STABILITY AND ERROR OF THE NEW NUMERICAL SOLUTION OF FRACTIONAL RIESZ SPACE TELEGRAPH EQUATION WITH TIME DELAY

In this paper, we propose a numerical method for Riesz space fractional telegraph equation with time delay. The Riesz fractional telegraph equation is approximated with the interpolating polynomial P2. First a system of fractional differential equations are obtained from the telegraph equation with respect to the time variable. Then our numerical algorithm is proposed. The convergence order and stability of the fractional order algorithms are proved. Finally, some numerical examples are constructed to describe the usefulness and profitability of the numerical method. Numerical results show that the accuracy of order O(t3)

The Effect of Cost Categories and the Origin of their stickiness on Earnings Forecast: A Comparative Study

The main aim of this study is to separate the origins of “selling, general, and administrative costs (SG&A)” and “cost of goods sold (COGS)” stickiness, and investigate their sources effects on earnings forecast accuracy (EFA). In previous research, various micro and macro factors have been shown to affect asymmetric cost behavior. These factors are rooted in the industry and firm-specific characteristics or specific events, which may occur each year at national or international scales. In this study, in the first step, a new methodology is presented to separate the sources of cost stickiness, including a novel method for calculating cost stickiness for each firm-year. In the second step, we investigated the effect of each firm-year stickiness and each source of stickiness on the EFA. The statistical population of the study consisted of all companies listed on the Tehran Stock Exchange, from which 1080 observations in 2014-2018 period were selected and reviewed. Our results indicated that EFA has a negative and significant relationship with SG&A and COGS stickiness, stickiness of each year and each company, but no significant relationship was found with stickiness of each industry. Our results demonstrated that the stickiness of SG&A to COGS has a greater effect on the EFA. The findings suggest that the events of each year and the intra-organizational events of each company have a greater impact on cost behavior. Hence, it is necessary for managers and financial analysts to take into account each source of cost stickiness, especially year-specific events and firm-specific characteristics, and consider their effects in earnings forecast to improve their EFA

Effect of 2% Chlorhexidine on Shear Bond Strength of Composite Resins to Dentin

Abstract Background and Aim: Intracanal medicaments can affect the bond strength of composite to dentin. The aim of this study was to evaluate the effect of 2% chlorhexidine (CHX) gel as an intracanal medicament on shear bond strength of three different composite resins to dentin. Materials and Methods: In this in-vitro study, 60 intact extracted human premolars were utilized. Each tooth was sectioned vertically and dentin of the buccal surface was exposed. Then, specimens were divided into six groups of 10 teeth. In groups 1-3, dentin was exposed to CHX and in groups 4-6, dentin was exposed to saline. All prepared surfaces were rinsed with distilled water and dentin bonding agent specific for each composite was applied on the dentin surfaces. Z100, Z350 and P90 composites were applied to the treated surfaces and cured. The shear bond strength was recorded in Newtons and converted to MPa. Data were analyzed using the Kruskal-Wallis and Dunn tests. Results: The lowest mean shear bond strength was reported for normal saline and Z100 composite group (18.47 MPa) and the highest for CHX and Z350 group (42.26 MPa). No statistically significant difference in bond strength values was found between normal saline and CHX groups (P>0.05). There was a significant difference in bond strength values of different composite resins in normal saline (P<0.05) and also in CHX groups (P<0.05). Conclusion: Application of 2% chlorhexidine gel slightly but not significantly increases the mean shear bond strength of composite to dentin. The type of composite influences the shear bond strength to denti

Improving management of respiratory tract infections in community pharmacies and promoting antimicrobial stewardship: a cluster randomised control trial with a self-report behavioural questionnaire and process evaluation

