Project description:The definition of a new case is a vital step in incidence studies in both epidemiology and pharmacoepidemiology, although with significant differences in methodology between the fields. We define and apply a framework for two different types of new cases of drug use, first-ever and recurrent, and show how the associated misclassifications related to length of run-in period can be expressed by the positive predictive value (PPV). In the study, we consider individual-level dispensations of statins 2006-2019 for 1,017,058 individuals with at least one dispensation in 2019 in Sweden. The incidence proportion for statins for both sexes of all ages in Sweden 2019 varied from 17.4/1000 with a run-in of 8 months, 9.45/1000 with 5 years and 8.4/1000 with 10 years. The PPV was 49% with 8 months and 89% for 5 years using 10 years as gold standard. We conclude that the interpretation of incidence and thus the selection of an appropriate run-in period, in pharmacoepidemiology, depends on whether first-ever use, recurrent treatment or both together (new cases) is the focus of the research question studied. At least five different misclassifications can be introduced depending on how incidence is defined.
Project description:In preparing for influenza pandemics, public health agencies stockpile critical medical resources. Determining appropriate quantities and locations for such resources can be challenging, given the considerable uncertainty in the timing and severity of future pandemics. We introduce a method for optimizing stockpiles of mechanical ventilators, which are critical for treating hospitalized influenza patients in respiratory failure. As a case study, we consider the US state of Texas during mild, moderate, and severe pandemics. Optimal allocations prioritize local over central storage, even though the latter can be deployed adaptively, on the basis of real-time needs. This prioritization stems from high geographic correlations and the slightly lower treatment success assumed for centrally stockpiled ventilators. We developed our model and analysis in collaboration with academic researchers and a state public health agency and incorporated it into a Web-based decision-support tool for pandemic preparedness and response.
Project description:Spontaneous activity of the human brain provides a window to explore intrinsic principles of functional organization. However, most studies have focused on interregional functional connectivity. The principles underlying rich repertoires of instantaneous activity remain largely unknown. We apply a recently proposed eigen-microstate analysis to three resting-state functional MRI datasets to identify basic modes that represent fundamental activity patterns that coexist over time. We identify five leading basic modes that dominate activity fluctuations. Each mode exhibits a distinct functional system-dependent coactivation pattern and corresponds to specific cognitive profiles. In particular, the spatial pattern of the first leading basis mode shows the separation of activity between the default-mode and primary and attention regions. Based on theoretical modelling, we further reconstruct individual functional connectivity as the weighted superposition of coactivation patterns corresponding to these leading basic modes. Moreover, these leading basic modes capture sleep deprivation-induced changes in brain activity and interregional connectivity, primarily involving the default-mode and task-positive regions. Our findings reveal a dominant set of basic modes of spontaneous activity that reflect multiplexed interregional coordination and drive conventional functional connectivity, furthering the understanding of the functional significance of spontaneous brain activity.
Project description:Histone H2A (1-10 microg/ml) added to Ehrlich ascite cell suspensions promoted: (i) Ca2+ influx, but no apparent intracellular Ca2+ mobilization; (ii) plasma-membrane depolarization and Na+ influx in Ca2+-free medium, which were recovered by Ca2+ readmission; (iii) influx of other cations such as Ba2+, Mn2+, choline+ and N-methyl-d-glucamine+, but not of propidium+, ethidium bromide and Trypan Blue. H2A-induced Ca2+ influx and cell depolarization were: (i) blocked by La3+ and Gd3+, but not by various inhibitors of receptor-activated Ca2+-influx pathways/channels; (ii) mimicked by various basic polypeptides, with Mr>4000; (iii) prevented or reversed by polyanions such as polyglutamate or heparin; (iv) present in other cell types, such as Jurkat, PC12 and Friend erythroleukaemia cells, but virtually absent from rat hepatocytes and thymocytes. We conclude that cationic proteins/polypeptides, by interacting in a cell-specific manner with the cell surface, can activate in those cells putative non-selective Ca2+ channels and membrane depolarization.
