text:
ORIGINAL RESEARCH article
Sec. Inflammation Pharmacology
Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis
- 1Department of Psychiatry, School of Medicine, University Hospital Virgen del Rocio-IBIS, Sevilla, Spain
- 2Spanish Network for Research in Mental Health (CIBERSAM), Sevilla, Spain
- 3Department of Psychiatry, University Hospital Marques de Valdecilla - Instituto de Investigacion Marques de Valdecilla (IDIVAL), Santander, Spain
- 4Department of Medicine and Psychiatry, School of Medicine, University of Cantabria, Santander, Spain
- 5Seville Biomedical Research Centre (IBiS), Sevilla, Spain
- 6Department of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville, University Hospital Virgen del Rocio, University of Seville, Salamanca, Spain
- 7Spanish Network for Research in Infectious Diseases (REIPI), Madrid, Spain
- 8Bioinformatics Service, Nucleus, University of Salamanca, Salamanca, Spain
- 9Spanish National Research Council (CSIC), Institute of Biomedicine and Biotechnology of Cantabria, Santander, Spain
Background: Antipsychotics modulate expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID-19-related immunological parameters.
Methods: Differential gene expression profiles of non-COVID-19 vs. COVID-19 RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with non-affective psychosis at baseline and after three months of aripiprazole treatment were identified. An integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients was performed.
Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher’s Exact Test, two tail; p value = 3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated non-affective psychosis patients (p adj<0.05). The most significant pathways were associated to immune responses and mechanisms of hyperinflammation-driven pathology (i.e.,“inflammatory bowel disease (IBD)” (the most significant pathway with a p adj of 0.00021), “Th1 and Th2 cell differentiation” and “B cell receptor signaling pathway”) that have been also associated with COVID19 clinical outcome.
Interpretation: This exploratory investigation may provide further support to the notion that a protective effect is exerted by aripiprazole (phenylpiperazine) by modulating the expression of genes that have shown to be altered in COVID-19 patients. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.
The SARS-CoV-2 epidemic has become the greatest challenge facing medicine today. Infected patients present with a wide range of clinical severity varying from asymptomatic to fatal condition (Wu et al., 2020). Advanced age, gender (male) and suffering comorbidities (diabetes, cardiovascular or chronic respiratory diseases) are risk factors for higher clinical severity, hospitalization rate and death from COVID-19 (Rubino et al., 2020; Zhou et al., 2020). The presence of these comorbidities may decrease resilience and lower the ability to tolerate additional cytokine storm (Mangalmurti and Hunter, 2020).
COVID-19 individuals who become critically and fatally ill seem to experience an indiscriminate and runaway immune response with an unchecked systemic overproduction of cytokines and immunological disbalance (Bhaskar et al., 2020; Manjili et al., 2020; Zeng et al., 2020). COVID-19 related immunopathogenesis is not understood just as an emergent cytokine storm but also as an impairment of protective T cell immunity (Chen et al., 2020).
There are no FDA-approved antivirals or vaccines for any coronavirus, including SARS-CoV-2, and current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA-approved drugs. Anti-inflammatory drugs such as dexamethasone have been shown to reduce deaths (Vabret et al., 2020). The crucial role of NLRP3 inflammasome activation in the pathogenesis of diseases caused by SARS-CoVs draws also attention toward potential role of its inhibitors in the treatment of COVID-19 (van den Berg and Te Velde, 2020). Wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials, seem to have a beneficial effect against MERS and SARS coronaviruses (Dyall et al., 2017). Weston et al., (2020) observed that, although infection cannot be prevented, chlorpromazine (typical antipsychotic drug) and chloroquine protect mice from severe clinical disease from SARS-CoV. Clozapine (atypical antipsychotic drug) has revealed to be effective in suppressing the proinflammatory cytokine expression by limiting the NLRP3 inflammasome activation in vitro (Giridharan et al., 2020). In the same line as above, Riva and colleagues (2020) analyzed approximately 12,000 drugs in clinical-stage or Food and Drug Administration (FDA)-approved small molecules to identify candidate drugs to treat COVID-19 and reported that elopiprazole (a never marketed phenylpiperazine antipsychotic drug) was listed among the 21 most potent compounds to inhibit SARS-CoV infection. Phenyl-piperazine derivatives had proved their utility as an effective source of antiviral compounds, with different mechanisms of action, for treatment of human adenovirus and cytomegalovirus (DNA viruses) (Sanchez-Cespedes et al., 2016).
Antipsychotics suppress expression of inflammatory cytokines and inducible inflammatory enzymes (i.e., cyclooxygenase) and microglia activation (Dinesh et al., 2020). These anti-inflammatory effects are elicited via the reduction of proinflammatory cytokines production, modulating monocytes response through TLR and the inhibition of the microglial activation by reducing the levels of inducible nitric oxide synthase (iNOS), IL-1β, IL-6, and TNF-α (Kato et al., 2007; Obuchowicz et al., 2017). In humans, the immunomodulatory effect of risperidone (pyridopyrimidines) and aripiprazole (marketed phenylpiperazine) has been demonstrated (Juncal-Ruiz et al., 2018), with aripiprazole demonstrating a greater anti-inflammatory effect on TNF-α, IL-13, IL-17α and fractalkine. Thus, the protective effect of phenylpiperazine marketed antipsychotics (aripiprazole) against a pernicious cytokine storm is a hypothesis that warrants further investigation with the aim of unrevealing new off-label drug to be use in severe COVID19 patients.
Prevalence and severity of COVID-19 infection in patients with severe mental disorders have yielded to inconsistent results, likely due to differences in the methodology utilized in these investigations. Lee and collaborators (2020) reported that diagnosis of a mental disorder was not associated with increased likelihood of SARS-CoV infection, but a slightly higher risk for severe clinical outcomes (Lee et al., 2020). Wang and colleagues (2021) reported a higher overall risk to get infected among schizophrenia patients. In a retrospective epidemiological study, we observed that vulnerable severe mental disorder individuals on long-acting injectable antipsychotics had a lower risk of SARS-CoV2 infection and a better outcome after infection (unpublished data).
The aim of the present study was to examine the potential beneficial effects of aripiprazole (antipsychotic) in COVID-19 infection by: 1.- analyzing the profile of gene expression of drug-naïve patients with psychosis at baseline and after three months of treatment with aripiprazole (PAFIP sample); and 2.- comparing the set of genes with altered expression in COVID-19 patients (Wuhan sample) with the set of genes modulated by aripiprazole in drug-naïve schizophrenia patients.
Materials and Methods
PAFIP Cohort of Aripiprazole-Treated Patients
Setting and Sample Study
The cohort analyzed to study the effect of aripiprazole was obtained at the University Hospital Marques de Valdecilla (Cantabria, Spain). Conforming to international standards for research ethics, this study was approved by the Cantabria Ethics Institutional Review Board (IRB). Patients meeting inclusion criteria for a first episode of non-affective psychosis (drug-naïve) provided written informed consent to be included in the study. After informed consent was signed, patients were included in a prospective, randomized, flexible-dose, open-label study (Crespo-Facorro et al., 2017; Mayoral Van-Son et al., 2021).
Blood samples were obtained from 57 fasting non-affective psychosis subjects (25 males and 32 females; mean age of 31.54 years) from 8:00 to 10:00 a.m. by the same staff and in the same setting. A detailed description of methodology followed to assess biochemical variables is available upon request to the authors. None of the patients had a chronic inflammation or infection, or were taking medication that could influence the results of blood tests.
Total RNA was extracted from blood using the Tempus™ Blood RNA Tube and the Tempus™ Spin RNA Isolation Kit (Applied Biosystems, Foster City, CA, United States) following the manufacturer’s protocols. To select only high-quality RNA, the RNA integrity number (RIN) was characterized with a Bioanalyzer (Agilent Technologies, Santa Clara, CA, United States) and samples with a RIN of at least 7.6 were used.
RNA Next-Generation Sequencing
Total RNA was extracted from peripheral blood of each individual. The messenger RNA (mRNA) obtained from blood was sequenced at the Centro Nacional de Análisis Genómico (CNAG) using Illumina HiSeq instruments (San Diego, CA, United States). The mRNA was isolated from the total RNA and was fragmented once transformed into complementary DNA (cDNA). Fragments of 300bp on average were selected to construct the cDNA libraries for sequencing. Pair-end sequences of 70 nucleotides for each end were produced. The mRNA from blood samples of 57 drug-naïve non-affective psychosis patients at baseline and after 3 months of continuous treatment with aripiprazole was sequenced.
Sequence files were aligned to the GRCh38 human reference genome (Gencode release 25) using the STAR aligner (Harrow et al., 2012; Dobin et al., 2013). Reads count were normalized with the Voom algorithm using the cyclic loess method (Law et al., 2014) and significant gene expression changes between treated and naïve patients were identified with lima (Smyth et al., 2005). We performed a paired analysis using a Wald test and a parametric fit type with an adjusted p-value cutoff of 0.01.
Wuhan COVID19 Dataset
COVID data was downloaded from the GSA server (Wang et al., 2017) with the CRA002390 identifier (Xiong et al., 2020). This research collected RNA-Seq samples of peripheral blood mononuclear cells (PBMC) from three COVID-19 patients (all were males; mean age of 45.3 years) and three healthy donors at Zhongnan Hospital of Wuhan University that were included in the present study. These data were analyzed with RaNA-Seq (Prieto and Barrios, 2020) cloud platform and differential expression genes were detected by means of DESeq2 (Love et al., 2014) cloud using a Wald test, a parametric fit type and setting an adjusted p-value cutoff of 0.01.
Statistical and Bioinformatic Analysis
Statistical significance of differential expression co-occurrence between COVID-19 and aripiprazole studies was calculated with a Fisher Exact test. Functional enrichment analyses, to identify biological pathways in the Biosystem database (downloaded on January 2020) (Geer et al., 2010) with a significant presence of differential expressed genes, were carried out with a Fisher Exact test. KEGG was used for representation and analysis of molecular networks (Kanehisa et al., 2010). Visualization and final representation of pathways were performed with the pathview R package (Luo and Brouwer, 2013).
Integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients:
COVID-19 Patients Versus Healthy Donors (Wuhan Sample)
We found 2,137 genes with significant differential expression between COVID-19 patients and controls (p adj value < 0.05) (Supplementary Table S1). The most significant gene was the Charcot-Leyden crystal galectin gene (CLC) with a p adj value of 7.8e-23.
Drug-Naïve Non-affective Psychosis Patients at Entry and After 3 months of Aripiprazole Treatment (PAFIP Sample)
We found 377 genes with significant differential expression before and after medication (p adj value < 0.05) (Supplementary Table S2). The two most significant genes were the LIM domain only 4 (LMO4) and the ATP binding cassette subfamily A member 9 (ABCA9) with a p adj value of 0.0039.
