Effect of Animal and Industrial Trans Fatty Acids on HDL and LDL Cholesterol Levels in Humans – A Quantitative Review

Background: Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA) on blood lipoproteins, and compared these with industrial trans fatty acids. Methodology/Principal Findings: We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95% CI 0.044-0.066) for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95% CI 0.012-0.065) for ruminant trans fatty acids, and 0.043 (95% CI 0.012-0.074) for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids). Conclusions/Significance: Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol

Orbital and spin physics in LiNiO2 and NaNiO2

We derive a spin-orbital Hamiltonian for a triangular lattice of e_g orbital degenerate (Ni^{3+}) transition metal ions interacting via 90 degree superexchange involving (O^{2-}) anions, taking into account the on-site Coulomb interactions on both the anions and the transition metal ions. The derived interactions in the spin-orbital model are strongly frustrated, with the strongest orbital interactions selecting different orbitals for pairs of Ni ions along the three different lattice directions. In the orbital ordered phase, favoured in mean field theory, the spin-orbital interaction can play an important role by breaking the U(1) symmetry generated by the much stronger orbital interaction and restoring the threefold symmetry of the lattice. As a result the effective magnetic exchange is non-uniform and includes both ferromagnetic and antiferromagnetic spin interactions. Since ferromagnetic interactions still dominate, this offers yet insufficient explanation for the absence of magnetic order and the low-temperature behaviour of the magnetic susceptibility of stoichiometric LiNiO_2. The scenario proposed to explain the observed difference in the physical properties of LiNiO_2 and NaNiO_2 includes small covalency of Ni-O-Li-O-Ni bonds inducing weaker interplane superexchange in LiNiO_2, insufficient to stabilize orbital long-range order in the presence of stronger intraplane competition between superexchange and Jahn-Teller coupling.Comment: 33 pages, 12 postscript figures, uses iopams.sty . This article features in New Journal of Physics as part of a Focus Issue on Orbital Physics - all contributions may be freely accessed at (http://stacks.iop.org/1367-2630/6/i=1/a=E05). The published version of this article may be found at http://stacks.iop.org/1367-2630/7/12

Endoscopic tri-modal imaging for surveillance in ulcerative colitis: randomised comparison of high-resolution endoscopy and autofluorescence imaging for neoplasia detection; and evaluation of narrow-band imaging for classification of lesions

Background: Endoscopic tri-modal imaging (ETMI) incorporates white light endoscopy (WLE), autofluorescence imaging (AFI) and narrow-band imaging (NBI). Aims: To assess the value of ETMI for the detection and classification of neoplasia in patients with longstanding ulcerative colitis. Design: Randomised comparative trial of tandem colonoscopies. Setting: Academic Medical Centre Amsterdam, Netherlands. Patients and methods: Fifty patients with ulcerative colitis underwent surveillance colonoscopy with ETMI. Each colonic segment was inspected twice, once with AFI and once with WLE, in random order. All detected lesions were inspected by NBI for Kudo pit pattern analysis and additional random biopsies were taken. Main outcome measures: Neoplasia miss-rates of AFI and WLE, and accuracy of the Kudo classification by NBI. Results: Among patients assigned to inspection with AFI first (n = 25), 10 neoplastic lesions were primarily detected. Subsequent WLE detected no additional neoplasia. Among patients examined with WLE first (n = 25), three neoplastic lesions were detected; subsequent inspection with AFI added three neoplastic lesions. Neoplasia miss-rates for AFI and WLE were 0% and 50% (p = 0.036). The Kudo classification by NBI had a sensitivity and specificity of 75% and 81%; however, all neoplasia was coloured purple on AFI (sensitivity 100%). No additional patients with neoplasia were detected by random biopsies. Conclusion: Autofluorescence imaging improves the detection of neoplasia in patients with ulcerative colitis and decreases the yield of random biopsies. Pit pattern analysis by NBI has a moderate accuracy for the prediction of histology, whereas AFI colour appears valuable in excluding the presence of neoplasia. Trial registration number: ISRCTN0527274

Evaluation of POSSUM for Patients Undergoing Pancreatoduodenectomy

Comparison of operative morbidity rates after pancreatoduodenectomy between units may be misleading because it does not take into account the physiological variable of the condition of the patients. The aim of the present study was to evaluate the Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) for pancreatoduodenectomy patients and to look for risk factors associated with morbidity in a high-volume center. Between January 1993 and April 2006, 652 patients underwent a pancreatoduodenectomy, 502 of them for malignant disease. POSSUM performance was evaluated by assessing the "goodness-of-fit" with the linear analysis method. Overall, 332 of the 652 patients (50.9%) had one or more complication after pancreatoduodenectomy, and 9 patients (1.4%) died. POSSUM had a significant lack of fit using goodness-of-fit analysis. In multivariate analysis, one statistically significant factor associated with morbidity and not incorporated in POSSUM (P < 0.05) was identified: ampulla of Vater adenocarcinoma (OR = 1.73, 95% CI: 1.07-2.80). Overall, there is a lack of calibration of POSSUM among patients who undergo pancreatoduodenectom

