HIV and antiretroviral treatment knowledge gaps and psychosocial burden among persons living with HIV in Lima, Peru

This study aims to describe knowledge on HIV and antiretroviral (ARV) treatment and psychosocial factors among people living with HIV (PLWH) in Lima, Perú, to explore characteristics associated to this knowledge, and determine its impact on sustained viral suppression. A cross-sectional survey was conducted among 171 PLWH at the largest referral health care center in Lima. The psychosocial factors measured were depression, risk of alcoholism, use of illegal drugs and disclosure. A participant had "poor knowledge" when less than 80% of replies were correct. Sustained viral suppression was defined as two consecutive viral loads under 50 copies/mL. A total of 49% and 43% had poor HIV and ARV knowledge respectively; 48% of the study population screened positive for depression and 27% reported feeling unsupported by the person they disclosed to. The largest gaps in HIV and ARV knowledge were among 98 (57%) that did not recognize that HIV increased the risk of cancer and among 57 (33%) participants that did not disagree with the statement that taking a double dose of ARV if they missed one. Moderate depression was significantly associated to poor HIV and ARV knowledge. Non-disclosure and being on ARVs for less than 6 months were associated with not achieving sustained viral suppression. Our findings highlight important HIV and ARV knowledge gaps of PLWH and a high burden of psychosocial problems, especially of depression, among PLWH in Lima, Peru. Increasing knowledge and addressing depression and disclosure could improve care of PLWH

Gaugino Anomaly Mediated SUSY Breaking: phenomenology and prospects for the LHC

We examine the supersymmetry phenomenology of a novel scenario of supersymmetry (SUSY) breaking which we call Gaugino Anomaly Mediation, or inoAMSB. This is suggested by recent work on the phenomenology of flux compactified type IIB string theory. The essential features of this scenario are that the gaugino masses are of the anomaly-mediated SUSY breaking (AMSB) form, while scalar and trilinear soft SUSY breaking terms are highly suppressed. Renormalization group effects yield an allowable sparticle mass spectrum, while at the same time avoiding charged LSPs; the latter are common in models with negligible soft scalar masses, such as no-scale or gaugino mediation models. Since scalar and trilinear soft terms are highly suppressed, the SUSY induced flavor and CP-violating processes are also suppressed. The lightest SUSY particle is the neutral wino, while the heaviest is the gluino. In this model, there should be a strong multi-jet +etmiss signal from squark pair production at the LHC. We find a 100 fb^{-1} reach of LHC out to m_{3/2}\sim 118 TeV, corresponding to a gluino mass of \sim 2.6 TeV. A double mass edge from the opposite-sign/same flavor dilepton invariant mass distribution should be visible at LHC; this, along with the presence of short-- but visible-- highly ionizing tracks from quasi-stable charginos, should provide a smoking gun signature for inoAMSB.Comment: 30 pages including 14 .eps figure

The Intermediate Scale MSSM, the Higgs Mass and F-theory Unification

Even if SUSY is not present at the Electro-Weak scale, string theory suggests its presence at some scale M_{SS} below the string scale M_s to guarantee the absence of tachyons. We explore the possible value of M_{SS} consistent with gauge coupling unification and known sources of SUSY breaking in string theory. Within F-theory SU(5) unification these two requirements fix M_{SS} ~ 5 x 10^{10} GeV at an intermediate scale and a unification scale M_c ~ 3 x 10^{14} GeV. As a direct consequence one also predicts the vanishing of the quartic Higgs SM self-coupling at M_{SS} ~10^{11} GeV. This is tantalizingly consistent with recent LHC hints of a Higgs mass in the region 124-126 GeV. With such a low unification scale M_c ~ 3 x 10^{14} GeV one may worry about too fast proton decay via dimension 6 operators. However in the F-theory GUT context SU(5) is broken to the SM via hypercharge flux. We show that this hypercharge flux deforms the SM fermion wave functions leading to a suppression, avoiding in this way the strong experimental proton decay constraints. In these constructions there is generically an axion with a scale of size f_a ~ M_c/(4\pi)^2 ~ 10^{12} GeV which could solve the strong CP problem and provide for the observed dark matter. The prize to pay for these attractive features is to assume that the hierarchy problem is solved due to anthropic selection in a string landscape.Comment: 48 pages, 8 figures. v3: further minor correction

