Simulating Changes in Regional Air Pollution over the Eastern United States Due to Changes in Global and Regional Climate and Emissions

[1] To simulate ozone (O3) air quality in future decades over the eastern United States, a modeling system consisting of the NASA Goddard Institute for Space Studies Atmosphere-Ocean Global Climate Model, the Pennsylvania State University/National Center for Atmospheric Research mesoscale regional climate model (MM5), and the Community Multiscale Air Quality model has been applied. Estimates of future emissions of greenhouse gases and ozone precursors are based on the A2 scenario developed by the Intergovernmental Panel on Climate Change (IPCC), one of the scenarios with the highest growth of CO2 among all IPCC scenarios. Simulation results for five summers in the 2020s, 2050s, and 2080s indicate that summertime average daily maximum 8-hour O3 concentrations increase by 2.7, 4.2, and 5.0 ppb, respectively, as a result of regional climate change alone with respect to five summers in the 1990s. Through additional sensitivity simulations for the five summers in the 2050s the relative impact of changes in regional climate, anthropogenic emissions within the modeling domain, and changed boundary conditions approximating possible changes of global atmospheric composition was investigated. Changed boundary conditions are found to be the largest contributor to changes in predicted summertime average daily maximum 8-hour O3 concentrations (5.0 ppb), followed by the effects of regional climate change (4.2 ppb) and the effects of increased anthropogenic emissions (1.3 ppb). However, when changes in the fourth highest summertime 8-hour O3 concentration are considered, changes in regional climate are the most important contributor to simulated concentration changes (7.6 ppb), followed by the effect of increased anthropogenic emissions (3.9 ppb) and increased boundary conditions (2.8 ppb). Thus, while previous studies have pointed out the potentially important contribution of growing global emissions and intercontinental transport to O3 air quality in the United States for future decades, the results presented here imply that it may be equally important to consider the effects of a changing climate when planning for the future attainment of regional-scale air quality standards such as the U.S. national ambient air quality standard that is based on the fourth highest annual daily maximum 8-hour O3 concentration

diagnosis of pain in small companion animals

It is now widely accepted that animals are able to experience pain in a similar way to humans. Acute and/or chronic pain is associated not only with many surgical procedures, but also with various medical diseases, where pain may increase morbidity and mortality. Moreover, some types of pain (e.g., neuropathic pain) can be considered as an illness in themselves. Recognizing pain and assessing its intensity are both essential for its effective management: If pain is not recognised, then it is unlikely to be treated. Two major problems account for the difficulties in pain diagnosis in veterinary patients: (1) animals are not able to verbalise and cannot refer to the state of pain they are experiencing and (2) almost all animal species tend instinctively to mask signs of pain and weakness. Therefore, pain recognition in a diseased animal may be challenging. However, practitioners can rely on different strategies, which can be put in place to reveal the presence of pain in their patients. A presumptive diagnosis, a clinical exam, the evaluation of psychomotor changes and pain expressions, the attribution of pain scores and the response to therapy are all tools which, especially when used in combination, can help the veterinary practitioner recognise a subject suffering from pain and allow a correct approach to therapy. This review summarizes the current available information regarding the methodology that could be applied in small companion animals for a correct diagnosis of pain, offering veterinarians with some "easy to use" tools to apply in their daily practice

Twin Analyses of Fatigue

Abstract Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects

Pain and Suffering in Invertebrates: An Insight on Cephalopods

Invertebrates are a broad group of animals that includes more than 90% of the estimated 10 million species in the world. Some species are abundantly used by man in scientific research and for human consumption. However, the current legislation is still very lacking about the protection toward conditions of pain, suffering, distress or lasting harm that these animals may suffer as a result of experimental practices, fishing and cooking. The purpose of this paper is to summarize what has already been stated by other Authors regarding the possibility that invertebrates (with a specific emphasis on cephalopods) can experience pain and suffering. The results of studies that show the existence, in these animals, of a number of elements that can be associated with the ability to feel pain and not only nociception are highlighted. Objective indicators (such as changes in physiological parameters) and behavioral attitudes of cephalopods that might be related to pain will be addressed as well

