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Showing papers by "Jagiellonian University published in 2006"


Book
19 Jun 2006
TL;DR: The goal of this book is to clarify the role of quantum entanglement in the study of convexity, colours and statistics and to show how this role has changed in the history of science.
Abstract: Preface 1 Convexity, colours and statistics 2 Geometry of probability distributions 3 Much ado about spheres 4 Complex projective spaces 5 Outline of quantum mechanics 6 Coherent states and group actions 7 The stellar representation 8 The space of density matrices 9 Purification of mixed quantum states 10 Quantum operations 11 Duality: maps versus states 12 Density matrices and entropies 13 Distinguishability measures 14 Monotone metrics and measures 15 Quantum entanglement Epilogue Appendices References Index

1,139 citations


Journal ArticleDOI
TL;DR: It is shown that cortical astrocytes in vivo possess a powerful mechanism for rapid vasodilation and are implicated in the control of local microcirculation and suggest that one of their physiological roles is to mediate vasodilated in response to increased neural activity.
Abstract: Local increase in blood flow during neural activity forms the basis for functional brain imaging, but its mechanism remains poorly defined. Here we show that cortical astrocytes in vivo possess a powerful mechanism for rapid vasodilation. We imaged the activity of astrocytes labeled with the calcium (Ca(2+))-sensitive indicator rhod-2 in somatosensory cortex of adult mice. Photolysis of caged Ca(2+) in astrocytic endfeet ensheathing the vessel wall was associated with an 18% increase in arterial cross-section area that corresponded to a 37% increase in blood flow. Vasodilation occurred with a latency of only 1-2 s, and both indomethacin and the cyclooxygenase-1 inhibitor SC-560 blocked the photolysis-induced hyperemia. These observations implicate astrocytes in the control of local microcirculation and suggest that one of their physiological roles is to mediate vasodilation in response to increased neural activity.

1,060 citations


Journal ArticleDOI
TL;DR: Preliminary evidence is provided that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects and in all national cohorts and for all major cancer sites.
Abstract: The frequency of micronuclei (MN) in peripheral blood lymphocytes (PBL) is extensively used as a biomarker of chromosomal damage and genome stability in human populations. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development, although prospective cohort studies are needed to validate MN as a cancer risk biomarker. A total of 6718 subjects from of 10 countries, screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance, were selected from the database of the HUman MicroNucleus (HUMN) international collaborative project and followed up for cancer incidence or mortality. To standardize for the inter-laboratory variability subjects were classified according to the percentiles of MN distribution within each laboratory as low, medium or high frequency. A significant increase of all cancers incidence was found for subjects in the groups with medium (RR = 1.84; 95% CI: 1.28-2.66) and high MN frequency (RR = 1.53; 1.04-2.25). The same groups also showed a decreased cancer-free survival, i.e. P = 0.001 and P = 0.025, respectively. This association was present in all national cohorts and for all major cancer sites, especially urogenital (RR = 2.80; 1.17-6.73) and gastro-intestinal cancers (RR = 1.74; 1.01-4.71). The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects. The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs.

911 citations


Journal ArticleDOI
01 Mar 2006-Immunity
TL;DR: It is shown that ASC- and NALP3-deficient mice also demonstrate an impaired contact hypersensitivity response to the hapten trinitrophenylchloride, suggesting that NALp3 plays a specific role in the caspase-1 activation pathway.

900 citations


Journal ArticleDOI
TL;DR: A full understanding of melanin function, and indeed its role in retarding or promoting the disease state, can only be obtained through a full mapping of key structure-property relationships in the main pigment types.
Abstract: In this article, we review the current state of knowledge concerning the physical and chemical properties of the eumelanin pigment. We examine properties related to its photoprotective functionality, and draw the crucial link between fundamental molecular structure and observable macroscopic behaviour. Where necessary, we also briefly review certain aspects of the pheomelanin literature to draw relevant comparison. A full understanding of melanin function, and indeed its role in retarding or promoting the disease state, can only be obtained through a full mapping of key structure-property relationships in the main pigment types. We are engaged in such an endeavor for the case of eumelanin.

