Dr. Sharpe was a leading eye movement researcher who had also been the editor of this journal. We wish to mark the 10th anniversary of his death by providing a sense of what he had achieved through some examples of his research.

We present the most sensitive and detailed view of the neutral hydrogen ( ${\rm H\small I}$ ) emission associated with the Small Magellanic Cloud (SMC), through the combination of data from the Australian Square Kilometre Array Pathfinder (ASKAP) and Parkes (Murriyang), as part of the Galactic Australian Square Kilometre Array Pathfinder (GASKAP) pilot survey. These GASKAP-HI pilot observations, for the first time, reveal ${\rm H\small I}$ in the SMC on similar physical scales as other important tracers of the interstellar medium, such as molecular gas and dust. The resultant image cube possesses an rms noise level of 1.1 K ( $1.6\,\mathrm{mJy\ beam}^{-1}$ ) $\mathrm{per}\ 0.98\,\mathrm{km\ s}^{-1}$ spectral channel with an angular resolution of $30^{\prime\prime}$ ( ${\sim}10\,\mathrm{pc}$ ). We discuss the calibration scheme and the custom imaging pipeline that utilises a joint deconvolution approach, efficiently distributed across a computing cluster, to accurately recover the emission extending across the entire ${\sim}25\,\mathrm{deg}^2$ field-of-view. We provide an overview of the data products and characterise several aspects including the noise properties as a function of angular resolution and the represented spatial scales by deriving the global transfer function over the full spectral range. A preliminary spatial power spectrum analysis on individual spectral channels reveals that the power law nature of the density distribution extends down to scales of 10 pc. We highlight the scientific potential of these data by comparing the properties of an outflowing high-velocity cloud with previous ASKAP+Parkes ${\rm H\small I}$ test observations.

In this era of spatially resolved observations of planet-forming disks with Atacama Large Millimeter Array (ALMA) and large ground-based telescopes such as the Very Large Telescope (VLT), Keck, and Subaru, we still lack statistically relevant information on the quantity and composition of the material that is building the planets, such as the total disk gas mass, the ice content of dust, and the state of water in planetesimals. SPace Infrared telescope for Cosmology and Astrophysics (SPICA) is an infrared space mission concept developed jointly by Japan Aerospace Exploration Agency (JAXA) and European Space Agency (ESA) to address these questions. The key unique capabilities of SPICA that enable this research are (1) the wide spectral coverage $10{-}220\,\mu\mathrm{m}$ , (2) the high line detection sensitivity of $(1{-}2) \times 10^{-19}\,\mathrm{W\,m}^{-2}$ with $R \sim 2\,000{-}5\,000$ in the far-IR (SAFARI), and $10^{-20}\,\mathrm{W\,m}^{-2}$ with $R \sim 29\,000$ in the mid-IR (SPICA Mid-infrared Instrument (SMI), spectrally resolving line profiles), (3) the high far-IR continuum sensitivity of 0.45 mJy (SAFARI), and (4) the observing efficiency for point source surveys. This paper details how mid- to far-IR infrared spectra will be unique in measuring the gas masses and water/ice content of disks and how these quantities evolve during the planet-forming period. These observations will clarify the crucial transition when disks exhaust their primordial gas and further planet formation requires secondary gas produced from planetesimals. The high spectral resolution mid-IR is also unique for determining the location of the snowline dividing the rocky and icy mass reservoirs within the disk and how the divide evolves during the build-up of planetary systems. Infrared spectroscopy (mid- to far-IR) of key solid-state bands is crucial for assessing whether extensive radial mixing, which is part of our Solar System history, is a general process occurring in most planetary systems and whether extrasolar planetesimals are similar to our Solar System comets/asteroids. We demonstrate that the SPICA mission concept would allow us to achieve the above ambitious science goals through large surveys of several hundred disks within $\sim\!2.5$ months of observing time.

In view of the increasing complexity of both cardiovascular implantable electronic devices (CIEDs) and patients in the current era, practice guidelines, by necessity, have become increasingly specific. This document is an expert consensus statement that has been developed to update and further delineate indications and management of CIEDs in pediatric patients, defined as ≤21 years of age, and is intended to focus primarily on the indications for CIEDs in the setting of specific disease categories. The document also highlights variations between previously published adult and pediatric CIED recommendations and provides rationale for underlying important differences. The document addresses some of the deterrents to CIED access in low- and middle-income countries and strategies to circumvent them. The document sections were divided up and drafted by the writing committee members according to their expertise. The recommendations represent the consensus opinion of the entire writing committee, graded by class of recommendation and level of evidence. Several questions addressed in this document either do not lend themselves to clinical trials or are rare disease entities, and in these instances recommendations are based on consensus expert opinion. Furthermore, specific recommendations, even when supported by substantial data, do not replace the need for clinical judgment and patient-specific decision-making. The recommendations were opened for public comment to Pediatric and Congenital Electrophysiology Society (PACES) members and underwent external review by the scientific and clinical document committee of the Heart Rhythm Society (HRS), the science advisory and coordinating committee of the American Heart Association (AHA), the American College of Cardiology (ACC), and the Association for European Paediatric and Congenital Cardiology (AEPC). The document received endorsement by all the collaborators and the Asia Pacific Heart Rhythm Society (APHRS), the Indian Heart Rhythm Society (IHRS), and the Latin American Heart Rhythm Society (LAHRS). This document is expected to provide support for clinicians and patients to allow for appropriate CIED use, appropriate CIED management, and appropriate CIED follow-up in pediatric patients.

