The Effect of auditor-provided non-audit services on auditor independence and Sarbanes-Oxley: What separates tax services from other non-audit services?

Objectives of the Study: The Sarbanes-Oxley Act prohibited a large number of individual auditor-provided non-audit services, which were seen to have a negative effect on auditor independence. Tax services were not included in the list, implying that the effects of these services should somehow differ from those of other consulting services. Research on all non-audit services however has yielded contradictory results. This study sets out to illustrate the possible effects of tax services using prior research on all services as a framework, and attempts to shed some light on the issue whether the effects of tax services actually are significantly different from those of the other non-audit services. Research Method and Data: The methods used in the paper follow the research of Frankel et al. (2002) which approaches independence concerns by examining whether strong economic bonds between auditor and client lead to opportunistic earnings management through the use of discretionary accruals. A modification to the method also allows a separate examination of auditor-provided tax services. The sample used in the models consists of financial statements from 2415 individual North American firms for the financial year 2010. Findings of the Study: This study provides heteroscedasticity-robust evidence that there is no statistically significant association between auditor-provided tax services and earnings management. The results are robust to differences in auditor fee composition, to the direction of earnings management as well as to audit client firm size. Since the goal of this paper and the methods used in it is not to measure possible knowledge spillovers, one can only speculate whether the absence of such an association could mean that there are no audit-quality improving knowledge spillovers retainable from the provision of tax services, or that the provision of tax services simply does not have an effect on auditor independence

Stapled truncated orexin peptides as orexin receptor agonists

The peptides orexin-A and -B, the endogenous agonists of the orexin receptors, have similar 19-amino-acid C-termini which retain full maximum response as truncated peptides with only marginally reduced potency, while further N-terminal truncations successively reduce the activity. The peptides have been suggested to bind in an α‐helical conformation, and truncation beyond a certain critical length is likely to disrupt the overall helical structure. In this study, we set out to stabilize the α‐helical conformation of orexin‐A15–33 via peptide stapling at four different sites. At a suggested hinge region, we varied the length of the cross-linker as well as replaced the staple with two α-aminoisobutyric acid residues. Modifications close to the peptide C‐terminus, which is crucial for activity, were not allowed. However, central and N‐terminal modifications yielded bioactive peptides, albeit with decreased potencies. This provides evidence that the orexin receptors can accommodate and be activated by α-helical peptides. The decrease in potency is likely linked to a stabilization of suboptimal peptide conformation or blocking of peptide backbone–receptor interactions at the hinge region by the helical stabilization or the modified amino acids.Peer reviewe

Genetic diversity in gooseberry (Ribes uva-crispa), as estimated with SSR markers

European gooseberry (Ribes uva-crispa L.) is a popular berry crop in many European countries, including Sweden, Denmark and Ukraine. There is no active gooseberry breeding programme in either Sweden or Denmark, but a successful programme is operating in Ukraine. In Sweden and Denmark, research on gooseberries is primarily focused on collection and phenotypic evaluation of genetic resources. As part of these activities, a large number of inventory finds have been collected but have not yet been characterised morphologically or molecularly. The goal of this study was thus to characterise gooseberry germplasm with 15 simple sequence repeat (SSR) markers. From 242 accessions analysed, 153 unique genotypes were identified. Cultivars that have been in widespread cultivation in Sweden, such as the Finnish cultivars 'Hinnonma & BULL;en Keltainen' and 'Hinnonma & BULL;en Punainen', had relatively large numbers of synonymous samples. While many inventory finds were identifiable as synonyms of known cultivars, several were found to constitute unique genotypes within the germplasm studied. The studied genotypes clustered relatively well in three posterior groups, consisting of cultivars originating before and after the American gooseberry mildew (Sphaerotheca mors-uvae) outbreak around 1900 and cultivars originating from the territory of the former Soviet Union. A fourth genetic cluster consisting mainly of inventory finds from central and northern Sweden was also identified. In addition, it was possible to verify recorded and stipulated parentages for some of the cultivars studied and to identify three likely parent-parent-child trios. Thus, inventories of local gooseberry germplasm and a subsequent genotyping proved successful in finding unique local genotypes, with potential local adaptation. The data obtained provide a foundation for future studies of gooseberry genetic re-sources, while also illustrating the importance of a well-curated and phenotypically characterised set of reference cultivars for future studies

Three Randomised Phase I/IIa Trials of 5% Cis-urocanic Acid Emulsion Cream in Healthy Adult Subjects and in Patients with Atopic Dermatitis

New treatment modalities are needed in atopic dermatitis. We evaluated the pharmacokinetics, safety, tolerability, and efficacy of topical cis-urocanic acid (cis-UCA) cream in randomised vehicle-controlled double-blinded clinical trials. The subjects received 5% cis-UCA emulsion cream and control vehicle on volar forearms after right–left randomisation. Study 1: 16 healthy subjects received one dose on the skin and, a week later, on DMSO-irritated skin. Study 2: 16 healthy subjects received 2 daily doses for 10 days. Study 3: 13 patients with mild to moderate disease were treated on selected skin lesions twice daily for 28 days. Study treatments were well tolerated. cis-UCA remained close to endogenous levels in plasma and urine. cis-UCA reduced transepidermal water loss (TEWL) both in healthy subjects and in the patients. Eczema area severity index and physician’s global assessment improved from baseline with both treatments. cis-UCA cream improved skin barrier function and suppressed inflammation in the human skin