Project description:N-methyl-d-aspartate receptors (NMDARs) are profound regulators of glutamate neurotransmission and behavior. To coordinate components of the limbic system, the dorsal and ventral striatum integrate cognitive and emotional information towards the execution of complex behaviors. Striatal outflow is conveyed by medium spiny neurons (MSNs), which can be dichotomized by expression of dopamine receptor subtype 1 (D1) or adenosine receptor subtype 2A (A2A). To examine how striatal NMDAR function modulates reward-related behaviors, we generated D1- and A2A-specific genetic deletions of the obligatory GluN1 subunit. Interestingly, we observed no differences in any GluN1-/- genotype in reward learning as assessed by acquisition or extinction of cocaine conditioned place preference (CPP). Control and A2A-GluN-/- mice exhibited robust cocaine-primed reinstatement, however this behavior was markedly absent in D1-GluN-/- mice. Interestingly, dual D1-/A2A-GluN-/- mice displayed an intermediate reinstatement phenotype. Next, we examined models of exploration, anxiety, and despair, states often associated with relapse to addiction-related behavior, to determine NMDAR contribution in D1 and A2A cell types to these behaviors. D1-GluN1-/- mice displayed aberrant exploratory locomotion in a novel environment, but the phenotype was absent in dual D1/A2A-GluN1-/- mice. In contrast A2A-GluN1-/- mice displayed a despair-resistant phenotype, and this phenotype persisted in dual D1/A2A-GluN-/- mice. These data support the hypothesis that cell type-specific NMDAR signaling regulates separable behavioral outcomes related to locomotion, despair, and relapse. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.
Project description:Basic peptides covalently linked to nucleic acids, or chemically modified nucleic acids, enable the insertion of such a conjugate into bacteria grown in liquid medium and mammalian cells in tissue culture. A unique peptide, derived from human T cells, has been employed in a chemical synthesis to make a conjugate with a morpholino oligonucleotide. This new conjugate is at least 10- to 100-fold more effective than previous peptides used in altering the phenotype of host bacteria if the external guide sequence methodology is employed in these experiments. Bacteria with target genes expressing chloramphenicol resistance, penicillin resistance, or gyrase A function can effectively be reduced in their expression and the host cells killed. Several bacteria are susceptible to this treatment, which has a broad range of potency. The loss in viability of bacteria is not due only to complementarity with a target RNA and the action of RNase P, but also to a non-gene-specific tight binding of the complexed nontargeted RNA to the basic polypeptide-morpholino oligonucleotide.
Project description:Using empirical orthogonal function (EOF) analysis of the monthly tropical Pacific subsurface ocean temperature anomalies (SOTA) from 1979 to 2014, we detected three leading modes in the tropical Pacific subsurface temperature. The first mode has a dipole pattern, with warming in the eastern Pacific and cooling in the western Pacific, and is closely related to traditional El Niño. The second mode has a monopole pattern, with only warming in the central Pacific subsurface. The third mode has a zonal tripole pattern, with warming in the off-equatorial central Pacific and cooling in the far eastern Pacific and western Pacific. The second and third modes are both related to El Niño Modoki. Mode 1 is linked with a Kelvin wave that propagates from the central to the eastern Pacific and is induced by the anomalous westerlies that propagate from the western to the central Pacific. Mode 2 is also linked with a Kelvin wave that propagates from the western to the central Pacific induced by the enhancement of westerlies over the western Pacific. Mode 3 is linked with a Rossby wave that propagates from the central to the western Pacific driven by the anomalous easterlies over the eastern Pacific.
Project description:The COVID-19 pandemic and discovery of new mutant strains have a devastating impact worldwide. Patients with severe COVID-19 require various equipment, such as ventilators, infusion pumps, and patient monitors, and a dedicated medical team to operate and monitor the equipment in isolated intensive care units (ICUs). Medical staff must wear personal protective equipment to reduce the risk of infection. This study proposes a tele-monitoring system for isolation ICUs to assist in the monitoring of COVID-19 patients. The tele-monitoring system consists of three parts: medical-device panel image processing, transmission, and tele-monitoring. This system can monitor the ventilator screen with obstacles, receive and store data, and provide real-time monitoring and data analysis. The proposed tele-monitoring system is compared with previous studies, and the image combination algorithm for reconstruction is evaluated using structural similarity index (SSIM) and peak signal-to-noise ratio (PSNR). The system achieves an SSIM score of 0.948 in the left side and a PSNR of 23.414 dB in the right side with no obstacles. It also reduces blind spots, with an SSIM score of 0.901 and a PSNR score of 18.13 dB. The proposed tele-monitoring system is compatible with both wired and wireless communication, making it accessible in various situations. It uses camera and performs live data monitoring, and the two monitoring systems complement each other. The system also includes a comprehensive database and an analysis tool, allowing medical staff to collect and analyze data on ventilator use, providing them a quick, at-a-glance view of the patient's condition. With the implementation of this system, patient outcomes may be improved and the burden on medical professionals may be reduced during the COVID-19 pandemic-like situations.