medical abdominal visceral pain in dogs

Abdominal visceral pain of medical origin is one of the most frequent reasons for request of medical treatment in humans. Its control is of paramount importance not only for ethical reasons, but also because, if untreated, pain can cause a stress response leading to alterations concerning many organs and apparatuses. Causes of acute or chronic medical visceral pain in men are numerous, with pain originating from various regions of the body. Considering the similarities with regard to the nervous system between humans and other mammals, it is very likely that pathological conditions that cause visceral pain in men are painful in animals as well. Despite this, in veterinary practice medical visceral pain is rarely considered and poorly treated, often for the difficulty in its identification and for a lack of specific guidelines addressing this specific topic. Moreover, no detailed and specific information on this subject are available in the current literature. The present review lists the main pathologies likely responsible of medical abdominal visceral pain in the canine species, trying to summarize, for each considered condition, the available information regarding the pathogenesis and the management of pain

Sensitivity of Present and Future Surface Temperatures to Precipitation Characteristics

A model simulation study shows that different diurnal cycles of precipitation are consistent with radically different present and future climate characteristics. In projected future climate scenarios, divergence in the time of day and type of precipitation had very divergent impacts on the radiation balance and consequently on surface temperatures. The relationship between the diurnal cycle of precipitation versus the present and future climate was examined using the GISS-MM5 (Goddard Institute for Space Studies Mesoscale Model 5) regional climate modeling system with 2 alternative moist convection schemes. June-August (JJA) mean surface temperatures of the 1990s, 2050s, and 2080s were simulated over the eastern US on a double nested 108/36 km domain, with the 36 km domain centered over the eastern US. In the 1990s, one model version simulated maxima in (convective) precipitation during the early morning, while the second model simulated the hour of precipitation maxima with considerable spatial variability (in better agreement with observations). In the futuristic climate scenarios, differences in the time of day of precipitation had very important impacts on the radiation balance at the surface. One version gave more precipitation at night and fewer clouds during the day, promoting higher surface temperatures. The alternative version created more precipitation during the day, consistent with diminished absorption of solar radiation at the surface and consequently lower surface temperatures. The results demonstrate the importance of improving cumulus parameterizations in regional mesoscale and global climate models and suggest that such improvements would lead to greater confidence in model projections of climate change

Slaying little dragons: the impact of the Guinea Worm Eradication Program on dracunculiasis disability averted from 1990 to 2016

Background: The objective of this study was to document the worldwide decline of dracunculiasis (Guinea worm disease, GWD) burden, expressed as disability-adjusted life years (DALYs), from 1990 to 2016, as estimated in the Global Burden of Disease study 2016 (GBD 2016). While the annual number of cases of GWD have been consistently reported by WHO since the 1990s, the burden of disability due to GWD has not previously been quantified in GBD.Methods: The incidence of GWD was modeled for each endemic country using annual national case reports. A literature search was conducted to characterize the presentation of GWD, translate the clinical symptoms into health sequelae, and then assign an average duration to the infection. Prevalence measures by sequelae were multiplied by disability weights to estimate DALYs.Results: The total DALYs attributed to GWD across all endemic countries (n=21) in 1990 was 50,725 (95% UI: 35,265–69,197) and decreased to 0.9 (95% UI: 0.5–1.4) in 2016. A cumulative total of 12,900 DALYs were attributable to GWD from 1990 to 2016.Conclusions: Using 1990 estimates of burden propagated forward, this analysis suggests that between 990,000 to 1.9 million DALYs have been averted as a result of the eradication program over the past 27 year

Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study.

