Development of non-destructive methodology using ATR-FTIR with PCA to differentiate between historical Pacific barkcloth

Barkcloths, non-woven textiles originating from the Pacific Islands, form part of many museum collections and date back to the 18th and 19th centuries. The ability to determine different plant species which have been used for producing barkcloth is required by art historians to help understand the origin and use of the cloths and by conservators for whom the species type may have an impact on textile durability, deterioration and hence conservation. However, to date the development of a non-destructive, robust analytical technique has been elusive. This article describes the use of Fourier transform infrared spectroscopy with attenuated total reflection (ATR-FTIR) and principal component analysis (PCA) todifferentiation between historic barkcloths. Three distinct groups of historic cloths were identified using PCA of the FTIR region between 1200 and 1600 cm−1 where molecular vibrations associated with tannins and lignins are dominant. Analysis of contemporary cloths only identified Pipturus albidus cloth as different and highlighted the difficulties around producing a representative textile sample to mimic the historic cloths. While the methodology does not itself identify species, the use of historically well-provenanced samples allows cloths showing similarities to group together and is a significant aid to identification

Linguistic Biases in Letters of Recommendation Written for Rheumatology Fellowship Applicants

Our study aimed to investigate for implicit linguistic biases in letters of recommendation written for applicants applying to our rheumatology program, and to determine if differences in gender and race exist between the applicants. Additionally, we wanted to compare these results to the gender, race, academic rank, and position of the letter writers. We found that among the preliminary 50 letters, they showed that our letters seemed to show the opposite trends than other published studies. We anticipate the need for further study, and look forward to the results

Siderocalin (Lcn 2) Also Binds Carboxymycobactins, Potentially Defending against Mycobacterial Infections through Iron Sequestration

SummarySiderocalin, a member of the lipocalin family of binding proteins, is found in neutrophil granules, uterine secretions, and at markedly elevated levels in serum and synovium during bacterial infection; it is also secreted from epithelial cells in response to inflammation or tumorigenesis. Identification of high-affinity ligands, bacterial catecholate-type siderophores (such as enterochelin), suggested a possible function for siderocalin: an antibacterial agent, complementing the general antimicrobial innate immune system iron-depletion strategy, sequestering iron as ferric siderophore complexes. Supporting this hypothesis, siderocalin is a potent bacteriostatic agent in vitro under iron-limiting conditions and, when knocked out, renders mice remarkably susceptible to bacterial infection. Here we show that siderocalin also binds soluble siderophores of mycobacteria, including M. tubercu losis: carboxymycobactins. Siderocalin employs a degenerate recognition mechanism to cross react with these dissimilar types of siderophores, broadening the potential utility of this innate immune defense

Treatment decision-making and the form of risk communication: results of a factorial survey

BACKGROUND: Prospective users of preventive therapies often must evaluate complex information about therapeutic risks and benefits. The purpose of this study was to evaluate the effect of relative and absolute risk information on patient decision-making in scenarios typical of health information for patients. METHODS: Factorial experiments within a telephone survey of the Michigan adult, non-institutionalized, English-speaking population. Average interview lasted 23 minutes. Subjects and sample design: 952 randomly selected adults within a random-digit dial sample of Michigan households. Completion rate was 54.3%. RESULTS: When presented hypothetical information regarding additional risks of breast cancer from a medication to prevent a bone disease, respondents reduced their willingness to recommend a female friend take the medication compared to the baseline rate (66.8% = yes). The decrease was significantly greater with relative risk information. Additional benefit information regarding preventing heart disease from the medication increased willingness to recommend the medication to a female friend relative to the baseline scenario, but did not differ between absolute and relative risk formats. When information about both increased risk of breast cancer and reduced risk of heart disease were provided, typical respondents appeared to make rational decisions consistent with Expected Utility Theory, but the information presentation format affected choices. Those 11% – 33% making decisions contrary to the medical indications were more likely to be Hispanic, older, more educated, smokers, and to have children in the home. CONCLUSIONS: In scenarios typical of health risk information, relative risk information led respondents to make non-normative decisions that were "corrected" when the frame used absolute risk information. This population sample made generally rational decisions when presented with absolute risk information, even in the context of a telephone interview requiring remembering rates given. The lack of effect of gender and race suggests that a standard strategy of presenting absolute risk information may improve patient decision-making

Ontogeny of Recognition Specificity and Functionality for the Broadly Neutralizing Anti-HIV Antibody 4E10

