Astronomy's climate emissions: Global travel to scientific meetings in 2019.

Travel to academic conferences-where international flights are the norm-is responsible for a sizeable fraction of the greenhouse gas (GHG) emissions associated with academic work. In order to provide a benchmark for comparison with other fields, as well as for future reduction strategies and assessments, we estimate the CO2-equivalent emissions for conference travel in the field of astronomy for the prepandemic year 2019. The GHG emission of the international astronomical community's 362 conferences and schools in 2019 amounted to 42,500 tCO2e, assuming a radiative-forcing index factor of 1.95 for air travel. This equates to an average of 1.0 ± 0.6 tCO2e per participant per meeting. The total travel distance adds up to roughly 1.5 Astronomical Units, that is, 1.5 times the distance between the Earth and the Sun. We present scenarios for the reduction of this value, for instance with virtual conferencing or hub models, while still prioritizing the benefits conferences bring to the scientific community.

Ventilator hyperinflation determined by peak airway pressure delivered: A randomized crossover trial.

AIM: The aim of this study was to see if a more sophisticated ventilator hyperinflation protocol might result in more sputum clearance compared to manual hyperinflation. BACKGROUND: Hyperinflation has been used to mobilize lung secretions in mechanically ventilated patients in the intensive care unit setting for almost 50 years. In the past decade, rather than using a bag external to the ventilator circuit to deliver hyperinflation (known as "bagging" or "manual hyperinflation"), a new technique has evolved using existing ventilator circuitry (known as "ventilator hyperinflation"). One conservative ventilator hyperinflation protocol has demonstrated equivalence with manual hyperinflation in sputum clearance. DESIGN: A randomized crossover study. METHOD: Patients received manual hyperinflation and ventilator hyperinflation in two randomly ordered treatments on the same day by the same physiotherapist, using a ventilator hyperinflation protocol involving titration of hyperinflation according to airway pressure. RESULTS: Between 2013 and 2018, 48 patients were enrolled in the study. Physiotherapy treatment using ventilator hyperinflation yielded significantly more wet weight sputum (median 2.84 g, IQR 1.81, 4.22) than treatment using manual hyperinflation (median 1.5 g, IQR 0.73, 2.31, P < .001), without significant differences in secondary measures. CONCLUSIONS: A more sophisticated approach to the titration of the volume delivered using ventilator hyperinflation relative to the airway pressure resulted in greater wet weight sputum cleared during physiotherapy treatment. RELEVANCE TO CLINICAL PRACTICE: The results presented in this paper demonstrate that the application of ventilator hyperinflation using peak airway pressure rather than tidal volume may be superior in facilitating sputum clearance and improved oxygenation without patient harm.

Illuminating dark fishing fleets in North Korea.

Illegal, unreported, and unregulated fishing threatens resource sustainability and equity. A major challenge with such activity is that most fishing vessels do not broadcast their positions and are "dark" in public monitoring systems. Combining four satellite technologies, we identify widespread illegal fishing by dark fleets in the waters between the Koreas, Japan, and Russia. We find >900 vessels of Chinese origin in 2017 and >700 in 2018 fished illegally in North Korean waters, catching an estimated amount of Todarodes pacificus approximating that of Japan and South Korea combined (>164,000 metric tons worth >$440 million). We further find ~3000 small-scale North Korean vessels fished, mostly illegally, in Russian waters. These results can inform independent oversight of transboundary fisheries and foreshadow a new era in satellite monitoring of fisheries.

Integrated Care in Ontario: Unicorn or Black Swan?

The movement away from traditional models to organize, finance and deliver healthcare toward integrated models focusing on delivering value has been under way in many health systems and jurisdictions in the world with varying degrees of intensity and success for much of the past 20 years. I have had the opportunity to lead aspects of a multi-state health system committed to the concepts of accountable care during the first 10 years of the Patient Protection and Affordable Care Act (PPACA) in the US. For the past two years, I have assumed the role as CEO of a large academic health sciences centre in Ontario as the province embarks on a shift in policies to support integrated models of care delivery similar to those associated with the PPACA. I will describe my observations comparing two countries' move toward integrated delivery models and potential lessons for Canada.

Response to Comment on "Tracking the global footprint of fisheries".

Amoroso et al demonstrate the power of our data by estimating the high-resolution trawling footprint on seafloor habitat. Yet we argue that a coarser grid is required to understand full ecosystem impacts. Vessel tracking data allow us to estimate the footprint of human activities across a variety of scales, and the proper scale depends on the specific impact being investigated.

