Integrating isotopes and documentary evidence : dietary patterns in a late medieval and early modern mining community, Sweden

We would like to thank the Archaeological Research Laboratory, Stockholm University, Sweden and the Tandem Laboratory (Ångström Laboratory), Uppsala University, Sweden, for undertaking the analyses of stable nitrogen and carbon isotopes in both human and animal collagen samples. Also, thanks to Elin Ahlin Sundman for providing the δ13C and δ15N values for animal references from Västerås. This research (Bäckström’s PhD employment at Lund University, Sweden) was supported by the Berit Wallenberg Foundation (BWS 2010.0176) and Jakob and Johan Söderberg’s foundation. The ‘Sala project’ (excavations and analyses) has been funded by Riksens Clenodium, Jernkontoret, Birgit and Gad Rausing’s Foundation, SAU’s Research Foundation, the Royal Physiographic Society of Lund, Berit Wallenbergs Foundation, Åke Wibergs Foundation, Lars Hiertas Memory, Helge Ax:son Johnson’s Foundation and The Royal Swedish Academy of Sciences.Peer reviewedPublisher PD

A high confidence, manually validated human blood plasma protein reference set

<p>Abstract</p> <p>Background</p> <p>The immense diagnostic potential of human plasma has prompted great interest and effort in cataloging its contents, exemplified by the Human Proteome Organization (HUPO) Plasma Proteome Project (PPP) pilot project. Due to challenges in obtaining a reliable blood plasma protein list, HUPO later re-analysed their own original dataset with a more stringent statistical treatment that resulted in a much reduced list of high confidence (at least 95%) proteins compared with their original findings. In order to facilitate the discovery of novel biomarkers in the future and to realize the full diagnostic potential of blood plasma, we feel that there is still a need for an ultra-high confidence reference list (at least 99% confidence) of blood plasma proteins.</p> <p>Methods</p> <p>To address the complexity and dynamic protein concentration range of the plasma proteome, we employed a linear ion-trap-Fourier transform (LTQ-FT) and a linear ion trap-Orbitrap (LTQ-Orbitrap) for mass spectrometry (MS) analysis. Both instruments allow the measurement of peptide masses in the low ppm range. Furthermore, we employed a statistical score that allows database peptide identification searching using the products of two consecutive stages of tandem mass spectrometry (MS3). The combination of MS3 with very high mass accuracy in the parent peptide allows peptide identification with orders of magnitude more confidence than that typically achieved.</p> <p>Results</p> <p>Herein we established a high confidence set of 697 blood plasma proteins and achieved a high 'average sequence coverage' of more than 14 peptides per protein and a median of 6 peptides per protein. All proteins annotated as belonging to the immunoglobulin family as well as all hypothetical proteins whose peptides completely matched immunoglobulin sequences were excluded from this protein list. We also compared the results of using two high-end MS instruments as well as the use of various peptide and protein separation approaches. Furthermore, we characterized the plasma proteins using cellular localization information, as well as comparing our list of proteins to data from other sources, including the HUPO PPP dataset.</p> <p>Conclusion</p> <p>Superior instrumentation combined with rigorous validation criteria gave rise to a set of 697 plasma proteins in which we have very high confidence, demonstrated by an exceptionally low false peptide identification rate of 0.29%.</p

Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee

<p>Abstract</p> <p>Background</p> <p>Extracts of chicory root have anti-inflammatory properties <it>in vitro </it>and in animal models of arthritis. The primary objective of this investigator-initiated, Phase 1, placebo-controlled, double blind, dose-escalating trial was to determine the safety and tolerability of a proprietary bioactive extract of chicory root in patients with osteoarthritis (OA). Secondary objectives were to assess effects on the signs and symptoms of this disorder.</p> <p>Methods</p> <p>Individuals greater than 50 years of age with OA of the hip or knee were eligible for trial entry. A total of 40 patients were enrolled in 3 cohorts and were treated with escalating chicory doses of 600 mg/day, 1200 mg/day and 1800 mg/day for 1 month. The ratio of active treatment to placebo was 5:3 in cohorts 1 and 2 (8 patients) each and 16:8 in cohort 3 (24 patients). Safety evaluations included measurement of vital signs and routine lab tests at baseline and the end of the treatment period. Efficacy evaluations at baseline and final visits included self-assessment questionnaires and measurement of the 25-foot walking time.</p> <p>Results</p> <p>In the highest dose cohort, 18 patients who completed treatment per protocol were analyzed for efficacy. In this group, 13 patients showed at least 20% improvement in the defined response domains of pain, stiffness and global assessment: 9 of 10 (90%) patients randomized to active treatment with chicory and 4 of 8 (50%) patients randomized to placebo (P = 0.06). In general, the treatment was well-tolerated. Only one patient who was treated with the highest dose of chicory had to discontinue treatment due to an adverse event.</p> <p>Conclusions</p> <p>The results of this pilot study suggest that a proprietary bioactive extract of chicory root has a potential role in the management of OA and merits further investigation. Clinicaltrials.gov identifier: NCT 01010919.</p