Differential Gene Expression Between COVID-19 and Aripiprazole-Treated Samples
82 out the 377 genes (21.7%) modified by aripiprazole treatment (PAFIP sample) are significantly also altered in COVID-19 patients (Wuhan sample) (Figure 1). The number of common genes to both analyses is significantly higher than expected by chance (Fisher’s Exact Test, two tail; p value = 3.2e-11).
FIGURE 1. Number of genes with expression altered in Wuhan sample (COVID-19) and PAFIP sample (aripiprazole-treated).
Interestingly, out of the 82 genes with expression altered in both analyzed cohorts 55 genes have decreased expression after aripiprazole medication and increased expression in COVID-19 patients; also, out of the 82 genes common to both cohorts 22 have increased expression after aripiprazole medication and decreased expression in COVID-19 patients. In total 77 genes out of 82 (93.9%) have altered expression in different direction when we compared the effects of COVID-19 and aripiprazole medication.
KEGG Pathways Significantly Enriched With Common Genes With Altered Expression in COVID-19 and Aripiprazole-Treated Samples
The analysis of pathways for enrichment of common genes with altered expression in COVID-19 and aripiprazole patients shows 11 pathways significantly enriched (p value Fisher <0.05) (Table 1). Several of those pathways are related to the immune system such as the “inflammatory bowel disease (IBD)” (the most significant pathway; p adj of 0.00021), “Th1 and Th2 cell differentiation” and “B cell receptor signaling pathway,” both related to the defense against infections.
TABLE 1. KEGG pathways significantly enriched with genes with altered expression in COVID19 patients and schizophrenia patients treated with aripiprazole.
Our results herein revealed that the differently expressed genes in COVID-19 patients and schizophrenia patients treated with aripiprazole were highly associated with numerous immune-related pathways, including “Inflammatory bowel disease (IBD)”, “Th1 and Th2 cell differentiation”, “Fc epsilon RI signaling pathway”, “B cell receptor signaling pathway”, “NF-kappa B signaling pathway” and “Th17 cell differentiation”. It is worth to remark that these immunological pathways have been associated with COVID19 clinical outcome. Thus, a wide array of host humoral and cellular immune response alterations associated with SARS-CoV-2 infection might cause an uncontrolled or insufficient immune response that may lead to immunopathology and cause severe damage to patients. (Tay et al., 2020; Wang et al., 2021). Lymphopenia marked by T cell and NK cell dysfunction, increases in proinflammatory markers and cytokines, and potential blood hypercoagulability characterize severe COVID-19 cases (Vabret et al., 2020).
In more severe COVID-19 cases, death results from hypoxemic respiratory failure in patients developing severe acute respiratory distress syndrome and is associated, in a substantial portion of patients, with an inflammatory syndrome and cytokine storm (Mehta et al., 2020) that may originate from immune cells (Chen et al., 2020). Longitudinal analysis of the immune response observed in a fatal case of COVID-19 revealed waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were until the fatal outcome (Bouadma et al., 2020).
The TH17 type response profoundly also contributes to the cytokine storm in pulmonary viral infection including SARS-CoV-2 (Josset et al., 2013). Compared with non-ICU COVID-19 patients, ICU COVID-19 patients have even higher levels of several cytokines specifically involved in TH17 type responses (Huang C. et al., 2020). It has been recently proposed that JAK2 inhibitor (Fedratinib@) can prevent the deteriorating outcomes of TH17 associated cytokine storm in COVID-19 by suppressing the production of several TH17 signature cytokines (Wu and Yang, 2020). Targeting the TH17 pathway may benefit the patients with TH17 dominant immune profiles.
Among biologic agents in patients with severe COVID-19 inhibiting Fc epsilon RI signaling has been proposed (Yalcin and Yalcin, 2021). Omalizumab specifically binds to the CH3 domain, is near to the binding site for the high affinity IgE Fc receptors type-I (also called FceRI) of human IgE (Metz et al., 2017). A critical issue in patients with Covid-19 is the viremia and the overresponse to this viremia with increase of ferritin, CRP and D-Dimer that are directly associated with the mortality (Huang I. et al., 2020). It has been described that omalizumab safely decreases the coagulant proteins (D-Dimer) and proinflammatory cytokines/mediators and increases the anti-coagulant proteins (protein C, S) in patients with sepsis (Yalcin et al., 2013; Criado et al., 2020). So, it could be anticipated that we may administer it for severe COVID-19 (Yalcin and Yalcin, 2021).
We observed that those genes differentially expressed in COVID-19 and aripiprazole-treated patients were involved in Inflammatory bowel disease (IBD). Autoinflammatory diseases (IBD) that present with bowel inflammation and intractable diarrhea owing to an inappropriate inflammatory response, with also altered key immune pathways underlying persistent inflammation such as excessive IL-1 signaling, constitutive NF-κB activation, and chronic type I IFN signaling (de Jesus et al., 2015). It is also of interest that JAK-STAT pathways, as well as in COVID19, play an important role in the inflammatory response characteristic of IBD and represent a promising therapeutic target for treatment of the disease. (Pedersen et al., 2014).
In our study, differentially expressed genes involved in NF-kappa B signaling pathway were identified according to KEGG pathway analysis. The activated NF-κB transcription factors serve as a “rapid acting” primary transcription factor regulating diverse cellular responses associated with chronic inflammatory states, septic shock syndrome and multiorgan failure (Zhang et al., 2017). Hyper-activation of the nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway has been implicated in the pathogenesis of the severe/critical COVID19 phenotype (Hirano and Murakami, 2020). Cromolyn, which inhibit NF-κB mediated cytokine production, has been suggested as a repurposing drug in the fight against COVID-19 (Karadsheh Adli, 2020). Many of the drugs currently effective in COVID disease appear to have links to the NF-κB cascade of immune regulation (Hariharan et al., 2020).
Despite all recent generated scientific knowledge, immune responses and mechanisms of hyperinflammation-driven pathology need to be further elucidated to address how these immune differences across patients or between different types of coronavirus infections dictate who succumbs to disease and who remains asymptomatic (Vabret et al., 2020).
The fact that antipsychotics have a demonstrated effect on immunological pathways, inducible inflammatory enzymes (i.e., cyclooxygenase), and microglia activation (Dinesh et al., 2020) may lead to the speculation about the beneficial effects of these drugs on controlling the acute hyper-inflammatory response that may be responsible for critical COVID19 illness. A recent study (Riva et al., 2020) profiled a library of approximately 12,000 drugs in clinical-stage or FDA-approved small molecules to identify candidate drugs to treat COVID-19. In the list of the 21 most potent compounds to inhibit infection validated in dose response across multiple cell lines there are two antipsychotic drugs, elopiprazole and 8-(3-Chlorostyryl) caffeine which are in phase I and preclinical stages respectively. Elopiprazole and aripiprazole belong to the class of organic compounds known as phenylpiperazines, containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group (Figure 2).
FIGURE 2. Chemical structures of two phenypiperazines with antipsychotic effects: elopiprazole and aripiprazole.
If our results herein prove to be certain one may expect a milder severity of COVID-19 in patients on aripiprazole (phenylpiperazine). Differences in the definitions and methodology utilized in recent investigations have yielded to inconsistent results about the prevalence and severity of COVID-19 infection among patients with severe mental disorders (Lee et al., 2020; Wang et al., 2021). It is of worth to pinpoint that Wang and colleagues (2021) reported that chronic schizophrenia patients have a lower association compared with recent diagnosis of schizophrenia (less than 1 year) (AOR = 1.48, 95% CI: 1.33–1.65 vs. AOR = 9.89, 95% CI: 8.68–11.26), giving place to the speculation that antipsychotic treatment may exert a protective effect. Nemani et al., (2021) recently described that schizophrenia spectrum diagnosis was associated with an increase of death or discharge to hospice outcome at 45 days following testing and highlighted the relevance of evaluating the potential protective effects of psychotropic medications. Our data retrospectively exploring an epidemiological sample of people with severe mental disorders who are on long-acting injectable antipsychotics revealed a lower risk of SARS-CoV2 infection and a better outcome after infection in this group of antipsychotic treated individuals compared to overall COVID-19 people (Canal-Rivero et al., 2021).
Some limitations need to be taken into when interpreting our results. First, differences in gender distribution between cohorts may limit the comparability of gene expression data. Second, the pattern of gene expression associated to COVID19 infection raises from three COVID19 patients and three healthy donors from whom there is limited access to subjects’ characteristics.
Given that the effect of aripiprazole in gene expression mainly revert the changes in expression caused by COVID19 infection, and that another never marked phenylpiperazine antipsychotic (elopiprazole) has been validated as potential treatment for COVID19, it may be suggested that aripiprazole might be used as treatment for COVID19. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but clearly require further studies and trials.
Data Availability Statement
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ebi.ac.uk/ena, PRJEB42627.
The studies involving human participants were reviewed and approved by the Cantabria Ethics Institutional Review Board (IRB). The patients/participants provided their written informed consent to participate in this study.
Study concept and design: BC-F, MR-V, CP, and JS; acquisition, analysis or interpretation of data: all authors; drafting of the manuscript: all authors; critical revision of the manuscript for important intellectual content: all authors; obtained funding: BC-F and JS; study supervision: BC-F, MR-V, CP, and JS.
The present study was part of a larger prospective longitudinal study, the “First Episode Psychosis Clinical Program 10” (PAFIP10) study. ClinicalTrials.gov Identifiers: NCT02200588, NCT03481465, and NCT03476473. No pharmaceutical industry or institutional sponsors participated in the study conception and design, data collection, analysis and interpretation of the results, or drafting of the manuscript. This work was supported by: SAF2016-76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F.
Conflict of Interest
