Modeling the cost of influenza: the impact of missing costs of unreported complications and sick leave

Background Estimating the economic impact of influenza is complicated because the disease may have non-specific symptoms, and many patients with influenza are registered with other diagnoses. Furthermore, in some countries like Norway, employees can be on paid sick leave for a specified number of days without a doctor's certificate ("self-reported sick leave") and these sick leaves are not registered. Both problems result in gaps in the existing literature: costs associated with influenza-related illness and self-reported sick leave are rarely included. The aim of this study was to improve estimates of total influenza-related health-care costs and productivity losses by estimating these missing costs. Methods Using Norwegian data, the weekly numbers of influenza-attributable hospital admissions and certified sick leaves registered with other diagnoses were estimated from influenza-like illness surveillance data using quasi-Poisson regression. The number of self-reported sick leaves was estimated using a Monte-Carlo simulation model of illness recovery curves based on the number of certified sick leaves. A probabilistic sensitivity analysis was conducted on the economic outcomes. Results During the 1998/99 through 2005/06 influenza seasons, the models estimated an annual average of 2700 excess influenza-associated hospitalizations in Norway, of which 16% were registered as influenza, 51% as pneumonia and 33% were registered with other diagnoses. The direct cost of seasonal influenza totaled US$22 million annually, including costs of pharmaceuticals and outpatient services. The annual average number of working days lost was predicted at 793 000, resulting in an estimated productivity loss of US$231 million. Self-reported sick leave accounted for approximately one-third of the total indirect cost. During a pandemic, the total cost could rise to over US$800 million. Conclusions Influenza places a considerable burden on patients and society with indirect costs greatly exceeding direct costs. The cost of influenza-attributable complications and the cost of self-reported sick leave represent a considerable part of the economic burden of influenza

Broad targeting of resistance to apoptosis in cancer

Apoptosis or programmed cell death is natural way of removing aged cells from the body. Most of the anti-cancer therapies trigger apoptosis induction and related cell death networks to eliminate malignant cells. However, in cancer, de-regulated apoptotic signaling, particularly the activation of an anti-apoptotic systems, allows cancer cells to escape this program leading to uncontrolled proliferation resulting in tumor survival, therapeutic resistance and recurrence of cancer. This resistance is a complicated phenomenon that emanates from the interactions of various molecules and signaling pathways. In this comprehensive review we discuss the various factors contributing to apoptosis resistance in cancers. The key resistance targets that are discussed include (1) Bcl-2 and Mcl-1 proteins; (2) autophagy processes; (3) necrosis and necroptosis; (4) heat shock protein signaling; (5) the proteasome pathway; (6) epigenetic mechanisms; and (7) aberrant nuclear export signaling. The shortcomings of current therapeutic modalities are highlighted and a broad spectrum strategy using approaches including (a) gossypol; (b) epigallocatechin-3-gallate; (c) UMI-77 (d) triptolide and (e) selinexor that can be used to overcome cell death resistance is presented. This review provides a roadmap for the design of successful anti-cancer strategies that overcome resistance to apoptosis for better therapeutic outcome in patients with cancer

Ultra-Fast Flash Observatory: Fast Response Space Missions for Early Time Phase of Gamma Ray Bursts

One of the unexplored domains in the study of gamma-ray bursts (GRBs) is the early time phase of the optical light curve. We have proposed Ultra-Fast Flash Observatory (UFFO) to address this question through extraordinary opportunities presented by a series of small space missions. The UFFO is equipped with a fast-response Slewing Mirror Telescope that uses a rapidly moving mirror or mirror array to redirect the optical beam rather than slewing the entire spacecraft or telescope to aim the optical instrument at the GRB position. The UFFO will probe the early optical rise of GRBs with sub-second response, for the first time, opening a completely new frontier in GRB and transient studies. Its fast response measurements of the optical emission of dozens of GRB each year will provide unique probes of the burst mechanism and test the prospect of GRB as a new standard candle, potentially opening up the z > 10 universe. We describe the current limit in early photon measurements, the aspects of early photon physics, our soon-to-be-launched UFFO-pathfinder mission, and our next planned mission, the UFFO-100

Phosphorescent Energy Downshifting for Diminishing Surface Recombination in Silicon Nanowire Solar Cells

Molecularly engineered Ir(III) complexes can transfer energy from short-wavelength photons (lambda < 450 nm) to photons of longer wavelength (lambda > 500 nm), which can enhance the otherwise low internal quantum efficiency (IQE) of crystalline Si (c-Si) nanowire solar cells (NWSCs) in the shortwavelength region. Herein, we demonstrate a phosphorescent energy downshifting system using Ir(III) complexes at short wavelengths (300-450 nm) to diminish the severe surface recombination that occurs in c-Si NWSCs. The developed Ir(III) complexes can be considered promising energy converters because they exhibit superior intrinsic properties such as a high quantum yield, a large Stokes shift, a long exciton diffusion length in crystalline film, and a reproducible synthetic procedure. Using the developed 1011) complexes, highly crystalline energy downshifting layers were fabricated by ultrasonic spray deposition to enhance the photoluminescence efficiency by increasing the radiative decay. With the optimized energy downshifting layer, our 1cm(2) c-Si NWSCs with Ir(III) complexes exhibited a higher IQE value for short-wavelength light (300-450 nm) compared with that of bare Si NWSCs without Ir(III) complexes, resulting in a notable increase in the short-circuit current density (from 34.4 mA.cm(-2) to 36.5 mA.cm(-2) )

