An investigation of how fungal infection influences drug penetration through onychomycosis patient's nail plates

This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)The treatment of onychomycosis remains problematic even though there are several potent antifungal agents available for patient use. The aim of this investigation was to understand if the structural modifications that arise when a patient's nail become infected plates influences the permeation of drugs into the nail following topical application. It was hoped that through improving understanding of the nail barrier in the diseased state, the development of more effective topical treatments for onychomycosis could be facilitated. The permeation of three compounds with differing hydrophobicities; caffeine, terbinafine and amorolfine, (clogD at pH 7.4 of -0.55, 3.72 and 4.49 respectively), was assessed across both healthy and onychomycosis infected, full thickness, human nail plate sections. Transonychial water loss (TOWL) measurements performed on the healthy and diseased nails supported previous observations that the nail behaves like a porous barrier given the lack of correlation between TOWL values with the thicker, diseased nails. The flux of the more hydrophilic caffeine was two-fold greater across diseased in comparison to the healthy nails, whilst the hydrophobic molecules terbinafine and amorolfine showed no statistically significant change in their nail penetration rates. Caffeine flux across the nail was found to correlate with the TOWL measurements, though no correlation existed for the more hydrophobic drugs. This data supported the notion that the nail pores, opened up by the infection, facilitated the passage of hydrophilic molecules, whilst the keratin binding of hydrophobic molecules meant that their transport through the nail plate was unchanged. Therefore, in order to exploit the structural changes induced by nail fungal infection it would be beneficial to develop a small molecular weight, hydrophilic antifungal agent, which exhibits low levels of keratin binding.Peer reviewe

Heterogeneity of luminal breast cancer characterised by immunohistochemical expression of basal markers

Background: Luminal A breast cancer defined as hormone receptor positive and human epidermal growth factor receptor 2 (HER2) negative is known to be heterogeneous. Previous study showed that luminal A tumours with the expression of basal markers ((cytokeratin (CK) 5 or CK5/6) or epidermal growth factor receptor (EGFR)) were associated with poorer prognosis compared with those that stained negative for basal markers. Prompted by this study, we assessed whether tumour characteristics and risk factors differed by basal marker status within luminal A tumours. Methods: We pooled 5040 luminal A cases defined by immunohistochemistry (4490 basal-negative ((CK5 (or CK5/6))− and EGFR−) and 550 basal-positive ((CK5 (or CK5/6+)) or EGFR+)) from eight studies participating in the Breast Cancer Association Consortium. Case–case comparison was performed using unconditional logistic regression. Results: Tumour characteristics and risk factors did not vary significantly by the expression of basal markers, although results suggested that basal-positive luminal tumours tended to be smaller and node negative, and were more common in women with a positive family history and lower body mass index. Conclusions: Most established breast cancer risk factors were similar in basal-positive and basal-negative luminal A tumours. The non-significant but suggestive differences in tumour features and family history warrant further investigations

The Earth: Plasma Sources, Losses, and Transport Processes

This paper reviews the state of knowledge concerning the source of magnetospheric plasma at Earth. Source of plasma, its acceleration and transport throughout the system, its consequences on system dynamics, and its loss are all discussed. Both observational and modeling advances since the last time this subject was covered in detail (Hultqvist et al., Magnetospheric Plasma Sources and Losses, 1999) are addressed

Inductive Electric Fields in the Magnetotail and Their Relation to Auroral and Substorm Phenomena

Qc 2012041

The Social Interaction between the Public Space and an Individual in the Shopping Mall