Testing the gaugino AMSB model at the Tevatron via slepton pair production

Gaugino AMSB models-- wherein scalar and trilinear soft SUSY breaking terms are suppressed at the GUT scale while gaugino masses adopt the AMSB form-- yield a characteristic SUSY particle mass spectrum with light sleptons along with a nearly degenerate wino-like lightest neutralino and quasi-stable chargino. The left- sleptons and sneutrinos can be pair produced at sufficiently high rates to yield observable signals at the Fermilab Tevatron. We calculate the rate for isolated single and dilepton plus missing energy signals, along with the presence of one or two highly ionizing chargino tracks. We find that Tevatron experiments should be able to probe gravitino masses into the ~55 TeV range for inoAMSB models, which corresponds to a reach in gluino mass of over 1100 GeV.Comment: 14 pages including 6 .eps figure

Robust automated detection of microstructural white matter degeneration in Alzheimer’s disease using machine learning classification of multicenter DTI data

Diffusion tensor imaging (DTI) based assessment of white matter fiber tract integrity can support the diagnosis of Alzheimer’s disease (AD). The use of DTI as a biomarker, however, depends on its applicability in a multicenter setting accounting for effects of different MRI scanners. We applied multivariate machine learning (ML) to a large multicenter sample from the recently created framework of the European DTI study on Dementia (EDSD). We hypothesized that ML approaches may amend effects of multicenter acquisition. We included a sample of 137 patients with clinically probable AD (MMSE 20.6±5.3) and 143 healthy elderly controls, scanned in nine different scanners. For diagnostic classification we used the DTI indices fractional anisotropy (FA) and mean diffusivity (MD) and, for comparison, gray matter and white matter density maps from anatomical MRI. Data were classified using a Support Vector Machine (SVM) and a Naïve Bayes (NB) classifier. We used two cross-validation approaches, (i) test and training samples randomly drawn from the entire data set (pooled cross-validation) and (ii) data from each scanner as test set, and the data from the remaining scanners as training set (scanner-specific cross-validation). In the pooled cross-validation, SVM achieved an accuracy of 80% for FA and 83% for MD. Accuracies for NB were significantly lower, ranging between 68% and 75%. Removing variance components arising from scanners using principal component analysis did not significantly change the classification results for both classifiers. For the scanner-specific cross-validation, the classification accuracy was reduced for both SVM and NB. After mean correction, classification accuracy reached a level comparable to the results obtained from the pooled cross-validation. Our findings support the notion that machine learning classification allows robust classification of DTI data sets arising from multiple scanners, even if a new data set comes from a scanner that was not part of the training sample

Moduli Spaces of Cold Holographic Matter

We use holography to study (3+1)-dimensional N=4 supersymmetric Yang-Mills theory with gauge group SU(Nc), in the large-Nc and large-coupling limits, coupled to a single massless (n+1)-dimensional hypermultiplet in the fundamental representation of SU(Nc), with n=3,2,1. In particular, we study zero-temperature states with a nonzero baryon number charge density, which we call holographic matter. We demonstrate that a moduli space of such states exists in these theories, specifically a Higgs branch parameterized by the expectation values of scalar operators bilinear in the hypermultiplet scalars. At a generic point on the Higgs branch, the R-symmetry and gauge group are spontaneously broken to subgroups. Our holographic calculation consists of introducing a single probe Dp-brane into AdS5 times S^5, with p=2n+1=7,5,3, introducing an electric flux of the Dp-brane worldvolume U(1) gauge field, and then obtaining explicit solutions for the worldvolume fields dual to the scalar operators that parameterize the Higgs branch. In all three cases, we can express these solutions as non-singular self-dual U(1) instantons in a four-dimensional space with a metric determined by the electric flux. We speculate on the possibility that the existence of Higgs branches may point the way to a counting of the microstates producing a nonzero entropy in holographic matter. Additionally, we speculate on the possible classification of zero-temperature, nonzero-density states described holographically by probe D-branes with worldvolume electric flux.Comment: 56 pages, 8 PDF images, 4 figure