BC-F has received unrestricted research funding from Instituto de Salud Carlos III, MINECO, Gobierno de Cantabria, Spanish Network for Research in Mental Health (CIBERSAM), from the seventh European Union Framework Program and Lundbeck. He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen Johnson & Johnson, Mylan, Lundbeck, and Otsuka Pharmaceuticals. MR-V has received unrestricted research funding from Instituto de Salud Carlos III. He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen, Lundbeck, and Otsuka Pharmaceuticals. JV-B has received unrestricted research funding from Instituto de Investigación Marqués de Valdecilla (IDIVAL). He has also received honoraria for his participation as a consultant and/or as a speaker at educational events from Janssen-Cilag and Lundbeck. JC has received honoraria as a speaker from Novartis, Astellas Pharma, Pfizer, MSD, Janssen Pharmaceuticals, and AstraZeneca, outside the submitted work. He has also received report grants from Instituto de Salud Carlos III, Spanish Government, co-financed by the European Development Regional Fund “A way to achieve Europe,” during the conduct of the study.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We are highly indebted to the participants and their families for their cooperation in this study. We also thank IDIVAL biobank (Inés Santiuste and Jana Arozamena) for clinical samples and data as well as the PAFIP members (Marga Corredera) for the data collection. We kindly thank all clinical staff at the Hospital Universitario Virgen del Rocio for support to collect clinical records and provide clinical care to COVID-19 patients. We also kindly thank Dra. Marisa Barrigon for helpful discussions regarding clinical data analysis, and Idalino Rocha for manuscript editing and formatting. This manuscript has been released as a pre-print at medRxiv. Available at: https://doi.org/10.1101/2020.12.05.20244590 (Crespo-Facorro et al., 2020).
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fphar.2021.646701/full#supplementary-material.
Bhaskar, S., Sinha, A., Banach, M., Mittoo, S., Weissert, R., Kass, J. S., et al. (2020). Cytokine storm in COVID-19-Immunopathological mechanisms, clinical considerations, and therapeutic approaches: the REPROGRAM consortium position paper. Front. Immunol. 11, 1648. doi:10.3389/fimmu.2020.01648
Bouadma, L., Wiedemann, A., Patrier, J., Surénaud, M., Wicky, P. H., Foucat, E., et al. (2020). Immune alterations in a patient with SARS-CoV-2-related acute respiratory distress syndrome. J. Clin. Immunol. 40 (8), 1082–1092. doi:10.1007/s10875-020-00839-x
Canal-Rivero, M., Barragán, R. C., García, A. R., Garrido-Torres, N., Crespo-Facorro, B., and Ruiz-Veguilla, M. (2021). Lower risk of SARS-CoV2 infection in individuals with severe mental disorders on antipsychotic treatment: A retrospective epidemiological study in a representative Spanish population. Schizophrenia Res. 229, 53–54. doi:10.1016/j.schres.2021.02.002
Chen, G., Wu, D., Guo, W., Cao, Y., Huang, D., Wang, H., et al. (2020). Clinical and immunological features of severe and moderate coronavirus disease 2019. J. Clin. Invest. 130 (5), 2620–2629. doi:10.1172/JCI137244
Crespo-Facorro, B., Ortiz-Garcia de la Foz, V., Suarez-Pinilla, P., Valdizan, E. M., Pérez-Iglesias, R., Amado-Señaris, J. A., et al. (2017). Effects of aripiprazole, quetiapine and ziprasidone on plasma prolactin levels in individuals with first episode nonaffective psychosis: analysis of a randomized open-label 1year study. Schizophr. Res. 189, 134–141. doi:10.1016/j.schres.2017.01.046
Crespo-Facorro, B., Ruiz-Veguilla, M., Vázquez-Bourgon, J., Sánchez-Hidalgo, A. C., Garrido-Torres, N., Cisneros, J. M., et al. (2020). Aripiprazole as a candidate treatment of COVID-19 identified through genomic analysis. MedRxiv. doi:10.1101/2020.12.05.20244590
Criado, P. R., Pagliari, C., Criado, R. F. J., Marques, G. F., and Belda, W. (2020). What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab during COVID-19 or asymptomatic infections due to SARS-CoV-2? Dermatol. Ther. 33 (6), e14068. doi:10.1111/dth.14068
de Jesus, A. A., Canna, S. W., Liu, Y., and Goldbach-Mansky, R. (2015). Molecular mechanisms in genetically defined autoinflammatory diseases: disorders of amplified danger signaling. Annu. Rev. Immunol. 33, 823–874. doi:10.1146/annurev-immunol-032414-112227
Dinesh, A. A., Islam, J., Khan, J., Turkheimer, F., and Vernon, A. C. (2020). Effects of antipsychotic drugs: cross talk between the nervous and innate immune system. CNS Drugs 34, 1229. doi:10.1007/s40263-020-00765-x
Dyall, J., Gross, R., Kindrachuk, J., Johnson, R. F., Olinger, G. G., Hensley, L. E., et al. (2017). Middle East respiratory syndrome and severe acute respiratory syndrome: current therapeutic options and potential targets for novel therapies. Drugs 77 (18), 1935–1966. doi:10.1007/s40265-017-0830-1
Giridharan, V. V., Scaini, G., Colpo, G. D., Doifode, T., Pinjari, O. F., Teixeira, A. L., et al. (2020). Clozapine prevents poly (I:C) induced inflammation by modulating NLRP3 pathway in microglial cells. Cells 9 (3), 577. doi:10.3390/cells9030577
Hariharan, A., Hakeem, A. R., Radhakrishnan, S., Reddy, M. S., and Rela, M. (2020). The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients. Inflammopharmacol., 1–10. doi:10.1007/s10787-020-00773-9
Harrow, J., Frankish, A., Gonzalez, J. M., Tapanari, E., Diekhans, M., Kokocinski, F., et al. 2012). GENCODE: the reference human genome annotation for the ENCODE Project. Genome Res. 22 (9), 1760–1774. doi:10.1101/gr.135350.111
Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., et al. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395 (10223), 497–506. doi:10.1016/S0140-6736(20)30183-5
Huang, I., Pranata, R., Lim, M. A., Oehadian, A., and Alisjahbana, B. (2020). C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis. Ther. Adv. Respir. Dis. 14, 1753466620937175. doi:10.1177/1753466620937175
Josset, L., Menachery, V. D., Gralinski, L. E., Agnihothram, S., Sova, P., Carter, V. S., et al. (2013). Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. MBio 4 (3), e00165–13. doi:10.1128/mBio.00165-13
Juncal-Ruiz, M., Riesco-Dávila, L., Ortiz-García de la Foz, V., Martínez-Garcia, O., Ramírez-Bonilla, M., Ocejo-Viñals, J. G., et al. (2018). Comparison of the anti-inflammatory effect of aripiprazole and risperidone in 75 drug-naïve first episode psychosis individuals: a 3 months randomized study. Schizophr. Res. 202, 226–233. doi:10.1016/j.schres.2018.06.039
Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M., and Hirakawa, M. (2010). KEGG for representation and analysis of molecular networks involving diseases and drugs. Nucleic Acids Res. 38, D355–D360. doi:10.1093/nar/gkp896
Karadsheh Adli, J. (2020). Re: Mahase Elisabeth. Covid-19: What treatments are being 478 investigated? BMJ 368, m1252. Available at https://www.bmj.com/content/368/bmj.m1252/rr-1
Kato, T., Monji, A., Hashioka, S., and Kanba, S. (2007). Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro. Schizophr. Res. 92 (1–3), 108–115. doi:10.1016/j.schres.2007.01.019
Lee, S. W., Yang, J. M., Moon, S. Y., Yoo, I. K., Ha, E. K., Kim, S. Y., et al. (2020). Association between mental illness and COVID-19 susceptibility and clinical outcomes in South Korea: a nationwide cohort study. Lancet Psychiatry 7 (12), 1025–1031. doi:10.1016/S2215-0366(20)30421-1
Mayoral Van-Son, J., Gómez-Revuelta, M., Ayesa-Arriola, R., Vázquez-Bourgón, J., Foz, V. O.-G. de. la., Ruiz-Veguilla, M., et al. (2021). Comparison of aripiprazole and risperidone effectiveness in first episode non-affective psychosis: rationale and design of a prospective, randomized, 3-phase, investigator-initiated study (PAFIP-3). Rev. Psiquiatr. Salud Ment. doi:10.1016/j.rpsm.2021.01.004
Mehta, P., McAuley, D. F., Brown, M., Sanchez, E., Tattersall, R. S., and Manson, J. J. (2020). COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 395 (10229), 1033–1034. doi:10.1016/S0140-6736(20)30628-0
Metz, M., Staubach, P., Bauer, A., Brehler, R., Gericke, J., Kangas, M., et al. (2017). Clinical efficacy of omalizumab in chronic spontaneous urticaria is associated with a reduction of FcεRI-positive cells in the skin. Theranostics 7 (5), 1266–1276. doi:10.7150/thno.18304
Nemani, K., Li, C., Olfson, M., Blessing, E. M., Razavian, N., Chen, J., et al. (2021). Association of psychiatric disorders with mortality among patients with COVID-19. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2020.4442
Obuchowicz, E., Bielecka-Wajdman, A. M., Paul-Samojedny, M., and Nowacka, M. (2017). Different influence of antipsychotics on the balance between pro- and anti-inflammatory cytokines depends on glia activation: an in vitro study. Cytokine 94, 37–44. doi:10.1016/j.cyto.2017.04.004
Pedersen, J., Coskun, M., Soendergaard, C., Salem, M., and Nielsen, O. H. (2014). Inflammatory pathways of importance for management of inflammatory bowel disease. World J. Gastroenterol. 20 (1), 64–77. doi:10.3748/wjg.v20.i1.64
Riva, L., Yuan, S., Yin, X., Martin-Sancho, L., Matsunaga, N., Pache, L., et al. (2020). Discovery of SARS-CoV-2 antiviral drugs through large-scale compound repurposing. Nature 586 (7827), 113–119. doi:10.1038/s41586-020-2577-1
Rubino, S., Kelvin, N., Bermejo-Martin, J. F., and Kelvin, D. (2020). As COVID-19 cases, deaths and fatality rates surge in Italy, underlying causes require investigation. J. Infect. Dev. Ctries. 14 (3), 265–267. doi:10.3855/jidc.12734
Sánchez-Céspedes, J., Martínez-Aguado, P., Vega-Holm, M., Serna-Gallego, A., Candela, J. I., Marrugal-Lorenzo, J. A., et al. (2016). New 4-Acyl-1-phenylaminocarbonyl-2-phenylpiperazine derivatives as potential inhibitors of adenovirus infection. Synthesis, biological evaluation, and structure-activity relationships. J. Med. Chem. 59 (11), 5432–5448. doi:10.1021/acs.jmedchem.6b00300
Smyth, G. K., Michaud, J., and Scott, H. S. (2005). Use of within-array replicate spots for assessing differential expression in microarray experiments. Bioinformatics 21 (9), 2067–2075. doi:10.1093/bioinformatics/bti270
Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., and Ng, L. F. P. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nat. Rev. Immunol. 20 (6), 363–374. doi:10.1038/s41577-020-0311-8
Wang, Q., Xu, R., and Volkow, N. D. (2021). Increased risk of COVID ‐19 infection and mortality in people with mental disorders: analysis from electronic health records in the United States. World Psychiatry 20 (1), 124–130. doi:10.1002/wps.20806
Weston, S., Coleman, C. M., Haupt, R., Logue, J., Matthews, K., Li, Y., et al. (2020). Broad anti-coronavirus activity of Food and drug administration-approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo. J. Virol. 94 (21), e01218-20. doi:10.1128/JVI.01218-20
Wu, C., Chen, X., Cai, Y., Xia, J., Zhou, X., Xu, S., et al. 2020). Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern. Med. 180 (7), 934–943. doi:10.1001/jamainternmed.2020.0994
Wu, D., and Yang, X. O. (2020). TH17 responses in cytokine storm of COVID-19: an emerging target of JAK2 inhibitor Fedratinib. J. Microbiol. Immunol. Infect. 53 (3), 368–370. doi:10.1016/j.jmii.2020.03.005
Xiong, Y., Liu, Y., Cao, L., Wang, D., Guo, M., Jiang, A., et al. (2020). Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients. Emerg. Microbes Infect. 9 (1), 761–770. doi:10.1080/22221751.2020.1747363
Yalcin, A. D., Cilli, A., Bisgin, A., Strauss, L. G., and Herth, F. (2013). Omalizumab is effective in treating severe asthma in patients with severe cardiovascular complications and its effects on sCD200, d-dimer, CXCL8, 25-hydroxyvitamin D and IL-1β levels. Expert Opin. Biol. Ther. 13 (9), 1335–1341. doi:10.1517/14712598.2013.819338
Zeng, Z., Yu, H., Chen, H., Qi, W., Chen, L., Chen, G., et al. (2020). Longitudinal changes of inflammatory parameters and their correlation with disease severity and outcomes in patients with COVID-19 from Wuhan, China. Crit. Care 24 (1), 525. doi:10.1186/s13054-020-03255-0
Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., et al. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395 (10229), 1054–1062. doi:10.1016/S0140-6736(20)30566-3
Keywords: psychosis, inflammation, immunology, coronavirus, repurposing drugs, elopiprazole, SARS-CoV-2
Citation: Crespo-Facorro B, Ruiz-Veguilla M, Vázquez-Bourgon J, Sánchez-Hidalgo AC, Garrido-Torres N, Cisneros JM, Prieto C and Sainz J (2021) Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis. Front. Pharmacol. 12:646701. doi: 10.3389/fphar.2021.646701
Received: 27 December 2020; Accepted: 08 February 2021;
Published: 02 March 2021.
Edited by:Siddappa N Byrareddy, University of Nebraska Omaha, United States
Reviewed by:Sanjay Rathod, University of Pittsburgh, United States
Subhash Chand, University of Nebraska Medical Center, United States
Copyright © 2021 Crespo-Facorro, Ruiz-Veguilla, Vázquez-Bourgon, Sánchez-Hidalgo, Garrido-Torres, Cisneros, Prieto and Sainz.. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Benedicto Crespo-Facorro, firstname.lastname@example.org
†These authors have contributed equally to this work
‡These authors share senior authorship