Pētījums aplūko publiskās telpas un indivīda sociālo mijiedarbību lielveikalā. Pētījumā izvirzīts apgalvojums, ka indivīda darbību lielveikalā nosaka tā specifiskā publiskās telpas organizācija un simbolika. Pētījuma novitāte ir projektētas telpas etnometodoloģiska studija, kas ļauj tieši aplūkot indivīdu darbības telpā. Novērojums veikts lielveikalos Spice un Olympia, kas atrodas Rīgā, Pārdaugavā. Novērojumu papildina materiālu analīze un autores ikdienas pieredze. Autore lielveikala apmeklējumu atspoguļo kā ceļojumu, kas sākas indivīda mājās ar lielveikala reklāmu un virtuālo telpu internetā. Ceļojums sākas ar tuvināšanos lielveikalam. Kā tipiski lielveikala apmeklējuma objekti aplūkoti ieeja, gaitenis, eskalators/kāpnes/lifts, telpa bērniem, kases zona un izeja. Lielveikalu kartes indivīdam ļauj plānot ceļojuma maršrutus.A statement is brought forward in the research that actions of an individual in a shopping mall are determined by specific organization and symbolic of its public space. Project’s novelty is an enthomethodological study of the projected space, which allows a direct observation of the actions of individuals in this space. Observation has been conducted in the shopping malls Spice and Olympia, located in Riga, Kurzemes suburb. Observations are supplemented by analysis of materials and author’s daily experience. Author reflects a visit to shopping mall as a journey that begins with a television advertisement at individual’s home or in a virtual internet space. As typical objects of visit in the shopping mall are - the entrance, the hallway, the escalator / stairway/ lift, space for children, the pay-box zone and the exit

Potential and Inductive Electric Fields in the Magnetosphere During Auroras

QC 2012041

Political responsibility in Latvia after renewal of independency

　　　　Darba tēma ir “Politiskais atbildīgums Latvijā pēc neatkarības atjaunošanas”. Bakalaura darba izpētes jautājums ir: Kādi faktori ietekmē Latvijas vadošo politiķu lēmumu uzņemties politisko atbildību? Tika apskatīta teorija par politiskā atbildīguma elementiem, noskaidrots politiķu viedoklis par politisko atbildību, kā arī veikta Latvijas likumdošanas izpēte . Autore analizēja piecu faktoru: partija, citi politiķi, masu mediji, sabiedrība un politiķa morālā apziņa , to ietekmi uz politiķu lēmumu uzņemties politisko atbildību . 　　　　Tika secināts, ka noteicošie faktori, kas varētu ietekmēt politiķi uzņemties politisko atbildību ir masu mediju un sabiedrības spiediens. Darbā tika izmantota mediju kontentanalīzes metode. Atslēgvārdi: politiskā atbildība, politiskā atskaitīšanās , faktori , politiķi.　　　The theme of this paper is “Political responsibility in Latvia after renewal of independency”. The research question of this paper is: What factors influence politicians decision to take political responsibility? The author of the work has included theory of political responsibility, politicians views, legislative analysis. 　　　The author analizyed five factors: political party, other politicians, the mass media, society, moral consciousness influence on the politicians decision to take political responsibility . 　　　It was concluded that the main factors, what influence politicians decisions are the mass media and society pressure. It was concluded using the gualitative research approach and the content analysis. Keywords: political accountability, political accountability, factors politicians

Ground-based observations of an onset of localized field-aligned currents during auroral breakup around magnetic midnight

The substorm on 2 March 1978 was selected for study as a relatively weak substorm, starting at about local magnetic midnight, that could be observed with instruments in Northern Scandinavia. The analysis is based on a comparative study of data from the IMS magnetometer network, all-sky cameras, pulsation magnetometers, and riometers in the Scandinavian area. In addition other data are used to support the results, e.g., a photograph from the DMSP-F2 satellite, showing the auroral situation over Scandinavia, and further west, immediately after the substorm onset. The substorm was preceded by a weak activation of aurora and magnetic disturbance about 3 min before the onset. After a fading that lasted for 20 s and could be observed only in optical aurora, the substorm onset led to a strong brightening of the aurora, an enhancement of the westward electrojet, a sudden rise in the ionospheric D-layer absorption, and Pi B type pulsations. Immediately after the onset, the ground magnetic data suggest the appearence of a pair of oppositely directed, localized, field-aligned currents (FACs). The main development of the signatures of the downward FAC was clearly delayed by about 3 min. There were significant correlations between the magnetic signatures of the two FACs and different features and spectra of the optical aurora, both in time and location. The observed Pi B type pulsations lasted as long as a growth in the local onset-connected FACs could be inferred. Within the first three minutes the localized three dimensional current system developed into a more sheet-like configuration. An expansion to the west, possibly accompanied by a westward travelling surge, was traced with riometers and magnetometers on Iceland and Greenland.           ARK: https://n2t.net/ark:/88439/y084828 Permalink: https://geophysicsjournal.com/article/208 &nbsp