The process of antibody ontogeny typically improves affinity, on-rate, and thermostability, narrows polyspecificity, and rigidifies the combining site to the conformer optimal for binding from the broader ensemble accessible to the precursor. However, many broadly-neutralizing anti-HIV antibodies incorporate unusual structural elements and recognition specificities or properties that often lead to autoreactivity. The ontogeny of 4E10, an autoreactive antibody with unexpected combining site flexibility, was delineated through structural and biophysical comparisons of the mature antibody with multiple potential precursors. 4E10 gained affinity primarily by off-rate enhancement through a small number of mutations to a highly conserved recognition surface. Controverting the conventional paradigm, the combining site gained flexibility and autoreactivity during ontogeny, while losing thermostability, though polyspecificity was unaffected. Details of the recognition mechanism, including inferred global effects due to 4E10 binding, suggest that neutralization by 4E10 may involve mechanisms beyond simply binding, also requiring the ability of the antibody to induce conformational changes distant from its binding site. 4E10 is, therefore, unlikely to be re-elicited by conventional vaccination strategies

Autotaxin, bile acid profile and effect of ileal bile acid transporter inhibition in primary biliary cholangitis patients with pruritus

Background and Aims Pruritus is a common symptom in patients with primary biliary cholangitis (PBC) for which ileal bile acid transporter (IBAT) inhibition is emerging as a potential therapy. We explored the serum metabonome and gut microbiota profile in PBC patients with pruritus and investigated the effect of GSK2330672, an IBAT inhibitor. Methods We studied fasting serum bile acids (BAs), autotaxin and faecal microbiota in 22 PBC patients with pruritus at baseline and after 2 weeks of GSK2330672 treatment. Control group included 31 asymptomatic PBC patients and 18 healthy volunteers. BA profiling was done by ultra performance liquid chromatography coupled to a mass spectrometry (UPLC‐MS). Faecal microbiomes were analysed by 16S ribosomal RNA gene sequencing. Results \ud In PBC patients with pruritus, serum levels of total and glyco‐conjugated primary BAs and autotaxin were significantly elevated. Autotaxin activity correlated significantly with tauro‐ and glyco‐conjugated cholic acid (CA) and chenodeoxycholic acid (CDCA), both at baseline and after GSK2330672. GSK2330672 significantly reduced autotaxin and all tauro‐ and glyco‐ conjugated BAs and increased faecal levels of CA (P = 0.048) and CDCA (P = 0.027). Gut microbiota of PBC patients with pruritus was similar to control groups. GSK2330672 increased the relative abundance of Firmicutes (P = 0.033) and Clostridia (P = 0.04) and decreased Bacteroidetes (P = 0.033) and Bacteroidia (P = 0.04). Conclusions Pruritus in PBC does not show a distinct gut bacterial profile but is associated with elevated serum bile acid and autotaxin levels which decrease after IBAT inhibition. In cholestatic pruritus, a complex interplay between BAs and autotaxin is likely and may be modified by IBAT inhibition

Technical note: development of a 3D printed subresolution sandwich phantom for validation of brain SPECT analysis

Purpose: To make an adaptable, head shaped radionuclide phantom to simulate molecular imaging of the brain using clinical acquisition and reconstruction protocols. This will allow the characterization and correction of scanner characteristics, and improve the accuracy of clinical image analysis, including the application of databases of normal subjects. Methods: A fused deposition modeling 3D printer was used to create a head shaped phantom made up of transaxial slabs, derived from a simulated MRI dataset. The attenuation of the printed polylactide (PLA), measured by means of the Hounsfield unit on CT scanning, was set to match that of the brain by adjusting the proportion of plastic filament and air (fill ratio). Transmission measurements were made to verify the attenuation of the printed slabs. The radionuclide distribution within the phantom was created by adding 99mTc pertechnetate to the ink cartridge of a paper printer and printing images of gray and white matter anatomy, segmented from the same MRI data. The complete subresolution sandwich phantom was assembled from alternate 3D printed slabs and radioactive paper sheets, and then imaged on a dual headed gamma camera to simulate an HMPAO SPECT scan. Results: Reconstructions of phantom scans successfully used automated ellipse fitting to apply attenuation correction. This removed the variability inherent in manual application of attenuation correction and registration inherent in existing cylindrical phantom designs. The resulting images were assessed visually and by count profiles and found to be similar to those from an existing elliptical PMMA phantom. Conclusions: The authors have demonstrated the ability to create physically realistic HMPAO SPECT simulations using a novel head-shaped 3D printed subresolution sandwich method phantom. The phantom can be used to validate all neurological SPECT imaging applications. A simple modification of the phantom design to use thinner slabs would make it suitable for use in PET