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BackgroundTotal calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units.MethodsSerum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen’s kappa (κ).ResultsAnalytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797–0.917; all P ConclusionsThe new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

A strategy to replicate fingerprint patterns formed by the self-assembly of lamella-forming block copolymer (BCP) was investigated. To accomplish this, liquid conformal layers were placed between the surfaces of a “master” BCP film and a transparent “replica” substrate that solidified and covalently bonded to the BCP upon exposure to light. The benzophenone-containing conformal layer enabled pattern replication over areas limited only by the size of the samples and exposure field. The replication step is light activated, occurs below the glass transition of the BCP, and takes less than 1 h. This demonstration used a poly(styrene-b-methyl methacrylate) BCP with a bulk domain periodicity of 42 nm, but it is possible that the chemistry may be generalized to many other BCPs. Control experiments conducted with alternative conformal layer compositions indicate that interfacial photosensitization of the BCP by excited benzophenone, followed by propagation to residual acrylate groups present in the conformal laye...

We compare HER2 receptor amplification analysis by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (real-time PCR) DNA copy-number assay following laser capture microdissection (LCM) in formalin-fixed paraffin embedded tissue from 40 women with verified ovarian cancer. We speculate that LCM should result in a more accurate assessment of HER2 amplification in our real-time PCR assay compared with IHC and FISH. HER2 overexpression measured by IHC, FISH, or real-time PCR was found in 5.0%, 5.0%, and 22.5%, respectively. HER2 negative results measured by IHC, FISH, or real-time PCR were found in 95%, 92.5%, and 60.0%, respectively. Analysis failed for IHC, FISH, or real-time PCR in 0%, 2.5%, or 17.5% of cases. Concordance between IHC and FISH, IHC and real-time PCR, or FISH and real-time PCR were 89.7%, 72.7%, or 78.1%, respectively. Only few ovarian cancer patients were HER2 overexpressed measured by IHC or FISH and thus could be eligible for antibody-based therapy with trastuzumab (Herceptin). Interestingly, we find an increased number of HER2 positive patients by real-time PCR analysis on microdissected cancer cells, suggesting a number of HER2 positive patients not detected by current methods. Thus, the concept of quantitative measurement of HER2 on microdissected cancer cells should be explored further.

Chemically patterned surfaces comprised of polymer mats and brushes of well-defined chemistry were fabricated at the length scale of 10 nm. A key concept is the integration of new materials, cross-linked polymer mats, with traditional lithographic processing. Resist was patterned on top of cross-linked polystyrene mats. After etching, regions of the remaining mat with dimensions ranging from 10 to 35 nm were separated by interspatial openings to the underlying substrate. End-grafted polymer brushes, in this case hydroxyl-terminated poly(2-vinylpyridine) or polystyrene-poly(methyl methaoylate) random copolymer, were grafted into the exposed, interspatial regions from films spin-coated over the patterned mat. Both block copolymer wetting studies, with polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA), and near-edge X-ray fine structure spectroscopy showed that with sufficient cross-linking the polymer mat chemistry was unaffected by the subsequent grafting of the polymer brush. The precise definition of both the chemistry and the geometry was demonstrated two sensitive application of nanoscale chmican patters: the site-specific immobilization of Au nanoparticles and the directed assembly of overlying PS-b-PMMA films.

The possible involvement of 3', 5'-cyclic AMP (cyclic AMP) in the mechanism of action of leucocyte migration inhbitory factory (LIF) was tested. LIF-treated human peripheral blood leucocytes were incubated at 37 degrees C for various times between 0 and 22 h. The concentrations of cyclic AMP in these cultures did not differ from those in controls. Furthermore, LIF did not affect the cellular release of cyclic AMP. Neither when testing purified neutrophils, which are the prime targets of LIF action, an effect of LIF was found. Cyclic AMP levels decreased with time of incubation, whether testing mononuclear cells (92 per cent lymphocytes), purified neutrophils (98 per cent), or buffy coat cells (72 per cent neutrophils; 22 per cent lymphocytes). However, a transient and as yet unexplained increase in the cyclic AMP levels of the latter mixed population of cells was manifested within 10 to 30 min of incubation.

Triazole formation via 1,3-dipolar cycloaddition, or "click" chemistry, is a powerful synthetic method for incorporating chemical functionality onto the surfaces of Au nanoparticles. To investigate the factors that govern azide/alkyne reactivity at particle surfaces, we measured the general kinetic trends for the uncatalyzed reaction using FTIR spectroscopy. This study examines the roles of ligand length, electronic substitution of the alkyne species, and solvent on the reaction under pseudo-first-order conditions. The conversion of azide to triazole is found to depend more strongly on the relative surface coverage of azide terminated alkanethiol than on the ligand length and solvent.

