Quantum creation and inflationary universes: a critical appraisal

We contrast the possibility of inflation starting a) from the universe's inception or b) from an earlier non-inflationary state. Neither case is ideal since a) assumes quantum mechanical reasoning is straightforwardly applicable to the early universe; while case b) requires that a singularity still be present. Further, in agreement with Vachaspati and Trodden [1] case b) can only solve the horizon problem if the non-inflationary phase has equation of state $\gamma<4/3$.Comment: 21 pages Late

Tisotumab Vedotin in Combination With Carboplatin, Pembrolizumab, or Bevacizumab in Recurrent or Metastatic Cervical Cancer: Results From the innovaTV 205/GOG-3024/ENGOT-cx8 Study.

PURPOSE: Tissue factor is highly expressed in cervical carcinoma and can be targeted by tisotumab vedotin (TV), an antibody-drug conjugate. This phase Ib/II study evaluated TV in combination with bevacizumab, pembrolizumab, or carboplatin for recurrent or metastatic cervical cancer (r/mCC). METHODS: This open-label, multicenter study (ClinicalTrials.gov identifier: NCT03786081) included dose-escalation arms that assessed dose-limiting toxicities (DLTs) and identified the recommended phase II dose (RP2D) of TV in combination with bevacizumab (arm A), pembrolizumab (arm B), or carboplatin (arm C). The dose-expansion arms evaluated TV antitumor activity and safety at RP2D in combination with carboplatin as first-line (1L) treatment (arm D) or with pembrolizumab as 1L (arm E) or second-/third-line (2L/3L) treatment (arm F). The primary end point of dose expansion was objective response rate (ORR). RESULTS: A total of 142 patients were enrolled. In dose escalation (n = 41), no DLTs were observed; the RP2D was TV 2 mg/kg plus bevacizumab 15 mg/kg on day 1 once every 3 weeks, pembrolizumab 200 mg on day 1 once every 3 weeks, or carboplatin AUC 5 on day 1 once every 3 weeks. In dose expansion (n = 101), the ORR was 54.5% (n/N, 18/33; 95% CI, 36.4 to 71.9) with 1L TV + carboplatin (arm D), 40.6% (n/N, 13/32; 95% CI, 23.7 to 59.4) with 1L TV + pembrolizumab (arm E), and 35.3% (12/34; 19.7 to 53.5) with 2L/3L TV + pembrolizumab (arm F). The median duration of response was 8.6 months, not reached, and 14.1 months, in arms D, E, and F, respectively. Grade ≥3 adverse events (≥15%) were anemia, diarrhea, nausea, and thrombocytopenia in arm D and anemia in arm F (none ≥15%, arm E). CONCLUSION: TV in combination with bevacizumab, carboplatin, or pembrolizumab demonstrated manageable safety and encouraging antitumor activity in treatment-naive and previously treated r/mCC

The fitness consequences of inbreeding in natural populations and their implications for species conservation – a systematic map

Background: Threatened species often have small and isolated populations where mating among relatives can result in inbreeding depression increasing extinction risk. Effective management is hampered by a lack of syntheses summarising the magnitude of, and variation in inbreeding depression. Here we describe the nature and scope of the literature examining phenotypic/fitness consequences of inbreeding, to provide a foundation for future syntheses and management. Methods: We searched the literature for articles documenting the impact of inbreeding in natural populations. Article titles, abstracts and full-texts were assessed against a priori defined criteria, and information relating to study design, quality and other factors that may influence inbreeding responses (e.g. population size) was extracted from relevant articles. Results: The searches identified 11457 articles, of which 614 were assessed as relevant and included in the systematic map (corresponding to 703 distinct studies). Most studies (663) assessed within-population inbreeding resulting from self-fertilisation or consanguineous pairings, while 118 studies assessed among-population inbreeding due to drift load. Plants were the most studied taxon (469 studies) followed by insects (52 studies) and birds (43 studies). Most studies investigated the effects of inbreeding on components of fitness (e.g. survival or fecundity; 648 studies) but measurements were typically under laboratory/greenhouse conditions (486 studies). Observations were also often restricted to the first inbred generation (607 studies) and studies frequently lacked contextual information (e.g. population size). Conclusions: Our systematic map describes the scope and quality of the evidence describing the phenotypic consequences of inbreeding. The map reveals substantial evidence relating to inbreeding responses exists, but highlights information is still limited for some aspects, including the effects of multiple generations of inbreeding. The systematic map allowed us to define several conservation-relevant questions, where sufficient data exists to support systematic reviews, e.g. How do inbreeding responses vary with population size? However, we found that such syntheses are likely to be constrained by incomplete reporting of critical contextual information. Our systematic map employed the same rigorous literature assessment methods as systematic review, including a novel survey of study quality and thus provides a robust foundation to guide future research and syntheses seeking to inform conservation decision-making