Low-Energy Probes of a Warped Extra Dimension

We investigate a natural realization of a light Abelian hidden sector in an extended Randall-Sundrum (RS) model. In addition to the usual RS bulk we consider a second warped space containing a bulk U(1)_x gauge theory with a characteristic IR scale of order a GeV. This Abelian hidden sector can couple to the standard model via gauge kinetic mixing on a common UV brane. We show that if such a coupling induces significant mixing between the lightest U(1)_x gauge mode and the standard model photon and Z, it can also induce significant mixing with the heavier U(1)_x Kaluza-Klein (KK) modes. As a result it might be possible to probe several KK modes in upcoming fixed-target experiments and meson factories, thereby offering a new way to investigate the structure of an extra spacetime dimension.Comment: 26 pages, 1 figure, added references, corrected minor typos, same as journal versio

Heterotic T-folds with a small number of neutral moduli

We discuss non-geometric supersymmetric heterotic string models in D=4, in the framework of the free fermionic construction. We perform a systematic scan of models with four a priori left-right asymmetric Z_2 projections and shifts. We analyze some 2^{20} models, identifying 18 inequivalent classes and addressing variants generated by discrete torsions. They do not contain geometrical or trivial neutral moduli, apart from the dilaton. However, we show the existence of flat directions in the form of exactly marginal deformations and identify patterns of symmetry breaking where product gauge groups, realized at level one, are broken to their diagonal at higher level. We also describe an "inverse Gepner map" from Heterotic to Type II models that could be used, in certain non geometric settings, to define "effective" topological invariants.Comment: 37 page

Senescence and Sexual Selection in a Pelagic Copepod

The ecology of senescence in marine zooplankton is not well known. Here we demonstrate senescence effects in the marine copepod Oithona davisae and show how sex and sexual selection accelerate the rate of ageing in the males. We show that adult mortality increases and male mating capacity and female fertility decrease with age and that the deterioration in reproductive performance is faster for males. Males have a limited mating capacity because they can fertilize < 2 females day−1 and their reproductive life span is 10 days on average. High female encounter rates in nature (>10 day−1), a rapid age-dependent decline in female fertility, and a high mortality cost of mating in males are conducive to the development of male choosiness. In our experiments males in fact show a preference for mating with young females that are 3 times more fertile than 30-day old females. We argue that this may lead to severe male-male competition for young virgin females and a trade-off that favours investment in mate finding over maintenance. In nature, mate finding leads to a further elevated mortality of males, because these swim rapidly in their search for attractive partners, further relaxing fitness benefits of maintenance investments. We show that females have a short reproductive period compared to their average longevity but virgin females stay fertile for most of their life. We interpret this as an adaptation to a shortage of males, because a long life increases the chance of fertilization and/or of finding a high quality partner. The very long post reproductive life that many females experience is thus a secondary effect of such an adaptation