Triazole formation by 1,3-dipolar cycloaddition reactions, “click” chemistry, has been used to functionalize the surfaces of Au nanoparticles. Au particle samples were first synthesized through standard procedures, the methyl-terminated chains partially exchanged with ω-bromo-functionalized thiol, and the Br termini converted to azides by reaction with NaN3. These particles were then reacted with a series of alkynyl derivatized small molecules in nonpolar solutions, which led to their attachment through the formation of a 1,2,3-triazole ring, confirmed through NMR and IR spectroscopies. Click reactions were used to impart chemical functionality to the Au particles, which is assessed using fluorescence spectroscopy and cyclic voltammetry.

A chemical pattern consisting of end-grafted polystyrene brushes (20 nm lines on a 40 nm pitch) on the native oxide of silicon wafers was defined by molecular transfer printing from assembled block co-polymer films. End-grafted hydroxyl-terminated poly(2-vinyl pyridine) brushes were selectively deposited in the interspatial regions. The poly(2-vinyl pyridine) regions selectively sequester acidic HAuCl4 from solution and form arrays of small Au nanoparticles upon exposure to oxygen plasma within the confines of the macromolecular brush layer. This print and fill process to pattern polymer brushes is a generalizable strategy to create functional chemical surface patterns. Online supplementary data available from stacks.iop.org/Nano/24/155602/mmedia

The synergy of self- and directed-assembly processes and lithography provides intriguing avenues to fabricate translationally ordered nanoparticle arrangements, but currently lacks the robustness necessary to deliver complex spatial organization. Here, we demonstrate that interparticle spacing and local orientation of gold nanorods (AuNR) can be tuned by controlling the Debye length of AuNR in solution and the dimensions of a chemical contrast pattern. Electrostatic and hydrophobic selectivity for AuNR to absorb to patterned regions of poly(2-vinylpyridine) (P2VP) and polystyrene brushes and mats was demonstrated for AuNR functionalized with mercaptopropane sulfonate (MS) and poly(ethylene glycol), respectively. For P2VP patterns of stripes with widths comparable to the length of the AuNR, single- and double-column arrangements of AuNR oriented parallel and perpendicular to the P2VP line were obtained for MS-AuNR. Furthermore, the spacing of the assembled AuNR was uniform along the stripe and related to the ionic strength of the AuNR dispersion. The different AuNR arrangements are consistent with predictions based on maximization of packing of AuNR within the confined strip.

Chemical patterns consisting of poly(2-vinyl pyridine) (P2VP) brushes in a background of a cross-linked polystyrene (PS) mat enabled the highly selective placement of citrate-stabilized Au nanoparticles (NPs) in arrays on surfaces. The cross-linked PS mat prevented the nonspecific binding of Au NPs, and the regions functionalized with P2VP brushes allowed the immobilization of the particles. Isolated chemical patterns of feature sizes from hundreds to tens of nanometers were prepared by standard lithographic techniques. The number of 13 nm Au NPs bound per feature increased linearly with increasing area of the patterns. This behavior is similar to previous reports using 40 nm particles or larger. Arrays of single NPs were obtained by reducing the dimensions of patterned P2VP brushes to below ~20 nm. To generate dense (center-to-center distance = 80 nm) linear chemical patterns for the placement of rows of single NPs, a block-copolymer (BCP)-assisted lithographic process was used. BCPs healed defects associated with the standard lithographic patterning of small dimensions at high densities and led to highly registered, linear, single NP arrays.

Directed Self-Assembly (DSA) of block copolymers is considered to be a potential lithographic solution to achieve higher feature densities than can be obtained by current lithographic techniques. However, it is still not well-established how amenable DSA of block copolymers is to an industrial fabrication environment in terms of defectivity and processing conditions. Beyond production-related challenges, precise manipulation of the geometrical and chemical properties over the substrate is essential to achieve high pattern fidelity upon the self-assembly process. Using our chemo-epitaxy DSA approach offers control over the surface properties of the slightly preferential brush material as well as those of the guiding structures. This allows for a detailed assessment of the critical material parameters for defect reduction. The precise control of environment afforded by industrial equipment allows for the selective analysis of material and process related boundary conditions and assessment of their effect on defect generation. In this study, the previously reported implementation of our feature multiplication process was used to investigate the origin of defects in terms of the geometry of the initial pre-patterns. Additionally, programmed defects were used to investigate the ability of the BCP to heal defects in the resist patterns and will aid to assess the capture capability of the inspection tool. Finally, the set-up of the infrastructure that will allow the study the generation of defects due to the interaction of the BCP with the boundary conditions has been accomplished at imec.