text:
S/2107 Antique Treen 19th Century Lignum Vitae Go to Bed
A small well turned lignum vitae go to bed, still retaining some of its original striker paper to the base, made of heart wood and sap wood, with a bone match holder to the top. The base unscrews to house the spare matches and the whole retains a patination.
2½ in. (6.5 cm.) High
1¼ in. (3 cm.) Diameter English Circa 1840

domain: history


text:
North and south book 2 episode 2
North and south book 1 episode 4 - Google ДокументиSeason 1 1. Simpsons Roasting on an Open Fire 2. Bart the Genius 3. Homer's Odyssey 4. There's No Disgrace Like Home 5. Bart the General 6. Moaning Lisa 7.
North and South 03 Epis 02 Book 3 Heaven and Hell Epis 2
North and South
Plex works best when items are named and structured properly before placement. Oh Brother, Where Art Thou! Lesley-Anne Down married assistant cameraman Don E. Nahasapeemapetilons 8.Available on Amazon. Old Money. Tony Frank. Secrets of a Successful Marriage.
Bart of Darkness 2. Politically Inept, Parker Stevenson People magazine. Charles Main 6 episodes, With Homer Simpson.
Episode Guide Hal Holbrook in North and South, Book II () North and South, Book II () Patrick Swayze and Heaven & Hell: North & South, Book III.
questions to ask your dad book
You May Also Like
I wish there was a way to disable all the metadata scanning that take ages and simply scan the filename and create a thumbnail like xbmc. This is the reason I stopped using Plex, although it is awesome on my Samsung. Plex Video Files Scanner. I have all the Perry Mason tv shows, sorted by Seasons 1 through 9. I stopped using plex a couple months ago and don't remember, but I do remember that some downloaded Podcasts end up having the same name because Plex is using embedded titles, but the filenames are different. The problem I am having is figuring out how to include tv show extras like The Sopranos extra interviews or True Blood series extras.
A young actress, gathers three former school chums to find out which is her mother. I'm Goin' to Praise Land Mountain of Madness Chris Douridas.
Homer Simpson, This is Your Wife. Jimmy Stewart. There's No Noth Like Home 5. Wolper's mini-series continues the saga based on the novels by John Jakes.Why on earth would Tennessee slave refugees head deep into Confederate territory, when they could have easily ended up in Union held cities like Nashville. Lesley-Anne Down. Edit Cast Series cast summary: Kirstie Alley And why was Berdan still in command of the Sharpshooters in this episode.
Delivery times may vary, especially during peak periods. Mobile Homer Waiting For Duffman Robert E.