860 citations


Journal ArticleDOI
TL;DR: It is found that the minimum conductivity of order e2/h at the Dirac point (when the electron and hole excitations are degenerate) is associated with a maximum of the Fano factor (the ratio of noise power and mean current).
Abstract: We calculate the mode-dependent transmission probability of massless Dirac fermions through an ideal strip of graphene (length $L$, width $W$, no impurities or defects) to obtain the conductance and shot noise as a function of Fermi energy. We find that the minimum conductivity of order ${e}^{2}/h$ at the Dirac point (when the electron and hole excitations are degenerate) is associated with a maximum of the Fano factor (the ratio of noise power and mean current). For short and wide graphene strips the Fano factor at the Dirac point equals $1/3$, 3 times smaller than for a Poisson process. This is the same value as for a disordered metal, which is remarkable since the classical dynamics of the Dirac fermions is ballistic.

724 citations


Journal ArticleDOI
TL;DR: The authors argue that language selection depends on a set of factors that vary according to the experience of the bilinguals, the demands of the production task, and the degree of activity of the nontarget language.
Abstract: Bilingual speech requires that the language of utterances be selected prior to articulation. Past research has debated whether the language of speaking can be determined in advance of speech planning and, if not, the level at which it is eventually selected. We argue that the reason that it has been difficult to come to an agreement about language selection is that there is not a single locus of selection. Rather, language selection depends on a set of factors that vary according to the experience of the bilinguals, the demands of the production task, and the degree of activity of the nontarget language. We demonstrate that it is possible to identify some conditions that restrict speech planning to one language alone and others that open the process to cross-language influences. We conclude that the presence of language nonselectivity at all levels of planning spoken utterances renders the system itself fundamentally nonselective.

539 citations


Journal Article
TL;DR: The effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels are focused on.
Abstract: Obesity and obesity related diseases are a major public health problem. Recent studies have shown that fat tissue is not a simple energy storage organ, but exerts important endocrine and immune functions. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like TNF-alpha, IL-6, MCP-1 (CCL-2), IL-1. All of those molecules may act on immune cells leading to local and generalized inflammation and may also affect vascular (endothelial) function by modulating vascular nitric oxide and superoxide release and mediating obesity related vascular disorders (including hypertension, diabetes, atherosclerosis, and insulin resistance) but also cancer or non-alcoholic fatty liver diseases. Present review, in a concise form, focuses on the effects of major adipocytokines, characteristic for adipose tissue like leptin, adiponectin, resistin and visfatin on the immune system, particularly innate and adaptive immunity as well as on blood vessels. Macrophages and T cells are populating adipose tissue which develops into almost an organized immune organ. Activated T cells further migrate to blood vessels, kidney, brain and other organs surrounded by infiltrated fat leading to their damage, thus providing a link between metabolic syndrome, inflammation and cardiovascular and other associated disorders. Ceretain treatments may lead to significant changes in adipocytokine levels. For example include beta-2 adrenoreceptor agonists, thiazolidinediones as well as androgens lead to decrease of plasma leptin levels. Moreover future treatments of metabolic system associated disorders should focus on the regulation of adipocytokines and their modes of action.

428 citations


Journal ArticleDOI
01 Sep 2006-Lethaia
TL;DR: The term ‘work of an animal' should be deleted from the code, and ichnotaxa should be based solely on trace fossils as defined herein, and the following emendations are proposed to the International Code of Zoological Nomenclature.
Abstract: The taxonomic treatment of trace fossils needs a uniform approach, independent of the ethologic groups concerned. To this aim, trace fossils are rigorously defined with regard to biological taxa and physical sedimentary structures. Potential ichnotaxobases are evaluated, with morphology resulting as the most important criterion. For trace fossils related to bioerosion and herbivory, substrate plays a key role, as well as composition for coprolites. Size, producer, age, facies and preservation are rejected as ichnotaxobases. Separate names for undertracks and other poorly preserved material should gradually be replaced by ichnotaxa based on well-preserved specimens. Recent traces may be identified using established trace fossil taxa but new names can only be based on fossil material, even if the distinction between recent and fossil may frequently remain arbitrary. It is stressed that ichnotaxa must not be incorporated into biological taxa in systematics. Composite trace fossil structures (complex structures made by the combined activity of two or more species) have no ichnotaxonomic standing but compound traces (complex structures made by one individual tracemaker) may be named separately under certain provisions. The following emendations are proposed to the International Code of Zoological Nomenclature: The term ‘work of an animal' should be deleted from the code, and ichnotaxa should be based solely on trace fossils as defined herein.