Inexpensive, large area patterning of ex-situ synthesized metallic nanoparticles (NPs) at the nanoscale may enable many technologies including plasmonics, nanowire growth, and catalysis. Here, site-specific localization of Au NPs onto nanoscale chemical patterns of polymer brushes is investigated. In this approach, patterns of hydroxyl-terminated poly(styrene) brushes are transferred from poly(styrene-block-methyl methacrylate) (PS-b-PMMA) block copolymer films onto a replica substrate via molecular transfer printing, and the remaining areas are filled with hydroxyl-terminated poly(2-vinyl pyridine) (P2VP-OH) brushes. Citrate-stabilized Au NPs (13 nm) selectively bind to P2VP-OH functionalized regions and the quality of the resulting assemblies depends on high chemical contrast in the patterned brushes. Minimization of the interpenetration of P2VP-OH chains into PS brushes during processing is the key for achieving high chemical contrast. Large area hexagonal arrays of single Au NPs with a placement accuracy of 3.4 nm were obtained on patterns (similar to 20 nm spots, similar to 40 nm pitch) derived from self-assembled cylinder-forming PS-b-PMMA films. Linear arrays of Au NPs were generated on patterns (40 nm lines, 80nm pitch) derived from lamellae-forming PS-b-PMMA that had been directed to assemble on lithographically defined masters.

The sections in this article are Introduction Magnetic Nanoparticle Synthesis Nanoparticle Functionalization Surface Adsorption Ligand Exchange Silanes and Siloxanes Monolayer Reactions Encapsulation Encapsulation: Silica (SiO2) Encapsulation: Metallic and Semiconductor Shells Encapsulation: Polymeric and Carbon Shells Encapsulation: Carbon Shells Lipids and Dendrimers Lipids Dendrimers Conclusions Keywords: nanoparticle; magnetic; encapsulation; monolayer; functionalization; ligand substitution; synthesis

Objectives. To study the influence of age, sex, season and diet on calcium status in normal subjects. Design. A random population study. Setting. Institutional clinic for large population studies. Subjects. The subjects were drawn randomly from the Danish Civil Registration System and represented a random sample of the background population in the area. The sample comprised 127 subjects (54 men and 73 women, aged 35–65 years). Main outcome measures. The effects of age, sex, season and diet on parathyroid hormone (PTH), 1,25- dihydroxyvitamin D (1,25(OH)2D) and 25-hydroxy-vitamin D (25-OHD). Results. There was no statistical significant difference for the serum concentrations of ionized calcium, PTH, 1,25(OH)2D and 25-OHD between the two sexes, nor any influence by age in either sex, in contrast to serum phosphate, which declined significantly in men (P < 0.05), but tended to increase in women. Serum PTH (P < 0.009) showed seasonal fluctuations, whereas serum concentrations of 1,25(OH)2D, 25-OHD, ionized calcium, phosphate and magnesium remained stable throughout the year. Dietary intake of calcium and vitamin D were not related to any serum variables. Conclusions. In healthy subjects differences between the two sexes exist regarding phosphate metabolism. Serum PTH shows seasonal fluctuations.

In a nested case-control study, calcium status was assessed by measurements of serum total calcium, magnesium, phosphate, ionized calcium, parathyroid hormone, albumin, total CO2 (bicarbonate), and free fatty acids in relation to gallstone formation. The subjects were recruited from a cohort study (n = 4,581) on the epidemiology of gallstones in Denmark. The cohort was examined with ultrasonography twice, in 1983 and 1988; 63 subjects developed gallstones, and among those who did not, 122 were randomly selected as controls. Subjects with gallstones had significantly increased serum concentrations of total calcium, magnesium, and bicarbonate as compared with normal subjects. The difference was only observed in women. Age, body mass index, alcohol consumption, and smoking did not influence the results when included as covariables in a logistic regression analysis. Multivariate analysis showed increased concentrations of magnesium, bicarbonate, and parathyroid hormone to be significantly associated with gallstone disease in women. No significant association was observed between gallstone disease and serum variables in men.

