Hall-plot of the phase diagram for Ba(Fe1-xCox)2As2

The Hall effect is a powerful tool for investigating carrier type and density. For single-band materials, the Hall coefficient is traditionally expressed simply by $R_H^{-1} = -en$, where $e$ is the charge of the carrier, and $n$ is the concentration. However, it is well known that in the critical region near a quantum phase transition, as it was demonstrated for cuprates and heavy fermions, the Hall coefficient exhibits strong temperature and doping dependencies, which can not be described by such a simple expression, and the interpretation of the Hall coefficient for Fe-based superconductors is also problematic. Here, we investigate thin films of Ba(Fe$_{1-x}$Co$_x$)$_2$As$_2$ with compressive and tensile in-plane strain in a wide range of Co doping. Such in-plane strain changes the band structure of the compounds, resulting in various shifts of the whole phase diagram as a function of Co doping. We show that the resultant phase diagrams for different strain states can be mapped onto a single phase diagram with the Hall number. This universal plot is attributed to the critical fluctuations in multiband systems near the antiferromagnetic transition, which may suggest a direct link between magnetic and superconducting properties in the BaFe$_2$As$_2$ system.Comment: Accepted for publication in Scientific Reports, 6 main figures plus Supplemental Information (8 figures

CT after interhospital transfer in acute ischemic stroke: Imaging findings and impact of prior intravenous contrast administration

Objectives: Large vessel occlusion (LVO) stroke patients routinely undergo interhospital transfer to endovascular thrombectomy capable centers. Imaging is often repeated with residual intravenous (IV) iodine contrast at post-transfer assessment. We determined imaging findings and the impact of residual contrast on secondary imaging. Anterior circulation LVO stroke patients were selected out of a consecutive cohort. Directly admitted patients were contrast naïve, and transferred patients had previously received IV iodine contrast for stroke assessment at the referring hospital. Two independent readers rated the visibility of residual contrast on non-contrast computed tomography (CT) after transfer and assessed the hyperdense vessel sign. Multivariate linear regression analysis was used to investigate the association of the Alberta Stroke Program Early CT score (ASPECTS) with prior contrast administration, time from symptom onset (TFSO), and CTP ischemic core volume in both directly admitted and transferred patients. Results: We included 161 patients, with 62 (39%) transferred and 99 (62%) directly admitted patients. Compared between these groups, transferred patients had a longer TFSO-to-imaging at our institution (median: 212 vs. 75 min, p < 0.001) and lower ASPECTS (median: 8 vs. 9, p < 0.001). Regression analysis presented an independent association of ASPECTS with prior contrast administration (β = −0.25, p = 0.004) but not with TFSO (β = −0.03, p = 0.65). Intergroup comparison between transferred and directly admitted patients pointed toward a stronger association between ASPECTS and CTP ischemic core volume in transferred patients (β = −0.39 vs. β = −0.58, p = 0.06). Detectability of the hyperdense vessel sign was substantially lower after transfer (66 vs. 10%, p < 0.001). Conclusion: Imaging alterations due to residual IV contrast are frequent in clinical practice and render the hyperdense vessel sign largely indetectable. Larger studies are needed to clarify the influence on the association between ASPECTS and ischemic core

SPL7013 Gel (VivaGel®) Retains Potent HIV-1 and HSV-2 Inhibitory Activity following Vaginal Administration in Humans