Tracking the global footprint of fisheries.

Although fishing is one of the most widespread activities by which humans harvest natural resources, its global footprint is poorly understood and has never been directly quantified. We processed 22 billion automatic identification system messages and tracked >70,000 industrial fishing vessels from 2012 to 2016, creating a global dynamic footprint of fishing effort with spatial and temporal resolution two to three orders of magnitude higher than for previous data sets. Our data show that industrial fishing occurs in >55% of ocean area and has a spatial extent more than four times that of agriculture. We find that global patterns of fishing have surprisingly low sensitivity to short-term economic and environmental variation and a strong response to cultural and political events such as holidays and closures.

Maintenance of S. aureus in Co-culture With P. aeruginosa While Growing as Biofilms.

Bacterial biofilms are found in various environmental niches and are mostly comprised by two or more bacterial species. One such example, are the mixed species bacterial biofilms found in chronic lung infections of cystic fibrosis (CF) patients, which include the Staphylococcus aureus and Pseudomonas aeruginosa bacterial species. S. aureus is one of the CF lung initial colonizers and is assumed to be abrogated when P. aeruginosa becomes established, eliminating its involvement as the infection evolves. Common models used in research do not mimic the actual progression of the mixed species biofilms thus, in this work we developed an in vitro model, where S. aureus biofilms establish prior to the introduction of P. aeruginosa, simulating a state that is phenotypically more similar to the one found in CF lungs. Overall our results demonstrate that S. aureus is not outcompeted, and that timing of inoculation and bacterial concentration affect the final bacterial ratio and quorum sensing related gene expression during the dual species biofilm development.

Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series.

BACKGROUND: One limitation of anti-VEGF therapy is the need for monthly retreatment to maintain efficacy. The purpose of this study was to determine the duration of effect in eyes with macular edema (ME) secondary to branch or central retinal vein occlusion (BRVO or CRVO) treated with anti-VEGF therapy plus sustained-release dexamethasone (DEX implant; Ozurdex). MATERIALS AND METHODS: This open-label, interventional case series included 62 eyes with ME due to RVO, central foveal thickness (CFT) >300 µm, and best-corrected visual acuity (BCVA) of 20/40 or worse. Each treatment cycle included an anti-VEGF injection followed 2 weeks later with DEX implant. Patients were eligible for retreatment if CFT increased to >290 µm or increased by >50 µm from the lowest measurement, or if BCVA decreased by six or more Snellen letters. Efficacy and safety were evaluated 2 and 4-6 weeks after the beginning of each treatment cycle and every 4 weeks thereafter until retreatment criteria were met. The primary outcome measure was time to retreatment. Secondary outcome measures included BCVA, CFT, and safety parameters. RESULTS: The mean reinjection interval for all patients was 135.5±36.4 days. There was no statistically significant difference in mean intertreatment interval for up to six cycles of treatment or between eyes with BRVO or CRVO (P≥0.058). Mean peak change in BCVA was 13.8 letters, and 47.6% of eyes gained three or more lines of BCVA. The mean peak decrease in CFT across all treatment cycles was 200.9 µm for eyes with BRVO and 219.2 µm for eyes with CRVO. The percentage of patients with CFT ≤300 µm at any time during a given treatment cycle ranged from 78% to 94% among eyes with BRVO and from 85% to 100% among eyes with CRVO. Intraocular pressure increased in 19 of 62 eyes, and 26 of 44 phakic eyes underwent cataract surgery. CONCLUSION: In eyes with ME due to RVO, treatment with an anti-VEGF agent plus DEX implant provided a predictable duration of effect, as well as significant improvements in BCVA and CFT.

What makes a compliant Phase III and pre-launch patient advocacy strategy?

BACKGROUND: A key task for the pharmaceutical industry is to understand the compliance implications of engaging with a patient advocacy group (PAG). This presents challenges for the industry to negotiate the ethical and reputational issues that can arise when working with a PAG. OBJECTIVE: To gain the views of pharmaceutical industry executives on future compliance challenges when working with PAGs. STUDY DESIGN: We conducted two surveys among two sets of industry executives: one group focussed on market access roles and the other focussed on non-market access roles. RESULTS: Transparency was identified as the biggest challenge, followed by project rationale and then by project ownership. CONCLUSION: We explore how this can be overcome and make recommendations on how best to work compliantly with PAGs.

A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.

Trapping and desorption of complex organic molecules in water at 20 K.