Acute back and neck strains are very common. In addition to administering analgesics, these strains are often treated with either heat or cold packs. The objective of this study was to compare the analgesic efficacy of heat and cold in relieving pain from back and neck strains. The authors hypothesized that pain relief would not differ between hot and cold packs.This was a randomized, controlled trial conducted at a university-based emergency department (ED) with an annual census of 90,000 visits. ED patients18 years old with acute back or neck strains were eligible for inclusion. All patients received 400 mg of ibuprofen orally and then were randomized to 30 minutes of heating pad or cold pack applied to the strained area. Outcomes of interest were pain severity before and after pack application on a validated 100-mm visual analog scale (VAS) from 0 (no pain) to 100 (worst pain), percentage of patients requiring rescue analgesia, subjective report of pain relief on a verbal rating scale (VRS), and future desire for similar packs. Outcomes were compared with t-tests and chi-square tests. A sample of 60 patients had 80% power to detect a 15-mm difference in pain scores.Sixty patients were randomized to heat (n = 31) or cold (n = 29) therapy. Mean (+/-standard deviation [SD]) age was 37.8 (+/-14.7) years, 51.6% were female, and 66.7% were white. Groups were similar in baseline patient and pain characteristics. There were no differences between the heat and cold groups in the severity of pain before (75 mm [95% CI = 66 to 83] vs. 72 mm [95% CI = 65 to 78]; p = 0.56) or after (66 mm [95% CI = 57 to 75] vs. 64 mm [95% CI = 56 to 73]; p = 0.75) therapy. Pain was rated better or much better in 16/31 (51.6%) and 18/29 (62.1%) patients in the heat and cold groups, respectively (p = 0.27). There were no between-group differences in the desire for and administration of additional analgesia. Twenty-five of 31 (80.6%) patients in the heat group and 22 of 29 (75.9%) patients in the cold group would use the same therapy if injured in the future (p = 0.65).The addition of a 30-minute topical application of a heating pad or cold pack to ibuprofen therapy for the treatment of acute neck or back strain results in a mild yet similar improvement in the pain severity. However, it is possible that pain relief is mainly the result of ibuprofen therapy. Choice of heat or cold therapy should be based on patient and practitioner preferences and availability.

The actual activity of ionised calcium (Ca2+) in gall bladder bile determined with an ion-selective electrode was significantly higher in patients with gall stone disease (n = 15) than in patients without gall stones (n = 10) (0.43 mmol/kg v 0.31 mmol/kg; p < 0.05). No change in the Ca2+ activity in any of the gall bladder bile samples was observed during equilibration with CO2. During titration with HCl/NaOH, however, the Ca2+ activity fell with increasing pH in a biphasic manner, with the breaking point occurring at a significantly lower median pH in patients with gall stones than in patients without (pH 7.1 v 8.2; p < 0.0001). The combination of a higher activity of calcium in bile and precipitation of bile salts taking place at a lower pH in patients with gall stone disease than in patients without gall stones suggests a major role for calcium and pH in the pathogenesis of gall stones. Strict anaerobic sampling is not necessary for the measurements of Ca2+ in gall bladder bile, because the Ca2+ was not significantly affected by the changes in pCO2. The metabolic studies suggest, however, that simultaneous measurements of the activity of Ca2+ and pH is important in order to interpret data for the calcium activity in gall bladder bile.

Background The major impediment to the expansion of oncology services is a shortage of personnel. Purpose To develop a distance learning course for radiation oncology trainees. Materials Under the sponsorship of the Asia Pacific Regional Cooperative Agreement administered by the International Atomic Energy Agency (IAEA), a CD ROM-based Applied Sciences of Oncology (ASOC) distance learning course of 71 modules was created. The course covers communications, critical appraisal, functional anatomy, molecular biology, pathology. The materials include interactive text and illustrations that require students to answer questions before they can progress. The course aims to supplement existing oncology curricula and does not provide a qualification. It aims to assist students in acquiring their own profession's qualification. The course was piloted in seven countries in Asia, Africa and Latin America during 2004. After feedback from the pilot course, a further nine modules were added to cover imaging physics (three modules), informed consent, burnout and coping with death and dying, Economic analysis and cancer care, Nutrition, cachexia and fatigue, radiation-induced second cancers and mathematical tools and background for radiation oncology. The course was widely distributed and can be downloaded from http://www.iaea.org/Publications/Training/Aso/register.html. ASOC has been downloaded over 1100 times in the first year after it was posted. There is a huge demand for educational materials but the interactive approach is labour-intensive and expensive to compile. The course must be maintained to remain relevant.