Spike-Timing Precision and Neuronal Synchrony Are Enhanced by an Interaction between Synaptic Inhibition and Membrane Oscillations in the Amygdala

The basolateral complex of the amygdala (BLA) is a critical component of the neural circuit regulating fear learning. During fear learning and recall, the amygdala and other brain regions, including the hippocampus and prefrontal cortex, exhibit phase-locked oscillations in the high delta/low theta frequency band (∼2–6 Hz) that have been shown to contribute to the learning process. Network oscillations are commonly generated by inhibitory synaptic input that coordinates action potentials in groups of neurons. In the rat BLA, principal neurons spontaneously receive synchronized, inhibitory input in the form of compound, rhythmic, inhibitory postsynaptic potentials (IPSPs), likely originating from burst-firing parvalbumin interneurons. Here we investigated the role of compound IPSPs in the rat and rhesus macaque BLA in regulating action potential synchrony and spike-timing precision. Furthermore, because principal neurons exhibit intrinsic oscillatory properties and resonance between 4 and 5 Hz, in the same frequency band observed during fear, we investigated whether compound IPSPs and intrinsic oscillations interact to promote rhythmic activity in the BLA at this frequency. Using whole-cell patch clamp in brain slices, we demonstrate that compound IPSPs, which occur spontaneously and are synchronized across principal neurons in both the rat and primate BLA, significantly improve spike-timing precision in BLA principal neurons for a window of ∼300 ms following each IPSP. We also show that compound IPSPs coordinate the firing of pairs of BLA principal neurons, and significantly improve spike synchrony for a window of ∼130 ms. Compound IPSPs enhance a 5 Hz calcium-dependent membrane potential oscillation (MPO) in these neurons, likely contributing to the improvement in spike-timing precision and synchronization of spiking. Activation of the cAMP-PKA signaling cascade enhanced the MPO, and inhibition of this cascade blocked the MPO. We discuss these results in the context of spike-timing dependent plasticity and modulation by neurotransmitters important for fear learning, such as dopamine

Buses, cars, bicycles and walkers the influence of the type of human transport on the flight responses of waterbirds

One way to manage disturbance to waterbirds in natural areas where humans require access is to promote the occurrence of stimuli for which birds tolerate closer approaches, and so cause fewer responses. We conducted 730 experimental approaches to 39 species of waterbird, using five stimulus types (single walker, three walkers, bicycle, car and bus) selected to mimic different human management options available for a controlled access, Ramsar-listed wetland. Across species, where differences existed (56% of 25 cases), motor vehicles always evoked shorter flight-initiation distances (FID) than humans on foot. The influence of stimulus type on FID varied across four species for which enough data were available for complete cross-stimulus analysis. All four varied FID in relation to stimuli, differing in 4 to 7 of 10 possible comparisons. Where differences occurred, the effect size was generally modest, suggesting that managing stimulus type (e.g. by requiring people to use vehicles) may have species-specific, modest benefits, at least for the waterbirds we studied. However, different stimulus types have different capacities to reduce the frequency of disturbance (i.e. by carrying more people) and vary in their capacity to travel around important habita