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model

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Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI): study protocol

Abstract Background The Study of Healthcare Personnel with Influenza and other Respiratory Viruses in Israel (SHIRI) prospectively follows a cohort of healthcare personnel (HCP) in two hospitals in Israel. SHIRI will describe the frequency of influenza virus infections among HCP, identify predictors of vaccine acceptance, examine how repeated influenza vaccination may modify immunogenicity, and evaluate influenza vaccine effectiveness in preventing influenza illness and missed work. Methods Cohort enrollment began in October, 2016; a second year of the study and a second wave of cohort enrollment began in June 2017. The study will run for at least 3 years and will follow approximately 2000 HCP (who are both employees and members of Clalit Health Services [CHS]) with routine direct patient contact. Eligible HCP are recruited using a stratified sampling strategy. After informed consent, participants complete a brief enrollment survey with questions about occupational responsibilities and knowledge, attitudes, and practices about influenza vaccines. Blood samples are collected at enrollment and at the end of influenza season; HCP who choose to be vaccinated contribute additional blood one month after vaccination. During the influenza season, participants receive twice-weekly short message service (SMS) messages asking them if they have acute respiratory illness or febrile illness (ARFI) symptoms. Ill participants receive follow-up SMS messages to confirm illness symptoms and duration and are asked to self-collect a nasal swab. Information on socio-economic characteristics, current and past medical conditions, medical care utilization and vaccination history is extracted from the CHS database. Information about missed work due to illness is obtained by self-report and from employee records. Respiratory specimens from self-collected nasal swabs are tested for influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, and coronaviruses using validated multiplex quantitative real-time reverse transcription polymerase chain reaction assays. The hemagglutination inhibition assay will be used to detect the presence of neutralizing influenza antibodies in serum. Discussion SHIRI will expand our knowledge of the burden of respiratory viral infections among HCP and the effectiveness of current and repeated annual influenza vaccination in preventing influenza illness, medical utilization, and missed workdays among HCP who are in direct contact with patients. Trial registration NCT03331991 . Registered on November 6, 2017.https://deepblue.lib.umich.edu/bitstream/2027.42/146186/1/12879_2018_Article_3444.pd

Direct Identification of the Meloidogyne incognita Secretome Reveals Proteins with Host Cell Reprogramming Potential

The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin) that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins). Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth). Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals

Proteomics Coupled with Metabolite and Cell Wall Profiling Reveal Metabolic Processes of a Developing Rice Stem Internode

Internodes of grass stems function in mechanical support, transport, and, in some species, are a major sink organ for carbon in the form of cell wall polymers. This study reports cell wall composition, proteomic, and metabolite analyses of the rice elongating internode. Cellulose, lignin, and xylose increase as a percentage of cell wall material along eight segments of the second rice internode (internode II) at booting stage, from the younger to the older internode segments, indicating active cell wall synthesis. Liquid-chromatography tandem mass spectrometry (LC-MS/MS) of trypsin-digested proteins from this internode at booting reveals 2,547 proteins with at least two unique peptides in two biological replicates. The dataset includes many glycosyltransferases, acyltransferases, glycosyl hydrolases, cell wall-localized proteins, and protein kinases that have or may have functions in cell wall biosynthesis or remodeling. Phospho-enrichment of internode II peptides identified 21 unique phosphopeptides belonging to 20 phosphoproteins including a leucine rich repeat-III family receptor like kinase. GO over-representation and KEGG pathway analyses highlight the abundances of proteins involved in biosynthetic processes, especially the synthesis of secondary metabolites such as phenylpropanoids and flavonoids. LC-MS/MS of hot methanol-extracted secondary metabolites from internode II at four stages (booting/elongation, early mature, mature, and post mature) indicates that internode secondary metabolites are distinct from those of roots and leaves, and differ across stem maturation. This work fills a void of in-depth proteomics and metabolomics data for grass stems, specifically for rice, and provides baseline knowledge for more detailed studies of cell wall synthesis and other biological processes characteristic of internode development, toward improving grass agronomic properties.This work was supported by the U.S. National Science Foundation (grant numbers EPS-0814361, 0923247, and CHE-1626372), the U.S. Department of Energy (DOE), Office of Science (DE-SC0006904), and the U.S. Department of Agriculture National Institute of Food and Agriculture, (2010-38502-21836). A portion of this research was performed in the Environmental Molecular Sciences Laboratory at the Pacific Northwest National Laboratory (PNNL). The Environmental Molecular Sciences Laboratory is a DOE Office of Biological and Environmental Research scientific user facility on the PNNL campus. PNNL is a multiprogram national laboratory operated by Battelle for the DOE under contract DE-AC05-76RL01830. Collaboration with EMSL was supported through Projects 49477 and 49510. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies. Open access fees fees for this article provided whole or in part by OU Libraries Open Access Fund.Ye