Reactions of Grignard and organolithium reagents are staple transformations in organic chemistry. However, their use in the chemical functionalization of monolayer-protected metallic nanoparticles is unprecedented. In this letter, we report the reaction of Au nanoparticles bearing a mixed monolayer of alkanethiol ligands that are methyl- and N-methoxy- N-methyl amide-terminated. The latter of these rapidly undergoes reaction with organometallic reagents, achieving high yields (in some cases, nearly quantitative) in only a few hours without the need for high pressure, temperature or catalysts. We assess the feasibility of this reaction with a range of organometallic reagents on the basis of both surface reaction yield and also the stability of the particles (defined as the mass % Au particles recovered vs a control). Demonstrating the utility of these strong organometallic reagents opens the door to a large class of reactions that are underutilized within the field of nanomaterials.

We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults.

Recent studies suggest that alternation in serum calcium influences the level of gallbladder bile ionized calcium (Ca2+). Theoretically, this could increase the risk of calcium precipitation in the gallbladder.We therefore measured serum and gallbladder bile minerals in patients with gallstones (n = 27) and without (n = 10, controls). The serum samples were taken just prior to induction of anaesthesia and gallbladder bile was aspirated before any manipulation of the gallbladder.The active molality of Ca2+ in gallbladder bile was not statistically significant different between cases and controls (0.44 +/- 0.16 vs. 0.40 +/- 0.10 mmol/kg), whereas pH was significantly lower (6.94 +/- 0.31 vs. 7.36 +/- 0.28, p0.0001) and cholesterol higher (4.37 +/- 2.70 vs. 1.79 +/- 1.33 mmol/l; p0.01) in gallbladder bile obtained from cases. Serum Ca2+ at actual pH, magnesium and phosphate were significantly higher among cases than in controls. Gallbladder bile active molality of Ca2+ was significantly correlated with bile total calcium in both groups (r = 0.72; p0.001 and r = 0.91; p0.001, respectively). In controls only, we observed a positive relationship between serum Ca2+ at actual pH and the active molality of Ca2+ in bile (r = 0.61; p0.05).Our study demonstrates that Ca2+ in gallbladder bile does not differ between cases and controls. The lack of correlation between serum and gallbladder bile constituents in cases compared to controls suggests that changes in calcium equilibration between bile and serum in patients with gallstone disease might be of importance for the formation of gallstones.

An ion-selective analyzer (NOVA 8 [previously NOVA CRT], NOVA Biomedical Waltham, USA) for simultaneous measurement of the concentration of ionized magnesium (cMG2+) and pH is investigated for linearity and influence of calcium ions on the Mg2+ results in different Mg2+ aqueous solutions with/without added calcium. Within the cMg2+ range 0-3.0 mmol/L, which covers most clinical values, we found cMg2+ values close to the line of identity, with a sensitivity about 94%, but 0.09 mmol/L lower in the absence of Ca2+. The analytical precision (CV) for human serum control was 1.7% in the physiological range. The accuracy and precision data for the Mg2+ electrode meet the demands for reliable results within the range for clinical use. We found a reference interval (95%) for cMg2+ of between 0.43 and 0.59 mmol/L serum, with a mean value of 0.51 mmol/L for healthy adults in the non-fasting state with no relation to sex or age. The mean cMg2+ was 61% of the mean concentration of plasma total magnesium (cTMg) ranging from (95%) 49% to 73%. No significant correlation was found between cMg2+ and total protein, albumin, phosphate, Ca2+, and total CO2. No significant difference was found between mean values for cMg2+ in whole blood, plasma, and serum. Serum samples could be stored for 24 h at 4 degrees C without significant change. Storage at -20 degrees C for 7 months caused a mean cMg2+ decrease of 8.3%. The mean slope delta lgcMg2+/delta pH measured after equilibration with different pCO2 values in each serum sample from the reference population was -0.0110, indicating a close agreement between the values for actual cMg2+ and adjusted cMg2+ (pH = 7.4).