domain: library


text:
Bad debt expense recognition is delayed under the direct write-off method, while the recognition is immediate under the allowance method. This results in higher initial profits under the direct write-off method. Bad Debts Expense$ XYZAccounts Receivable$ XYZDirect write-off method does not use any allowance or reserve account.
- If the transaction tells you what the new balance in the account should be, we must calculate the amount of the change.
- A contra account’s natural balance is the opposite of the associated account.
- A contra account is an account used in a general ledger to reduce the value of a related account.
- The direct write-off method is one of the easier ways to manage bad debt.
- But, under the direct write off method, the loss may be recorded in a different accounting period than when the original invoice was posted.
Cohen & Company is not rendering legal, accounting or other professional advice. Information contained in this post is considered accurate as of the date of publishing. Any action taken based on information in this blog should be taken only after a detailed review of the specific facts, circumstances and current law. An employee who’s struggling financially might prematurely write off receivables or overbill customers and then divert the subsequent collections to his or her personal bank account. Such scams are often successful, because fraudsters know that most companies are remiss in monitoring old, written-off receivables, especially in periods of high stress and uncertainty. In general, once a receivable is four months overdue, collectability is doubtful. However, that benchmark varies based on the industry, the economy, the company’s credit policy and other risk factors.
This makes a company appear more profitable, at least in the short term, than it really is. For a business that provides a service or sells goods on credit, bad debts might be inevitable. You can use your bad debt rate from previous years to determine the amount to set aside for your bad debt reserve. For example, last year you brought in $30,000, but you sold $40,000 worth of goods. Under the allowance method, you could predict 25% of your profits will be bad debts. Resolve’s credit assessment uses proprietary financial databases and algorithms to assess your customers without needing a single thing from them. When a customer is approved, Resolve provides an advance of up to 90% of each invoice, paid into your account within 1 day.
It has extensive reporting functions, multi-user plans and an intuitive interface. Easily save this report to your computer or print it at any time. The matching principle states that any transaction that affects one account needs to affect another account during that same period. Although only publicly held companies must abide by GAAP rules, it is still worth considering the implications of knowingly violating GAAP.
Balance SheetA balance sheet is one of the financial statements of a company that presents the shareholders’ equity, liabilities, and assets of the company at a specific point in time. It is based on the accounting equation that states that the sum of the total liabilities and the owner’s capital equals the total assets of the company. When using an allowance method, it is critical to know what you are calculating. If using sales in the calculation, you are calculating the amount of bad debt expense.
Each write-off scenario will differ but usually, expenses will also be reported on the income statement, deducting from any revenues already reported. In this case, $600 would be a credit entry to your company’s revenue and a debit entry of $600 would be made to accounts receivable. After a few months of trying to collect on the $600 invoice, you come to the realization that you won’t be paid for your services. Using the direct write-off method, a debit to the bad debt expense account for $600 will be made and a credit of $600 to accounts receivable will be made. With the allowance method, you predict that you won’t receive payment for credit sales from all your customers. As a result, you debit bad debts expense and credit allowance for doubtful accounts.
Every time a business extends payment terms to a customer, that business is taking on risk. When a customer defaults on an amount due, this is called bad debt. During the COVID-19 crisis, many companies have been unable to execute their normal operating activities — and it’s still unclear how long the economic effects of the pandemic will last.
These include white papers, government data, original reporting, and interviews with industry experts. We also reference original research from other reputable publishers where appropriate. You can learn more about the standards we follow in producing accurate, unbiased content in oureditorial policy.
For example, writing off a large and material account immediately might not be proper. For example, Wayne spends months trying to collect payment on a $500 invoice from one of his customers. However, all of the invoices and letters he has mailed have been returned. The Coca-Cola Company , like other U.S. publicly-held companies, files its financial statements in an annual filing called a Form 10-K with the Securities & Exchange Commission . Let’s try and make accounts receivable more relevant or understandable using an actual company. The amount used will be the ESTIMATED amount calculated using sales or accounts receivable. Save money and don’t sacrifice features you need for your business.
This situation is an unfortunate, but not unusual part of doing business. The direct write-off method is the simpler of two primary methods businesses use to record uncollectible accounts.
Easy Way To Understand Accounting Terms
This way, the primary A/R can run reports without bad debts affecting it, but you can still track each collection account. In this lesson, you’ll learn more about cost of goods sold and how to properly write down your cost of goods sold and then transfer it into the right job order entry so your financial records are accurate. Inventory valuation methods are ways that companies place a monetary value on the items they have in their inventory. Discover different inventory valuation methods, including specific identification, First-In-First-Out , Last-In-First-Out , and weighted average.
At this point, the $500 would be considered uncollectible, so Wayne needs to remove it from his accounts receivable account. If he does not write the bad debt off, it will stay as an open receivable item, artificially inflating his accounts receivable balance. GAAP mandates that expenses be matched with revenue during the same accounting period. But, under the direct write off method, the loss may be recorded in a different accounting period than when the original invoice was posted. The IRS allows bad debts to be written off as a deduction from total taxable income, so it’s important to keep track of these unpaid invoices in one way or another. It’s also important to note that unpaid invoices are categorized as assets, which are debited in accounting. You sell one to a customer for $2,500, but they do not pay immediately.
Tax credits are applied to taxes owed, lowering the overall tax bill directly. Peggy James is a CPA with over 9 years of experience in accounting and finance, including corporate, nonprofit, and personal finance environments. She most recently worked at Duke University and is the owner of Peggy James, CPA, PLLC, serving small businesses, nonprofits, solopreneurs, freelancers, and individuals.
Accounting Accounting software helps manage payable and receivable accounts, general ledgers, payroll and other accounting activities. Business Checking Accounts BlueVine Business Checking The BlueVine Business Checking account is an innovative small business bank account that could be a great choice for today’s small businesses. Learn more about how you can improve payment processing at your business today. The direct write off method is also known as the direct charge-off method. When you make a large sale and don’t receive payment, you can even hire a collection agency. If you win a civil case against a client and are awarded a judgment, you then have to take action to collect payment. If a client has closed down their physical premises or becomes unresponsive, collecting debt becomes more time-consuming and expensive.
The Direct Write Off Method And Gaap
As stated previously, the amount of bad debt under the allowance method is based on either a percentage of sales or a percentage of accounts receivable. When doing the calculations, it is important to understand what the resulting number actually represents. Because one method relates to the income statement and the other relates to the balance sheet , the calculated amount is related to the same statement. When using the percentage of sales method, the resulting amount is the amount of bad debt that should be recorded.
When using allowance method the write-off of a receivable?
Under the allowance method, if a specific customer’s accounts receivable is identified as uncollectible, it is written off by removing the amount from Accounts Receivable.
The direct write-off method is an accounting method by which uncollectible accounts receivable are written off as bad debt. In essence, the bad debts expense account is debited and accounts receivable is credited. This method is required for U.S. income tax reporting and should not be confused with the allowance method, which also accounts for bad debt. The bad debts account, being an expense, gets debited and the accounts receivable account is credited immediately after an invoice is determined to be uncollectible in the direct write off method. The direct write-off method does not involve estimates of bad debt expense. Instead, it relies on reports of accounts receivable the company has determined will not be collected. If write off is not material, this method can be used in financial reports.
When there is a bad debt, you will credit accounts receivable and debit allowance for doubtful accounts. Two methods for the accounting of uncollectible accounts is typically used by the businesses – the direct write off method and the allowance method. The direct write off method allows businesses to write off bad debts when they realize that the buyer is not going to make the payment. On the other hand, under the allowance method, businesses are required to make an estimate of their bad debt at the end of the year.
The account had a credit balance of $17,000 before the adjustment. The entry from December 31 would be added to that balance, making the adjusted balance $60,500. The percentage of sales method does not factor in the existing balance in Allowance for Doubtful Accounts. Without careful monitoring, the balance in the account could grow indefinitely. It is important for management to monitor the balance to ensure the balance is reasonable.
For a partly worthless debt, file your claim by three years after filing the original return or two years from when you paid the tax, whichever is later. Even if you have a judgment against a client, it doesn’t mean you’ll be able to collect payment. If the client files for bankruptcy, the full amount of the debt may be unrecoverable. To keep DSO from being skewed, bad debt might be written off after a certain number of days. For example, if your company’s average DSO is 75 days, you might decide that after an additional 90 or 120 days, the debt should be sent to collections and written off. It makes the company look more profitable than it really is, at least for a short period of time.
Since the unadjusted balance is $9,000, we need to record bad debt of $5,360. The calculation here is a few more steps but uses the same methodology used in all the other methods. Once you know how much from each time period, add them to direct write off method get the total allowance balance. The aging method is a modified percentage of receivables method that looks at the age of the receivables. The longer a debt has been outstanding, the less likely it is that the balance will be collected.
In the event that a customer decides to pay what they owe later on, the accounts receivable account would be debited and the bad debt expense would be reduced. In the allowance method, an estimate is calculated every year that is debited to the bad debt expense account. Write-offs affect both balance sheet and income statement accounts on your financial statement, so it’s important to be accurate when handling bad debt write-offs. While the direct write-off method is the easiest way to eliminate bad debt, it should be used infrequently and with caution. The allowance method follows GAAP matching principle since we estimate uncollectible accounts at the end of the year. We use this estimate to record Bad Debt Expense and to setup a reserve account called Allowance for Doubtful Accounts based on previous experience with past due accounts.
Depreciation Expense Account Vs Allowance For A Depreciation Account
If you consistently have uncollectible accounts, use the allowance method for writing off bad debt, as it follows GAAP rules while keeping financial statements accurate. Using the allowance method can also help you prepare more accurate financial projections for your business. The alternative to the direct write off method is to create a provision for bad debts in the same period that you recognize revenue, which is based upon an estimate of what bad debts will be. This approach matches revenues with expenses, and so is considered the more acceptable accounting method. It’s also important to note that the direct write-off method violates the matching principle, which states that expenses should be reported during the period in which they were incurred. This is because with the direct write-off method, a bad debt is reported when the accounts receivable is written off.
You can solve the problem by using the allowance method in which you create an allowance account for bad debt in the same accounting period when you earn the revenue. Natalie has many customers who purchase goods from her on credit and pay on account. One of her customers purchased products worth $ 1,500 a year ago, and Natalie still hasn’t been able to collect the payment. After trying to contact the customer number of times, Natalie finally decides that she will never be able to recover these $ 1,500 and decides to write off the balance from such a customer. Using the direct write-off method, Natalie would debit the bad debts expenses account by $ 1,500 and credit the accounts receivable account with the same amount. Companies turn to the allowance method to properly report revenues and the related expenses in the periods that they were earned and incurred. The allowance shows up as a contra-asset to offset receivables on the balance sheet and as bad debt expense to offset sales on the income statement.

domain: finance


text:
FdSc Counselling, Registered MBACP
Every professional displayed on Counselling Directory has been independently
verified by our team to ensure they have suitable credentials to practise.
Every professional displayed on Counselling Directory has been independently verified by our team to ensure they have suitable credentials to practise.
Welcome. I’m a counsellor and psychotherapist and have worked with hundreds of clients.
I am a BACP-certified counsellor, who takes an empathetic, integrative approach to helping my clients reach their potential as people.
Every one of us is different, and as such I tailor my approach to each individual client’s needs and focus closely on the client-therapist relationship. For me, respect, trust and empowerment are fundamental to this relationship.
Often talking to a neutral non-judgemental person, such as me, can really help. Together we can work on what troubles you - maybe you have been feeling low for too long and want to change; perhaps you need some help with your anger or to stop feeling so anxious. Maybe you are grieving and need some help. I focus very much on the relationship between client and therapist - a working relationship that is built on respect, trust and empowerment.
As a qualified, sensitive and committed counsellor I can offer you a safe, confidential and comfortable space where you can talk freely and openly about your concerns without the fear of being judged.
What is my approach?
My approach is to work with you, get to know you and understand how you want to change and move forward. I use an integrative approach which includes Psycho-dynamic work, Person Centred Therapy, Transactional Analysis and Relational work. This allows flexibility and enables me to find the most suitable therapy for your individual needs - be this short or long term. I work in a non-judgemental and empathic way.
Training, qualifications & experience
- FdSc in Integrative Counselling, University of Greenwich
- BACP Registered Counsellor / Psychotherapist
- Certificate in Couple Dynamics
- CBT Certificate - ongoing
- Mindfulness - ongoing
- Current certificate in Safeguarding
- DBS - Disclosure and Barring Service Certificate
My experience includes private practice work and my past work as a Volunteer counsellor at the Fountain Centre, at the Royal surrey County Hospital - a charity run to support cancer sufferers, their families and carers.
I have also worked with, for example:
Low self esteem
Lack of meaning or direction / confusion with life choices
Relationship issues with couples
Living with chronic illness
Bereavement and loss
British Association for Counselling & Psychotherapy (BACP)
BACP is one of the UK’s leading professional bodies for counselling and psychotherapy with around 60,000 members. The Association has several different categories of membership, including Student Member, Individual Member, Registered Member MBACP, Registered Accredited Member MBACP (Accred) and Senior Registered Accredited Member MBACP (Snr Acccred).
Registered and accredited members are listed on the BACP Register, which shows that they have demonstrated BACP’s recommended standards for training, proficiency and ethical practice. The BACP Register was the first register of psychological therapists to be accredited by the Professional Standards Authority (PSA).
Accredited and senior accredited membership are voluntary categories for members who choose to undertake a rigorous application and assessment process to demonstrate additional standards around practice, training and supervision.
Individual members will have completed an appropriate counselling or psychotherapy course and started to practise, but they won’t appear on the BACP Register until they've demonstrated that they meet the standards for registration. Student members are still in the process of completing their training.
All members are bound by the BACP Ethical Framework and a Professional Conduct Procedure.
Accredited register membership
Accredited Register Scheme
The Accredited Register Scheme was set up in 2013 by the Department of Health (DoH) as a way to recognise organisations that hold voluntary registers which meet certain standards. These standards are set by the Professional Standards Authority (PSA).
This therapist has indicated that they belong to an Accredited Register.
Areas of counselling I deal with
Other areas of counselling I deal with
Couples counselling as well as individual counselling.
The effect of chronic and terminal illness / counselling for either the sufferer, the family member or the carer.
£60.00 per session
Free initial online session
Cost: £60.00 per session for individuals and £75 for couples - please feel free to call me on 07803 084224 to talk over any queries/thoughts you may have without obligation.
Each session lasts 50 minutes.
When I work
With the recent social distancing restrictions, face to face counselling is not possible so I offer Skype, WhatsApp or phone sessions at times to suit us both.
I have worked within the NHS as a nurse and midwife for over ten years. This has given me extensive experience of working with people which has enhanced my work as a counsellor.
I am a fully insured counsellor working within the BACP Code of Ethics.