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9–RAGE–NF-κB–JunB pathway in brain metastases as a potential mediator of resistance in this organ. Targeting this pathway genetically or pharmacologically was sufficient to revert the WBRT resistance and increase therapeutic benefits in vivo at lower doses of radiation. In patients with primary melanoma, lung or breast adenocarcinoma developing brain metastasis, endogenous S100A9 levels in brain lesions correlated with clinical response to WBRT and underscored the potential of S100A9 levels in the blood as a noninvasive biomarker. Collectively, we provide a molecular framework to personalize WBRT and improve its efficacy through combination with a radiosensitizer that balances therapeutic benefit and toxicity.We thank all members of the Brain Metastasis Group and A. Chalmers, E. Wagner, O. Fernández-Capetillo, R. Ciérvide and A. Hidalgo for critical discussion of the manuscript; the CNIO Core Facilities for their excellent assistance; and Fox Chase Cancer Center Transgenic Facility for generation of S100A9 mice. We thank EuCOMM repository for providing S100A9 targeted embryonic stem cells. We also thank J. Massagué (MSKCC) for some of the BrM cell lines and M. Bosenberg (Yale) for the YUMM1.1 cell line. Samples from patients included in this study that provided by the Girona Biomedical Research Institute (IDIBGI) (Biobanc IDIBGI, B.0000872) are integrated into the Spanish National Biobanks Network and in the Xarxa de Bancs de Tumors de Catalunya (XBTC) financed by the Pla Director d’Oncologia de Catalunya. All patients consented to the storage of these samples in the biobank and for their use in research projects. This study was funded by MINECO (SAF2017-89643-R) (M.V.), Fundació La Marató de TV3 (201906-30-31-32) (J.B.-B., M.V. and A.C.), Fundación Ramón Areces (CIVP19S8163) (M.V.) and CIVP20S10662 (E.O.P.), Worldwide Cancer Research (19-0177) (M.V. and E.C.-J.M.), Cancer Research Institute (Clinic and Laboratory Integration Program CRI Award 2018 (54545) (M.V.), AECC (Coordinated Translational Groups 2017 (GCTRA16015SEOA) (M.V.), LAB AECC 2019 (LABAE19002VALI) (M.V.), ERC CoG (864759) (M.V.), Portuguese Foundation for Science and Technology (SFRH/bd/100089/2014) (C.M.), Boehringer-Ingelheim Fonds MD Fellowship (L.M.), La Caixa International PhD Program Fellowship-Marie Skłodowska-Curie (LCF/BQ/DI17/11620028) (P.G.-G.), La Caixa INPhINIT Fellowship (LCF/BQ/DI19/11730044) (A.P.-A.), MINECO-Severo Ochoa PhD Fellowship (BES-2017-081995) (L.A.-E.) and an AECC postdoctoral fellowship (POSTD19016PRIE) (N.P.). M.V. is an EMBO YIP member (4053). Additional support was provided by Gertrud and Erich Roggenbuck Stiftung (M.M.), Science Foundation Ireland Frontiers for the Future Award (19/FFP/6443) (L.Y.), Science Foundation Ireland Strategic Partnership Programme, Precision Oncology Ireland (18/SPP/3522) (L.Y.), Breast Cancer Now Fellowship Award with the generous support of Walk the Walk (2019AugSF1310) (D.V.), Science Foundation Ireland (20/FFP-P/8597) (D.V.), Paradifference Foundation (C.F.-T.), “la Caixa” Foundation (ID 100010434) (A.I.), European Union’s Horizon 2020 research and innovation programme under Marie Skłodowska-Curie grant agreement 847648 (CF/BQ/PI20/11760029) (A.I.), Champalimaud Centre for the Unknown (N.S.), Lisboa Regional Operational Programme (Lisboa 2020) (LISBOA01-0145-FEDER-022170) (N.S.), NCI (R01 CA227629; R01 CA218133) (S.I.G.), Fundació Roses Contra el Càncer (J.B.-B.), Ministerio de Universidades FPU Fellowship (FPU 18/00069) (P.T.), MICIN-Agencia Estatal de Investigación Fellowships (PRE2020-093032 and BES-2017-080415) (P.M. and E. Cintado, respectively), Ministerio de Ciencia, Innovación y Universidades-E050251 (PID2019-110292RB-I00) (J.L.T.), FCT (PTDC/MED-ONC/32222/2017) (C.C.F.), Fundação Millennium bcp (C.C.F.), private donations (C.C.F.) and the Foundation for Applied Cancer Research in Zurich (E.L.R. and M.W.)