SPL7013 Gel (VivaGel®) is a microbicide in development for prevention of HIV and HSV. This clinical study assessed retention and duration of antiviral activity following vaginal administration of 3% SPL7013 Gel in healthy women. Participants received 5 single doses of product with ≥5 days between doses. A cervicovaginal fluid (CVF) sample was collected using a SoftCup™ pre-dose, and immediately, or 1, 3, 12 or 24 h post-dose. HIV-1 and HSV-2 antiviral activities of CVF samples were determined in cell culture assays. Antiviral activity in the presence of seminal plasma was also tested. Mass and concentration of SPL7013 in CVF samples was determined. Safety was assessed by reporting of adverse events. Statistical analysis was performed using the Wilcoxon signed-rank test with Bonferroni adjustment; p≤0.003 was significant. Eleven participants completed the study. Inhibition of HIV-1 and HSV-2 by pre-dose CVF samples was negligible. CVF samples obtained immediately after dosing almost completely inhibited (median, interquartile range) HIV-1 [96% (95,97)] and HSV-2 [86% (85,94)], and activity was maintained in all women at 3 h (HIV-1 [96% (95,98), p = 0.9]; HSV-2 [94% (91,97), p = 0.005]). At 24 h, >90% of initial HIV-1 and HSV-2 inhibition was maintained in 6/11 women. SPL7013 was recovered in CVF samples obtained at baseline (46% of 105 mg dose). At 3 and 24 h, 22 mg and 4 mg SPL7013, respectively, were recovered. More than 70% inhibition of HIV-1 and HSV-2 was observed if there was >0.5 mg SPL7013 in CVF samples. High levels of antiviral activity were retained in the presence of seminal plasma. VivaGel was well tolerated with no signs or symptoms of vaginal, vulvar or cervical irritation reported. Potent antiviral activity was observed against HIV-1 and HSV-2 immediately following vaginal administration of VivaGel, with activity maintained for at least 3 h post-dose. The data provide evidence of antiviral activity in a clinical setting, and suggest VivaGel could be administered up to 3 h before coitus

LC-MS/MS bioanalysis of loratadine (Claritin) in dried blood spot (DBS) samples collected by subjects in a clinical research study

A high-performance liquid chromatography-tandem mass spectrometric (LC-MS/MS) method has been developed and validated for the quantitative analysis of loratadine, an H1 histamine antagonist, in human dried blood spot (DBS) samples following a single self-administered 20 mg oral dose. The samples were produced by spotting approximately 30 μl of whole blood onto PE-226 cards. Two 3 mm discs were cut from the DBS samples and extracted using aqueous methanol containing the internal standard. After transfer and drying of the sample extract, the reconstituted residues were chromatographed using a Waters XSelect C18 column and isocratic elution for MS/MS detection. The possible impacts due to hematocrit, volume of blood sample, storage temperature, and humidity, on the accuracy of measured DBS results were investigated. The results showed that only the spotted blood volume had a significant impact; a small volume (10 µl) tended to give more negative bias in the measured value. The current method was fully validated over the range of 0.200 to 20.0 ng/ml with correlation coefficients (r2) for three validation batches equal to or better than 0.991. The intraday accuracy and precision at the LLOQs were -11.5 to 0.0 % bias and 6.4 to 8.9 % CV, respectively. For the other QC samples (0.600, 3.00, 10.0 and 15.0 ng/mL), the precision ranged from 4.2 to 9.8% CV and from 6.3 to 8.1% CV, respectively, in the intra-day and interday evaluations; the accuracy ranged from -1.7 to 10.0% and 2.7 to 5.3% bias, respectively, in the intra-day and inter-day batches. Loratadine is stable in the DBS samples for at least 271 days at ambient temperature in a desiccator and for at least 24 hrs at 60C or under 80% relative humidity, followed by re-conditioning at ambient temperature in a desiccator. The current methodology has been applied to determine the loratadine levels in DBS samples collected by subjects in a clinical study to evaluate pharmacokinetic sampling in point-of-care setting

Liquid Microjunction Surface Sampling-HPLC-MS/MS Profiling of Acetaminophen, Terfenadine and Their Metabolites in Whole-Body Rat Thin Tissue Sections

ABSTRACT Background: The aim of this work was to evaluate the analytical performance of a fully automated droplet-based surface sampling system utilizing a commercially available autosampler coupled with high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for determining the distribution of drugs acetaminophen (APAP) and terfenadine (TER), and their metabolites in rat thin tissue sections. Results: The mass spectral peak areas recorded were used to create heatmaps of APAP and TER and their respective metabolites sampled from dosed rat whole-body thin tissue sections. The rank order of APAP concentration observed in tissues was stomach > small intestine > liver, while the concentrations of its glucuronide and sulphate metabolites were greatest in the liver and small intestine. TER was most concentrated in the liver and kidney while its major metabolite fexofenadine was found in the liver and small intestine. Conclusion: The spatial distributions of both drugs and their respective metabolites observed in this work were consistent with previous studies using radiolabeled drugs. Specifically, the rank order of APAP distribution found by liquid extraction-based surface sampling was identical to that determined by radio thin layer chromatography (RTLC) in rats. Likewise, the distribution of unchanged TER was in good agreement with results obtained by quantitative whole-body autoradiography (QWBA)