427 citations


Journal ArticleDOI
TL;DR: Laparoscopic surgery was found to be clearly superior for patients with a presumable diagnosis of perforated peptic ulcer, acute cholecystitis, appendicitis, or pelvic inflammatory disease.
Abstract: Emergency laparoscopic exploration can be used to identify the causative pathology of acute abdominal pain. Laparoscopic surgery also allows treatment of many intraabdominal disorders. This report was prepared to describe the effectiveness of laparoscopic surgery compared to laparotomy or nonoperative treatment. A panel of European experts in abdominal and gynecological surgery was assembled and participated in a consensus conference using Delphi methods. The aim was to develop evidence-based recommendations for the most common diseases that may cause acute abdominal pain. Laparoscopic surgery was found to be clearly superior for patients with a presumable diagnosis of perforated peptic ulcer, acute cholecystitis, appendicitis, or pelvic inflammatory disease. In the emergency setting, laparoscopy is of unclear or limited value if adhesive bowel obstruction, acute diverticulitis, nonbiliary pancreatitis, hernia incarceration, or mesenteric ischemia are suspected. In stable patients with acute abdominal pain, noninvasive diagnostics should be fully exhausted before considering explorative surgery. However, diagnostic laparoscopy may be useful if no diagnosis can be found by conventional diagnostics. More clinical data are needed on the use of laparoscopy after blunt or penetrating trauma of the abdomen. Due to diagnostic and therapeutic advantages, laparoscopic surgery is useful for the majority of conditions underlying acute abdominal pain, but noninvasive diagnostic aids should be exhausted first. Depending on symptom severity, laparoscopy should be advocated if routine diagnostic procedures have failed to yield results.

347 citations


Journal ArticleDOI
TL;DR: This review summarizes current views on melanogenesis in Pro- and Eukaryotic microorganisms in terms of their biotechnological and biomedical importance.
Abstract: Melanins form a diverse group of pigments synthesized in living organisms in the course of hydroxylation and polymerization of organic compounds. Melanin production is observed in all large taxa from both Pro- and Eukaryota. The basic functions of melanins are still a matter of controversy and speculation, even though their adaptative importance has been proved. Melanogenesis has probably evolved parallel in various groups of free living organisms to provide protection from environmental stress conditions, but in pathogenic microorganisms it correlates with an increased virulence. The genes responsible for melanization are collected in some cases within operons which find a versatile application in genetic engineering. This review summarizes current views on melanogenesis in Pro- and Eukaryotic microorganisms in terms of their biotechnological and biomedical importance.

Journal ArticleDOI
TL;DR: Basic properties of complex Hadamard matrices are reviewed and a catalogue of inequivalent cases known for the dimensions N = 2, 16, 12, 14 and 16 are presented.
Abstract: Complex Hadamard matrices, consisting of unimodular entries with arbitrary phases, play an important role in the theory of quantum information. We review basic properties of complex Hadamard matrices and present a catalogue of inequivalent cases known for the dimensions N = 2,..., 16. In particular, we explicitly write down some families of complex Hadamard matrices for N = 12,14 and 16, which we could not find in the existing literature.

Journal ArticleDOI
TL;DR: Group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid- type CAs.
Abstract: Previous studies have suggested that the frequency of chromosomal aberrations (CAs), but not of sister chromatid exchanges (SCEs), predicts cancer risk. We have further examined this relationship in European cohorts comprising altogether almost 22,000 subjects, in the framework of a European collaborative project (CancerRiskBiomarkers). The present paper gives an overview of some of the results of the project, especially as regards CAs and SCEs. The results confirm that a high level of CAs is associated with an increased risk of cancer and indicate that this association does not depend on the time between CA analysis and cancer detection, i.e., is obviously not explained by undetected cancer. The present evidence indicates that both chromatid-type and chromosome-type CAs predict cancer, even though some data suggest that chromosome-type CAs may have a more pronounced predictive value than chromatid-type CAs. CA frequency appears to predict cancers at various sites, although there seems to be a particular association with gastrointestinal cancers. SCE frequency does not appear to have cancer predictive value, at least partly due to uncontrollable technical variation. A number of genetic polymorphisms of xenobiotic metabolism, DNA repair, and folate metabolism affect the level of CAs and might collectively contribute to the cancer predictivity of CAs. Other factors that may influence the association between CAs and cancer include, e.g., exposure to genotoxic carcinogens and internal generation of genotoxic species. Although the association between CA level and cancer is seen at the group level, an association probably also exists for the individual, although it is not known if an individual approach could be feasible. However, group level evidence should be enough to support the use of CA analysis as a tool in screening programs and prevention policies in occupational and environmental health.