ABSTRACT IMPACT: We compare the cost-effectiveness of treatments for early prostate cancer, and propose how to maximize the value of care within an increasingly cost-constrained healthcare climate. OBJECTIVES/GOALS: Each year 192,000 men in the United States are diagnosed with prostate cancer. With various treatment options available, there is a growing role for cost-effectiveness analyses which may help maximize the value of care to the patient. In this review we compare the cost-effectiveness of primary treatments for clinically localized prostate cancer. METHODS/STUDY POPULATION: In this systematic review we aim to compare the cost-effectiveness or cost-utility of primary treatment strategies for clinically localized prostate cancer. This review, which adheres to 2009 PRISMA guidelines, included studies of men with clinically localized prostate cancer comparing at least two treatment strategies using the incremental cost-effectiveness ratio (ICER). We included analyses only of the United States healthcare system with at least 10 years of follow-up. These studies were published from 2006 to 2019 and generally included men with low or low to intermediate risk prostate cancer. Most studies reported outcomes for men age 65-70. All studies were prospective simulated trials and used a Markov model to simulate patient outcomes. RESULTS/ANTICIPATED RESULTS: Ten articles were included in the analysis. All studies used a Markov model to simulate a randomized trial. Six studies primarily compared radiation modalities, and four compared observation with immediate treatment. There was substantial heterogeneity in treatment protocols and the patients being simulated. Sensitivity analyses showed these models to be influenced by utility values and length of follow-up. A meta-analysis was not possible as no studies reported the variance of the primary outcome. Heterogeneity in study design limited comparisons of treatments across studies. However, these models were sensitive to patient-specific clinical factors, including life expectancy and the utility during and after each treatment. DISCUSSION/SIGNIFICANCE OF FINDINGS: These studies indicate collectively that the cost-effectiveness of prostate cancer treatment for similarly staged men may be heavily impacted by comorbidities and personal preferences. As the US moves towards value-based care, patient preferences may continue to drive the preferred treatment for newly diagnosed prostate cancer.

Previous studies have reported the basic reproduction number (R0) of coronavirus disease from publicly reported data that lack information such as onset of symptoms, presence of importations or known super-spreading events. Using data from the Republic of Korea, we illustrated how estimates of R0 can be biased and provided improved estimates with more detailed data. We used COVID-19 contact trace system in Korea, which can provide symptom onset date and also serial intervals between contacted people. The total R0 was estimated as 2.10 (95% confidence interval (CI) 1.84–2.42). Also, early transmission of COVID-19 differed by regional or social behaviours of the population. Regions affected by a specific church cluster, which showed a rapid and silent transmission under non-official religious meetings, had a higher R0 of 2.40 (95% CI 2.08–2.77).

Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.

This paper investigates and questions the relevance of product-centric circularity indicators in a product design context. To do so, reviews of eco-design tools and critical analyses of circularity indicators at the micro level of circular economy implementation are combined with a new workshop experimenting four of these indicators with the aim to improve the circularity performance of an industrial product. On this basis, the four tool-based circularity indicators tested are mapped on the engineering design and development process, and are positioned among the pool of main eco-design tools.

Introduction: Many cardiac arrest survivors die later due to hemorrhage or thromboembolism, thought to be caused by acquired coagulopathy in post-cardiac arrest syndrome (PCAS) from shock and reperfusion injury. Understanding PCAS is a priority identified by the AHA for the prevention of complications in cardiac arrest survivors. Shock dysregulates both coagulation and fibrinolysis. The key effector enzyme thrombin (Th), is responsible for both up- and down-regulating coagulation and fibrinolysis. Measuring early Th activity may allow for predicting PCAS coagulopathy, and early medical intervention in the ED. Therefore, we aimed to characterize the time-course profile of early coagulation using an established pig model of cardiac arrest. Methods: Yorkshire pigs were anaesthetised and intubated, had VF-arrest induced by pacing, and were resuscitated per ACLS. Rotational thromboelastometry (ROTEM) was performed on whole blood at four times: baseline, intra-arrest, post-arrest, and death, using the fibrin-based test with tissue factor to initiate clotting in the presence of a platelet inhibitor cytochalasin D (FIBTEM). Clot time (CT), clot formation time (CFT), alpha-angle during clot formation (Alpha), clot amplitude at 10 min (A10), maximum clot firmness (MCF), and maximum lysis as total percentage (ML%) were quantified. The primary outcome is the overall coagulation initiation measured by CFT, while secondary outcomes include ROTEM parameters reflecting Th activity. Parameters are compared over time in SPSS using repeated measures ANOVA and Bonferroni correction. Results: Pilot data from one experiment show that cardiac arrest causes immediate early changes to coagulation that subsequently normalized with ROSC (Figure 1). CFT was impaired immediately upon cardiac arrest (2.3-fold increase), normalized with ROSC, and impaired again at death when compared with baseline. Consistent with clotting impairment, A10, Alpha, and MCF were all reduced with cardiac arrest, normalized with ROSC, and impaired again at death. Conclusion: Higher initial indices of coagulopathy in patients with cardiac arrest appear to correlate with death and thromboembolism. In this pilot, CFT is acutely modified by cardiac arrest. Since CFT is affected by overall Th activity, early Th dysregulation may be a critical driver of coagulopathy. Th may therefore be a lead target that is modifiable in the emergency post-arrest setting to decrease morbidity and mortality from PCAS in cardiac arrest survivors.