Trastuzumab and pertuzumab without chemotherapy in early-stage HER2+ breast cancer: a plain language summary of the PHERGain study

This is a summary of a publication about the PHERGain study, which was published in The Lancet Oncology in May 2021. The study includes 376 women with a type of breast cancer called HER2-positive breast cancer that can be removed by surgery. In the study, researchers wanted to learn if participants could be treated with two medicines called trastuzumab and pertuzumab without the need for chemotherapy. To identify HER2-positive tumors with more sensitivity to anti-HER2 therapies, the researchers used a type of imaging called a FDG-PET scan to check how well the treatments were working.Participants took a treatment before surgery, consisting of either chemotherapy (docetaxel and carboplatin) plus trastuzumab and pertuzumab (group A) or trastuzumab and pertuzumab alone (plus hormone therapy if the tumor was hormone receptor-positive; group B). After two cycles of treatment, participants underwent a FDG-PET scan. Participants assigned to group A completed 6 cycles of treatment regardless of 18F-FDG-PET results. Participants in group B continued the same treatment until surgery if their FDG-PET scan showed the treatment was working. While participants who did not show a response started treatment with chemotherapy in addition to trastuzumab and pertuzumab. All participants then had surgery.The results revealed that, of the participants in group B who showed a response using FDG-PET scan, 37.9% achieved a disappearance of all invasive cancer in the breast and axillary lymph nodes. This rate appears to be higher than those reported in previous studies evaluating the same treatment. These participants also had less side effects and improved overall quality of life compared with participants taking chemotherapy plus trastuzumab and pertuzumab.Early monitoring of how well participants respond to treatment by FDG-PET scan seems to identify participants with operable HER2-positive breast cancer who were more likely to benefit from trastuzumab and pertuzumab without the need to have chemotherapy. The PHERGain study is still ongoing and results on long-term survival are expected to be released in 2023. Clinical Trial Registration: NCT03161353 (ClinicalTrials.gov)

Flux and Instanton Effects in Local F-theory Models and Hierarchical Fermion Masses

We study the deformation induced by fluxes and instanton effects on Yukawa couplings involving 7-brane intersections in local F-theory constructions. In the absence of non-perturbative effects, holomorphic Yukawa couplings do not depend on open string fluxes. On the other hand instanton effects (or gaugino condensation on distant 7-branes) do induce corrections to the Yukawas. The leading order effect may also be captured by the presence of closed string (1,2) IASD fluxes, which give rise to a non-commutative structure. We check that even in the presence of these non-perturbative effects the holomorphic Yukawas remain independent of magnetic fluxes. Although fermion mass hierarchies may be obtained from these non-perturbative effects, they would give identical Yukawa couplings for D-quark and Lepton masses in SU(5) F-theory GUT's, in contradiction with experiment. We point out that this problem may be solved by appropriately normalizing the wavefunctions. We show in a simple toy model how the presence of hypercharge flux may then be responsible for the difference between D-quarks and Lepton masses in local SU(5) GUT's.Comment: 84 pages, 1 figure. v2: minor corrections and references adde

Probing natural SUSY from stop pair production at the LHC

We consider the natural supersymmetry scenario in the framework of the R-parity conserving minimal supersymmetric standard model (called natural MSSM) and examine the observability of stop pair production at the LHC. We first scan the parameters of this scenario under various experimental constraints, including the SM-like Higgs boson mass, the indirect limits from precision electroweak data and B-decays. Then in the allowed parameter space we study the stop pair production at the LHC followed by the stop decay into a top quark plus a lightest neutralino or into a bottom quark plus a chargino. From detailed Monte Carlo simulations of the signals and backgrounds, we find the two decay modes are complementary to each other in probing the stop pair production, and the LHC with $\sqrt{s}= 14$ TeV and 100 $fb^{-1}$ luminosity is capable of discovering the stop predicted in natural MSSM up to 450 GeV. If no excess events were observed at the LHC, the 95% C.L. exclusion limits of the stop masses can reach around 537 GeV.Comment: 19 pages, 10 figures, version accepted by JHE

Yukawa hierarchies at the point of E8E_8 in F-theory

We analyse the structure of Yukawa couplings in local SU(5) F-theory models with $E_8$ enhancement. In this setting the $E_8$ symmetry is broken down to SU(5) by a 7-brane configuration described by T-branes, all the Yukawa couplings are generated in the vicinity of a point and only one family of quarks and leptons is massive at tree-level. The other two families obtain their masses when non-perturbative effects are taken into account, being hierarchically lighter than the third family. However, and contrary to previous results, we find that this hierarchy of fermion masses is not always appropriate to reproduce measured data. We find instead that different T-brane configurations breaking $E_8$ to SU(5) give rise to distinct hierarchical patterns for the holomorphic Yukawa couplings. Only some of these patterns allow to fit the observed fermion masses with reasonable local model parameter values, adding further constraints to the construction of F-theory GUTs. We consider an $E_8$ model where such appropriate hierarchy is realised and compute its physical Yukawas, showing that realistic charged fermions masses can indeed be obtained in this case.Comment: 46 pages + appendices, 5 figures. v2, added references and typos corrected, version accepted on JHEP. v3, typos correcte

