Project description:Simulated stratospheric temperatures over the period 1979-2016 in models from the Chemistry-Climate Model Initiative (CCMI) are compared with recently updated and extended satellite observations. The multi-model mean global temperature trends over 1979- 2005 are -0.88 ± 0.23, -0.70 ± 0.16, and -0.50 ± 0.12 K decade-1 for the Stratospheric Sounding Unit (SSU) channels 3 (~40-50 km), 2 (~35-45 km), and 1 (~25-35 km), respectively. These are within the uncertainty bounds of the observed temperature trends from two reprocessed satellite datasets. In the lower stratosphere, the multi-model mean trend in global temperature for the Microwave Sounding Unit channel 4 (~13-22 km) is -0.25 ± 0.12 K decade-1 over 1979-2005, consistent with estimates from three versions of this satellite record. The simulated stratospheric temperature trends in CCMI models over 1979-2005 agree with the previous generation of chemistry-climate models. The models and an extended satellite dataset of SSU with the Advanced Microwave Sounding Unit-A show weaker global stratospheric cooling over 1998-2016 compared to the period of intensive ozone depletion (1979-1997). This is due to the reduction in ozone-induced cooling from the slow-down of ozone trends and the onset of ozone recovery since the late 1990s. In summary, the results show much better consistency between simulated and satellite observed stratospheric temperature trends than was reported by Thompson et al. (2012) for the previous versions of the SSU record and chemistry-climate models. The improved agreement mainly comes from updates to the satellite records; the range of simulated trends is comparable to the previous generation of models.
Project description:BackgroundDrug shortages represent a growing global problem, with potentially serious consequences to patients and the health care system. Our study investigates the impacts of a major recall and shortage of valsartan, an angiotensin receptor blocker (ARB), in July 2018 in Canada.MethodsWe conducted a time-series analysis of antihypertensive drugs dispensed in Canada between 2015 and 2019 using commercially available retail prescription data. Using autoregressive integrated moving average (ARIMA) modelling, we evaluated the change in valsartan use after the recall. We also measured the overall use of ARBs, angiotensin-converting-enzyme (ACE) inhibitors and other antihypertensive drug classes for the same period.ResultsAfter the recall in July 2018, valsartan use decreased 57.8%, from 362 231 prescriptions dispensed in June 2018 to 152 892 in September 2018 (difference = 209 339, p < 0.0001). Overall use of the ARB drug class decreased 2.0%, from 1 577 509 prescriptions dispensed in June 2018 to 1 545 591 in September 2018 (difference = 31 918, p = 0.0003), but use of non-valsartan ARBs increased 14.6%, from 1 215 278 to 1 392 699 prescriptions dispensed (difference = 177 421, p < 0.0001) in the same time frame. Although use of ACE inhibitors initially declined, this reduction was not sustained. The valsartan recall was not associated with a significant impact on use of other antihypertensive drug classes.InterpretationOur findings illustrate the impact of a major drug shortage, with the immediate and substantial reduction of valsartan dispensed and cascading effects on other ARBs, though future research is warranted to understand the consequences of such extensive shortages on clinical outcomes and health system costs. Improved policy strategies are needed to address the underlying causes of drug shortages and to mitigate their effects.
Project description:Advances in RNA-sequencing technologies have led to the development of intriguing experimental setups, a massive accumulation of data, and high demand for tools to analyze it. To answer this demand, computational scientists have developed a myriad of data analysis pipelines, but it is less often considered what the most appropriate one is. The RNA-sequencing data analysis pipeline can be divided into three major parts: data pre-processing, followed by the main and downstream analyses. Here, we present an overview of the tools used in both the bulk RNA-seq and at the single-cell level, with a particular focus on alternative splicing and active RNA synthesis analysis. A crucial part of data pre-processing is quality control, which defines the necessity of the next steps; adapter removal, trimming, and filtering. After pre-processing, the data are finally analyzed using a variety of tools: differential gene expression, alternative splicing, and assessment of active synthesis, the latter requiring dedicated sample preparation. In brief, we describe the commonly used tools in the sample preparation and analysis of RNA-seq data.