domain: psychology


text:
Solemnity of Pentecost Introduction 1. Human beings have always been in search of happiness and meaning. Augustine well expressed it: This statement already poses the problem of the tension between profound desire and moral choices, whether conscious or not.
By Thomas Levy and David Noel Freedman February Although the great American scholar William Foxwell Albright passed away many years ago, he is still regarded by most Levantine archaeologists, biblical scholars, and other Near Eastern researchers of the world of the Bible as a genius.
Albright was a master of so many disciplines linked to the study of the ancient Near East, in particular the world of the Old Testament Hebrew Biblethat he is considered one of the last great orientalists. Having its origins as far back as the 12th century, orientalism was the study of the synthetic and simultaneous study of the history, languages, and culture of the peoples of Asia.
While the idea of the orientalist took on negative overtones through the work of postmodern researchers in the late s and s, more objective approaches by scholars such as the anthropologist Ernest Gellner and others have shown that orientalist scholars such as the German Gustav Dalman, Palestinian Toufic Canaan, Alois Musil from Moravia now Czech Republicand men like Albright carried out their works more from a sense of humanism and a profound interest in the history of the peoples of the Bible lands rather than as cynical tools of imperial powers.
Even today ASOR American Schools of Oriental Researchthe flagship scholarly organization that Albright helped develop in the 20th century, retains the name that harkens back to the days when orientalism had a positive connotation. In biblical scholar Harry M. At that time there were approximately entries that spanned 30 years of scholarly work—an incredible amount of research that any scholar would be proud of.
The grand total is just under 1, items, including Bible 110 interpretation project, peer-reviewed articles, notes, book reviews, and other items that must surely set a record for productivity in the field of ancient Near Eastern studies and related fields.
Freedman, and was published as a book by the American Schools of Oriental Research. The fields of scholarly research that Albright controlled were vast and included archaeology, Semitic linguistics including all branches of the great family of languages, especially the numerous dialects of Northwest Semitic, but not neglecting Akkadian and Arabicepigraphy, orthography, ancient history, chronology, historical topography, mythology—in short, all facets of ancient Near Eastern civilization from the Chalcolithic period ca.
Professor Albright was the recipient of an unparalleled number of honorary degrees and a multiplicity of honors and awards from distinguished universities, learned societies, and other institutions around the world. The honor he prized most was his election to the National Academy of Sciences.
It is ironic that Albright chose to be a member of its Anthropology Section, since his quarrels with anthropologists of different schools were well known at the time. While archaeology in the English-speaking world—primarily the United States and the United Kingdom—was undergoing a major paradigm shift in the s with the birth of the new archaeology, archaeologists working in Syro-Palestine insulated themselves from this fundamental intellectual change.
The board appointed them to go to Chile, where the Rev.
For the young Albright growing up in Chile in the late 19th century with a crippled left hand and severe nearsightedness was difficult. Nevertheless, he felt himself crippled from the age of five. Faced with taunts from the poor children of the nearby barrio where Albright lived in Chile, the child faced a barrage of name calling such as gringo and canuto protestant.
By the time he was 10 years old his parents promised to buy him his most cherished wish, provided he would fetch bread from the local bakery to help save the family money. Rogers of Drew University. By the time Albright was 22 he earned himself a much needed scholarship to Johns Hopkins University.
Shortly before embarking on his studies, he confided to his mother and aunt his passion for the life of scholarship that awaited him in Baltimore by saying: This welcome news came at a time when Albright wrote on several occasions that he felt he was on the edge of a nervous breakdown.
He felt that if only his eyesight and his mental stability would continue strong until his written exams, he would prevail in his studies; and they did.
By the end of his third year he spent 18 hours a day for three days at Prof. By the summer of Albright passed his oral exam and was awarded the Ph.
Not long after earning his doctoral degree Albright received his military draft questionnaire, filled it out, and dutifully returned it. With poor eyesight and a crippled hand, neither he nor his family expected he would be drafted or involved in the war in any way.
However, by July while relaxing at home in Iowa and studying Ethiopic in a rocking chair, he received his call-up and was inducted into the U. Army for limited service.
For just over six months Albright became a potato peeler and dishwasher for the war effort. By Christmas he was discharged and returned to Baltimore to resume his postdoctoral studies and teaching duties. At this time funds were short and to save money Albright was still wearing his army uniform around town.Date setters, making irresponsible predictions!
Misleading the ignorant masses for higher TV ratings and book sales!
An untold number of people have tried to predict the Lord's return by using elaborate time tables. Oct 09, · Bibl Interpretation Project 1 Ryan Wright BIBL The verses before and after Matthew all seem to have a common theme. I have spent a number of hours over this past weekend perusing through the long-awaited Ignatius Catholic Study Bible New Testament (ICSBNT).
(The edition I am reviewing is the hardback one.) Simply put, it is fantastic and a great tool for Catholics. Over the past year or so, we have been blessed with an increase in the amount and quality of Bible . BIBL Quiz 2. STUDY. PLAY. What did Jesus give the disciples power to do?
don't force an interpretation on every point-Augustine details each has its own lesson many applications.
miracle. Bible Test Chapter 5 Practice.
65 terms. religion final study guide. OTHER SETS BY THIS CREATOR. The historicity of the Bible is the question of the Bible's "acceptability as a history", in the words of Thomas L. Thompson, a scholar who has written widely on this topic as it relates to the Old Testament.
This can be extended to the question of the Christian New Testament as an accurate record of the historical Jesus and the Apostolic Age.. Many fields of study span the Bible . INTRODUCTION 4. 1. Modern times have made Christians more aware of the close fraternal bonds that unite them to the Jewish people.
During the second world war (), tragic events, or more precisely, abominable crimes subjected the Jewish people to a terrible ordeal that threatened their very existence throughout most of Europe.


text:
Actor and director Robert Redford is taking a stand to close horse slaughterhouses across the U.S. and protect horses from mistreatment and death.
Roughly 40 Japanese commuters teamed up to save a woman who became trapped under a train on Monday morning.
Albert Einstein said “If the bee disappeared off the face of the earth, man would only have four years left to live.”
This decade has seen an increased awareness of climate issues and many commitments, by both world powerhouses and developing countries, to lower national carbon emissions; however, the world’s collective action
With the launch of his long-awaited tour, John Mayer makes it clear that he is not just “Waiting on the World to Change,” but is committed to making a difference
Metal rock and sustainable gardens do not usually go hand-in-hand, but members of the metal band Korn are breaking stereotypes while recording their new album “The Paradigm Shift.” The Grammy

domain: news


text:
Major Irish retailer accepts beef up to 36 months of age
A major Irish retailer has stated that it allows for beef derived from cattle aged up to 36 months at slaughter to be sold at its supermarkets.
The development follows repeated claims from Meat Industry Ireland (MII) ruling out any changes to factory specifications for the 30-month age limit for slaughtering cattle.
Despite extensive farmer opposition to the 30-month rule – labelled by many of the country’s farm organisations as an “anti-competitive practice” – the meat processor representative body, as recently as yesterday, Tuesday, August 27, said that the specification for many of the key customers of Irish beef is for under 30-month beef.
However, new information obtained by AgriLand suggests that this is not the case.
In response to a query from Fianna Fáil TD, Anne Rabbitte, who represents the Galway East constituency, Aoife Clarke, the head of communications for Lidl Ireland and Northern Ireland, stated the following:
“I can confirm that Lidl’s requirement allows for beef derived from animals up to 36 months old and our minimum certification requirement is for Bord Bia Quality Assured beef under the Bord Bia Quality Assurance Scheme.”
Speaking to AgriLand, Eoin Donnelly – who was the lead negotiator for the Beef Plan Movement during the recent round-table beef sector reform talks – responded to the statement from Lidl.
“This information is not coming from someone insignificant, this is coming from the head of communications at Lidl – a person of authority.
“This is a retail specification and our frustration now lies with Bord Bia reporting firstly that all retailers in Ireland require under 30-month beef – an issue we contested at the talks.
At the meeting we asked Bord Bia to disclose what retailers, from an Irish or UK perspective, have stated that it’s under 30-month beef that they require. Bord Bia could not disclose the position that those retailers held.
“To us that is unacceptable. A requirement that all farmers have to comply with is being hidden by anonymity. As genuine farmers we want it declared openly exactly what the requirement is.
“And, more importantly, we want to see the scientific substance behind why they want 30-month-old beef if that is the case – everything has to be open and transparent. They have to show us why it is a legitimate requirement,” said Donnelly.
On the Department of Agriculture, Food and the Marine’s market access portal it is stated that the 30-month age rule for slaughtered animals is a necessary condition for exporting frozen, boneless beef products to China.
The terms and conditions are outlined as part of the export certificate, in which the rule is included.
Officials from China are currently in Ireland to inspect 16 Irish meat plants, with a view to opening access for additional Irish beef plants to the Chinese market – approval has already been previously granted for seven processors.


