Anniversary Bushfire Exhibit

Our team developed a travelling museum exhibit for the Fire Service Museum of Victoria to present the impact of major Victorian bushfires, and tell the stories of those affected by them. Our project group researched newspaper, book, and video archives and conducted interviews with firefighters. The gathered information was incorporated into the exhibit in the form of several displays, iPad-based interactive timelines, and museum artifacts. The Anniversary Bushfire Exhibit will be displayed in different locations across Victoria, thus, all exhibit components were designed to be portable and easily configurable to any room size

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

CMB-S4---the next-generation ground-based cosmic microwave background (CMB) experiment---is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the Universe, from the highest energies at the dawn of time through the growth of structure to the present day. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semi-analytic projection tool, targeted explicitly towards optimizing constraints on the tensor-to-scalar ratio, $r$, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2--3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments given a desired scientific goal. To form a closed-loop process, we couple this semi-analytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for $r > 0.003$ at greater than $5\sigma$, or, in the absence of a detection, of reaching an upper limit of $r < 0.001$ at $95\%$ CL.Comment: 24 pages, 8 figures, 9 tables, submitted to ApJ. arXiv admin note: text overlap with arXiv:1907.0447

CMB-S4

We describe the stage 4 cosmic microwave background ground-based experiment CMB-S4

CMB-S4: Forecasting Constraints on Primordial Gravitational Waves

Abstract: CMB-S4—the next-generation ground-based cosmic microwave background (CMB) experiment—is set to significantly advance the sensitivity of CMB measurements and enhance our understanding of the origin and evolution of the universe. Among the science cases pursued with CMB-S4, the quest for detecting primordial gravitational waves is a central driver of the experimental design. This work details the development of a forecasting framework that includes a power-spectrum-based semianalytic projection tool, targeted explicitly toward optimizing constraints on the tensor-to-scalar ratio, r, in the presence of Galactic foregrounds and gravitational lensing of the CMB. This framework is unique in its direct use of information from the achieved performance of current Stage 2–3 CMB experiments to robustly forecast the science reach of upcoming CMB-polarization endeavors. The methodology allows for rapid iteration over experimental configurations and offers a flexible way to optimize the design of future experiments, given a desired scientific goal. To form a closed-loop process, we couple this semianalytic tool with map-based validation studies, which allow for the injection of additional complexity and verification of our forecasts with several independent analysis methods. We document multiple rounds of forecasts for CMB-S4 using this process and the resulting establishment of the current reference design of the primordial gravitational-wave component of the Stage-4 experiment, optimized to achieve our science goals of detecting primordial gravitational waves for r > 0.003 at greater than 5σ, or in the absence of a detection, of reaching an upper limit of r < 0.001 at 95% CL

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Anniversary Bushfire Exhibit

Our team developed a travelling museum exhibit for the Fire Service Museum of Victoria to present the impact of major Victorian bushfires, and tell the stories of those affected by them. Our project group researched newspaper, book, and video archives and conducted interviews with firefighters. The gathered information was incorporated into the exhibit in the form of several displays, iPad-based interactive timelines, and museum artifacts. The Anniversary Bushfire Exhibit will be displayed in different locations across Victoria, thus, all exhibit components were designed to be portable and easily configurable to any room size.