In England, 81% of all antibiotic prescriptions originate in primary care/community settings, of which up to 20% are thought to be inappropriate. Community pharmacies are often the first point of community contact for patients with suspected infections; providing an opportunity for community pharmacy teams to promote antimicrobial stewardship (AMS). The objective of the study was to improve the management of infections and antimicrobial stewardship in community pharmacies. The study methodology included a non-blinded cluster randomised control trial with pharmacy staff in 272 community pharmacies in England. The intervention arm received an AMS webinar and a patient facing respiratory tract infection (RTI) leaflet (TARGET TYI-RTI) for use in everyday practice for four weeks. The control arm received a webinar on how to participate in the study. The primary outcome was self-reported referrals to general practitioners (GPs). The secondary outcomes were; provision of self-care advice/ written information to patients, referrals to pharmacists, sign-posting to non-prescription medicines and common barriers and facilitators to advice-giving in community pharmacies. Ethics approval was granted by the Public Health England Research Ethics and Governance Group. 66.91% (182 of 272) of pharmacies provided 3649 patient consultation data reports across both arms. Use of the leaflet was associated with a lower likelihood of referrals to GPs for certain RTIs (p < 0.05) and a more frequent provision of self-care advice than the control (p = 0.06). Opportunities to deliver self-care advice were limited due to lack of time. Pharmacy staff had good motivation and capability for managing self-limiting infections but the opportunity to do so was a perceived barrier. Use of the TARGET leaflet facilitated pharmacy staff to give more self-care advice and decreased referrals to GPs

Validation of plasma protein glycation and oxidation biomarkers for the diagnosis of autism

Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder in children. It is currently diagnosed by behaviour-based assessments made by observation and interview. In 2018 we reported a discovery study of a blood biomarker diagnostic test for ASD based on a combination of four plasma protein glycation and oxidation adducts. The test had 88% accuracy in children 5–12 years old. Herein, we present an international multicenter clinical validation study (N = 478) with application of similar biomarkers to a wider age range of 1.5–12 years old children. Three hundred and eleven children with ASD (247 male, 64 female; age 5.2 ± 3.0 years) and 167 children with typical development (94 male, 73 female; 4.9 ± 2.4 years) were recruited for this study at Sidra Medicine and Hamad Medical Corporation hospitals, Qatar, and Hospital Regional Universitario de Málaga, Spain. For subjects 5–12 years old, the diagnostic algorithm with features, advanced glycation endproducts (AGEs)—Nε-carboxymethyl-lysine (CML), Nω-carboxymethylarginine (CMA) and 3-deoxyglucosone-derived hydroimidazolone (3DG-H), and oxidative damage marker, o,o’-dityrosine (DT), age and gender had accuracy 83% (CI 79 – 89%), sensitivity 94% (CI 90–98%), specificity 67% (CI 57–76%) and area-under-the-curve of receiver operating characteristic plot (AUROC) 0.87 (CI 0.84–0.90). Inclusion of additional plasma protein glycation and oxidation adducts increased the specificity to 74%. An algorithm with 12 plasma protein glycation and oxidation adduct features was optimum for children of 1.5–12 years old: accuracy 74% (CI 70–79%), sensitivity 75% (CI 63–87%), specificity 74% (CI 58–90%) and AUROC 0.79 (CI 0.74–0.84). We conclude that ASD diagnosis may be supported using an algorithm with features of plasma protein CML, CMA, 3DG-H and DT in 5–12 years-old children, and an algorithm with additional features applicable for ASD screening in younger children. ASD severity, as assessed by ADOS-2 score, correlated positively with plasma protein glycation adducts derived from methylglyoxal, hydroimidazolone MG-H1 and Nε(1-carboxyethyl)lysine (CEL). The successful validation herein may indicate that the algorithm modifiable features are mechanistic risk markers linking ASD to increased lipid peroxidation, neuronal plasticity and proteotoxic stress.</p

SARS-CoV-2 infection rates of antibody-positive compared with antibody-negative health-care workers in England: a large, multicentre, prospective cohort study (SIREN).