text:
Andy is all grown up, and his Green Army Men are ready to move on. Join them as they set off on a brand-new adventure in this Step 2 reader based on Disney/Pixar's Toy Story 3!Book Details:Format: PaperbackPublication Date: 1/11/2011Pages: 32Reading Level: Age 5 and Up
Animals move! Follow them as they swing, dance, float, leap, and slide from page to page, then learn why these animals move the way they do.Move! is a playful introduction to motion in the animal kingdom that invites young readers to guess some of the unusual ways that animals get around.Action is the name of the game, so Move!Book Details:Format: Library BindingPublication Date: 4/24/2006Pages: 32Reading Level: Age 4 and Up
It was time for a little bunny to be on the move. From here to there, a bunny goes where a bunny must."And so Little Bunny's journey begins: over the hills, through the woods, past the little girl who wants to take him home. But where is Little Bunny going?"Bunny, bunny, going down the path,Bunny, bunny, aren't you turning back?Where are you going, Little Bunny?"By the time Little Bunny reaches his destination--his very own place, with all the other little bunnies--readers will be thoroughly enchanted. Simple and accessible, Little Bunny on the Move takes us on a classic picture book journey with a most satisfying conclusion. Little Bunny on the Move is a 1999 New York Times Book Review Best Illustrated Book of the Year.Book Details:Format: PaperbackPublication Date: 3/1/2003Pages: 32Reading Level: Age 4 and Up
According to Publishers Weekly in a starred review, this picture book "capture[s] the exuberance of the creative spirit alongside the quirks of a character accepting his limitations." Mario is a squirrel who loves to invent amazing moves, like the Super Looper and Tail, Don't Fail. But though his parents ooh and ahh at whatever he does, his friend Isabelle is not so easily impressed. When she points out that anyone can have a move, Mario must find some other way to stand out.Sometimes being amazing is hard work, as shown in this zany yet accessible picture book from Jill McElmurry, illustrator of The One and Only Marigold and Little Blue Truck. Young readers will instantly recognize themselves in Mario, as he searches for his one-of-a-kind talent. Here is a hilarious read-aloud that will have little ones oohing and ahhing—and trying out some moves of their own.Book Details:Format: HardcoverPublication Date: 5/8/2012Pages: 32Reading Level: Age 3 and Up
Join a pack of woolly mammoths as they trek south for the winter, braving fierce storms, deadly predators, and raging rivers while making their slow journey across the gorgeous unspoiled lands of this continent until finally they reach their goal.With the same jouncy and joyous rhythms of her youngest picture book texts, Lisa Wheeler introduces readers to one of the most awesome beasts to ever walk the earth: the massive, hairy--legendary--wonderful woolly mammoth!This factually based book includes an author's note. (20060315)Book Details:Format: HardcoverPublication Date: 4/1/2006Pages: 32Reading Level: Age 4 and Up
This set of Alex Craft's Shrinky Dinks includes 9 precut preprinted vehicles with printed stands, 8 colored pencils and instructions.Product Dimensions (inches): 1.5 (L) x 6 (W) x 6 (H)Age: 5 to 9 years
Let's-Read-and-Find-Out about Exercise What would happen if you did nothing but watch TV all day? Why is it important to get up and play? Read and find out all about exercise with Sid the Science Kid! Introduce basic science concepts to young children and help satisfy their curiosity about how the world works. Book Details:Format: PaperbackPublication Date: 5/11/2010Pages: 32Reading Level: Age 4 and Up
A new title to get you on your feet and moving! This brand-new title from the Wee Sing library guarantees to get you on your feet and moving along with the songs! From Ring Around the Rosy, to The Hokey Pokey to The Animal Parade, adults and kids alike will love dancing and singing to these special and classic songs. With a book and CD, this package is a bargain at $9.99!Book Details:Format: PaperbackPublication Date: 11/12/2009Pages: 64Reading Level: Age 2 and Up
Video Games & Systems > Playstation 3 > "playstation move bundles"
Sony, Microsoft, Turtle Beach - we have them all! We work hard to make our prices as competitive as possible, and offer some of the lowest prices online. We encourage you to compare prices. And here's the best part: we deliver everything to your door in 1-2 days for free on orders of $49 or more. In many ways you could say our main product is customer support. It's what we work on the hardest.
�2005 - 2013, Quidsi, Inc. or its Affiliates. YoYo.com is operated by Quidsi Solutions LLC. Products on YoYo.com are sold by Quidsi Retail LLC. Gift Cards and E-Gift Cards sold on YoYo.com are sold by Quidsi Gift Cards, Inc.


text:
|Desenvolver um Software
||I need a way to get [url removed, login to view] video URLs like this:
[url removed, login to view]:a880:800:a1::796:9001&ipbits=0&expire=1490317721&sparams=ip,ipbits,expire,id,itag,source,requiressl,ttl,mm,mn,ms,mv,pl,ei,mime,lmt&signature=AF7F75B92D2581A53B8F71C315158C120ACB8E6C.801E7FA9C1983AB243ADA06294AF2FA66B2F7E2A&key=ck2&app=explorer&jparams=MTg5LjYxLjY4LjIxM...
||Mar 23, 2017
||Mar 23, 20175d 15h
|Animated Music Video Designer
||I need a custom animated cartoon music video. It could be anime as well, but it must be a custom, original music video that aligns with my song. No footage can be used that's owned by someone else. The song is less than 4 minutes.
||Animation, Caricature & Cartoons
||Mar 23, 2017
||Mar 23, 20175d 10h
|Design some Business Cards
||Hi, I would like some business cards designed with a logo.
Typical size ultimately for cards at 300dpi.
Text to include:
Logo: Open to interpretation
Name: Baby Lemonade Lamarr
Mob: 0430123 123.............. (To advise on winner)
Email: missbabylem@.......(To advise on winner)
Singer, Songwriter, Actress, Entertainer Extraordinaire
Yes, she is a singer!! Open to any design that jumps ou...
||Business Cards, Graphic Design
||Mar 23, 2017
||Mar 23, 20173d 4h
|I would like to hire an Animator
||3-5 minute short animated film, no dialogue; just music playing. Sort of a short music video with a narrative. Please be based in London or Essex. No deadline required, so if you need to take your time that is fine. Animation will need to be edited to fit the soundtrack being used, also needs to be edited to include things such as title cards and credits. Looking for more of an Anime sort of style...
||Illustrator, Editing, Animation, 3D Animation, Motion Graphics
||Mar 21, 2017
||Mar 21, 20173d 8h
|Anime Background / Environments & CG Artist Wanted
||I'll keep this brief and then give details to people who clearly read the information.
Are you experienced with drawing backgrounds or dynamic anime screenshots for visual novels? Can you match the style to our official character artist? (attachment below) Well we want you. Just have a link to your work outside freelancer (Deviantart, Tumblr, ect) and give a quote on how ...
||Mar 20, 2017
||Mar 20, 20171d 21h
|MMORPG and Gaming journalist with knowledge of SEO and Wordpress
||MMOExaminer is looking for an editor and a full-time writer. Our budget is limited and can currently offer a symbolic 1$ per post pay.
We strive to cover the latest gaming related news and reward our readers with giveaways. Articles are required to be between 300-400 words minimum.
We are looking for writers who have a good knowledge of:
||SEO, WordPress, Articles
||Mar 19, 2017
||Mar 19, 20171d
|Create Google Drive streaming script like kissanime, 9anime, MasterAnime, and FMovies
||Today google updated something and my drive script stopped working so i need someone who can Fix Google Drive streaming script like kissanime or 9anime or fmovies
Please read this properly before bidding. What I am after is a script that I can use on my own website that allows me to upload videos to Google Drive and embed them through a custom video player, whether that is JW Player, or ...
||PHP, Website Design, Graphic Design, Web Scraping, HTML
||Mar 19, 2017
||Mar 19, 201722h 49m
|I would like to hire an Animator - 12/03/2017 00:15 EST
||A friend and I have a Youtube channel, a comedy lets play channel, where we play games new and old in an attempt to entertain everyone involved. We are two really close people who have been watching Youtube channels for a long time and have finally weighed in to try and make a difference and have our voices heard in our own way through comedy. We are currently looking to have an introduction for o...
||Animation, YouTube, Motion Graphics
||Mar 18, 2017
||Mar 18, 20178h 45m
||Hello I look for a cartoonist to do 20 characters in 5 views and 6 expressions, I look for the cartoonist to know how to make anime, furry, and mythological creatures.
I look for the person to understand the Spanish.
As I am independent my maximum budget is 100 euros
hola busco dibujante para hacer 20 personajes en 5 vistas y 6 expresiones, busco que el dibujante sepa hacer personajes anime...
||Graphic Design, Photoshop, Illustrator, Illustration, Photoshop Design
||Jan 17, 2017
||Jan 17, 2017Ended

domain: artistic


The slowest burning N100 series rifle powder from Vihtavuori and one of the slowest canister reloading powders generally available from any manufacturer. It will fit applications similar to Hodgdon H1000 and Accurate 8700. Good performances in most of the belted Magnum cartridges like .300 Weatherby Magnum and suitable also for .300 Remington Ultra Magnum and .338 Lapua Magnum. Premium N100 Powders The N100 series powders are primarily rifle powders with different burning rates to optimize your loads.
POWDER IS A REGULATED ITEM ACCORDING TO SOUTH AFRICAN LAW. POWDER HAS TO BE SIGNED OUT OF A REGISTER IN STORE TO A MAXIMUM OF 1 TIN PER VALID SOUTH AFRICAN FIREARM LISENCE.
PROPELLANTS CAN NOT BE TRANSPORTED


Under-occupation of homes not limited to social housing sector
ACROSS the UK, 47 per cent of privately owned households are ‘tumbleweeders’ who occupy homes that are too large for their needs, according to new research.
This is the first time that researchers have analysed under-occupation data for private homes, rather than for social housing, across the country.
Lack of supply is often cited as the biggest issue facing the housing industry in the UK. However, these figures clearly show under-occupation is an equally huge issue.
In Strutt and Parker’s Housing Futures report, they have defined a ‘tumbleweeder’ as those who have two or more bedrooms than required for the number of people living in their home (a couple is defined as needing one bedroom for their needs).
As might be expected, under-occupation becomes greater in the peripheral areas of the UK.