Самоподобие массивов сетевых публикаций по компьютерной вирусологии

Описан подход к организации анализа потока тематических публикаций по компьютерной вирусологии, представленных в web-пространстве. Обоснована фрактальная природа информационных потоков, описаны основные алгоритмы, применяемые в процессе исследований, а также приведены прогнозные выводы на основе свойств персистентности временных рядов.Описано підхід до організації аналізу потоку тематичних публікацій з комп’ютерної вірусології, які наведені у web-просторі. Обґрунтовано фрактальну природу інформаційних потоків, описано основні алгоритми, що застосовуються в процесі досліджень, а також наведено прогнозні висновки на базі властивостей персистентності часових рядів.An approach to the organization of the analysis of a thematic publications stream on computer virology, submitted in web-space, is described. The fractal nature of information streams is proved, the basic algorithms used during researches are described and forecasts conclusions on the basis of persistent properties of time series are given

Metal detector by the principle phasemeter

Рассмотрен новый способ обработки сигнала металлоискателя, основанный на измерениях фазы разностного сигнала. Определены преимущества над разработанными металлоискателями имеющих фазометрическую схему. Изучена зависимость фазы разностного сигнала от амплитуды входных сигналов и разности их фаз. Проведен анализ чувствительностей к разности амплитуд входных сигналов и разности фаз. Установлено, что данный металлоискатель обладает большей чувствительности по сравнению с известными разработками и способен детектировать металл при малейшем изменении выходного сигнала первичного преобразователя. Разработана структурная схема для предлагаемого металлоискателя и приведено описание принципа работы

Key challenges in normal tissue complication probability model development and validation:towards a comprehensive strategy

Normal Tissue Complication Probability (NTCP) models can be used for treatment plan optimisation and patient selection for emerging treatment techniques. We discuss and suggest methodological approaches to address key challenges in NTCP model development and validation, including: missing data, non-linear response relationships, multicollinearity between predictors, overfitting, generalisability and the prediction of multiple complication grades at multiple time points. The methodological approaches chosen are aimed to improve the accuracy, transparency and robustness of future NTCP-models. We demonstrate our methodological approaches using clinical data

Comprehensive toxicity risk profiling in radiation therapy for head and neck cancer:A new concept for individually optimised treatment

Background and purpose: A comprehensive individual toxicity risk profile is needed to improve radiation treatment optimisation, minimising toxicity burden, in head and neck cancer (HNC) patients. We aimed to develop and externally validate NTCP models for various toxicities at multiple time points. Materials and methods: Using logistic regression, we determined the relationship between normal tissue irradiation and the risk of 22 toxicities at ten time points during and after treatment in 750 HNC patients. The toxicities involved swallowing, salivary, mucosal, speech, pain and general complaints. Studied pre-dictors included patient, tumour and treatment characteristics and dose parameters of 28 organs. The resulting NTCP models were externally validated in 395 HNC patients. Results: The NTCP models involved 14 organs that were associated with at least one toxicity. The oral cavity was the predominant organ, associated with 12 toxicities. Other important organs included the parotid and submandibular glands, buccal mucosa and swallowing muscles. In addition, baseline toxicity, treatment modality, and tumour site were common predictors of toxicity. The median discrimination performance (AUC) of the models was 0.71 (interquartile range: 0.68-0.75) at internal validation and 0.67 (interquartile range: 0.62-0.71) at external validation. Conclusion: We established a comprehensive individual toxicity risk profile that provides essential insight into how radiation exposure of various organs translates into multiple acute and late toxicities. This comprehensive understanding of radiation-induced toxicities enables a new radiation treatment optimisation concept that balances multiple toxicity risks simultaneously and minimises the overall tox-icity burden for an individual HNC patient who needs to undergo radiation treatment. (C) 2021 The Author(s). Published by Elsevier B.V

An Angiotensin I-Converting Enzyme Mutation (Y465D) Causes a Dramatic Increase in Blood ACE via Accelerated ACE Shedding

Angiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE.HEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE--between Arg1203 and Ser1204--was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another.The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase)