Dose-Optimal Vaccine Allocation over Multiple Populations

Vaccination is an effective way to prevent an epidemic. It results in immunity for the vaccinated individuals, but it also reduces the infection pressure for unvaccinated people. Thus people may actually escape infection without being vaccinated: the so-called “herd effect.” We analytically study the relation between the herd effect and the vaccination fraction for the seminal SIR compartmental model, which consists of a set of differential equations describing the time course of an epidemic. We prove that the herd effect is in general convex-concave in the vaccination fraction and give precise conditions on the epidemic for the convex part to arise. We derive the significant consequences of these structural insights for allocating a limited vaccine stockpile to multiple non-interacting populations. We identify for each population a unique vaccination fraction that is most efficient per dose of vaccine: our dose-optimal coverage. We characterize the solution of the vaccine allocation problem and we show the crucial importance of the dose-optimal coverage. A single dose of vaccine may be a drop in the ocean, but multiple doses together can save a population. To benefit from this, policy makers should select a subset of populations to which the vaccines are allocated. Focusing on a limited number of populations can make a significant difference, whereas allocating equally to all populations would be substantially less effective

Benzo(a)pyrene induces similar gene expression changes in testis of DNA repair proficient and deficient mice

<p>Abstract</p> <p>Background</p> <p>Benzo [a]pyrene (B[a]P) exposure induces DNA adducts at all stages of spermatogenesis and in testis, and removal of these lesions is less efficient in nucleotide excision repair deficient <it>Xpc</it>^-/-mice than in wild type mice. In this study, we investigated by using microarray technology whether compromised DNA repair in <it>Xpc</it>^-/-mice may lead to a transcriptional reaction of the testis to cope with increased levels of B[a]P induced DNA damage.</p> <p>Results</p> <p>Two-Way ANOVA revealed only 4 genes differentially expressed between wild type and <it>Xpc</it>^-/-mice, and 984 genes between testes of B[a]P treated and untreated mice irrespective of the mouse genotype. However, the level in which these B[a]P regulated genes are expressed differs between Wt and <it>Xpc</it>^-/-mice (p = 0.000000141), and were predominantly involved in the regulation of cell cycle, translation, chromatin structure and spermatogenesis, indicating a general stress response. In addition, analysis of cell cycle phase dependent gene expression revealed that expression of genes involved in G1-S and G2-M phase arrest was increased after B[a]P exposure in both genotypes. A slightly higher induction of average gene expression was observed at the G2-M checkpoint in <it>Xpc</it>^-/-mice, but this did not reach statistical significance (P = 0.086). Other processes that were expected to have changed by exposure, like apoptosis and DNA repair, were not found to be modulated at the level of gene expression.</p> <p>Conclusion</p> <p>Gene expression in testis of untreated <it>Xpc</it>^-/-and wild type mice were very similar, with only 4 genes differentially expressed. Exposure to benzo(a)pyrene affected the expression of genes that are involved in cell cycle regulation in both genotypes, indicating that the presence of unrepaired DNA damage in testis blocks cell proliferation to protect DNA integrity in both DNA repair proficient and deficient animals.</p

Complete transposition of the aorta and pulmonary artery in a Belgian Blue crossbreed calf: A case report

<p>Abstract</p> <p>Background</p> <p>Complete transposition of the great arteries is a congenital cardiac malformation occasionally encountered in cattle and other species. The objective of the present report was to provide a detailed clinical, echocardiographic and post mortem description of a calf presenting with this condition.</p> <p>Case presentation</p> <p>A 6-week old male Belgian Blue cross-breed calf was examined for respiratory distress and exercise intolerance. The patient was bright, alert and responsive without any neurologic abnormalities but was exercise intolerant, had marked cyanosis, tachycardia, tachypnea, a pansystolic heart murmur as well as a bilaterally palpable thrill over the heart. Arterial blood gas analysis revealed marked hypoxemia (PaO₂= 23 mmHg, O₂sat = 41.1%), mild hypercapnia and compensated respiratory acidosis. Echocardiographic examination revealed a complete transposition of the great arteries in combination with a ventricular septal defect through which blood shunted bidirectionally. Cardiac catheterization confirmed that arterialization of blood of the systemic circulation solely occurred in the right ventricle through blood shunting from the left into the right ventricle. Results of post mortem examination are presented.</p> <p>Conclusion</p> <p>Complete transposition of the great arteries is a cyanotic congenital anomaly repeatedly reported in calves that should be considered as differential diagnosis in patients presenting with hypoxemia more severe than commonly encountered with other congenital cyanotic heart conditions. We give a comprehensive summary of the clinical presentation, diagnostic work-up and post mortem examination of a Belgian Blue cross-breed calf with complete transposition of the great arteries</p

