Spread, circulation, and evolution of the Middle East respiratory syndrome coronavirus

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1

Viral shedding and antibody response in 37 patients with MERS-coronavirus infection

Background. The Middle East respiratory syndrome (MERS) coronavirus causes isolated cases and outbreaks of severe respiratory disease. Essential features of the natural history of disease are poorly understood. Methods. We studied 37 adult patients infected with MERS coronavirus for viral load in the lower and upper respiratory tracts (LRT and URT, respectively), blood, stool, and urine. Antibodies and serum neutralizing activities were determined over the course of disease. Results. One hundred ninety-nine LRT samples collected during the 3 weeks following diagnosis yielded virus RNA in 93% of tests. Average (maximum) viral loads were 5 × 106 (6 × 1010) copies/mL. Viral loads (positive detection frequencies) in 84 URT samples were 1.9 × 104 copies/mL (47.6%). Thirty-three percent of all 108 serum samples tested yielded viral RNA. Only 14.6% of stool and 2.4% of urine samples yielded viral RNA. All seroconversions occurred during the first 2 weeks after diagnosis, which corresponds to the second and third week after symptom onset. Immunoglobulin M detection provided no advantage in sensitivity over immunoglobulin G (IgG) detection. All surviving patients, but only slightly more than half of all fatal cases, produced IgG and neutralizing antibodies. The levels of IgG and neutralizing antibodies were weakly and inversely correlated with LRT viral loads. Presence of antibodies did not lead to the elimination of virus from LRT. Conclusions. The timing and intensity of respiratory viral shedding in patients with MERS closely matches that of those with severe acute respiratory syndrome. Blood viral RNA does not seem to be infectious. Extrapulmonary loci of virus replication seem possible. Neutralizing antibodies do not suffice to clear the infection

Investigating immunological responses of WC1+ gamma delta T cells in cattle naturally infected with mycobacterium avium subspecies paratuberculosis (MAP)

In these studies, we used non-infected cattle and cattle naturally infected with MAP that were either in the subclinical or clinical stage of infection to test the hypothesis that infection status influences WC1+ γδ T cells frequency, proliferation, and cytokine production. We found no significant differences between subclinical and clinical cattle with regard to WC1+ γδ T cells frequency in peripheral blood or in the ileum, a primary site for MAP infection. In PBMCs taken from MAP-infected cattle, WC1+ γδ T cells responded diffrentially to stimulation with PPD-J. In the clinical group, WC1+ γδ T cells failed to proliferate and the WC1.1 subset did not produce IFN-γ or IL-10 suggesting unresponsiveness. We evaluated the cytokine profile (mRNA) of the WC1+ γδ T cell subset in the ileum. Our data indicate a significant increase in the numbers of WC1+ γδ T cells expressing IL-10 in ileal tissues obtained from clinical cattle compared to subclinical and non-infected cattle. Expression of IFN-γ, TNF-α, IL-17 and TGF-β by the WC1+ γδ T cell subset in the ileum was comparable among the examined groups. We used subclinical infected cattle to evaluate the impact of WC1+ γδ T cell depletion on cytokine production by PBMCs stimulated ex vivo with PPD-J. Independent of antigen (PPD), depletion of WC1+ γδ T cells resulted in a significant decrease in IL-4 secretion and a significant increase in IL-10 secretion suggesting a modulatory role for the WC1+ subset in this system. The present dissertation supports our hypothesis that MAP infection status influences immunological responses of WC1+ γδ T cells in peripheral blood and at the sites of MAP infection. Our data suggest that the WC1+ γδ T cell subset may contribute to the immune responses that control MAP infection during the subclinical stage and those that promote disease progression during the terminal stages of MAP infection

Systematic review of the safety of medication use in inpatient, outpatient and primary care settings in the Gulf Cooperation Council countries

