2,589 research outputs found

    Prohibition on research involving psychiatric patients subject to coercion

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    This paper compares legislation on clinical research conducted on patients subject to coercion in the Scandinavian countries and the UK, examines it from a human rights perspective, and problematizes the Danish legal model as the only one employing a total ban on this kind of research. Reference is made to the consequences to evidence-based psychiatric care improvements and international ethical principle statements generally entitling psychiatric patients to treatment under similar ethical and scientific conditions as patients with other illnesses, given the absolute premise that the patient does not object to research participation and always retains the right to withdraw

    The vegetation history of an Amazonian domed peatland

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    The peatland pole forests of the Pastaza-Marañón Foreland Basin (PMFB), Peru, are the most carbon-dense ecosystems known in Amazonia once below ground carbon stores are taken into account. Here we present the first multiproxy palaeoenvironmental record including pollen data from one of these peatlands, San Jorge in northern Peru, supported by an age model based on radiocarbon and 210Pb dating. The pollen data indicate that vegetation changes during the early phases of peat initiation resulted from autogenic succession in combination with fluvial influence. The overall pattern of vegetation change is not straightforward: the record does not reflect a process of unidirectional, progressive terrestrialization, but includes a reversal in the succession and vegetation transitions, which omit predicted successional phases. This complexity is similar to that seen in the only other existing pollen record from a PMFB peatland, at Quistococha, but contrasts with peat records from Panama and Southeast Asia where successional patterning appears more predictable. Our dating results provide the first evidence from a PMFB peatland that peat accumulation may have been discontinuous, with evidence for reduced rates of peat accumulation, or a possible hiatus, around 1300–400 cal yr BP. An ecological shift from open lake to palm swamp occurs at this time, possibly driven by climatic change. The pollen data indicate that the present pole forest vegetation at San Jorge began to assemble c. 200–150 cal yr BP. Given this young age, it is likely that the pole forest at this site remains in a state of transition

    The 10,000- year biocultural history of fallow deer and its implications for conservation policy

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    This is the final version. Available on open access from the National Academy of Sciences via the DOI in this recordData, Materials, and Software Availability: Genetics data have been deposited in GenBank (https://www.ncbi.nlm.nih.gov/nuccore (35, 36): H1 OR220344 H2 OR220345 H3 OR220346 H4 OR220347 H5 OR220348 H6 OR220349 H7 OR220350 H8 OR220351 H9 OR220352 H10 OR220353 H11 OR220354 H12 OR220355 H13 OR220356 H14 OR220357 H15 OR220358 H16 OR220359 H17 OR220360 H18 OR220361 H19 OR220362 H20 OR220363 H21 OR220364 H22 OR220365 H23 OR220366 H24 OR220367 H25 OR220368 H26 OR220369 H27 OR220370 H28 OR220371 H29 OR220372 H30 OR220373 H31 OR220374 H32 OR220375 H33 OR220376 H34 OR220377 H35 OR220378 H36 OR220379 H37 OR220380 H38 OR220381 H39 OR220382 H40 OR220383 H41 OR220384 H42 OR220385 H43 OR220386 H44 OR220387 H45 OR220388 H46 OR220389 H47 KY564399.1 1 H48 KY564400.1 2 H49 KY564402.1 4 H50 KY564415.1 17 H51 KY564405.1 7 H52 KY564406.1 8 H53 KY564408.1 10 H54 KY564409.1 11 H55 KY564410.1 12 H56 KY564411.1 13 H57 KY564416.1 18 H58 KY564418.1 20 H59 KY564417.1 19 H60 KY564413.1 15 H61 KY564414.1 16 H62 KY564420.1 22 H63 OR531442 n/a H64 OR531443 n/a H65 KY564422.1 24 H66 KY564421.1 23,25,26 H67 KY564426.1 28 H68 KY564427.1 29 H69 KY564425.1 27 H70 KY564428.1 30,32 H71 KY564432.1 34 H72 KY564431.1 33 Dama mesopotamica XIV AF291896 n/a XV JN632630 n/a XVI OR531435 n/a XVII OR531436 n/a XVIII OR531437 n/a XIX OR531438 n/a XX OR531439 n/a XXI OR531440 n/a XXII OR531441 n/a). All other data are included in the manuscript and/or supporting information.Over the last 10,000 y, humans have manipulated fallow deer populations with varying outcomes. Persian fallow deer (Dama mesopotamica) are now endangered. European fallow deer (Dama dama) are globally widespread and are simultaneously considered wild, domestic, endangered, invasive and are even the national animal of Barbuda and Antigua. Despite their close association with people, there is no consensus regarding their natural ranges or the timing and circumstances of their human- mediated trans-locations and extirpations. Our mitochondrial analyses of modern and archaeological specimens revealed two distinct clades of European fallow deer present in Anatolia and the Balkans. Zooarchaeological evidence suggests these regions were their sole glacial refugia. By combining biomolecular analyses with archaeological and textual evidence, we chart the declining distribution of Persian fallow deer and demonstrate that humans repeatedly translocated European fallow deer, sourced from the most geographically distant populations. Deer taken to Neolithic Chios and Rhodes derived not from nearby Anatolia, but from the Balkans. Though fallow deer were translocated throughout the Mediterranean as part of their association with the Greco- Roman goddesses Artemis and Diana, deer taken to Roman Mallorca were not locally available Dama dama, but Dama mesopotamica. Romans also initially introduced fallow deer to Northern Europe but the species became extinct and was reintroduced in the medieval period, this time from Anatolia. European colonial powers then transported deer populations across the globe. The biocultural histories of fallow deer challenge preconceptions about the divi-sions between wild and domestic species and provide information that should underpin modern management strategiesArts and Humanities Research Council (AHRC)National Environmental Isotope FacilityLeverhulme TrustScience Fund of the Republic of Serbi

