08) and the number requiring more than 12 months to conceive (three studies, 15% v 9%, 1.45, 0.89 to 2.37). Although the rates for total miscarriages (10 studies; 4.6% v 2.8%, 1.04, 0.90 to 1.21) and miscarriage in the first trimester (four studies; 9.8% v 8.4%, 1.16, 0.80 to 1.69) was similar for treated and untreated women, cervical treatment was associated with a significantly increased risk of miscarriage in the second trimester. The rate was higher for treated women than for untreated women (eight studies; 1.6% v 0.4%, 16,558 women; 2.60, 1.45 to 4.67). The number of ectopic pregnancies (1.6% v 0.8%; 1.89, 1.50 to 2.39) and terminations (12.2% v 7.4%; 1.71, 1.31 to 2.22) was also higher for treated women. CONCLUSION: There is no evidence suggesting that treatment for cervical intraepithelial neoplasia adversely affects fertility, although treatment was associated with a significantly increased risk of miscarriages in the second trimester. Research should explore mechanisms that may explain this increase in risk and stratify the impact that treatment may have on fertility and early pregnancy outcomes by the size of excision and treatment method used

Evaluating PET-CT in the detection and management of recurrent cervical cancer: Systematic reviews of diagnostic accuracy and subjective elicitation

Background: Positron emission tomography-computed tomography (PET-CT) is recommended to triage women for exenterative surgery and surveillance after treatment for advanced cervical cancer. Objective: To evaluate diagnostic accuracy of additional whole body PET-CT compared with CT/magnetic resonance imaging (MRI) alone in women with suspected recurrent/persistent cervical cancer and in asymptomatic women as surveillance. Design: Systematic reviews. Subjective elicitation to supplement diagnostic information. Search strategy/Selection criteria/Data collection and analysis: Searches of electronic databases were performed to June 2013. Studies in women with suspected recurrent/persistent cervical cancer and in asymptomatic women undergoing follow up with sufficient numeric data were included. We calculated sensitivity, specificity and corresponding 95% confidence intervals. Meta-analyses employed a bivariate model that included a random-effects term for between-study variations (CT studies) and univariate random effects meta-analyses (PET-CT studies) for sensitivity and specificity separately. Subjective elicitation: Prevalence of recurrence and the accuracy of imaging elicited using the allocation of points technique. Coherence of elicited subjective probabilities with estimates in the literature examined. Results: We identified 15 relevant studies; none directly compared additional PET-CT with MRI or CT separately. Most CT and MRI studies used older protocols and the majority did not distinguish between asymptomatic and symptomatic women. Meta-analysis of nine PET-CT studies in mostly symptomatic women showed sensitivity of 94.8 (95% CI 91.2-96.9), and specificity of 86.9% (95% CI 82.2-90.5). The summary estimate of the sensitivity of CT for detection of recurrence was 89.64% (95% CI 81.59-94.41) and specificity was 76% (95% CI 43.68-92.82). Meta-analysis for MRI test accuracy studies was not possible because of clinical heterogeneity. The sensitivity and specificity of MRI in pelvic recurrence varied between 82 and 100% and between 78 and 100%, respectively. Formal statistical comparisons of the accuracy of index tests were not possible. Subjective elicitation provided estimates comparable to the literature. Subjective estimates of the increase in accuracy from the addition of PET-CT were less than elicited increases required to justify the use in PET-CT for surveillance. Conclusion: Evidence to support additional PET-CT is scarce, of average quality and does not distinguish between application for surveillance and diagnosis. Guidelines recommending PET-CT in recurrent cervical cancer need to be reconsidered in the light of the existing evidence base

Positron emission tomography/computerised tomography imaging in detecting and managing recurrent cervical cancer: systematic review of evidence, elicitation of subjective probabilities and economic modelling.

© Queen’s Printer and Controller of HMSO 2013. This work was produced by Meads et al. under the terms of a commissioning contract issued by the Secretary of State for Health. This issue may be freely reproduced for the purposes of private research and study and extracts (or indeed, the full report) may be included in professional journals provided that suitable acknowledgement is made and the reproduction is not associated with any form of advertising.Cancer of the uterine cervix is a common cause of mortality in women. After initial treatment women may be symptom free, but the cancer may recur within a few years. It is uncertain whether it is more clinically effective to survey asymptomatic women for signs of recurrence or to await symptoms or signs before using imaging.National Institute for Health Research Health Technology Assessment programm

Experimental tests for the Babu-Zee two-loop model of Majorana neutrino masses

The smallness of the observed neutrino masses might have a radiative origin. Here we revisit a specific two-loop model of neutrino mass, independently proposed by Babu and Zee. We point out that current constraints from neutrino data can be used to derive strict lower limits on the branching ratio of flavour changing charged lepton decays, such as $\mu \to e \gamma$. Non-observation of Br($\mu \to e \gamma$) at the level of $10^{-13}$ would rule out singly charged scalar masses smaller than 590 GeV (5.04 TeV) in case of normal (inverse) neutrino mass hierarchy. Conversely, decay branching ratios of the non-standard scalars of the model can be fixed by the measured neutrino angles (and mass scale). Thus, if the scalars of the model are light enough to be produced at the LHC or ILC, measuring their decay properties would serve as a direct test of the model as the origin of neutrino masses.Comment: 14 pages, 16 figure