The formation, chemical, and thermal processing of complex organic molecules (COMs) is currently a topic of much interest in interstellar chemistry. The isomers glycolaldehyde, methyl formate, and acetic acid are particularly important because of their role as pre-biotic species. It is becoming increasingly clear that many COMs are formed within interstellar ices which are dominated by water. Hence, the interaction of these species with water ice is crucially important in dictating their behaviour. Here, we present the first detailed comparative study of the adsorption and thermal processing of glycolaldehyde, methyl formate, and acetic acid adsorbed on and in water ices at astrophysically relevant temperatures (20 K). We show that the functional group of the isomer dictates the strength of interaction with water ice, and hence the resulting desorption and trapping behaviour. Furthermore, the strength of this interaction directly affects the crystallization of water, which in turn affects the desorption behaviour. Our detailed coverage and composition dependent data allow us to categorize the desorption behaviour of the three isomers on the basis of the strength of intermolecular and intramolecular interactions, as well as the natural sublimation temperature of the molecule. This categorization is extended to other C, H, and O containing molecules in order to predict and describe the desorption behaviour of COMs from interstellar ices.

Adsorption and Thermal Processing of Glycolaldehyde, Methyl Formate, and Acetic Acid on Graphite at 20 K.

We present the first detailed comparative study of the adsorption and thermal processing of the three astrophysically important C2O2H4 isomers glycolaldehyde, methyl formate, and acetic acid adsorbed on a graphitic grain analogue at 20 K. The ability of the individual molecule to form intermolecular hydrogen bonds is extremely important, dictating the growth modes of the ice on the surface and the measured desorption energies. Methyl formate forms only weak intermolecular bonds and hence wets the graphite surface, forming monolayer, bilayer, and multilayer ices, with the multilayer having a desorption energy of 35 kJ mol(-1). In contrast, glycolaldehyde and acetic acid dewet the surface, forming clusters even at the very lowest coverages. The strength of the intermolecular hydrogen bonding for glycolaldehyde and acetic acid is reflected in their desorption energies (46.8 and 55 kJ mol(-1), respectively), which are comparable to those measured for other hydrogen-bonded species such as water. Infrared spectra show that all three isomers undergo structural changes as a result of thermal processing. In the case of acetic acid and glycolaldehyde, this can be assigned to the formation of well-ordered, crystalline, structures where the molecules form chains of hydrogen-bonded moieties. The data reported here are of relevance to astrochemical studies of hot cores and star-forming regions and can be used to model desorption from interstellar ices during the warm up phase with particular importance for complex organic molecules.

Sociodemographic correlates of 25-hydroxyvitamin D test utilization in Calgary, Alberta.

BACKGROUND: Increasing laboratory test utilization is a major challenge facing clinical laboratories. However, in most instances we lack population level information on the patient groups to which increased testing is directed. Much recent work has been published on the sociodemographic correlates of 25-hydroxyvitamin D deficiency. An unanswered question, however, is whether testing is preferentially directed towards individuals with a higher likelihood of deficiency. In this paper we examine this question by combining laboratory information system data on testing rates with Census Canada data. METHODS: We examined 1,436 census dissemination areas within the city of Calgary, Alberta, Canada. For each census dissemination area we determined age and sex-specific 25-hydroxyvitamin D testing rates over a one year period. We then compared these testing rates with the following sociodemographic variables obtained from Census Canada: first nations status, education level, household income, visible minority status, and recent immigrant status. RESULTS: Overall, 6.9% of males in the city of Calgary were tested during the study period. Females were 1.7 times more likely to be tested than males. Testing rate increased with increasing age, with 16.8% of individuals 66 years and over tested during the one-year study period. Individuals having at least some university education were less likely to be tested (RR = 0.60; p < 0.0001). Interestingly, although visible minorities were over twice as likely to be tested as compared to non-visual minorities (RR = 2.25; p < 0.0001), recent immigrants, a group known to exhibit low 25 hydroxyvitamin D levels, were significantly less likely to be tested than non-recent immigrants (RR = 0.72; p = 0.0174). While median household income was modestly associated with increased testing (RR = 1.02; p < 0.0001), First Nations status and non-English speaking were not significant predictors of 25-hydroxyvitamin D testing. CONCLUSIONS: Testing for 25-hydroxyvitamin D is in part directed toward populations at higher risk of deficiency (visible minorities) and at higher risk of osteoporosis (older females), but a particularly high risk group (recent immigrants) is being tested at a lower rate than other patient groups.

Ethical pharmaceutical promotion and communications worldwide: codes and regulations.