BACKGROUND: Increased understanding of whether individuals who have recovered from COVID-19 are protected from future SARS-CoV-2 infection is an urgent requirement. We aimed to investigate whether antibodies against SARS-CoV-2 were associated with a decreased risk of symptomatic and asymptomatic reinfection. METHODS: A large, multicentre, prospective cohort study was done, with participants recruited from publicly funded hospitals in all regions of England. All health-care workers, support staff, and administrative staff working at hospitals who could remain engaged in follow-up for 12 months were eligible to join The SARS-CoV-2 Immunity and Reinfection Evaluation study. Participants were excluded if they had no PCR tests after enrolment, enrolled after Dec 31, 2020, or had insufficient PCR and antibody data for cohort assignment. Participants attended regular SARS-CoV-2 PCR and antibody testing (every 2-4 weeks) and completed questionnaires every 2 weeks on symptoms and exposures. At enrolment, participants were assigned to either the positive cohort (antibody positive, or previous positive PCR or antibody test) or negative cohort (antibody negative, no previous positive PCR or antibody test). The primary outcome was a reinfection in the positive cohort or a primary infection in the negative cohort, determined by PCR tests. Potential reinfections were clinically reviewed and classified according to case definitions (confirmed, probable, or possible) and symptom-status, depending on the hierarchy of evidence. Primary infections in the negative cohort were defined as a first positive PCR test and seroconversions were excluded when not associated with a positive PCR test. A proportional hazards frailty model using a Poisson distribution was used to estimate incidence rate ratios (IRR) to compare infection rates in the two cohorts. FINDINGS: From June 18, 2020, to Dec 31, 2020, 30 625 participants were enrolled into the study. 51 participants withdrew from the study, 4913 were excluded, and 25 661 participants (with linked data on antibody and PCR testing) were included in the analysis. Data were extracted from all sources on Feb 5, 2021, and include data up to and including Jan 11, 2021. 155 infections were detected in the baseline positive cohort of 8278 participants, collectively contributing 2 047 113 person-days of follow-up. This compares with 1704 new PCR positive infections in the negative cohort of 17 383 participants, contributing 2 971 436 person-days of follow-up. The incidence density was 7·6 reinfections per 100 000 person-days in the positive cohort, compared with 57·3 primary infections per 100 000 person-days in the negative cohort, between June, 2020, and January, 2021. The adjusted IRR was 0·159 for all reinfections (95% CI 0·13-0·19) compared with PCR-confirmed primary infections. The median interval between primary infection and reinfection was more than 200 days. INTERPRETATION: A previous history of SARS-CoV-2 infection was associated with an 84% lower risk of infection, with median protective effect observed 7 months following primary infection. This time period is the minimum probable effect because seroconversions were not included. This study shows that previous infection with SARS-CoV-2 induces effective immunity to future infections in most individuals. FUNDING: Department of Health and Social Care of the UK Government, Public Health England, The National Institute for Health Research, with contributions from the Scottish, Welsh and Northern Irish governments

Coagulase gene polymorphism of Staphylococcus aureus isolated from clinical and sub-clinical bovine mastitis in Isfahan and Chaharmahal va Bakhtiari provinces of Iran

Mastitis is a common disease in dairy cattle and is an inflammatory response of the breast tissue to bacterial attack to this tissue. Mastitis causes considerable loss to the dairy industry, among the several bacterial pathogens that can cause mastitis; Staphylococcus aureus is probably the most lethal agent because it causes chronic and deep infection in the mammary glands that is extremely difficult to cure. Several virulence factors including coagulase gene are produced by S. aureus and may contribute to its pathogenicity. This study was conducted to investigate the coagulase gene polymorphism of S. aureus isolated from clinical and sub-clinical bovine mastitis milk samples in Isfahan and Chaharmahal va Bakhtiari provinces of Iran. Amplification of the coagulase gene from 86 S. aureus strains isolates by specific primers showed 31 specimens contained 970 bp fragment, and 11 strains contained 730 bp fragment relevant to coa gene (coagulase) in PCR. After enzymatic digestion with AluI, 31 specimens contained three bands: 320, 490, and 160 bp (genotype I) and 11 specimens contained two bands: 490 and 240 bp (genotype VIII) in the RFLP