How robust are value judgements of health inequality aversion? Testing for framing and cognitive effects

Background: Empirical studies have found that members of the public are inequality averse and value health gains for disadvantaged groups with poor health many times more highly than gains for better off groups. However, these studies typically use abstract scenarios that involve unrealistically large reductions in health inequality, and face-to-face survey administration. It is not known how robust these findings are to more realistic scenarios or anonymous online survey administration. Methods: This study aimed to test the robustness of questionnaire estimates of inequality aversion by comparing the following: (1) small versus unrealistically large health inequality reductions; (2) population-level versus individual-level descriptions of health inequality reductions; (3) concrete versus abstract intervention scenarios; and (4) online versus face to face mode of administration. Fifty-two members of the public participated in face-to-face discussion groups, while 83 members of the public completed an online survey. Participants were given a questionnaire instrument with different scenario descriptions for eliciting aversion to social inequality in health. Results: The median respondent was inequality averse under all scenarios. Scenarios involving small rather than unrealistically large health gains made little difference in terms of inequality aversion, as did population-level rather than individual-level scenarios. However, the proportion expressing extreme inequality aversion fell 19 percentage points when considering a specific health intervention scenario rather than an abstract scenario, and was 11-21 percentage points lower among online public respondents compared to the discussion group. Conclusions: Our study suggests that both concrete scenarios and online administration reduce the proportion expressing extreme inequality aversion but still yield median responses implying substantial health inequality aversion

Model studies of dense water overflows in the Faroese Channels Topical Collection on the 5th International Workshop on Modelling the Ocean (IWMO) in Bergen, Norway 17-20 June 2013

The overflow of dense water from the Nordic Seas through the Faroese Channel system was investigated through combined laboratory experiments and numerical simulations using the Massachusetts Institute of Technology General Circulation Model. In the experimental study, a scaled, topographic representation of the Faroe-Shetland Channel, Wyville-Thomson Basin and Ridge and Faroe Bank Channel seabed bathymetry was constructed and mounted in a rotating tank. A series of parametric experiments was conducted using dye-tracing and drogue-tracking techniques to investigate deep-water overflow pathways and circulation patterns within the modelled region. In addition, the structure of the outflowing dense bottom water was investigated through density profiling along three cross-channel transects located in the Wyville-Thomson Basin and the converging, up-sloping approach to the Faroe Bank Channel. Results from the dye-tracing studies demonstrate a range of parametric conditions under which dense water overflow across the Wyville-Thomson Ridge is shown to occur, as defined by the Burger number, a non-dimensional length ratio and a dimensionless dense water volume flux parameter specified at the Faroe-Shetland Channel inlet boundary. Drogue-tracking measurements reveal the complex nature of flow paths and circulations generated in the modelled topography, particularly the development of a large anti-cyclonic gyre in the Wyville-Thompson Basin and up-sloping approach to the Faroe Bank Channel, which diverts the dense water outflow from the Faroese shelf towards the Wyville-Thomson Ridge, potentially promoting dense water spillage across the ridge itself. The presence of this circulation is also indicated by associated undulations in density isopycnals across the Wyville-Thomson Basin. Numerical simulations of parametric test cases for the main outflow pathways and density structure in a similarly-scaled Faroese Channels model domain indicate excellent qualitative agreement with the experimental observations and measurements. In addition, the comparisons show that strong temporal variability in the predicted outflow pathways and circulations have a strong influence in regulating the Faroe Bank Channel and Wyville-Thomson Ridge overflows, as well as in determining the overall response in the Faroese Channels to changes in the Faroe-Shetland Channel inlet boundary conditions. © 2014 Springer-Verlag Berlin Heidelberg

Emerging Concepts for Pelvic Organ Prolapse Surgery: What is Cure?

