Minimal Seesaw as an Ultraviolet Insensitive Cure for the Problems of Anomaly Mediation

We show that an intermediate scale supersymmetric left-right seesaw scenario with automatic R-parity conservation can cure the problem of tachyonic slepton masses that arises when supersymmetry is broken by anomaly mediation, while preserving ultraviolet insensitivity. The reason for this is the existence of light B - L = 2 higgses with yukawa couplings to the charged leptons. We find these theories to have distinct predictions compared to the usual mSUGRA and gauge mediated models as well as the minimal AMSB models. Such predictions include a condensed gaugino mass spectrum and possibly a correspondingly condensed sfermion spectrum.Comment: 19 pages, 1 figur

Spontaneous R-Parity Breaking in SUSY Models

We investigate a mechanism for spontaneous R-parity breaking in a class of extensions of the minimal supersymmetric standard model with an extra Abelian gauge symmetry which is a linear combination of B-L and weak hypercharge. Both U(1)_X and R-parity are broken by the vacuum expectation value of the right-handed sneutrinos which is proportional to the soft SUSY masses. In these models the mechanism for spontaneous R-parity violation can be realized even with positive soft masses. In this context one has a realistic mechanism for generating neutrino masses as well as a realistic spectrum. We briefly discuss the possible collider signals which could be used to test the theory, the contributions for proton decay and the possibility of a gravitino as a dark matter candidate.Comment: 9 pages, typos corrected, to appear in Physical Review

Seesaw Extended MSSM and Anomaly Mediation without Tachyonic Sleptons

Superconformal anomalies provide an elegant and economical way to understand the soft breaking parameters in SUSY models; however, implementing them leads to the several undesirable features including: tachyonic sleptons and electroweak symmetry breaking problems in both the MSSM and the NMSSM. Since these two theories also have the additonal problem of massless neutrinos, we have reconsidered the AMSB problems in a class of models that extends the NMSSM to explain small neutrino masses via the seesaw mechanism. In a recent paper, we showed that for a class of minimal left-right extensions, a built-in mechanism exists which naturally solves the tachyonic slepton problem and provides new alternatives to the MSSM that also have automatic R-parity conservation. In this paper, we discuss how electroweak symmetry breaking arises in this model through an NMSSM-like low energy theory with a singlet VEV, induced by the structure of the left-right extension and of the right magnitude. We then study the phenomenological issues and find: the LSP is an Higgsino-wino mix, new phenomenology for chargino decays to the LSP, degenerate same generation sleptons and a potential for a mild squark-slepton degeneracy. We also discuss possible collider signatures and the feasibility of dark matter in this model.Comment: 40 pages, 10 figures, 5 tables; v3: Added addendum and three new references; v4: Added reference that was inadvertently omitte

When Anomaly Mediation is UV Sensitive

Despite its successes---such as solving the supersymmetric flavor problem---anomaly mediated supersymmetry breaking is untenable because of its prediction of tachyonic sleptons. An appealing solution to this problem was proposed by Pomarol and Rattazzi where a threshold controlled by a light field deflects the anomaly mediated supersymmetry breaking trajectory, thus evading tachyonic sleptons. In this paper we examine an alternate class of deflection models where the non-supersymmetric threshold is accompanied by a heavy, instead of light, singlet. The low energy form of this model is the so-called extended anomaly mediation proposed by Nelson and Weiner, but with potential for a much higher deflection threshold. The existence of this high deflection threshold implies that the space of anomaly mediated supersymmetry breaking deflecting models is larger than previously thought.Comment: 14 pages, 1 figure (version to appear in JHEP

Correction to: Clinical management of ageing people living with HIV in Europe: the view of the care providers.