An integrative proteomics method identifies a regulator of translation during stem cell maintenance and differentiation

To characterize molecular changes during cell type transitions, the authors develop a method to simultaneously measure protein expression and thermal stability changes. They apply this approach to study differences between human pluripotent stem cells, their progenies, parental and allogeneic cells. Detailed characterization of cell type transitions is essential for cell biology in general and particularly for the development of stem cell-based therapies in regenerative medicine. To systematically study such transitions, we introduce a method that simultaneously measures protein expression and thermal stability changes in cells and provide the web-based visualization tool ProteoTracker. We apply our method to study differences between human pluripotent stem cells and several cell types including their parental cell line and differentiated progeny. We detect alterations of protein properties in numerous cellular pathways and components including ribosome biogenesis and demonstrate that modulation of ribosome maturation through SBDS protein can be helpful for manipulating cell stemness in vitro. Using our integrative proteomics approach and the web-based tool, we uncover a molecular basis for the uncoupling of robust transcription from parsimonious translation in stem cells and propose a method for maintaining pluripotency in vitro

Mixed-Method Evaluation of a Community Pharmacy Antimicrobial Stewardship Intervention (PAMSI)

The community pharmacy antimicrobial stewardship intervention (PAMSI) is multi-faceted and underpinned by behavioural science, consisting of the TARGET Antibiotic Checklist, staff e-Learning, and patient-facing materials. This mixed-method study evaluated the effect of PAMSI on community pharmacy staffs' self-reported antimicrobial stewardship (AMS) behaviours. Data collection included staff pre- and post-intervention questionnaires, qualitative interviews, and TARGET Antibiotic Checklists. Quantitative data were analysed by a multivariate ordinal linear mixed effect model; qualitative data were analysed thematically. A total of 101 staff participated from 66 pharmacies, and six completed semi-structured interviews. The statistical model indicated very strong evidence ( < 0.001) that post-intervention, staff increased their antibiotic appropriateness checks and patient advice, covering antibiotic adherence, antibiotic resistance, infection self-care, and safety-netting. Staff reported feeling empowered to query antibiotic appropriateness with prescribing clinicians. The TARGET Antibiotic Checklist was completed with 2043 patients. Topics patients identified as requiring advice from the pharmacy team included symptom duration, alcohol and food consumption guidance, antibiotic side-effects, and returning unused antibiotics to pharmacies. Pharmacy staff acknowledged the need for improved communication across the primary care pathway to optimise antimicrobial use, and PAMSI has potential to support this ambition if implemented nationally. To support patients not attending a pharmacy in person, an online information tool will be developed

c-Met activation leads to the establishment of a TGFβ-receptor regulatory network in bladder cancer progression

Treatment of muscle-invasive bladder cancer remains a major clinical challenge. Aberrant HGF/c-MET upregulation and activation is frequently observed in bladder cancer correlating with cancer progression and invasion. However, the mechanisms underlying HGF/c-MET-mediated invasion in bladder cancer remains unknown. As part of a negative feedback loop SMAD7 binds to SMURF2 targeting the TGFβ receptor for degradation. Under these conditions, SMAD7 acts as a SMURF2 agonist by disrupting the intramolecular interactions within SMURF2. We demonstrate that HGF stimulates TGFβ signalling through c-SRC-mediated phosphorylation of SMURF2 resulting in loss of SMAD7 binding and enhanced SMURF2 C2-HECT interaction, inhibiting SMURF2 and enhancing TGFβ receptor stabilisation. This upregulation of the TGFβ pathway by HGF leads to TGFβ-mediated EMT and invasion. In vivo we show that TGFβ receptor inhibition prevents bladder cancer invasion. Furthermore, we make a rationale for the use of combinatorial TGFβ and MEK inhibitors for treatment of high-grade non-muscle-invasive bladder cancers