Journal ArticleDOI
TL;DR: In this article, natural origin hydroxyapatite (HAp) was extracted from animal bones by their treatment with hot NaOH solution and carbonate groups and small amounts of magnesium were found, usually not present in the synthetic HAp.
Abstract: Natural origin hydroxyapatite (HAp) was extracted from animal bones by their treatment with hot NaOH solution. The remaining organic material oxidized in air atmosphere at moderate temperatures. In the material of this kind carbonate groups and small amounts of magnesium were found, usually not present in the synthetic HAp. Ca/P ratio in pig cortical bones was higher than that in the stoichiometric (synthetic) material. Fraction of carbonate groups decreased with temperature and CaO appeared at higher temperatures, but structure of hydroxyapatite became preserved even at 1000 °C, the highest temperature applied in this investigation. At temperatures >700 °C crystallite growth became intensive, specific surface area of the powder decreased and compacts of such powder started to shrink. Biological test showed that CAL-72 (human osteosarcoma) cells growth depended on heat treatment temperature of the natural HAp substrate.

Journal ArticleDOI
TL;DR: The correlation between RP-HPLC retention parameter log K (the logarithm of capacity factor K) and various calculated log P data is shown and the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed as well.

Journal ArticleDOI
TL;DR: The results showed that the Young's modulus of pathological erythrocytes was higher than in normal cells, indicating possible changes in the organization of cell cytoskeleton associated with various diseases.

Journal ArticleDOI
TL;DR: In this article, FT-Raman, ATR-IR, and NIR spectroscopy are applied in order to establish new, fast, and nondestructive calibration methods for quantification of lycopene and β-carotene content in tomato fruits and related products.
Abstract: Tomatoes and various products derived from thermally processed tomatoes are major sources of lycopene, but apart from this micronutrient, other carotenoids such as β-carotene also are present in the fruit. They occur in tomato fruits and various tomato products in amounts of 2.62−629.00 (lycopene) and 0.23−2.83 mg/100 g (β-carotene). Standard methods for determining the carotenoid content require the extraction of the analyte as well as other cleanup steps. In this work, FT-Raman, ATR-IR, and NIR spectroscopy are applied in order to establish new, fast, and nondestructive calibration methods for quantification of lycopene and β-carotene content in tomato fruits and related products. The best prediction quality was achieved using a model based on IR spectroscopy (R2 = 0.98 and 0.97, SECV = 33.20 and 0.16 for lycopene and β-carotene, respectively). In spite of the fact that Raman spectra of tomato products show characteristic key bands of the investigated carotenoids, this method gives slightly lower reliab...

Journal ArticleDOI
01 May 2006-Carbon
TL;DR: The high level of viability of the examined cells in contact with the nanotubes, the slight increase of collagen formation, the lack of pro-inflammatory IL-6 cytokine as well as the induction of free radicals confirm a good biocompatibility of nanot tubes, which is similar to that of polysulfone currently used in medicine.

Journal ArticleDOI
TL;DR: In this article, structural and magnetic aspects of polynuclear systems built by the non-rigid octacyanometalate anionic precursors, from zero-dimensional clusters to three-dimensional frameworks, are discussed.