Project description:ObjectiveExamine the impact of the 2011 shortage of the drug cytarabine on patient receipt and timeliness of induction treatment for Acute Myeloid Leukemia (AML).Study designA retrospective cohort was utilized to examine odds of receipt of inpatient induction chemotherapy and time to first dose across major (N = 105) and moderate (N = 316) shortage time periods as compared to a nonshortage baseline (N = 1,147).Data collection/extraction methodsDe-identified patient data from 2008 to 2011 Surveillance, Epidemiology, and End Results (SEER) were linked to 2007-2013 Medicare claims and 2007-2013 Hospital Characteristics.Principal findingsCompared to prior nonshortage time period, patients diagnosed during a major drug shortage were 47 percent less likely (p < .05) to receive inpatient chemotherapy within 14 days of diagnosis. Patients who were younger, had a lower Charlson Comorbidity score, and for whom AML was a first primary cancer were prioritized across all periods.ConclusionsPeriod of major shortage of a generic oncolytic, without an equivalent therapeutic substitute, reduced timely receipt of induction chemotherapy treatment. More favorable economic and regulatory policies for generic drug suppliers might result in greater availability of essential, older generic drug products that face prolonged or chronic shortage.
Project description:We genotyped 135 new samples (121 samples from 10 Uralic-speaking and 14 samples from 8 non-Uralic-speaking populations) and combined these data with previously published data to characterize the population structure of Uralic-speaking populations in the context of their geographic neighbours across Eurasia
Project description:How and when the Americas were populated remains contentious. Using ancient and modern genome-wide data, we find that the ancestors of all present-day Native Americans, including Athabascans and Amerindians, entered the Americas as a single migration wave from Siberia no earlier than 23 thousand years ago (KYA), and after no more than 8,000-year isolation period in Beringia. Native Americans diversified into two basal genetic branches around 13 KYA, one in North and South America and the other restricted to North America. Subsequent gene flow resulted in some Native Americans sharing ancestry with present-day East Asians and Australo-Melanesians, the latter possibly through the ancestors of Aleutian Islanders. Putative relict populations in South America, including the historical Pericúes and Fuego-Patagonians, are not directly related to modern Australo-Melanesians.
Project description:BackgroundNumerous cortical and subcortical structures have been studied extensively concerning alterations of their integrity as well as their neurotransmitters in depression. However, connections between these structures have received considerably less attention.ObjectiveThis systematic review presents results from recent neuroimaging as well as neuropathologic studies conducted on humans and other mammals. It aims to provide evidence for impaired white matter integrity in individuals expressing a depressive phenotype.MethodsA systematic database search in accordance with the PRISMA guidelines was conducted to identify imaging and postmortem studies conducted on humans with a diagnosis of major depressive disorder, as well as on rodents and primates subjected to an animal model of depression.ResultsAlterations are especially apparent in frontal gyri, as well as in structures establishing interhemispheric connectivity between frontal regions. Translational neuropathological findings point to alterations in oligodendrocyte density and morphology, as well as to alterations in the expression of genes related to myelin synthesis. An important role of early life adversities in the development of depressive symptoms and white matter alterations across species is thereby revealed. Data indicating that stress can interfere with physiological myelination patterns is presented. Altered myelination is most notably present in regions that are subject to maturation during the developmental stage of exposure to adversities.ConclusionTranslational studies point to replicable alterations in white matter integrity in subjects suffering from depression across multiple species. Impaired white matter integrity is apparent in imaging as well as neuropathological studies. Future studies should focus on determining to what extent influencing white matter integrity is able to improve symptoms of depression in animals as well as humans.