BackgroundInternal tandem duplication mutations in FLT3 are common in acute myeloid leukaemia and are associated with rapid relapse and short overall survival. The clinical benefit of FLT3 inhibitors in patients with acute myeloid leukaemia has been limited by rapid generation of resistance mutations, particularly in codon Asp835 (D835). We aimed to assess the highly selective oral FLT3 inhibitor gilteritinib in patients with relapsed or refractory acute myeloid leukaemia.MethodsIn this phase 1-2 trial, we enrolled patients aged 18 years or older with acute myeloid leukaemia who either were refractory to induction therapy or had relapsed after achieving remission with previous treatment. Patients were enrolled into one of seven dose-escalation or dose-expansion cohorts assigned to receive once-daily doses of oral gilteritinib (20 mg, 40 mg, 80 mg, 120 mg, 200 mg, 300 mg, or 450 mg). Cohort expansion was based on safety and tolerability, FLT3 inhibition in correlative assays, and antileukaemic activity. Although the presence of an FLT3 mutation was not an inclusion criterion, we required ten or more patients with locally confirmed FLT3 mutations (FLT3mut+) to be enrolled in expansion cohorts at each dose level. On the basis of emerging findings, we further expanded the 120 mg and 200 mg dose cohorts to include FLT3mut+ patients only. The primary endpoints were the safety, tolerability, and pharmacokinetics of gilteritinib. Safety and tolerability were assessed in the safety analysis set (all patients who received at least one dose of gilteritinib). Responses were assessed in the full analysis set (all patients who received at least one dose of study drug and who had at least one datapoint post-treatment). Pharmacokinetics were assessed in a subset of the safety analysis set for which sufficient data for concentrations of gilteritinib in plasma were available to enable derivation of one or more pharmacokinetic variables. This study is registered with ClinicalTrials.gov, number NCT02014558, and is ongoing.FindingsBetween Oct 15, 2013, and Aug 27, 2015, 252 adults with relapsed or refractory acute myeloid leukaemia received oral gilteritinib once daily in one of seven dose-escalation (n=23) or dose-expansion (n=229) cohorts. Gilteritinib was well tolerated; the maximum tolerated dose was established as 300 mg/day when two of three patients enrolled in the 450 mg dose-escalation cohort had two dose-limiting toxicities (grade 3 diarrhoea and grade 3 elevated aspartate aminotransferase). The most common grade 3-4 adverse events irrespective of relation to treatment were febrile neutropenia (97 [39%] of 252), anaemia (61 [24%]), thrombocytopenia (33 [13%]), sepsis (28 [11%]), and pneumonia (27 [11%]). Commonly reported treatment-related adverse events were diarrhoea (92 [37%] of 252]), anaemia (86 [34%]), fatigue (83 [33%]), elevated aspartate aminotransferase (65 [26%]), and increased alanine aminotransferase (47 [19%]). Serious adverse events occurring in 5% or more of patients were febrile neutropenia (98 [39%] of 252; five related to treatment), progressive disease (43 [17%]), sepsis (36 [14%]; two related to treatment), pneumonia (27 [11%]), acute renal failure (25 [10%]; five related to treatment), pyrexia (21 [8%]; three related to treatment), bacteraemia (14 [6%]; one related to treatment), and respiratory failure (14 [6%]). 95 people died in the safety analysis set, of which seven deaths were judged possibly or probably related to treatment (pulmonary embolism [200 mg/day], respiratory failure [120 mg/day], haemoptysis [80 mg/day], intracranial haemorrhage [20 mg/day], ventricular fibrillation [120 mg/day], septic shock [80 mg/day], and neutropenia [120 mg/day]). An exposure-related increase in inhibition of FLT3 phosphorylation was noted with increasing concentrations in plasma of gilteritinib. In-vivo inhibition of FLT3 phosphorylation occurred at all dose levels. At least 90% of FLT3 phosphorylation inhibition was seen by day 8 in most patients receiving a daily dose of 80 mg or higher. 100 (40%) of 249 patients in the full analysis set achieved a response, with 19 (8%) achieving complete remission, ten (4%) complete remission with incomplete platelet recovery, 46 (18%) complete remission with incomplete haematological recovery, and 25 (10%) partial remission INTERPRETATION: Gilteritinib had a favourable safety profile and showed consistent FLT3 inhibition in patients with relapsed or refractory acute myeloid leukaemia. These findings confirm that FLT3 is a high-value target for treatment of relapsed or refractory acute myeloid leukaemia; based on activity data, gilteritinib at 120 mg/day is being tested in phase 3 trials.FundingAstellas Pharma, National Cancer Institute (Leukemia Specialized Program of Research Excellence grant), Associazione Italiana Ricerca sul Cancro