Scientists’ Warning on Climate Change and Medicinal Plants

The recent publication of a World Scientists’ Warning to Humanity highlighted the fact that climate change, absent strenuous mitigation or adaptation efforts, will have profound negative effects for humanity and other species, affecting numerous aspects of life. In this paper, we call attention to one of these aspects, the effects of climate change on medicinal plants. These plants provide many benefits for human health, particularly in communities where Western medicine is unavailable. As for other species, their populations may be threatened by changing temperature and precipitation regimes, disruption of commensal relationships, and increases in pests and pathogens, combined with anthropogenic habitat fragmentation that impedes migration. Additionally, medicinal species are often harvested unsustainably, and this combination of pressures may push many populations to extinction. A second issue is that some species may respond to increased environmental stresses not only with declines in biomass production but with changes in chemical content, potentially affecting quality or even safety of medicinal products. We therefore recommend actions including conservation and local cultivation of valued plants, sustainability training for harvesters and certification of commercial material, preservation of traditional knowledge, and programs to monitor raw material quality, in addition to, of course, efforts to mitigate climate change

Autonomous decision-making against induced seismicity in deep fluid injections

The rise in the frequency of anthropogenic earthquakes due to deep fluid injections is posing serious economic, societal, and legal challenges to geo-energy and waste-disposal projects. We propose an actuarial approach to mitigate this risk, first by defining an autonomous decision-making process based on an adaptive traffic light system (ATLS) to stop risky injections, and second by quantifying a "cost of public safety" based on the probability of an injection-well being abandoned. The ATLS underlying statistical model is first confirmed to be representative of injection-induced seismicity, with examples taken from past reservoir stimulation experiments (mostly from Enhanced Geothermal Systems, EGS). Then the decision strategy is formalized: Being integrable, the model yields a closed-form ATLS solution that maps a risk-based safety standard or norm to an earthquake magnitude not to exceed during stimulation. Finally, the EGS levelized cost of electricity (LCOE) is reformulated in terms of null expectation, with the cost of abandoned injection-well implemented. We find that the price increase to mitigate the increased seismic risk in populated areas can counterbalance the heat credit. However this "public safety cost" disappears if buildings are based on earthquake-resistant designs or if a more relaxed risk safety standard or norm is chosen.Comment: 8 pages, 4 figures, conference (International Symposium on Energy Geotechnics, 26-28 September 2018, Lausanne, Switzerland

The Portrayal of Complementary and Alternative Medicine in Mass Print Magazines Since 1980

Objectives: The objectives of this study were to examine and describe the portrayal of complementary and alternative medicine (CAM) in mass print media magazines. Design: The sample included all 37 articles found in magazines with circulation rates of greater than 1 million published in the United States and Canada from 1980 to 2005. The analysis was quantitative and qualitative and included investigation of both manifest and latent magazine story messages. Results: Manifest analysis noted that CAM was largely represented as a treatment for a patient with a medically diagnosed illness or specific symptoms. Discussions used biomedical terms such as patient rather than consumer and disease rather than wellness. Latent analysis revealed three themes: (1) CAMs were described as good but not good enough; (2) individualism and consumerism were venerated; and (3) questions of costs were raised in the context of confusion and ambivalence

Improved ventricular function during inhalation of PGI(2) aerosol partly relies on enhanced myocardial contractility

Inhaled prostacyclin (PGI(2)) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular ( RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI(2) analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng center dot kg(-1) center dot min(-1)) and, consecutively, ILO (60 ng center dot kg(-1) center dot min(-1)) for 20 min each. We measured pulmonary artery pressure ( PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E-es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E-es was enhanced during all doses tested, which reached statistical significance during EPO25ng and ILO, but not during EPO50ng. PGI(2) aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function. Copyright (C) 2005 S. Karger AG, Basel

The impact of exercise-induced core body temperature elevations on coagulation responses.

OBJECTIVES: Exercise induces changes in haemostatic parameters and core body temperature (CBT). We aimed to assess whether exercise-induced elevations in CBT induce pro-thrombotic changes in a dose-dependent manner. DESIGN: Observational study. METHODS: CBT and haemostatic responses were measured in 62 participants of a 15-km road race at baseline and immediately after finishing. As haemostasis assays are routinely performed at 37°C, we corrected the assay temperature for the individual's actual CBT at baseline and finish in a subgroup of n=25. RESULTS: All subjects (44±11 years, 69% male) completed the race at a speed of 12.1±1.8km/h. CBT increased significantly from 37.6±0.4°C to 39.4±0.8°C (p<0.001). Post-exercise, haemostatic activity was increased, as expressed by accelerated thrombin generation and an attenuated plasmin response. Synchronizing assay temperature to the subjects' actual CBT resulted in additional differences and stronger acceleration of thrombin generation parameters. CONCLUSIONS: This study demonstrates that exercise induces a prothrombotic state, which might be partially dependent on the magnitude of the exercise-induced CBT rise. Synchronizing the assay temperature to approximate the subject's CBT is essential to obtain more accurate insight in the haemostatic balance during thermoregulatory challenging situations. Finally, this study shows that short-lasting exposure to a CBT of 41.2°C does not result in clinical symptoms of severe coagulation. We therefore hypothesize that prolonged exposure to a high CBT or an individual-specific CBT threshold needs to be exceeded before derailment of the haemostatic balance occurs