The CanMars Mars Sample Return analogue mission

The return of samples from known locations on Mars is among the highest priority goals of the international planetary science community. A possible scenario for Mars Sample Return (MSR) is a series of 3 missions: sample cache, fetch, and retrieval. The NASA Mars 2020 mission represents the first cache mission and was the focus of the CanMars analogue mission described in this paper. The major objectives for CanMars included comparing the accuracy of selecting samples remotely using rover data versus a traditional human field party, testing the efficiency of remote science operations with periodic pre-planned strategic observations (Strategic Traverse Days), assessing the utility of realistic autonomous science capabilities to the remote science team, and investigating the factors that affect the quality of sample selection decision-making in light of returned sample analysis. CanMars was conducted over two weeks in November 2015 and continued over three weeks in October and November 2016 at an analogue site near Hanksville, Utah, USA, that was unknown to the Mission Control Team located at the University of Western Ontario (Western) in London, Ontario, Canada. This operations architecture for CanMars was based on the Phoenix and Mars Exploration Rover missions together with previous analogue missions led by Western with the Mission Control Team being divided into Planning and Science sub-teams. In advance of the 2015 operations, the Science Team used satellite data, chosen to mimic datasets available from Mars-orbiting instruments, to produce a predictive geological map for the landing ellipse and a set of hypotheses for the geology and astrobiological potential of the landing site. The site was proposed to consist of a series of weakly cemented multi-coloured sedimentary rocks comprising carbonates, sulfates, and clays, and sinuous ridges with a resistant capping unit, interpreted as inverted paleochannels. Both the 2015 CanMars mission, which achieved 11 sols of operations, and the first part of the 2016 mission (sols 12–21), were conducted with the Mars Exploration Science Rover (MESR) and a series of integrated and hand-held instruments designed to mimic the payload of the Mars 2020 rover. Part 2 of the 2016 campaign (sols 22–39) was implemented without the MESR rover and was conducted exclusively by the field team as a Fast Motion Field Test (FMFT) with hand-carried instruments and with the equivalent of three sols of operations being executed in a single actual day. A total of 8 samples were cached during the 39 sols from which the Science Team prioritized 3 for “return to Earth”. Various science autonomy capabilities, based on flight-proven or near-future techniques intended for actual rover missions, were tested throughout the 2016 CanMars activities, with autonomous geological classification and targeting and autonomous pointing refinement being used extensively during the FMFT. Blind targeting, contingency sequencing, and conditional sequencing were also employed. Validation of the CanMars cache mission was achieved through various methods and approaches. The use of dedicated documentarians in mission control provided a detailed record of how and why decisions were made. Multiple separate field validation exercises employing humans using traditional geological techniques were carried out. All 8 of the selected samples plus a range of samples from the landing site region, collected out-of-simulation, have been analysed using a range of laboratory analytical techniques. A variety of lessons learned for both future analogue missions and planetary exploration missions are provided, including: dynamic collaboration between the science and planning teams as being key for mission success; the more frequent use of spectrometers and micro-imagers having remote capabilities rather than contact instruments; the utility of strategic traverse days to provide additional time for scientific discussion and meaningful interpretation of the data; the benefit of walkabout traverse strategies along with multi-sol plans with complex decisions trees to acquire a large amount of contextual data; and the availability of autonomous geological targeting, which enabled complex multi-sol plans gathering large suites of geological and geochemical survey data. Finally, the CanMars MSR activity demonstrated the utility of analogue missions in providing opportunities to engage and educate children and the public, by providing tangible hands-on linkages between current robotic missions and future human space missions. Public education and outreach was a priority for CanMars and a dedicated lead coordinated a strong presence on social media (primarily Twitter and Facebook), articles in local, regional, and national news networks, and interaction with the local community in London, Ontario. A further core objective of CanMars was to provide valuable learning opportunities to students and post-doctoral fellows in preparation for future planetary exploration missions. A learning goals survey conducted at the end of the 2016 activities had 90% of participants “somewhat agreeing” or “strongly agreeing” that participation in the mission has helped them to increase their understanding of the four learning outcomes