Comparison of Clostripain and Neutral Protease as Supplementary Enzymes for Human Islet Isolation

Although human islet transplantation has been established as valid and safe treatment for patients with type 1 diabetes, the utilization rates of human pancreases for clinical islet transplantation are still limited and substantially determined by the quality and composition of collagenase blends. While function and integrity of collagenase has been extensively investigated, information is still lacking about the most suitable supplementary neutral proteases. The present study compared islet isolation outcome after pancreas digestion by means of collagenase used alone or supplemented with either neutral protease (NP), clostripain (CP), or both proteases. Decent amounts of islet equivalents (IEQ) were isolated using collagenase alone (3090 +/- 550 IEQ/g), or in combination with NP (2340 +/- 450 IEQ/g) or CP (2740 +/- 280 IEQ/g). Nevertheless, the proportion of undigested tissue was higher after using collagenase alone (21.1 +/- 1.1%, P &lt; 0.05) compared with addition of NP (13.3 +/- 2.2%) or CP plus NP (13.7 +/- 2.6%). Likewise, the percentage of embedded islets was highest using collagenase only (13 +/- 2%) and lowest adding NP plus CP (4 +/- 1%, P &lt; 0.01). The latter combination resulted in lowest post-culture overall survival (42.7 +/- 3.9%), while highest survival was observed after supplementation with CP (74.5 +/- 4.8%, P &lt; 0.01). An insulin response toward glucose challenge was present in all experimental groups, but the stimulation index was significantly decreased using collagenase plus NP (2.0 +/- 0.12) compared with supplementation with CP (3.16 +/- 0.4, P &lt; 0.001). This study demonstrates for the first time that it is possible to isolate significant numbers of human islets combining collagenase only with CP. The supplementation with CP is an effective means to substantially reduce NP activity, which significantly decreases survival and viability after culture. This will facilitate the manufacturing of enzyme blends with less harmful characteristics

Liquid microjunction surface sampling of acetaminophen, terfenadine and their metabolites in thin tissue sections

Background: The aim of this work was to evaluate the analytical performance of a fully automated droplet-based surface-sampling system for determining the distribution of the drugs acetaminophen and terfenadine, and their metabolites, in rat thin tissue sections. Results: The rank order of acetaminophen concentration observed in tissues was stomach > small intestine > liver, while the concentrations of its glucuronide and sulfate metabolites were greatest in the liver and small intestine. Terfenadine was most concentrated in the liver and kidney, while its major metabolite, fexofenadine, was found in the liver and small intestine. Conclusion: The spatial distributions of both drugs and their respective metabolites observed in this work were consistent with previous studies using radiolabeled drugs

An integrated outsourcing practice of nonclinical LC-MS bioanalysis and toxicokinetics at Novartis small molecule drug development

With decommissioning of internal regulated bioanalytical (BA) and toxicokinetic (TK) capabilities, Novartis has relied on external service providers (ESPs) for all nonclinical LC-MS BA and majority of the associated TK work since 2017. This paper outlines an integrated outsourcing practice of the Novartis nonclinical LC-MS BA/TK group, which covers the roles and responsibilities of Novartis nonclinical LC-MS BA/TK expert scientific monitors, selection of ESPs for Novartis nonclinical LC-MS BA/TK studies, qualification of BA/TK ESPs, study conduct and completion, ESP oversight and evaluation, issue mitigation, and future perspectives

WTAQ, a computer program for calculating drawdowns and estimating hydraulic properties for confined and water-table aquifers /

Shipping list no.: 2000-0088-P."A product of the Ground Water Resources Program."Includes bibliographical references (p. 36-37).Mode of access: Internet