Search for high-mass diboson resonances with boson-tagged jets in proton-proton collisions at √s=8 TeV with the ATLAS detector

A search is performed for narrow resonances decaying into WW, WZ, or ZZ boson pairs using 20.3 fb−1 of proton-proton collision data at a centre-of-mass energy of √s=8 TeV recorded with the ATLAS detector at the Large Hadron Collider. Diboson resonances with masses in the range from 1.3 to 3.0 TeV are sought after using the invariant mass distribution of dijets where both jets are tagged as a boson jet, compatible with a highly boosted W or Z boson decaying to quarks, using jet mass and substructure properties. The largest deviation from a smoothly falling background in the observed dijet invariant mass distribution occurs around 2 TeV in the WZ channel, with a global significance of 2.5 standard deviations. Exclusion limits at the 95% confidence level are set on the production cross section times branching ratio for the WZ final state of a new heavy gauge boson, W′, and for the WW and ZZ final states of Kaluza-Klein excitations of the graviton in a bulk Randall-Sundrum model, as a function of the resonance mass. W′ bosons with couplings predicted by the extended gauge model in the mass range from 1.3 to 1.5 TeV are excluded at 95% confidence level

Search for W W/W Z resonance production in ℓνqq final states in pp collisions at √s=13 TeV with the ATLAS detector

A search is conducted for new resonances decaying into a W W or W Z boson pair, where one W boson decays leptonically and the other W or Z boson decays hadronically. It is based on proton-proton collision data with an integrated luminosity of 36.1 fb −1 collected with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of s=13 TeV in 2015 and 2016. The search is sensitive to diboson resonance production via vector-boson fusion as well as quark-antiquark annihilation and gluon-gluon fusion mechanisms. No significant excess of events is observed with respect to the Standard Model backgrounds. Several benchmark models are used to interpret the results. Limits on the production cross section are set for a new narrow scalar resonance, a new heavy vector-boson and a spin-2 Kaluza-Klein graviton.[Figure not available: see fulltext.]

Search for heavy resonances decaying into WW in the eνμν eνμν final state in pp collisions at √s=13 TeV with the ATLAS detector

A search for neutral heavy resonances is performed in the WW→eνμν decay channel using pp collision data corresponding to an integrated luminosity of 36.1fb−1, collected at a centre-of-mass energy of 13TeV by the ATLAS detector at the Large Hadron Collider. No evidence of such heavy resonances is found. In the search for production via the quark–antiquark annihilation or gluon–gluon fusion process, upper limits on σX×B(X→WW) as a function of the resonance mass are obtained in the mass range between 200GeV GeV and up to 5TeV for various benchmark models: a Higgs-like scalar in different width scenarios, a two-Higgs-doublet model, a heavy vector triplet model, and a warped extra dimensions model. In the vector-boson fusion process, constraints are also obtained on these resonances, as well as on a Higgs boson in the Georgi–Machacek model and a heavy tensor particle coupling only to gauge bosons

Search for long-lived charginos based on a disappearing-track signature in pp collisions at s √ =13 s=13 TeV with the ATLAS detector

This paper presents a search for direct electroweak gaugino or gluino pair production with a chargino nearly mass-degenerate with a stable neutralino. It is based on an integrated luminosity of 36.1 fb−1 of pp collisions at s √ =13 s=13 TeV collected by the ATLAS experiment at the LHC. The final state of interest is a disappearing track accompanied by at least one jet with high transverse momentum from initial-state radiation or by four jets from the gluino decay chain. The use of short track segments reconstructed from the innermost tracking layers significantly improves the sensitivity to short chargino lifetimes. The results are found to be consistent with Standard Model predictions. Exclusion limits are set at 95% confidence level on the mass of charginos and gluinos for different chargino lifetimes. For a pure wino with a lifetime of about 0.2 ns, chargino masses up to 460 GeV are excluded. For the strong production channel, gluino masses up to 1.65 TeV are excluded assuming a chargino mass of 460 GeV and lifetime of 0.2 ns