Fullerene-based Biocomponents : New Concepts For Functionalising Membranes

Lipophilic hexakisadducts of fullerene C60 form unprecedented rod-like nanoaggregates in phospholipid-membrane bilayers, resulting in modification of the micromechanic properties and stabilisation of the membrane. Lipofullerenes with amphiphilic side chains enable additionally derivatisation and molecular recognition at the membrane surface. The amphiphilic spacer acts as a transmembrane anchor and provides the terminal functionality outside of the membrane. New systems derived from parent compound 3 carry two functional groups each and can be easily modified due to the modular synthesis. Terminal functionalities to be investigated include D(+)-biotin and IDA (iminodiacetic acid) ligands, as used in nickel-histidine tags. Modification of the lipophilic region, for instance with unsaturated addends is also possible. These addends should allow polymerisation inside the membrane and potentially lead to a tremendous increase of the membrane rigidity. Furthermore, mono- and bilayer-forming fullerene derivatives without the membrane-forming support of lecithins are investigated and exhibit interesting features

Magnetism and Pairing in Hubbard Bilayers.

We study the Hubbard model on a bilayer with repulsive on-site interactions, $U$, in which fermions undergo both intra-plane ($t$) and inter-plane ($t_z$) hopping. This situation is what one would expect in high-temperature superconductors such as YBCO, with two adjacent CuO$_2$ planes. Magnetic and pairing properties of the system are investigated through Quantum Monte Carlo simulations for both half- and quarter-filled bands. We find that in all cases inter-planar pairing with $d_{x^2-z^2}$ symmetry is dominant over planar pairing with $d_{x^2-y^2}$ symmetry, and that for $t_z$ large enough pair formation is possible through antiferromagnetic correlations. However, another mechanism is needed to make these pairs condense into a superconducting state at lower temperatures. We identify the temperature for pair formation with the spin gap crossover temperature. [Submitted to Phys. Rev. B]Comment: 7 pages, uuencoded self-unpacking PS file with text and figures

Vibrational spectroscopy: a promising approach to discriminate neurodegenerative disorders

Neurodegenerative diseases are a growing burden in modern society, thus crucially calling for the development of accurate diagnostic strategies. These diseases are currently incurable, a fact which has been attributed to their late diagnosis, after brain damage has already become widespread. An earlier and improved diagnosis is necessary for the enrolment of patients into clinical trials and can pave the way for the development of therapeutic tactics. Novel analytical techniques, such as mass spectrometry and vibrational spectroscopy, have been able to successfully detect and characterise neurodegenerative disorders. It is critical to globally support and make use of innovative basic research and techniques, which could ultimately lead to the creation of a cost-effective diagnostic test. Minimally invasive samples, such as biological fluids, have also been shown to reveal information for these diseases; utilising them could simplify sample collection/analysis and be more preferable to patients

Soft masses in SUSY SO(10) GUTs with low intermediate scales

The specific shape of the squark, slepton and gaugino mass spectra, if measured with suficient accuracy, can provide invaluable information not only about the dynamics underpinning their origin at some very high scale such as the unification scale MG, but also about the intermediate scale physics encountered throughout their RGE evolution down to the energy scale accessible for the LHC. In this work, we study general features of the TeV scale soft SUSY breaking parameters stemming from a generic mSugra configuration within certain classes of SUSY SO(10) GUTs with different intermediate symmetries below MG. We show that particular combinations of soft masses show characteristic deviations from the mSugra limit in different models and thus, potentially, allow to distinguish between these, even if the new intermediate scales are outside the energy range probed at accelerators. We also compare our results to those obtained for the three minimal seesaw models with mSugra boundary conditions and discuss the main differences between those and our SO(10) based models.Comment: 18 pages, 12 figures, 5 table

Renormalization group parameter evolution of the minimal supersymmetric standard model with R-parity violation

A comparison of spectra obtained using the 1-loop MSSM and 2-loop R-parity violating MSSM renormalization group equations is presented. Influence of higher loop corrections and R-parity violating terms is discussed. Some numerical constraints on the R-parity violating parameters are also given.Comment: 4 pages, 1 figure, using RevTE

Right-handed Sneutrinos as Nonthermal Dark Matter

When the minimal supersymmetric standard model is augmented by three right-handed neutrino superfields, one generically predicts that the neutrinos acquire Majorana masses. We postulate that all supersymmetry (SUSY) breaking masses as well as the Majorana masses of the right-handed neutrinos are around the electroweak scale and, motivated by the smallness of neutrino masses, assume that the lightest supersymmetric particle (LSP) is an almost-pure right-handed sneutrino. We discuss the conditions under which this LSP is a successful dark matter candidate. In general, such an LSP has to be nonthermal in order not to overclose the universe, and we find the conditions under which this is indeed the case by comparing the Hubble expansion rate with the rates of the relevant thermalizing processes, including self-annihilation and co-annihilation with other SUSY and standard model particles.Comment: 17 pages v.2: References adde