The international pharmaceutical industry has made significant efforts towards ensuring compliant and ethical communication and interaction with physicians and patients. This article presents the current status of the worldwide governance of communication practices by pharmaceutical companies, concentrating on prescription-only medicines. It analyzes legislative, regulatory, and code-based compliance control mechanisms and highlights significant developments, including the 2006 and 2012 revisions of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Code of Practice.Developments in international controls, largely built upon long-established rules relating to the quality of advertising material, have contributed to clarifying the scope of acceptable company interactions with healthcare professionals. This article aims to provide policy makers, particularly in developing countries, with an overview of the evolution of mechanisms governing the communication practices, such as the distribution of promotional or scientific material and interactions with healthcare stakeholders, relating to prescription-only medicines.

Initial management of traumatic brain injury in the rural setting.

Healthcare workers in the rural setting face unique problems when dealing with head injured patients however the basic principle of medical management are the same in any situation. The key initial elements remain aggressive early resuscitation followed by a comprehensive assessment of conscious level and either early consultation or transfer to a neurosurgical facility. What has improved considerably over recent years is the understanding of the pathophysiology of traumatic brain injury and as such some of the medical management strategies have changed. A basic understanding of some of these concepts is useful in the clinical setting and serves to emphasis the importance of effective early medical management. Thereafter consideration must be given to which patients require radiological investigations and possible discussion with or transfer to a neurosurgical facility.

Association of vitamin D status with socio-demographic factors in Calgary, Alberta: an ecological study using Census Canada data.

BACKGROUND: Low 25-hydroxyvitamin D levels are a global health problem with northern countries such as Canada at particular risk. A number of sociodemographic factors have been reported to be associated with low vitamin D levels but prior studies have been limited by the ability of the researchers to gather this data directly from clinical trial participants. The purpose of this study was to use a novel methodology of inferring sociodemographic variables to evaluate the correlates of vitamin D levels in individuals dwelling in the City of Calgary, Alberta, Canada. METHODS: We utilized data on vitamin D test results from Calgary Laboratory Services between January 1 2010 and August 31 2011. In addition to vitamin D level, we recorded age, sex, and vitamin D testing month as individual-level variables. We inferred sociodemographic variables by associating results with census dissemination areas and using Census Canada data to determine immigration status, education, median household income and first nations status as clustered variables. Associations between vitamin D status and the individual- and dissemination area-specific variables were examined using the population-averaged regression model by a generalized estimating equations approach to account for the clustering in the data. RESULTS: 158,327 individuals were included. Age, sex, month of vitamin D testing (at an individual level), and education, immigrant status, first nations status and income (at an aggregate level) were all statistically significant predictors of vitamin D status. CONCLUSIONS: Vitamin D status was associated with a number of sociodemographic variables. Knowledge of these variables may improve targeted education and public health initiatives.

A possible role for systemic hypoxia in the reactive component of pulmonary hypertension in heart failure.

BACKGROUND: The mechanisms underlying the reactive component of pulmonary hypertension (PH) in heart failure (HF) are unclear. We examined whether resting systemic oxygen levels are related to pulmonary hemodynamics in HF. METHODS AND RESULTS: Thirty-nine HF patients underwent right heart catheterization. Subsequently, patients were classified as having: 1) no PH (n = 12); 2) passive PH (n = 10); or 3) reactive PH (n = 17). Blood was drawn from the radial and pulmonary arteries for the determination of PaO(2), SaO(2), PvO(2), SvO(2), and vasoactive neurohormones. PaO(2) and PvO(2) were lower in reactive PH versus no PH and passive PH patients (65.3 ± 8.6 vs 78.3 ± 11.4 mm Hg and 74.5 ± 14.0 mm Hg; 29.2 ± 4.1 vs 36.2 ± 2.8 mm Hg and 33.4 ± 2.3 mm Hg; P < .05). SaO(2) and SvO(2) were lower in reactive PH versus no PH patients (93 ± 3% vs 96 ± 3%; 51 ± 11% vs 68 ± 4%; P < .05), but not different versus passive PH patients. The transpulmonary pressure gradient (TPG) was inversely related to PaO(2), PvO(2), SaO(2), and SvO(2) in the reactive PH patients only (r ≤ -0.557; P < .05). Similarly, plasma endothelin-1 correlated with PaO(2), PvO(2), SvO(2) (r ≤ -0.495), and TPG (r = 0.662; P < .05) in reactive PH patients only. CONCLUSIONS: Systemic hypoxia may play a role in the reactive component of PH in HF, potentially via a hypoxia-induced increase in endothelial release of the vasoconstrictor endothelin-1.