    Comparison of Post-injection Site Pain Between Technetium Sulfur Colloid and Technetium Tilmanocept in Breast Cancer Patients Undergoing Sentinel Lymph Node Biopsy

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    BACKGROUND: No prior studies have examined injection pain associated with Technetium-99m Tilmanocept (TcTM). METHODS: This was a randomized, double-blinded study comparing postinjection site pain between filtered Technetium Sulfur Colloid (fTcSC) and TcTM in breast cancer lymphoscintigraphy. Pain was evaluated with a visual analogue scale (VAS) (0–100 mm) and the short-form McGill Pain Questionnaire (SF-MPQ). The primary endpoint was mean difference in VAS scores at 1-min postinjection between fTcSC and TcTM. Secondary endpoints included a comparison of SF-MPQ scores between the groups at 5 min postinjection and construction of a linear mixed effects model to evaluate the changes in pain during the 5-min postinjection period. RESULTS: Fifty-two patients underwent injection (27-fTcSC, 25-TcTM). At 1-min postinjection, patients who received fTcSC experienced a mean change in pain of 16.8 mm (standard deviation (SD) 19.5) compared with 0.2 mm (SD 7.3) in TcTM (p = 0.0002). At 5 min postinjection, the mean total score on the SF-MPQ was 2.8 (SD 3.0) for fTcSC versus 2.1 (SD 2.5) for TcTM (p = 0.36). In the mixed effects model, injection agent (p < 0.001), time (p < 0.001) and their interaction (p < 0.001) were associated with change in pain during the 5-min postinjection period. The model found fTcSC resulted in significantly more pain of 15.2 mm (p < 0.001), 11.3 mm (p = 0.001), and 7.5 mm (p = 0.013) at 1, 2, and 3 min postinjection, respectively. CONCLUSIONS: Injection with fTcSC causes significantly more pain during the first 3 min postinjection compared with TcTM in women undergoing lymphoscintigraphy for breast cancer

    Cell-based expression cloning for identification of polypeptides that hypersensitize mammalian cells to mitotic arrest

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    Microtubule inhibitors such as Vinblastine and Paclitaxel are chemotherapy agents that activate the mitotic spindle checkpoint, arresting cells in mitosis and leading to cell death. The pathways that connect mitotic arrest to cell death are not well characterized. We developed a mammalian cell-based cDNA cloning method to isolate proteins and protein fragments whose expression inhibits colony formation in the presence of microtubule inhibitors. Understanding how these proteins impact cellular responses to microtubule drugs will lead to better understanding of the biochemical pathways connecting mitotic arrest and cell death in mammalian cells and may provide novel targets that can enhance microtubule inhibitor-mediated chemotherapy

    Towards an automated analysis of bacterial peptidoglycan structure.

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    Peptidoglycan (PG) is an essential component of the bacterial cell envelope. This macromolecule consists of glycan chains alternating N-acetylglucosamine and N-acetylmuramic acid, cross-linked by short peptides containing nonstandard amino acids. Structural analysis of PG usually involves enzymatic digestion of glycan strands and separation of disaccharide peptides by reversed-phase HPLC followed by collection of individual peaks for MALDI-TOF and/or tandem mass spectrometry. Here, we report a novel strategy using shotgun proteomics techniques for a systematic and unbiased structural analysis of PG using high-resolution mass spectrometry and automated analysis of HCD and ETD fragmentation spectra with the Byonic software. Using the PG of the nosocomial pathogen Clostridium difficile as a proof of concept, we show that this high-throughput approach allows the identification of all PG monomers and dimers previously described, leaving only disambiguation of 3-3 and 4-3 cross-linking as a manual step. Our analysis confirms previous findings that C. difficile peptidoglycans include mainly deacetylated N-acetylglucosamine residues and 3-3 cross-links. The analysis also revealed a number of low abundance muropeptides with peptide sequences not previously reported. Graphical Abstract The bacterial cell envelope includes plasma membrane, peptidoglycan, and surface layer. Peptidoglycan is unique to bacteria and the target of the most important antibiotics; here it is analyzed by mass spectrometry

    Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

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    BACKGROUND: Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm(3) on small arterial elasticity (SAE) and large artery elasticity (LAE). METHODS: Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. RESULTS: Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm(3) and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. CONCLUSIONS: Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity
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