Physics of Interacting Supernova Light Curves

When a supernova explodes within a dense circumstellar environment, it creates a highly energetic shockwave that can be observed across the entire electromagnetic spectrum. The shockwave emission can be used as an observational probe to infer the properties of the circumstellar medium (CSM), and learn about how the progenitor star lived out its final moments before death. Numerous explanations have been proposed to explain the CSM, with each physical model varying in the amount of expelled mass, its spatial extent, and geometry. Due to the inherent difficulty in modeling the shock emission from circumstellar interaction, simplified analytic and numerical models are widely used to interpret observational data. However, the assumptions made in these simplified models, their range of applicability, and their ability to accurately infer physical quantities is not clear. In this thesis, I have extended the Monte Carlo radiative transfer code Sedona with advanced multi-physics simulation capabilities, including one-dimensional finite-volume arbitrary Lagrangian-Eulerian hydrodynamics, inline multi-group non-LTE opacities, and non-thermal electron populations. I leverage these capabilities to perform extensive radiation hydrodynamics simulations of interacting supernovae, and construct a broad theoretical framework with which to interpret their resulting light curves. I find that CSM interaction can produce a wide range of light curve durations and luminosities, with timescales ranging from hours to months. I demonstrate their viability in powering a broad range of unusual supernovae. In particular, I show how CSM interaction is a plausible explanation for the recently-discovered class of fast blue optical transients, and constrain the CSM properties inferred for this type. For the specific case of the Type II subclass of interacting supernovae, I perform non-equilibrium multi-group radiation hydrodynamics simulations to construct time-dependent panchromatic radio to X-ray spectral energy distributions of the combined supernova and shock emission. I find that analytic expectations used in the literature disagree with the numerical light curves due to an evolving non-thermal electron energy population with contributions from both the forward and reverse shocks, compounded by the effects of inverse Compton scattering and photo-absorption by a cold dense shell

Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines - Exploratory Analyses within a Randomised Controlled Trial

Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.peer-reviewe

Predictions of summertime overheating: comparison of dynamic thermal models and measurements in synthetically occupied test houses

Summertime overheating in UK dwellings is seen as a risk to occupants' health and well-being. Dynamic thermal simulation programs are widely used to assess the overheating risk in new homes, but how accurate are the predictions? Results from two different dynamic thermal simulation programs used by four different experienced modellers are compared with measurements from a pair of traditional, semi-detached test houses. The synthetic occupancy in the test houses replicated curtain operation and the CIBSE TM59 internal heat gain profiles and internal door opening profiles. In one house, the windows were always closed and in the other they operated following the TM59 protocol. Sensors monitored the internal temperatures in five rooms and the local weather during a 21-day period in the summer of 2017. Model evaluation took place in two phases: blind and open. In the blind phase, modellers received information about the houses, the occupancy profiles and the weather conditions. In the open phase, modellers received the test house temperature measurements and, with the other modellers, adjusted their models to try and improve predictions. The data provided to modellers is openly available as supplementary information to this paper. In both phases, during warm weather, the models consistently predicted higher peak temperatures and larger diurnal swings than were measured. The models' predicted hours of overheating were compared with the measured hours using the CIBSE static threshold of 26℃ for bedrooms and the BSEN15251 Category II threshold for living rooms. The models developed in each phase were also used to predict the annual hours of overheating using the CIBSE TM59 procedure. The inter-model variation was quantified as the Simulation Resolution. For these houses, the blind phase models produced Simulation Resolution values of approximately 3% ± 3 percentage points for TM59 Criterion A and 1% ± 1 percentage point for TM59 Criterion B. The Simulation Resolution concept offers a valuable aid to modellers when assessing the compliance of dwellings with the TM59 overheating criteria. Further work to produce Simulation Resolution values for different dwelling archetypes and weather conditions is recommended

Endovascular revascularization strategies for aortoiliac and femoropopliteal artery disease: a meta-analysis.

AIMS Optimal endovascular management of intermittent claudication (IC) remains disputed. This systematic review and meta-analysis compares efficacy and safety outcomes for balloon angioplasty (BA), bare-metal stents (BMS), drug-coated balloons (DCB), drug-eluting stents (DES), covered stents, and atherectomy. METHODS AND RESULTS Electronic databases were searched for randomized, controlled trials (RCT) from inception through November 2021. Efficacy outcomes were primary patency, target-lesion revascularization (TLR), and quality-of-life (QoL). Safety endpoints were all-cause mortality and major amputation. Outcomes were evaluated at short-term (<1 year), mid-term (1-2 years), and long-term (≥2 years) follow-up. The study was registered on PROSPERO (CRD42021292639). Fifty-one RCTs enrolling 8430 patients/lesions were included. In femoropopliteal disease of low-to-intermediate complexity, DCBs were associated with higher likelihood of primary patency [short-term: odds ratio (OR) 3.21, 95% confidence interval (CI) 2.44-4.24; long-term: OR 2.47, 95% CI 1.93-3.16], lower TLR (short-term: OR 0.33, 95% CI 0.22-0.49; long-term: OR 0.42, 95% CI 0.29-0.60) and similar all-cause mortality risk, compared with BA. Primary stenting using BMS was associated with improved short-to-mid-term patency and TLR, but similar long-term efficacy compared with provisional stenting. Mid-term patency (OR 1.64, 95% CI 0.89-3.03) and TLR (OR 0.50, 95% CI 0.22-1.11) estimates were comparable for DES vs. BMS. Atherectomy, used independently or adjunctively, was not associated with efficacy benefits compared with drug-coated and uncoated angioplasty, or stenting approaches. Paucity and heterogeneity of data precluded pooled analysis for aortoiliac disease and QoL endpoints. CONCLUSION Certain devices may provide benefits in femoropopliteal disease, but comparative data in aortoiliac arteries is lacking. Gaps in evidence quantity and quality impede identification of the optimal endovascular approach to IC

Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova: Pre-explosion Emission and a Rapidly Rising Luminous Transient

We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 ± 0.1 mag hr-1) and luminous (Mg,peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (Lbol ≳ 3 × 1044 erg s-1), the short rise time (trise = 3 days in g band), and the blue colors at peak (g-r ∼ -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (Teff ≳ 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (Mg ∼ Mr ≈ mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E γ,iso \u3c 4.9 × 10 48 erg, a limit on X-ray emission LX \u3c 1040 erg s-1, and a limit on radio emission ν Lν ≲ 1037 erg s-1. Taken together, we find that the early (\u3c 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3 × 1014 cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (\u3e 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study.

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH

The Swiss Primary Hypersomnolence and Narcolepsy Cohort study (SPHYNCS): Study protocol for a prospective, multicentre cohort observational study

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead.

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%. To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals. In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85). Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety 'Mode of Action' framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology

The Death Throes of a Stripped Massive Star: An Eruptive Mass-Loss History Encoded in Pre-Explosion Emission, a Rapidly Rising Luminous Transient, and a Broad-Lined Ic Supernova SN2018gep

We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.3 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The rapid rise to peak bolometric luminosity and blue colors at peak (t_(rise)∼0.5-3 days, L_(bol)≳3×10^(44) erg sec^(−1), g−r = −0.3) resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) < 4.9×10^(48) erg, a limit on X-ray emission L_X < 10^(40) erg sec^(−1), and a limit on radio emission νL_ν ≲ 10^(37) erg sec^(−1). Taken together, we find that the data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3×10^(14)cm) that was ejected in eruptive pre-explosion mass-loss episodes