Background Errors in medication use are a patient safety concern globally, with different regions reporting differing error rates, causes of errors and proposed solutions. The objectives of this review were to identify, summarise, review and evaluate published studies on medication errors, drug related problems and adverse drug events in the Gulf Cooperation Council (GCC) countries. Methods A systematic review was carried out using six databases, searching for literature published between January 1990 and August 2016. Research articles focussing on medication errors, drug related problems or adverse drug events within different healthcare settings in the GCC were included. Results Of 2094 records screened, 54 studies met our inclusion criteria. Kuwait was the only GCC country with no studies included. Prescribing errors were reported to be as high as 91% of a sample of primary care prescriptions analysed in one study. Of drug-related admissions evaluated in the emergency department the most common reason was patient non-compliance. In the inpatient care setting, a study of review of patient charts and medication orders identified prescribing errors in 7% of medication orders, another reported prescribing errors present in 56% of medication orders. The majority of drug related problems identified in inpatient paediatric wards were judged to be preventable. Adverse drug events were reported to occur in 8.5–16.9 per 100 admissions with up to 30% judged preventable, with occurrence being highest in the intensive care unit. Dosing errors were common in inpatient, outpatient and primary care settings. Omission of the administered dose as well as omission of prescribed medication at medication reconciliation were common. Studies of pharmacists’ interventions in clinical practice reported a varying level of acceptance, ranging from 53% to 98% of pharmacists’ recommendations. Conclusions Studies of medication errors, drug related problems and adverse drug events are increasing in the GCC. However, variation in methods, definitions and denominators preclude calculation of an overall error rate. Research with more robust methodologies and longer follow up periods is now required.Peer reviewe

Androgen Receptor (AR) ablation encumbers the expansion and function of T regulatory cells (Treg) in a male mouse model

Background: Many autoimmune diseases have a higher prevalence in females than males but there is no clear explanation for this phenomenon. Naturally occurring CD4+CD25+FOXP3+ Treg cells carry out a vital role in immune tolerance.  We postulate that androgen may influence Treg cells differentiation and function.Methods: Eight to twelve weeks old wild-type (WT) and androgen receptor knockout (ARKO) male mice (C57BL/6) were utilized. Treg cells in diverse lymphoid organs were separated with an easySep selection kit and sorted with FACSAria. Treg cells were phenotypically and functionally characterized by flow cytometry analysis (FACS) and an in vitro immune suppressive assay. Results: Significantly Lower prevalence of thymic and peripheral Treg cells were noted in ARKO mice compared to the WT mice. Sorted ARKO Treg cells were functionally less suppressive than their counterparts in WT mice.Conclusion: Our data suggest that the androgen receptor (AR) signaling pathway may be implicated in Treg cell expansion and function. To our knowledge, this study is the first to look into how AR knockout affects Treg cells. Therefore, it might flashlight the mechanisms of inflammatory and autoimmune disease.Keywords: Androgen receptor; ARKO mice; Immunity; Immunosuppression; Treg cell

Estimating potential incidence of MERS-CoV associated with Hajj pilgrims to Saudi Arabia, 2014

Between March and June 2014 the Kingdom of Saudi Arabia (KSA) had a large outbreak of MERS-CoV, renewing fears of a major outbreak during the Hajj this October. Using KSA Ministry of Health data, the MERS-CoV Scenario and Modeling Working Group forecast incidence under three scenarios. In the expected incidence scenario, we estimate 6.2 (95% Prediction Interval [PI]: 1-17) pilgrims will develop MERS-CoV symptoms during the Hajj, and 4.0 (95% PI: 0-12) foreign pilgrims will be infected but return home before developing symptoms. In the most pessimistic scenario, 47.6 (95% PI: 32-66) cases will develop symptoms during the Hajj, and 29.0 (95% PI: 17-43) will be infected but return home asymptomatic. Large numbers of MERS-CoV cases are unlikely to occur during the 2014 Hajj even under pessimistic assumptions, but careful monitoring is still needed to detect possible mass infection events and minimize introductions into other countries