Journal ArticleDOI
TL;DR: Heme oxygenase-1 overexpression increased viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of tumor-bearing mice, suggesting that induction of HO-1 may be detrimental in anti-cancer therapy of melan cancer.
Abstract: Heme oxygenase-1 (HO-1), a cytoprotective enzyme, can be induced in tumors in response to anti-cancer therapies We investigated the role of HO-1 in B16(F10), S91, and Sk-mel188 melanoma cells Overexpression of HO-1 after transduction with adenoviral vectors increased cell proliferation, resistance to oxidative stress generated by H2O2, and angiogenic potential as determined by induction of endothelial cell divisions Likewise, cells stably transfected with HO-1 cDNA (B16-HO-1) showed higher proliferation, stress resistance, and angiogenic activity than the wild-type line (B16-WT) HO-1 overexpression in tumors significantly shortened survival of mice after subcutaneous injection of cancer cells (38 and 22 days for B16-WT and B16-HO-1, respectively; P = 0017) This also resulted in development of more packed tumors, with more melanoma cells, and reduced inflammatory edemas Mice injected with B16-HO-1 had lower levels of tumor necrosis factor and higher serum concentrations of its soluble receptor tumor necrosis factor-RI, whereas tumors overexpressing HO-1 displayed augmented vascularization and stronger production of vascular endothelial growth factor Finally, B16-HO-1 cells injected intravenously formed more metastases in lungs Thus, HO-1 overexpression increased viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of tumor-bearing mice, suggesting that induction of HO-1 may be detrimental in anti-cancer therapy of melanoma

Journal ArticleDOI
TL;DR: The complex treatment of the injured hand at specialist centers allows for shorter treatment duration, improved treatment results, and decreased indirect expenses.
Abstract: Background Hand injuries are considered to be the most frequent body injuries, the treatment of which is of long duration and great community expense. The aim of this study was to define the most frequent causes of hand injury in the investigated materials; the severity of hand injuries and outcome of treatment performed in the typical trauma surgery ward; and overall costs of hand-injury treatment. Methods Between 1987 and 2000, 1199 patients (average age 37.0 years (± 15) were treated for complex hand injuries in II Surgery Clinic in Cracow. Causes, places, and mechanisms of hand injuries were evaluated as were types and duration of treatment. We also estimated also total (direct and indirect) treatment costs. Results Of all hand injuries, 45.3% occurred at home and 19.7% at work. Hand injuries caused by mechanical equipment predominated (34.9%) and were the most severe. Up to 26.7% of injuries occurred after alcohol consumption. Average total treatment time was 76.9 days (± 67). Hand impairment of variable severity was found in 58.5% of patients. Indirect costs constituted a dominant part of overall costs (96%). Conclusions The complex treatment of the injured hand at specialist centers allows for shorter treatment duration, improved treatment results, and decreased indirect expenses.

Journal ArticleDOI
TL;DR: It seems plausible that the difference of activity observed for TiO2 and F-TiO2 is not related to various types of generated hydroxyl radicals, but rather to competition between electron- transfer processes (formation of radicals) and energy-transfer processes ( formation of singlet oxygen).
Abstract: Substitution of surface -OH groups of TiO2 may influence competition between photoinduced energy and electron-transfer processes and lead to improved singlet oxygen generation. In contrast to neat TiO2, surface modified titanium dioxide can photocatalyze degradation of a very stable substance, cyanuric acid. Presented results are in contradiction to usually accepted hypothesis of the mechanism of cyanuric acid photodegradation in the presence of fluorinated TiO2 (F-TiO2) in which "bulk" hydroxyl radicals play a key role. It seems plausible that the difference of activity observed for TiO2 and F-TiO2 is not related to various types of generated hydroxyl radicals, but rather to competition between electron-transfer processes (formation of radicals) and energy-transfer processes (formation of singlet oxygen).

Journal ArticleDOI
TL;DR: Of special interest is the enzymatic activity found in a few members of the lipocalin family, as well as the interaction with natural membranes, both directly with lipids and through membrane-localized protein receptors.

Journal ArticleDOI
08 Jun 2006-Oncogene
TL;DR: Results indicate that heme oxygenase-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.
Abstract: Photodynamic therapy is a promising antitumor treatment modality approved for the management of both early and advanced tumors. The mechanisms of its antitumor action include generation of singlet oxygen and reactive oxygen species that directly damage tumor cells and tumor vasculature. A number of mechanisms seem to be involved in the protective responses to PDT that include activation of transcription factors, heat shock proteins, antioxidant enzymes and antiapoptotic pathways. Elucidation of these mechanisms might result in the design of more effective combination strategies to improve the antitumor efficacy of PDT. Using DNA microarray analysis to identify stress-related genes induced by Photofrin-mediated PDT in colon adenocarcinoma C-26 cells, we observed a marked induction of heme oxygenase-1 (HO-1). Induction of HO-1 with hemin or stable transfection of C-26 with a plasmid vector encoding HO-1 increased resistance of tumor cells to PDT-mediated cytotoxicity. On the other hand, zinc (II) protoporphyrin IX, an HO-1 inhibitor, markedly augmented PDT-mediated cytotoxicity towards C-26 and human ovarian carcinoma MDAH2774 cells. Neither bilirubin, biliverdin nor carbon monoxide, direct products of HO-1 catalysed heme degradation, was responsible for cytoprotection. Importantly, desferrioxamine, a potent iron chelator significantly potentiated cytotoxic effects of PDT. Altogether our results indicate that HO-1 is involved in an important protective mechanism against PDT-mediated phototoxicity and administration of HO-1 inhibitors might be an effective way to potentiate antitumor effectiveness of PDT.