text:
“the gift of the magi” get full essay critics have noted the irony of the young couple sacrificing their most treasured possessions—della’s hair. O henry is known for his twist endings, and the ending of the gift of the magi is probably the most famous of them all at the end of the story della cuts and sells her hair to buy jim a chain for his watch, and jim sells his watch to buy della combs for her hair. The gift of the magi essaysin the short story ³the gift of the magi², by o henry, the couple, mr and mrs dillingham young sacrificed their. The gift of the magi is a well-known short story by american short the gift of the magi is a classic example of irony in go to 9th grade essay. The story “the gift of the magi” which is written by o henry theme in the gift of the magi english literature essay print to reveal situational irony. Literary analysis of the gift of the magi introduction the popular short story ‘the gift of the magi’ was written by essay checker the irony of the. True meaning of christmas in the gift of the magi by o henry - the “gift of the magi” by o henry is a short story that has an interesting theme the main themes in this short.
The gift of the magi and the necklace share particular similarities in characters, irony and theme in both stories the main characters, della and mathilde, share similar. The gift of the magi quotes - shmoop characters analysis questions quizzes flashcards best of the web write essay lit glossary table of contents shmoop premium the gift of the magi by o henry: summary, theme & analysis jul 10, 2015 the gift of the magi is a classic example of irony in literature. Plan your lesson in short stories and writing process with helpful tips from teachers like you students will be able to analyze the short story for theme and irony. An essay or paper on irony in the necklace and the gift of the magi the irony in the short stories, the necklace and the gift of the magi, ought to be further analyzed. In the space below, write a 500-word essay describing the theme of o henry’s “the gift of the magi” explain how the author uses irony as an essential - 2952450. Read o henry's story, the last leaf, compare its themes of sacrifice and irony with the gift of the magi essay prompt #1: describe your own philosophy of gift giving (and receiving) and what makes for the most meaningful gifts.
Those all can be found in the story the gift of the magi up being a useless gift but there is no doubt irony made international baccalaureate world. The gift of the magi homework help questions how does point of view (including the narrator and his language) help to explain the irony and in o henry's the gift of the magi, the theme of the story is that of selfless giving from the heart, like that of the magi or wise men in the christmas story.
Free the gift of the magi irony papers, essays, and research papers. The couple in the gift of the magi is della and jim dillingham jim and della are young and poor yet infected by the culture of abundance felt during the industrialization and consumerism at the beginning of 20th century america. ‘the gift of the magi’ by o henry and ‘the necklace’ by guy de maupassant are two short stories that share some similarities namely, they are both ironic the two main characters in both also happen to be husband and. Essay writing accounts payable stanford college essays history el hombre mediocre analysis essay ap language and composition argument essay ppt airport essays.
The twists and turns of the plot as it unfolds within o henry’s “the gift of the magi” are what the irony of the turnout of haven't found the essay. Situational irony is when a character’s actions have the opposite of their intended effect there are clear instances of situational irony found in the short stories, “prodigal son”, “the gift of the magi”, and “the yellow wallpaper” all of these stories have characters that found themselves in an unexpected circumstance.
Getting positive feedback on an essay subject youre learning for the first time in bar review - quantum computer research papers ecotourism essay conclusion essay about african culture and traditions 20 dissertation temps vecu money writing a good narrative essay neededhampton college peterborough admissions essay essay on smoking. Irony within “the gift of the magi” “irony is a disciplinarian feared only by those who do not know it, but cherished by those who do”, soren kierkegaard knew what he was talking about when he said these famous words “the gift of the magi”, written by william sidney porter, often known by his pen name o henry. ‘the necklace’ and ‘the gift of the magi the irony in ‘the necklace’ becomes apparent as the very item that had brought get your custom essay sample.
Essays - largest database of quality sample essays and research papers on irony in the gift of the magi. “gift of the magi” essay: irony analysis heading: assessment rubric total points possible=40 criteria hua (blossoming). Irony in the gift of the magi essays: results research paper how to write a compare and contrast essay thesis quizlet related post of irony in the gift of. [in the following essay, ward considers o henry's impact on the american short story and deems “the gift of the magi” the pinnacle of his literary achievement many english readers in the present generation received their first introduction to the american language in o henry's pages. The gift of the magi is a short story the plot and its twist ending are well-known, and the ending is generally considered an example of comic irony.
Irony in the gift of the magi essay about myself (get paid doing homework) read tagore's timeless essay religion of man in 'tagore at 150' issue of pioneer on sunday. What is the verbal irony in the gift of the magi please help what quote from the story proves this i've poured over the story for hours and i don't get it. Comparing irony: the gift of the magi--lesson 3 of 3 this lesson is the third in a series of three based on o henry's short story the gift of the magi. @aliabenassi what's the website we find the art history essay thingys on i lost the paper he handed out research paper on nanotechnology.

domain: literature


text:
Zeng, Qi, 1892-1951Variant names
Chinese political leader; founder and leader, Young China Party; adviser to Chiang Kai-shek.
From the description of Zeng Qi papers, 1925-1951. (Unknown). WorldCat record id: 754865224
Zeng Qi (1892-1951) was a distinguished political leader, government official, journalist, and poet. Founder and head of the Young China Party, Zeng Qi was one of the leading figures of modern China's "third-force" democratic movements. During times of national peril, Zeng Qi addressed the Chinese people, saying that nationalism was the only way to save the country from subjugation and that democracy was the key to China's survival and development.
Zeng Qi's political career began shortly after his graduation from Sichuan Law School in Chengdu. He later studied in Japan at Chuo University (1916) and in France, where he became involved with sundry nationalistic movements. In 1923, Zeng Qi served as a special correspondent from Paris to Xin Wen Pao, a daily newspaper based in Shanghai. He also worked with Zhou Enlai to organize the Association of Chinese Clubs in France, which campaigned against foreign control of Chinese railways. It was in France that Zeng Qi, along with Li Huang, Chen Qitiang, and Zuo Shunsheng, founded the anticommunist, antifascist Young China Party.
As a journalist, Zeng Qi wrote many articles for the Chengdu Shang Bao (Chengdu Commercial Gazette) and the Sichuan Gong Bao (Sichuan Impartial Journal). He also founded and edited several daily newspapers and periodicals, including the Min Guo Xin Bao (New Republic) and Xing Shi (Awakened Lion).
Although once opposed to Chiang Kai-shek, in 1937 Zeng Qi joined forces with the Generalissimo in the campaign against Japan. After Japan's surrender, Zeng Qi was the leading delegate of the Young China Party to the Political Consultative Conference at Chongqing. In the winter of 1946, he became a representative to the National Assembly of Constitution Making and was selected as a member of the presidium. On behalf of the Young China Party, he signed, together with the Kuomintang and the China Democratic Socialist League, led by Zhang Junmai (aka Carson Chang), the Common Political Program and consequently became a state councilor in the Nationalist government after it was reorganized in April 1947.
After Chiang was inaugurated as president of the Chinese Republic, Zeng Qi was appointed his supreme adviser. During the Truman administration, in 1948, Zeng Qi came to the United States to study its constitutional government and worked fervently to garner U.S. support against the Chinese Communists. Zeng Qi died in 1951 in Washington, D.C.
From the guide to the Zeng Qi papers, 1925-1951, (Hoover Institution Archives)
|associatedWith||Zhongguo qing nian dang.||corporateBody|
|Place Name||Admin Code||Country|


Data from marine citizen scientists reveal how fish biodiversity patterns across the Caribbean are linked to sea temperature.
A study published today in the Journal of Biogeography has utilised the power of the people in the form of “citizen science” to produce a new map of marine fish biodiversity across the Caribbean and tropical western Atlantic.
A marine citizen scientist collecting data for the REEF fish survey project. Credit Jeffrey D Haines.
The work, performed by scientists from the Center for Macroecology, Evolution & Climate in Denmark and the Marine Biological Association, studied a huge data base collected by volunteer SCUBA diving enthusiasts to produce the map and find that fish biodiversity is strongly linked to sea temperatures. However, results also show that while fish biodiversity is higher in warmer waters, the very hottest sites in fact have fewer species than sites with intermediate temperatures, something not shown before in previous studies. These results will be of concern given the rising water temperatures in the region.
This ground-breaking research is based on data collected by thousands of marine citizen scientists working within the Reef Environmental Education Foundation’s (REEF, www.reef.org) SCUBA diving based fish survey project. These volunteers have been recording data on the fish species they see during dives for over 25 years and inputting their records into REEF database. This work has enabled researchers to compare different coral reefs and other coastal sites across this tropical region for the first time. The resulting map shows high diversity areas in the Dutch Antilles and the Florida Keys, whereas relatively few species were found in Bermuda, the Gulf of Mexico and Northern Florida.
In order to examine potential explanations for these patterns the research team looked at potential environmental factors that might be associated with them, including natural factors, such as temperature, salinity and depth, and human-based factors, such as population density. Analysis proved the number of fish species recorded at a site could be predicted by how warm the water was at that site, and, to a lesser extent, how deep the site was. While a positive relationship between temperature and biodiversity has been demonstrated in previous research of global patterns, the fine scale detail provided by this huge citizen science dataset facilitated the discovery of important details of this relationship within the wider Caribbean. Senior author Dr Ben Holt said:
"Rather than being a simple relationship, whereby warmer waters equal more fish species, the relationship seen in the REEF data was “hump-shaped”; warmer sites tend to have more species up to an optimal temperature of around 27oC and then the hottest sites become less diverse.”
Further analysis suggests that this result may be partly driven by a fewer species being adapted to the warmest temperatures. The findings of this study will inevitably be of concern given the fast rising temperatures of Caribbean water but the research team urge caution extrapolating their results based on future climate predictions. Dr Holt said:
“The efforts of citizen scientists have provided an invaluable opportunity to study spatial patterns of marine biodiversity. Their data suggest that the hottest reefs are not the most biodiverse but it does not necessarily mean that the diversity of any particular site will change as seawater temperatures change. This is an important area for further research given the importance of these habitats within the Caribbean and around the world.”Dr Holt is currently based at the Marine Biological Association of the UK in Plymouth and can be contacted on 0786 6862865 or firstname.lastname@example.org


text:
At Not Just Minerals you are guaranteed a one of a kind creation. Everything is personally hand~crafted with Love and Good intent. All my designs come infused with Crystals. Custom orders, healing pendants ...... Plus many many new ideas in store.
Where to Find Me
Best place to contact me would be through my group on Facebook. I seem to always be there and list my creations in the weekly Auctions. The group is called Not Just Minerals Artisans and Gems, I am the Administrator there. I work with a team of sellers and we are always creating New and Interesting items. Below is the link to the group. Hope to see you there!!!
*Photo taken by Deborah Blount
Custom orders are never a problem. I have created looks for that were intended for beauty as well as healing. Whatever it is you are looking for I will do my best to provide it. If I don't have it chances are one of my sellers does and it can always be ordered. Pictured here is a healing pendant I made several months ago.
Accept debit or credit cards
Debit & Credit cards accepted
nice products and fast shipping
Everything she sells she puts her heart in,. Handmade too!! I've always been pleased with all her items from pillows to crystals..
Everything is hand crafted and a new creation and is unique