Determinants of Capital Structure: the case of MENA countries

This thesis examines the determinants of capital structure in the MENA coun- tries. The main interest is to investigate both financial firms specially banks and non-financial firms. This study test the main theories of capital structure, namely: trade off theory and pecking order theory. The countries included in this thesis are Saudi Arabia, United Arab Emirates (Include both Abo-Dhabi and Dubai stock indexes), Bahrain, Qatar, Kuwait, Oman, Egypt, Morocco, Tunisia, Palestine and Jor- dan. The characteristics it covers as suggested by previous literature are tangibility, profitability, risk, debt tax shield, growth, dividends,size, cash flow and liquidity. It will also investigate the effect of the industry, credit rating and ownership structure on the capital structure This study also investigates the determinants of capital structure in Islamic and conventional banks. This is one of the first attempts to empirically examine the determinants of capital structure in Islamic and conventional banks in general and in MENA countries in particular. This study fills the gap in this important area of research and can provide a base for future research on capital structure in Islamic banks. This thesis use different models to test the capital structure and these are Panel data models (OLS, Fixed, and Random); Tobit and Dynamical model (Arellano-Bover Blundell-Bond), Structural Equation Modeling (SEM) and Generalised Regression Neural Networks (GRNN). The results suggest that the three methods used in this study lead to similar re- sults with a few exceptions in some countries. This thesis finds that the relation between leverage and the determinants of capital structure is different when using the market or the book leverage. It also finds that the determinants of capital struc- ture between the MENA countries are different. For example, profitability attribute relation with leverage follow the trade-off theory in some countries and follow the picking order theory in other countries. Also, liquidity is significant in all the countries in the sample and have a negative relation to leverage. In addition, tangibility is found to have a mixed results with some countries following the trade-off theory and other countries which follow the trade-off theory but overall it is a key determinant of capital structure. Additionally, the findings show that although that the majority of firms in the MENA countries don’t pay dividends the relation between the long term debt and leverage is negative in all the countries in the sample. The growth opportunities have a negative relation in Bahrain, Egypt, Jordan, Kuwait, Morocco, Palestine, Qatar and Tunisia but positive in rest of the countries. The cash flow attribute have a negative relation with leverage in all the countries in the sample except Saudi Arabia and Qatar when using the short and long term debt. Furthermore, the ownership variable is expected to have a negative relation when the ultimate owner is an institution. The results show that overall when there is an ultimate owner the leverage will have a negative relation. Suggesting that ultimate owners will force managers to keep a low debt in firms capital structure. This PhD also attempt to investigate the capital structure in banks within the MENA countries. A special focus is on the differences between the Islamic banks and conventional banks capital structure. First, the findings show that the banks follow the same determinants of capital structure as non-financial firms and that regulations are not the main determinant of capital structure in banks. Then, This study show that there is a difference in capital structure of Islamic banks in com- parison with conventional banks. The findings for the dividends variable show that Islamic banks do not follow the pecking order theory but conventional banks don’t. The results of the size variable show that when Islamic banks are large they use less debt in their capital structure. Growth variable show mixed results depending on the use of book or market leverage. Ownership structure show that when there is an ultimate owner leverage increase which is the reverse of the relation in the non-financial firms. The age variable is negative in relation to the book leverage and positive with the market leverage. Also, credit rating relation is different between the two banks, as it is positive with the conventional banks and negative with Islamic banks. Therefore, this study conclude that the main capital structure theories are applicable to MENA countries. Also indicate that Islamic banks have a different capital structure to conventional banks.Saudi Electronic Universit

The effect of twitter dissemination on cost of equity: A big data approach

Reducing information asymmetry between investors and a firm can have an impact on the cost of equity, especially in an environment or times of uncertainty. New technologies can potentially help disseminate corporate financial information, reducing such asymmetries. In this paper we analyse firms’ dissemination decisions using Twitter, developing a comprehensive measure of the amount of financial information that a company makes available to investors (iDisc) from a big data of firms’ tweets (1,197,208 tweets). Using a sample of 4131 firm-year observations for 791 non-financial firms listed on the US NASDAQ stock exchange over the period 2009–2015, we find evidence that iDisc significantly reduces the cost of equity. These results are pronounced for less visible firms which are relatively small in size, have a low analyst following and a small number of investors. Highly visible firms are less likely to benefit from iDisc in influencing their cost of equity as other communication channels may have widely disseminated their financial information. Our investigations encourage managers to consider the benefits of directly spreading a firm’s financial information to stakeholders and potential investors using social media in order to reduce firm equity premium (COE)