Journal Article
TL;DR: In this paper, the authors studied the formation and evolution of the Outer Carpathian Basin domain and showed that tectonic and sedimentary subsidence of this basin was controlled both by syn-rift and thermal post-rift processes.
Abstract: The Outer Carpathian Basin domain developed in its initial stage as a Jurassic-Early Cretaceous rifted passive margin that faced the eastern parts of the oceanic Alpine Tethys. Following closure of this oceanic basin during the Late Cretaceous and collision of the Inner Western Carpathian orogenic wedge with the Outer Carpathian passive margin at the Cretaceous-Paleocene transition, the Outer Carpathian Basin domain was transformed into a foreland basin that was progressively scooped out by nappes and thrust sheets. In the pre- and syn-orogenic evolution of the Outer Carpathian basins the following prominent periods can be distinguished: (1) Middle Jurassic-Early Cretaceous syn-rift opening of basins followed by Early Cretaceous post-rift thermal subsidence, (2) latest Cretaceous-Paleocene syn-collisional inversion, (3) Late Paleocene to Middle Eocene flexural subsidence and (4) Late Eocene-Early Miocene synorogenic closure of the basins. In the Outer Carpathian domain driving forces of tectonic subsidence were syn-rift and thermal post-rift processes, as well as tectonic loads related to the emplacement of nappes and slab-pull. Similar to other orogenic belts, folding of the Outer Carpathians commenced in their internal parts and progressed in time towards the continental foreland. This process was initiated at the end of the Paleocene at the Pieniny Klippen Belt/Magura Basin boundary and was completed during early Burdigalian in the northern part of the Krosno Flysch Basin. During Early and Middle Miocene times the Polish Carpathian Foredeep developed as a peripheral foreland basin in front of the advancing Carpathian orogenic wedge. Subsidence of this basin was controlled both by tectonic and sedimentary loads. The Miocene convergence of the Carpathian wedge with the foreland resulted in outward migration of the foredeep depocenters and onlap of successively younger deposits onto the foreland.

Journal ArticleDOI
TL;DR: Advice on the use of the minimal important difference (MID) is short, indeed much too short and it is advocated that dichotomizing the scores of patient-reported outcome measures facilitate interpretability of clinical trial results for those who need to understand trial results after a labelling claim has been granted.
Abstract: The evaluation and use of patient reported outcome (PRO) measures requires detailed understanding of the meaning of the outcome of interest. The Food and Drug Administration (FDA) recently presented its draft guidance and view on the use of PRO measures as endpoints in clinical trials. One section of the guidance document specifically deals with advice about the use of the minimal important difference (MID) that we redefined as the smallest difference in score in the outcome of interest that informed patients or informed proxies perceive as important. The advice, however, is short, indeed much too short. We believe that expanding the section and making it more specific will benefit all stakeholders: patients, clinicians, other clinical decision makers, those designing trials and making claims, payers and the FDA. There is no "gold standard" methodology of estimating the MID or achieving the meaningfulness of clinical trial results based on patient reported outcomes. There are many methods of estimating the MID usually grouped into two distinct categories: anchor-based methods, that examine the relationship between scores on the target instrument and some independent measure, and distribution-based methods resorting to the statistical characteristics of the obtained scores. Estimation of an MID and interpretation of clinical trial results that present patient important outcomes is demanding but vital for informing the decision to recommend approve a given intervention. Investigators are encouraged to use reliable and valid methods to achieve meaningfulness of their results, preferably those that rely on patients to estimate what constitutes a minimal important, small, moderate, or large difference. However, acquiring the meaningfulness of PRO measures transcends beyond a concept of the MID and we advocate that dichotomizing the scores of patient-reported outcome measures facilitate interpretability of clinical trial results for those who need to understand trial results after a labelling claim has been granted. Irrespective of the strategy investigators use to estimate these values, from the individual patient perspective it is much more relevant if investigators report both the estimated thresholds and the proportion of patients achieving that benefit.