Effect of combination therapy with bevacizumab and dexamethasone intravitreal implant in patients with retinal vein occlusion.

OBJECTIVE: The objective of this study was to determine if dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc) with bevacizumab (Avastin; Genentech, Inc) therapy can be synergistic, providing further improvements in visual acuity, sustainability, and macular thickness when compared with dexamethasone intravitreal implant 0.7 mg alone. METHODS: This is a prospective, interventional case series intended to monitor changes in visual acuity and macular thickness in patients diagnosed with retinal vein occlusion (RVO), after injection of bevacizumab followed by a scheduled dexamethasone intravitreal implant. This study was designed to emulate patient care as received in the typical ophthalmology practice. Patients diagnosed with RVO, who were seen between September 2009 and July 2010, were included in this study if they had received previous anti-vascular endothelial growth factor therapy. Patients were included in analysis if the previous anti-vascular endothelial growth factor therapy was at least 6 weeks before and optical coherence tomography (OCT) was >300 µm on spectral-domain OCT. Exclusion criteria included history of vitrectomy, and/or rubeotic or advanced glaucoma. All patients were evaluated with Snellen visual acuity and measured for macular thickness (calculated by spectral-domain OCT) and intraocular pressure. At baseline, all patients were injected with bevacizumab, followed by dexamethasone intravitreal implant injection 2 weeks later. These patients were reexamined on a monthly basis and retreated when edema occurred. RESULTS: The primary outcome measure was the time to reinjection based on OCT and vision criteria. The secondary outcomes were increases in visual acuity and the reduction of OCT thickness during that period. Thirty-four eyes of 33 patients, with a mean age of 72.8 years, were identified. Thirty-five percent were diagnosed with central RVO, while the other 65% were with branch RVO. Of these patients, 97% gained vision during the study. Mean visual acuity improved from initially 11 letters to a maximum of 25 letters during the study period. In addition, vision improved by at least 15 letters in 29% of patients initially up to 64% during the study period. Macular thickness decreased with the combination treatment by OCT, and the effect continued an average of 126 days from the initial bevacizumab treatment. Retreatment was unnecessary in 18% of the population during the 6-month study period. CONCLUSION: This study demonstrates efficacy and the duration of effect using a combination of bevacizumab and dexamethasone versus dexamethasone alone. The combination is synergistic, increasing visual acuity and prolonging the time between injections, compared with either of these medications alone. Therefore, the combination of a vascular endothelial growth factor inhibitor and a dexamethasone implant may be a valuable option for RVO treatment.

A pulmonary hypertension gas exchange severity (PH-GXS) score to assist with the assessment and monitoring of pulmonary arterial hypertension.

Submaximal exercise gas analysis may be a useful method to assess and track pulmonary arterial hypertension (PAH) severity. The aim of the present study was to develop an algorithm, using exercise gas exchange data, to assess and monitor PAH severity. Forty patients with PAH participated in the study, completing a range of clinical tests and a novel submaximal exercise step test, which lasted 6 minutes and incorporated rest (2 minutes), exercise (3 minutes), and recovery (1 minute) ventilatory gas analysis. Using gas exchange data, including breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse, a pulmonary hypertension gas exchange severity (PH-GXS) score was developed. Patients were retested after about 6 months. There was significant separation between healthy controls and patients with moderate PAH (World Health Organization [WHO] class I/II) and those with more severe PAH (WHO class III/IV) for breathing efficiency, end-tidal carbon dioxide, oxygen saturation, and oxygen pulse. The PH-GXS score was significantly correlated with WHO class (r = 0.51), 6-minute walking distance (r = -0.59), right ventricular systolic pressure (r = 0.49), log N-terminal pro-B-type natriuretic peptide (r = 0.54), and pulmonary vascular resistance (r = 0.71). The PH-GXS score remained unchanged in 22 patients retested (1.50 ± 0.92 vs 1.48 ± 0.94), as did WHO class (2.3 ± 0.8 vs 2.3 ± 0.8) and 6-minute walking distance (455 ± 120 vs 456 ± 103 m). Small individual changes were observed in the PH-GXS score, with 8 patients improving and 8 deteriorating. In conclusion, the PH-GXS score differentiated between patients with PAH and was correlated with traditional clinical measures. The PH-GXS score was unchanged in our cohort after 6 months, consistent with traditional clinical metrics, but individual differences were evident. A PH-GXS score may be a useful way to track patient responses to therapy.