Top Quarks as a Window to String Resonances

We study the discovery potential of string resonances decaying to $t\bar{t}$ final state at the LHC. We point out that top quark pair production is a promising and an advantageous channel for studying such resonances, due to their low Standard Model background and unique kinematics. We study the invariant mass distribution and angular dependence of the top pair production cross section via exchanges of string resonances. The mass ratios of these resonances and the unusual angular distribution may help identify their fundamental properties and distinguish them from other new physics. We find that string resonances for a string scale below 4 TeV can be detected via the $t\bar{t}$ channel, either from reconstructing the $t\bar{t}$ semi-leptonic decay or recent techniques in identifying highly boosted tops.Comment: 22 pages, 6 figure

A Threshold Value for the Time Delay to TB Diagnosis

The original publication is available at http:/www.plosone.orgIncludes bibliographyBackgound. In many communities where TB occurs at high incidence, the major force driving the epidemic is transmission. It is plausible that the typical long delay from the onset of infectious disease to diagnosis and commencement of treatment is almost certainly the major factor contributing to the high rate of transmission. Methodology/Principal Findings. This study is confined to communities which are epidemiologically relatively isolated and which have low HIV incidence. The consequences of delays to diagnosis are analyzed and the existence of a threshold delay value is demonstrated. It is shown that unless a sufficient number of cases are detected before this threshold, the epidemic will escalate. The method used for the analysis avoids the standard computer integration of systems of differential equations since the intention is to present a line of reasoning that reveals the essential dynamics of an epidemic in an intuitively clear way that is nevertheless quantitatively realistic. Conclusions/Significance. The analysis presented here shows that typical delays to diagnosis present a major obstacle to the control of a TB epidemic. Control can be achieved by optimizing the rapid identification of TB cases together with measures to increase the threshold value. A calculated and aggressive program is therefore necessary in order to bring about a reduction in the prevalence of TB in a community by decreasing the time to diagnosis in all its ramifications. Intervention strategies to increase the threshold value relative to the time to diagnosis and which thereby decrease disease incidence are discussed. © 2007 Uys et al.Publishers' Versio

Non-linear effects of drought under shade: reconciling physiological and ecological models in plant communities

The combined effects of shade and drought on plant performance and the implications for species interactions are highly debated in plant ecology. Empirical evidence for positive and negative effects of shade on the performance of plants under dry conditions supports two contrasting theoretical models about the role of shade under dry conditions: the trade-off and the facilitation hypotheses. We performed a meta-analysis of field and greenhouse studies evaluating the effects of drought at two or more irradiance levels on nine response variables describing plant physiological condition, growth, and survival. We explored differences in plant response across plant functional types, ecosystem types and methodological approaches. The data were best fit using quadratic models indicating a humped-back shape response to drought along an irradiance gradient for survival, whole plant biomass, maximum photosynthetic capacity, stomatal conductance and maximal photochemical efficiency. Drought effects were ameliorated at intermediate irradiance, becoming more severe at higher or lower light levels. This general pattern was maintained when controlling for potential variations in the strength of the drought treatment among light levels. Our quantitative meta-analysis indicates that dense shade ameliorates drought especially among drought-intolerant and shade-tolerant species. Wet tropical species showed larger negative effects of drought with increasing irradiance than semiarid and cold temperate species. Non-linear responses to irradiance were stronger under field conditions than under controlled greenhouse conditions. Non-linear responses to drought along the irradiance gradient reconciliate opposing views in plant ecology, indicating that facilitation is more likely within certain range of environmental conditions, fading under deep shade, especially for drought-tolerant species

Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish

BACKGROUND: The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII) including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26) and their receptors (HCRII). Despite the report of a near complete pufferfish (Takifugu rubripes) genome sequence, these genes remain undescribed in fish. RESULTS: We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF). Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. CONCLUSION: We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish

NOMAD spectrometer on the ExoMars trace gas orbiter mission: part 2—design, manufacturing, and testing of the ultraviolet and visible channel

NOMAD is a spectrometer suite on board the ESA/Roscosmos ExoMars Trace Gas Orbiter, which launched in March 2016. NOMAD consists of two infrared channels and one ultraviolet and visible channel, allowing the instrument to perform observations quasi-constantly, by taking nadir measurements at the day- and night-side, and during solar occultations. Here, in part 2 of a linked study, we describe the design, manufacturing, and testing of the ultraviolet and visible spectrometer channel called UVIS. We focus upon the optical design and working principle where two telescopes are coupled to a single grating spectrometer using a selector mechanism