Journal ArticleDOI
TL;DR: The goal of the International Federation of Clinical Chemistry and Laboratory Medicine, Scientific Division, Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD-WG-SEPOCT) is to reach a global consensus on reporting results, which recommends reporting the concentration of glucose in plasma (in the unit mmol/L), irrespective of sample type or measurement technique.
Abstract: In current clinical practice, plasma and blood glucose are used interchangeably with a consequent risk of clinical misinterpretation In human blood, glucose is distributed, like water, between erythrocytes and plasma The molality of glucose (amount of glucose per unit water mass) is the same throughout the sample, but the concentration is higher in plasma, because the concentration of water and therefore glucose is higher in plasma than in erythrocytes Different devices for the measurement of glucose may detect and report fundamentally different quantities Different water concentrations in the calibrator, plasma, and erythrocyte fluid can explain some of the differences Results for glucose measurements depend on the sample type and on whether the method requires sample dilution or uses biosensors in undiluted samples If the results are mixed up or used indiscriminately, the differences may exceed the maximum allowable error for glucose determinations for diagnosing and monitoring diabetes mellitus, thus complicating patient treatment The goal of the International Federation of Clinical Chemistry and Laboratory Medicine, Scientific Division, Working Group on Selective Electrodes and Point of Care Testing (IFCC-SD-WG-SEPOCT) is to reach a global consensus on reporting results The document recommends reporting the concentration of glucose in plasma (in the unit mmol/L), irrespective of sample type or measurement technique A constant factor of 111 is used to convert concentration in whole blood to the equivalent concentration in plasma The conversion will provide harmonized results, facilitating the classification and care of patients and leading to fewer therapeutic misjudgments

Journal ArticleDOI
TL;DR: In this paper, the mesoporous silica supports modified with transition metal oxides were tested as catalysts of the selective reduction of NO with ammonia, and the results showed that the mixture of water vapor into the reaction mixture only slightly decreased the NO conversion and selectivity towards N2 over the MCM-48, SBA-15, MCF, and MCF modified with copper or iron oxide.
Abstract: Mesoporous silicas (MCM-48, SBA-15, MCF), reflecting various porous structures, were modified with copper and iron oxides by two different methods. For a first series of the samples the molecular designed dispersion (MDD) method using acetylacetonate complexes of copper and iron was applied for the deposition of transition metal oxides on the silica supports. A second series of the catalysts was obtained by the incipient impregnation technique using aqueous solutions of the suitable metal nitrates. The modified materials were characterized with respect to the texture (BET), composition (electron microprobe analysis), coordination of the transition metals (UV–vis–DRS) and surface acidity (NH3-TPD, FTIR). The mesoporous silica supports modified with transition metal oxides were tested as catalysts of the selective reduction of NO with ammonia. The catalytic performance of the studied samples depended on the method used for the deposition of transition metal oxide as well as the kind of mesoporous silica used as a catalytic support. In general, the Cu-containing mesoporous samples effectively operated at lower temperatures than silicas modified with iron. The samples obtained by the MDD method have been found to be more active and selective compared to the analogous samples prepared by the impregnation technique. An introduction of water vapor into the reaction mixture only slightly decreased the NO conversion and selectivity towards N2 over the MCF mesoporous silica modified with copper or iron oxide.

Journal ArticleDOI
TL;DR: The results may be of public health importance because delayed psychomotor or mental performance in infants is assumed to be an indicator of later neurocognitive development in children, which may persist into adult life.

Journal ArticleDOI
TL;DR: Chemerin, a dendritic cell and macrophage chemoattractant activated by serine proteases of the coagulation, fibrinolytic, and inflammatory cascades is described, which is critical for both systemic leukocyte positioning by triggering integrin activation and subsequent recruitment from circulation, and local intratissue leukocytes positioning via chemotaxis.