Project description:The loss of biodiversity during the Anthropocene is a constant topic of discussion, especially in the top biodiversity hotspots, such as Madagascar. In this regard, the study of preserved organisms through time, like those included in "Madagascar copal", is of relevance. "Madagascar copal" originated from the leguminous tree Hymenaea verrucosa, which produced and produces resin abundantly. In the last 20 years, interest has focused on the scientific study of its biological inclusions, mainly arthropods, described in dozens of publications. The age and origin of the deposits of "Madagascar copal" have not yet been resolved. Our objectives are to determine its age and geographical origin, and thus increase its scientific value as a source of biological/palaeobiological information. Although Hymenaea was established in Madagascar during the Miocene, we did not find geological deposits of copal or amber in the island. It is plausible that the evolution of those deposits was negatively conditioned by the type of soil, by the climate, and by the development of soil/litter microorganisms, which inhibit preservation of the resin pieces in the litter and subsoil over 300 years. Our results indicate that "Madagascar copal" is a Recent resin, up to a few hundred years old, that originated from Hymenaea trees growing in the lowland coastal forests, one of the most endangered ecosystems in the world. The included and preserved biota is representative of that ecosystem today and during historical times. Inclusions in this Recent resin do not have the palaeontological significance that has been mistakenly attributed to them, but they do have relevant implications for studies regarding Anthropocene biodiversity loss in this hottest hotspot.
Project description:BackgroundLeprosy is remaining prevalent in the poorest areas of the world. Intensive control programmes with multidrug therapy (MDT) reduced the number of registered cases in these areas, but transmission of Mycobacterium leprae continues in most endemic countries. Socio-economic circumstances are considered to be a major determinant, but uncertainty exists regarding the association between leprosy and poverty. We assessed the association between different socio-economic factors and the risk of acquiring clinical signs of leprosy.Methods and findingsWe performed a case-control study in two leprosy endemic districts in northwest Bangladesh. Using interviews with structured questionnaires we compared the socio-economic circumstances of recently diagnosed leprosy patients with a control population from a random cluster sample in the same area. Logistic regression was used to compare cases and controls for their wealth score as calculated with an asset index and other socio-economic factors. The study included 90 patients and 199 controls. A recent period of food shortage and not poverty per se was identified as the only socio-economic factor significantly associated with clinical manifestation of leprosy disease (OR 1.79 (1.06-3.02); p = 0.030). A decreasing trend in leprosy prevalence with an increasing socio-economic status as measured with an asset index is apparent, but not statistically significant (test for a trend: OR 0.85 (0.71-1.02); p = 0.083).ConclusionsRecent food shortage is an important poverty related predictor for the clinical manifestation of leprosy disease. Food shortage is seasonal and poverty related in northwest Bangladesh. Targeted nutritional support for high risk groups should be included in leprosy control programmes in endemic areas to reduce risk of disease.
Project description:Drug shortages frequently and persistently affect healthcare institutions, posing formidable financial, logistical, and ethical challenges. Despite plentiful evidence characterizing the impact of drug shortages, there is a remarkable dearth of data describing current shortage management practices. Hospitals within the same state or region may not only take different approaches to shortages but may be unaware of shortages proximate facilities are facing. Our goal is to explore how hospitals in Michigan handle drug shortages to assess potential need for comprehensive drug shortage management resources. We conducted semi-structured interviews with diverse stakeholders throughout the state to describe experiences managing drug shortages, approaches to recent shortages, openness to inter-institutional engagement, ideas for a shared resource, and potential obstacles to implementation. To solicit additional feedback on ideas for a shared resource gathered from the interviews, we held focus groups with pharmacists, physicians, ethicists, and community representatives. Among participants representing a heterogeneous sample of institutions, three themes were consistent: (1) numerous drug shortage strategies occurring simultaneously; (2) inadequate resources and lead time to proactively manage shortages; and (3) interest in, but varied attitudes toward, a collaborative approach. These data provide insight to help develop and test a shared drug shortage management resource for enhancing fair allocation of scarce drugs. A shared resource may help institutions adopt accepted best practices and more efficiently access or share finite resources in times of shortage.