info:eu-repo/semantics/publishedVersio

Bayesian intravoxel incoherent motion parameter mapping in the human heart

Background: Intravoxel incoherent motion (IVIM) imaging of diffusion and perfusion in the heart suffers from high parameter estimation error. The purpose of this work is to improve cardiac IVIM parameter mapping using Bayesian inference. Methods: A second-order motion-compensated diffusion weighted spin-echo sequence with navigator-based slice tracking was implemented to collect cardiac IVIM data in early systole in eight healthy subjects on a clinical 1.5 T CMR system. IVIM data were encoded along six gradient optimized directions with b-values of 0–300 s/mm2. Subjects were scanned twice in two scan sessions one week apart to assess intra-subject reproducibility. Bayesian shrinkage prior (BSP) inference was implemented to determine IVIM parameters (diffusion D, perfusion fraction F and pseudo-diffusion D*). Results were compared to least-squares (LSQ) parameter estimation. Signal-to-noise ratio (SNR) requirements for a given fitting error were assessed for the two methods using simulated data. Reproducibility analysis of parameter estimation in-vivo using BSP and LSQ was performed. Results: BSP resulted in reduced SNR requirements when compared to LSQ in simulations. In-vivo, BSP analysis yielded IVIM parameter maps with smaller intra-myocardial variability and higher estimation certainty relative to LSQ. Mean IVIM parameter estimates in eight healthy subjects were (LSQ/BSP): 1.63 ± 0.28/1.51 ± 0.14·10−3 mm2/s for D, 13.13 ± 19.81/13.11 ± 5.95% for F and 201.45 ± 313.23/13.11 ± 14.53·10−3 mm2/s for D ∗. Parameter variation across all volunteers and measurements was lower with BSP compared to LSQ (coefficient of variation BSP vs. LSQ: 9% vs. 17% for D, 45% vs. 151% for F and 111% vs. 155% for D ∗). In addition, reproducibility of the IVIM parameter estimates was higher with BSP compared to LSQ (Bland-Altman coefficients of repeatability BSP vs. LSQ: 0.21 vs. 0.26·10−3 mm2/s for D, 5.55 vs. 6.91% for F and 15.06 vs. 422.80·10−3 mm2/s for D*). Conclusion: Robust free-breathing cardiac IVIM data acquisition in early systole is possible with the proposed method. BSP analysis yields improved IVIM parameter maps relative to conventional LSQ fitting with fewer outliers, improved estimation certainty and higher reproducibility. IVIM parameter mapping holds promise for myocardial perfusion measurements without the need for contrast agents

Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome

A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression

Presence and Persistence of Ebola or Marburg Virus in Patients and Survivors: A Rapid Systematic Review

Background: The 2013-15 Ebola outbreak was unprecedented due to sustainedtransmission within urban environments and thousands of survivors. In 2014 the World Health Organization stated that there was insufficient evidence to give definitive guidance about which body fluids are infectious and when they pose a risk to humans. We report a rapid systematic review of published evidence on the presence of filoviruses in body fluids of infected people and survivors. Methods: Scientific articles were screened for information about filovirus in human body fluids. The aim was to find primary data that suggested high likelihood of actively infectious filovirus in human body fluids (viral RNA). Eligible infections were from Marburg virus (MARV or RAVV) and Zaire, Sudan, Taï Forest and Bundibugyo species of Ebola. [1] Cause of infection had to be laboratory confirmed (in practice either tissue culture or RT-PCR tests), or evidenced by compatible clinical history with subsequent positivity for filovirus antibodies or inflammatory factors. Data were extracted and summarized narratively. Results: 6831 unique articles were found, and after screening, 33 studies were eligible. For most body fluid types there were insufficient patients to draw strong conclusions, and prevalence of positivity was highly variable. Body fluids taken >16 days after onset were usually negative. In the six studies that used both assay methods RT-PCR tests for filovirus RNA gave positive results about 4 times more often than tissue culture. Conclusions: Filovirus was reported in most types of body fluid, but not in every sample from every otherwise confirmed patient. Apart from semen, most non-blood, RT-PCR positive samples are likely to be culture negative and so possibly of low infectious risk. Nevertheless, it is not apparent how relatively infectious many body fluids are during or after illness, even when culture-positive, not least because most test results come from more severe cases. Contact with blood and blood-stained body fluids remains the major risk for disease transmission because of the known high viral loads in blood

Considering Intra-individual Genetic Heterogeneity to Understand Biodiversity

In this chapter, I am concerned with the concept of Intra-individual Genetic Hetereogeneity (IGH) and its potential influence on biodiversity estimates. Definitions of biological individuality are often indirectly dependent on genetic sampling -and vice versa. Genetic sampling typically focuses on a particular locus or set of loci, found in the the mitochondrial, chloroplast or nuclear genome. If ecological function or evolutionary individuality can be defined on the level of multiple divergent genomes, as I shall argue is the case in IGH, our current genetic sampling strategies and analytic approaches may miss out on relevant biodiversity. Now that more and more examples of IGH are available, it is becoming possible to investigate the positive and negative effects of IGH on the functioning and evolution of multicellular individuals more systematically. I consider some examples and argue that studying diversity through the lens of IGH facilitates thinking not in terms of units, but in terms of interactions between biological entities. This, in turn, enables a fresh take on the ecological and evolutionary significance of biological diversity