Clinical Practice Guideline: Hoarseness (Dysphonia) (Update) Executive Summary

Objective This guideline provides evidence-based recommendations on treating patients presenting with dysphonia, which is characterized by altered vocal quality, pitch, loudness, or vocal effort that impairs communication and/or quality of life. Dysphonia affects nearly one-third of the population at some point in its life. This guideline applies to all age groups evaluated in a setting where dysphonia would be identified or managed. It is intended for all clinicians who are likely to diagnose and treat patients with dysphonia. Purpose The primary purpose of this guideline is to improve the quality of care for patients with dysphonia, based on current best evidence. Expert consensus to fill evidence gaps, when used, is explicitly stated and supported with a detailed evidence profile for transparency. Specific objectives of the guideline are to reduce inappropriate variations in care, produce optimal health outcomes, and minimize harm. For this guideline update, the American Academy of Otolaryngology-Head and Neck Surgery Foundation selected a panel representing the fields of advanced practice nursing, bronchoesophagology, consumer advocacy, family medicine, geriatric medicine, internal medicine, laryngology, neurology, otolaryngology-head and neck surgery, pediatrics, professional voice, pulmonology, and speech-language pathology. Action Statements The guideline update group made strong recommendations for the following key action statements (KASs): (1) Clinicians should assess the patient with dysphonia by history and physical examination to identify factors where expedited laryngeal evaluation is indicated. These include but are not limited to recent surgical procedures involving the head, neck, or chest; recent endotracheal intubation; presence of concomitant neck mass; respiratory distress or stridor; history of tobacco abuse; and whether the patient is a professional voice user. (2) Clinicians should advocate voice therapy for patients with dysphonia from a cause amenable to voice therapy. The guideline update group made recommendations for the following KASs: (1) Clinicians should identify dysphonia in a patient with altered voice quality, pitch, loudness, or vocal effort that impairs communication or reduces quality of life (QOL). (2) Clinicians should assess the patient with dysphonia by history and physical examination for underlying causes of dysphonia and factors that modify management. (3) Clinicians should perform laryngoscopy, or refer to a clinician who can perform laryngoscopy, when dysphonia fails to resolve or improve within 4 weeks or irrespective of duration if a serious underlying cause is suspected. (4) Clinicians should perform diagnostic laryngoscopy, or refer to a clinician who can perform diagnostic laryngoscopy, before prescribing voice therapy and document/communicate the results to the speech-language pathologist (SLP). (5) Clinicians should advocate for surgery as a therapeutic option for patients with dysphonia with conditions amenable to surgical intervention, such as suspected malignancy, symptomatic benign vocal fold lesions that do not respond to conservative management, or glottic insufficiency. (6) Clinicians should offer, or refer to a clinician who can offer, botulinum toxin injections for the treatment of dysphonia caused by spasmodic dysphonia and other types of laryngeal dystonia. (7) Clinicians should inform patients with dysphonia about control/preventive measures. (8) Clinicians should document resolution, improvement or worsened symptoms of dysphonia, or change in QOL of patients with dysphonia after treatment or observation. The guideline update group made a strong recommendation against 1 action: (1) Clinicians should not routinely prescribe antibiotics to treat dysphonia. The guideline update group made recommendations against other actions: (1) Clinicians should not obtain computed tomography (CT) or magnetic resonance imaging (MRI) for patients with a primary voice complaint prior to visualization of the larynx. (2) Clinicians should not prescribe antireflux medications to treat isolated dysphonia, based on symptoms alone attributed to suspected gastroesophageal reflux disease (GERD) or laryngopharyngeal reflux (LPR), without visualization of the larynx. (3) Clinicians should not routinely prescribe corticosteroids in patients with dysphonia prior to visualization of the larynx. The policy level for the following recommendation about laryngoscopy at any time was an option: (1) Clinicians may perform diagnostic laryngoscopy at any time in a patient with dysphonia. Differences from Prior Guideline (1) Incorporating new evidence profiles to include the role of patient preferences, confidence in the evidence, differences of opinion, quality improvement opportunities, and any exclusion to which the action statement does not apply (2) Inclusion of 3 new guidelines, 16 new systematic reviews, and 4 new randomized controlled trials (3) Inclusion of a consumer advocate on the guideline update group (4) Changes to 9 KASs from the original guideline (5) New KAS 3 (escalation of care) and KAS 13 (outcomes) (6) Addition of an algorithm outlining KASs for patients with dysphonia