The objective of this review is to discuss emerging concepts in pelvic organ prolapse, in particular, “What is cure?” In a post-trial data analysis of the CARE (Colpopexy and Urinary Reduction Efforts) trial, treatment success varied tremendously depending on the definition used (19.2%–97.2%). Definitions that included the absence of vaginal bulge symptoms had the strongest relationships with the patients’ assessment of overall improvement and treatment success. As demonstrated by this study, there are several challenges in defining cure in prolapse surgery. Additionally, the symptoms of prolapse are variable. The degree of prolapse does not correlate directly with symptoms. There are many surgical approaches to pelvic organ prolapse. Multiple ways to quantify prolapse are used. There is a lack of standardized definition of cure. The data on prolapse surgery outcomes are heterogeneous. The goal of surgical repair is to return the pelvic organs to their original anatomic positions. Ideally, we have four main goals: no anatomic prolapse, no functional symptoms, patient satisfaction, and the avoidance of complications. The impact of transvaginal mesh requires thoughtful investigation. The driving force should be patient symptoms in defining cure of prolapse

Body size in early life and risk of epithelial ovarian cancer: results from the Nurses' Health Studies

Adult body mass index (BMI) has been associated with ovarian cancer risk, but few studies have examined body size earlier in life. We prospectively examined associations of body fatness at ages 5 and 10, BMI at age 18, height, and birthweight with risk of epithelial ovarian cancer in the Nurses' Health Study (NHS: 110 311 women, 735 cases) and Nurses' Health Study II (NHSII: 113 059 women, 137 cases). Cox proportional hazards regression was used to estimate relative risks (RRs) and 95% confidence intervals (CIs). There was a weak inverse association between average body fatness at ages 5 and 10 and risk in the NHS (RR for heaviest vs most lean=0.81, 95% CI: 0.53–1.24, P for trend=0.04) and a nonsignificant positive association in the NHSII (RR=2.09, 95% CI: 0.98–4.48, P for trend=0.10), possibly due to differences in age and menopausal status. Height was positively associated with risk in both cohorts (RR for ⩾1.75 vs <1.6 m=1.43, 95% CI: 1.05–1.96, P for trend=0.001). Body mass index at the age of 18 years and birthweight were not associated with risk. Further research should examine the biological mechanisms underlying the observed associations

An Event-Related fMRI Study of Phonological Verbal Working Memory in Schizophrenia

Background: While much is known about the role of prefrontal cortex (PFC) in working memory (WM) deficits of schizophrenia, the nature of the relationship between cognitive components of WM and brain activation patterns remains unclear. We aimed to elucidate the neural correlates of the maintenance component of verbal WM by examining correct and error trials with event-related fMRI. Methodology/Findings: Twelve schizophrenia patients (SZ) and thirteen healthy control participants (CO) performed a phonological delayed-matching-to-sample-task in which a memory set of three nonsense words was presented, followed by a 6-seconds delay after which a probe nonsense word appeared. Participants decided whether the probe matched one of the targets, and rated the confidence of their decision. Blood-oxygen-level-dependent (BOLD) activity during WM maintenance was analyzed in relation to performance (correct/error) and confidence ratings. Frontal and parietal regions exhibited increased activation on correct trials for both groups. Correct and error trials were further segregated into true memory, false memory, guess, and true error trials. True memory trials were associated with increased bilateral activation of frontal and parietal regions in both groups but only CO showed deactivation in PFC. There was very little maintenancerelated cortical activity during guess trials. False memory was associated with increased left frontal and parietal activation in both groups. Conclusion: These findings suggest that a wider network of frontal and parietal regions support WM maintenance in correct trials compared with error trials in both groups. Furthermore, a more extensive and dynamic pattern of recruitment of the frontal and parietal networks for true memory was observed in healthy controls compared with schizophrenia patients. These results underscore the value of parsing the sources of memory errors in fMRI studies because of the non-linear nature of the brain-behavior relationship, and suggest that group comparisons need to be interpreted in more specific behavioral contexts