Purpose: With the advent of high-sensitivity cardiac troponins (hscTn), detectable levels have become the norm and clinical challenge lies within distinction of normal and abnormal. We therefore sought to describe diagnostic and prognostic implications of the clinical introduction of hscTn. Methods: Myocardial infarction (MI) adjudication was based on hsTnT (Roche Diagnostics) and clinical setting. The 99% upper reference limit (URL) of 30 ng/L (10% CV) in the 4th generation TnT assay corresponds to 50 ng/L URL in the hsTnT assay. First, we used a 50 ng/L cut off (+dynamic changes) after the introduction of hsTnT in order to parallel MI diagnosis with the 4th generation assay. MI was then re-adjudicated by hsTnT levels >99% URL (>14 ng/L) with an absolute (abs.) change as rise/fall >50% of URL (>7 ng/L). We then compared hsTnT with a contemporary sensitivity TnI assay (sTnI) (Siemens Vista), with a 15 ng/L detection limit, a 45 ng/L 99% URL and significant abs. change of 20 ng/L. Results: In 335 chest pain patients with at least 2 values, 46 (13.7%) had MI by the 50 ng/l cut off. Re-adjudicating MI resulted in a 67% increase with 69 (20.6%) MI, 74% of the additional MI were type II. STnI only identified 51 of re-defined MI with modest 73.9% sensitivity (sens.) but high 95.9% specificity, yielding only 4.1% false positives, which was doubled (7.9%) with hsTnT. In 586 patients with at least 1 hsTnT value, 105 (17.9%) had undetectable levels (< 3 ng/L) at admission, ruling out all 1 year mortality [n = 81 (13.8%)] and all MI [n = 85 (14.5%)] with 100% sens. and NPV. 313 (53.4%) patients had hsTnT levels

An internal reference method is used for the first time to clearly demonstrate the glass transition temperature (Tg) depression effect in 5 nm thick polystyrene films spin-cast on silicon wafers. Initially flat films exhibit depressed Tg at approximately 85 °C. Temperature-induced dewetting on hexamethyldisilazane-treated silicon substrates leads to formation of discontinuous films with average effective thickness of 15-30 nm. Dewetted films demonstrate Tg close to the bulk value (≈ 100 °C) and are used as internal references. Data both for continuous and discontinuous films are obtained in the same experimental run for the same sample, which allows direct comparison between datasets. Phase-modulated ellipsometry in vacuum is used to monitor glass transition. Both traditional linear temperature scan method and a novel temperature modulated technique have been employed in the measurements.

In man, parathyroid hormone (PTH) is one of the main regulators of 1,25-dihydroxyvitamin D (1,25(OH)2D) production. However, conflicting results have been reported concerning the regulatory significance of PTH on 1,25(OH)2D in primary hyperparathyroidism. We measured the plasma concentrations of intact PTH, ionized calcium (pH 7.4), phosphate, creatinine, 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D and urine creatinine in a standardised regime in 17 patients with primary hyperparathyroidism. The nephrogeneous cyclic adenosine-3,5-monophosphate (NcAMP) was measured and so provides an "in vivo receptor assay' for biologically active PTH in the circulation. Multiple regression analysis was used to identify variables with a possible influence on the plasma concentration of 1,25(OH)2D. The only variable showing a significant correlation to the plasma concentration of 1,25(OH)2D was 25(OH)D (r=0.6, p0.03). Our results indicate that the plasma concentration of 25(OH)D may be very central for the regulation of 1,25(OH)2D production in primary hyperparathyroidism.

Extended abstract of a paper presented at Microscopy and Microanalysis 2004 in Savannah, Georgia, USA, August 1–5, 2004.

The implementation of our previously reported chemo-epitaxy method for directed self-assembly (DSA) of block copolymers (BCPs) on 300-mm wafers is described in detail. Some challenges to be addressed include edge bead removal control of the layers forming the exposure stack and uniformity of the deposited films across the wafer. With the fine tuning of the process conditions, this flow provides chemically nanopatterned substrates with well-defined geometry and chemistry. After a film of BCP is annealed on the chemical patterns, high degrees of perfection are achieved. A BCP with natural periodicity of 25 nm was assembled on100-nm pitch prepatterns, obtaining 4X feature multiplication. Top-down scanning electron microscope images show a wide process window with depth of focus >200 nm and exposure latitude >40% for lines and spaces of 12.5-nm half-pitch. We provide a platform for future study of the origin of DSA generated defects and their relationship to process conditions and materials that are amenable to use by the semiconductor industry.

A so-called osteoporosis-profile has become increasingly popular among Danish doctors. Future bone loss in peri- and postmenopausal women is estimated by means of an algorithm comprising serum osteocalcin and alkaline phosphatases as markers of bone formation and urinary calcium and hydroxyproline excretions, corrected for creatinine, as markers of bone resorption. The osteoporosis-profile, performed by Medi-Lab, was tested in six females aged 46-56 years. Three different diets were used on three successive week-ends, each ending with a collagen-free supper and an overnight fast. Individual changes in estimated bone loss of up to 200-300% were found, demonstrating that the test was useless in a single person.