Molecular targets for the protodynamic action of cis-urocanic acid in human bladder carcinoma cells

<p>Abstract</p> <p>Background</p> <p>cis-urocanic acid (cis-UCA) is an endogenous amino acid metabolite capable of transporting protons from the mildly acidic extracellular medium into the cell cytosol. The resulting intracellular acidification suppresses many cellular activities. The current study was aimed at characterizing the molecular mechanisms underlying cis-UCA-mediated cytotoxicity in cultured cancer cells.</p> <p>Methods</p> <p>5367 bladder carcinoma cells were left untreated or treated with cis-UCA. Cell death was assessed by measuring caspase-3 activity, mitochondrial membrane polarization, formation and release of cytoplasmic histone-associated DNA fragments, and cellular permeabilization. Cell viability and metabolic activity were monitored by colorimetric assays. Nuclear labelling was used to quantify the effects of cis-UCA on cell cycle. The activity of the ERK and JNK signalling pathways was studied by immunoblotting with specific antibodies. Phosphatase activity in cis-UCA-treated cells was determined by assay kits measuring absorbance resulting from the dephosphorylation of an artificial substrate. All statistical analyses were performed using the two-way Student's t-test (p < 0.05).</p> <p>Results</p> <p>Here we report that treatment of the 5637 human bladder carcinoma cells with 2% cis-UCA induces both apoptotic and necrotic cell death. In addition, metabolic activity of the 5637 cells is rapidly impaired, and the cells arrest in cell cycle in response to cis-UCA. Importantly, we show that cis-UCA promotes the ERK and JNK signalling pathways by efficiently inhibiting the activity of serine/threonine and tyrosine phosphatases.</p> <p>Conclusions</p> <p>Our studies elucidate how cis-UCA modulates several cellular processes, thereby inhibiting the proliferation and survival of bladder carcinoma cells. These anti-cancer effects make cis-UCA a potential candidate for the treatment of non-muscle invasive bladder carcinoma.</p

ERICA-hätäkeskustietojärjestelmän riskinarvion osuvuus Helsingin Pelastuslaitoksella

Suomessa otettiin käyttöön vuonna 2018 uusi hätäkeskustietojärjestelmä ERICA. Järjestelmä on valtakunnallinen ja kaikkien hätäkeskustoimintaan osallistuvien toimijoiden yhteisessä käytössä. ERICA:n käyttöönoton on huomattu nostavan etenkin A- ja B-kiireellisyysluokan tehtävämäärää ensihoidossa. Opinnäytetyö toteutettiin yhteistyössä HUS Akuutti ensihoito Helsingin sekä Helsingin pelastuslaitoksen kanssa. Tarkoituksena oli tutkia, miten ERICA-hälytysjärjestelmän riskinarvio vastaa potilaan todellista avuntarvetta Helsingin pelastuslaitoksen ensihoitotehtävillä, sekä mitä eroja on hätäkeskuksen tehtävänkäsittelyohjeella verrattuna ensihoitokertomuksen esitietoihin. Aineisto kerättiin Helsingin pelastuslaitoksen Merlot Medi -potilastietojärjestelmän ensihoitokertomuksista ajalta 1.8.-31.10.2019 ja rajattiin koskemaan tehtävälajeja 702 (tajuttomuus), 703 (hengitysvaikeus), 752 (myrkytys), 781 (vatsakipu) ja 200 (tieliikenneonnettomuus). Aineisto analysoitiin sekä määrällisin että laadullisin menetelmin. Tavoitteena oli tuottaa riskinarvion osuvuudesta uutta tietoa, jota voidaan käyttää riskianalyysirungon toimivuuden arvioimiseen ja mahdolliseen kehittämiseen tulevaisuudessa. Opinnäytetyön tuloksena selvisi, että hätäkeskuksen riskinarvion osuvuus ei ole erityisen hyvä. Lähes puolessa käsitellyistä ensihoitotehtävistä avuntarve oli hätäkeskuksen toimesta yliarvioitu. Eniten kiireellisyyden yliarviointia tapahtui A- ja B-tehtävissä ja selvästi eniten tehtäväkoodissa 702 (tajuttomuus). Aineiston perusteella hätäkeskuksen valitsema hälytyskoodi vastasi potilaan pääasiallista terveysongelmaa reilussa puolessa tehtävistä. Kiireellisyysluokitus taas oli arvioitu oikeaksi hieman alle puolessa tehtävistä. Noin neljäsosassa tehtävistä ensihoidolle ei ollut lainkaan tarvetta. Toisaalta tehtäväkiireellissyden aliarviointi oli hyvin vähäistä