This study modifies the authors’ previously reported directed self-assembly (DSA) process of polystyrene-block-poly(methyl methacrylate) (PS-b-PMMA) in order to meet the throughput and material-related requirements of a semiconductor manufacturing environment. It is demonstrated that all of the bottleneck steps in the authors’ DSA process, including the deposition of the cross-linkable mat and the deposition of the brush layer, can be done in minutes on a hot plate in an N2 atmosphere, which simulates the processing environment of a lithography track module. A 25-nm-pitch pattern resulting from a 4:1 density multiplication was demonstrated with a manufacturing-compatible organic solvent. A preliminary uniformity study on 300 mm wafers was also presented. The modified DSA process presents a viable solution to some of the anticipated throughput-related challenges to DSA commercialization and thus, brings integration of DSA within reach of the semiconductor manufacturing industry.

The serum concentrations of actual ionized calcium (at actual pH), adjusted ionized calcium (at pH 7.4), pH, intact parathyroid hormone (PTH) and phosphate were studied in ten patients during and between two hemodialysis sessions using a dialysate containing 1.66 mmol/l of calcium. Actual ionized calcium and adjusted ionized calcium increased during hemodialysis from 1.19 to 1.38 and 1.43 mmol/l, respectively (mean values) and returned to predialysis values within five and nine hours postdialysis. Serum PTH decreased from 165 ng/l to 55 ng/l (median values) during hemodialysis but two-hour postdialysis the level did not differ significantly from the predialysis level. Serum phosphate decreased from 2.05 mmol/l to 1.11 mmol/l during hemodialysis, and increased slowly towards the predialysis level. The level of pH increased from 7.40 to 7.47 during hemodialysis and reached predialysis level after nine hours. In a multivariate analysis including actual and adjusted ionized calcium, pH, phosphate and PTH, only actual or adjusted ionized calcium was associated with the level of PTH. We conclude that the effect of dialysate calcium on the levels of ionized calcium and PTH is of very short duration postdialysis.

In a time study we compared the analytical and clinical performance of the Tandem Icon QSR CK-MB enzyme-immunoassay (Hybritech) (creatine kinase-MB) and a creatine kinase-MB immunoinhibition method (Boehringer Mannheim GmbH) (creatine kinase-B). Two hundred and ninety-nine serum samples from 38 patients suspected of acute myocardial infarction were collected at regular intervals during 48 hours. Twenty-nine patients were diagnosed as having acute myocardial infarction, of whom 19 received thrombolytic therapy. Although highly correlated, the large scatter around the regression line at low values indicated a different clinical performance of the two methods. We evaluated and compared test performance at different decision levels by means of frequency distributions and predictive values of positive and negative results. For early diagnosis of acute myocardial infarction (4 hours after onset of pain) the Hybritech creatine kinase-MB method gives acceptable predictive values. In thrombolytic treated acute myocardial infarction patients, the peak creatine kinase-MB and creatine kinase-B concentrations were reached after 13.0 h and 13.6 h after the onset of pain, compared with 19.8 h and 17.8 h for patients without thrombolytic therapy.

It is the activity that determines the direction of chemical processes, transport, etc. and thus provides the clinically more relevant information. Direct reading glucose electrodes consume glucose at a rate proportional to the glucose activity in the sample. The activity equals the molality (mmol glucose per kg water), so results from direct reading glucose electrodes must differ from the conventionally measured glucose concentration. This was observed in 159 whole blood samples which gave higher results from a direct reading glucose electrode than by our conventional method (y = 1.21x − 0.37 mmol/l). However, adjustment for the different water concentration due to salt, plasma proteins, and hemoglobin occupying space, gave results equal to the concentrations (y = 1.OOx − 0.28 mmol/l, r = 0.997). Furthermore, results for samples with constant glucose concentration and varying albumin concentration correlated with the albumin concentration (r = 0.989), but not after adjustment for water concentration (r = 0.037, n.s.).

We report results for adjusted ionized calcium (at pH 7.4) and actual ionized calcium (at actual pH) in capillary blood from 183 patients with disorders of calcium metabolism (primary hyperparathyroidism, secondary hyperparathyroidism of malabsorption, primary hypoparathyroidism, Paget's disease, acromegaly, hypercalcemia of malignancy, osteoporosis, sarcoidosis, idiopathic hypercalciuria, and familial hypocalciuric hypercalcemia). The correlation and the equation for the linear regression between adjusted ionized calcium (y) and actual ionized calcium (x) were y = 1.011x + 0.005 mmol/L, r = 0.992, Sy,x = 0.021 mmol/L. Results were similar within each diagnostic group. Consistent agreement between adjusted and ionized calcium was observed in 96.7% of patients representing a variety of the most frequently encountered disorders of calcium metabolism. Thus we find adjusted ionized calcium to be as useful as actual ionized calcium for evaluation of patients with such disorders. Adjusted ionized calcium may therefore also be a logical choice for establishing agreement between laboratories for reference intervals in healthy adults.

Measurement of ionized calcium and cAMP in plasma and urine are used as sensitive parameters for the evaluation of calcium disorders. Ionized calcium is accepted as the biologically active form of calcium in the extracellular fluid, while urine cAMP provides an in vivo receptor assay for the biologically active parathyroid hormone. When urine is included as part of the calcium metabolic investigation it usually requires 24 h urine collection with a variety of different laboratory tests. Ionized calcium and cAMP are described in the literature in terms of several derived quantities, nomenclatures, and units which are rather unsystematic. The author developed reliable techniques and proposed systematic names and symbols and reference values for these quantities. Due to the lack of guidelines for the collection of urines in calcium metabolic evaluation, the author presented a simplified protocol (4 h standardized urine collection). In clinical investigation plasma and urine cAMP have been used to differentiate idiopathic hypoparathyroidism from pseudohypoparathyroidism (PsHP) based on the results of i.v. injection of parathyroid hormone (PTH). Nephrogenous cAMP has also been used for the detection of primary and secondary hyperparathyroidism with a high nosographic sensitivity (90%) (Broadus). The author showed that measurement of cAMP after i.v. PTH was a reliable and sensitive test to establish the diagnosis of PsHP, and that the urinary cAMP was useful for the diagnosis of secondary hyperparathyroidism in patients with jejunoileal bypass, but could not confirm the high nosographic sensitivity for the diagnosis of primary hyperparathyroidism. Further data are needed for proper conclusion. Although pursued vigorously the research into idiopathic stone formation using different protocols has not prevented stone recurrence nor indicated where further progress might be made. For the evaluation of recurrent calcium disease, the author proposed a simplified 4 h standardized urine collection with plasma albumin, urinary pH, standardized excretion rate of calcium, plasma phosphate glomerular filtration rate, and nephrogenous cAMP as the most important parameters. In this way the author obtained a sensitivity of 93% and specificity of 95.6% for the diagnosis of recurrent stone former. The test may therefore be of value for predicting the risk of recurrent stone formation in the single stone former.

The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity.

We investigated the in vitro and in vivo relation between pH and ionized calcium during acute respiratory pH changes. The in vitro slope ΔlgcCa2+/ΔpH determined in 20 healthy volunteers after equilibration at two different pCO2 values was -0.22 ± 0.04 (mean ± 2 SD) for whole blood and -0.24 ± 0.04 (mean ± SD) for serum. The in vivo slope ΔlgcCa2+/ΔpH during acute respiratory changes in 10 healthy volunteers was -0.17 ± 0.04 (mean ± 2 SD) for capillary blood.A mathematical formula which describes the relation between pH and ionized calcium is presented.

We evaluated the analytical performance of six commercial direct radioimmunoassays of 17 beta-estradiol, those from Radioassay Systems Laboratories, IRE Medgenix, Biotecx Laboratories, Farmos Spectria, International CIS, and Diagnostic Products Corp. The mean value for estradiol (E2) and the within- and between-run CVs were determined for serum pools and control materials, measured in seven to 10 runs with each method. Mean values for E2 in pooled sera deviated by 75% to 350% from the means measured with our routinely used extraction method. Between-run CVs ranged from 4% to 14% for the direct assays as compared with 10% for the extraction assay. We also investigated, for two of the direct assays, the effect of extraction with diethyl ether before radioimmunoassay, with respect to improvement in the agreement with our extraction method. All of the assays were easy to perform and results were obtained within 4-5 h, but we conclude that matrix effects may be expected in direct assays of estradiol.

An effect of erythrocytes on the liquid junction potential of the junction “concentrated KCl ‖ whole blood” has previously been described, the effect being a positive bias of +1,4 mV with a high erythrocyte volume fraction (0.75).We have studied the erythrocyte effect with different concentrated salt solutions, and found a similar positive bias with KBr, KJ, KNO3, K2SO4, but a negative bias with NaCl, NaNO3, LiCl and CaCl2.The erythrocyte bias may be eliminated by mixing salts with opposite effect, e.g. KCl + NaCl (1.0 + 7.0 mol/1), KNO3 + NaNO3 (1.0 + 3.0 mol/1) KNO3 + Li-acetate (0.15 + 4.0 mol/1).The use of a mixed salt bridge solution may be advantageous for eliminating the erythrocyte bias when measuring ionic activity (e.g. Na+, K+, Ca2+) directly in whole blood.