Visualizing metabolic activity on a genome-wide scale.
To enhance the exploration of gene expression data in a metabolic context, one requires an application that allows the integration of this data and which represents this data in a (genome-wide) metabolic map. The layout of this metabolic map must be highly flexible to enable discoveries of biological phenomena. Moreover, it must allow the simultaneous representation of additional information about genes and enzymes. Since the layout and properties of existing maps did not fulfill our requirements, we developed a new way of representing gene expression data in metabolic charts. ViMAc generates user-specified (genome-wide) metabolic maps to explore gene expression data. To enhance the interpretation of these maps information such as sub-cellular localization is included. ViMAc can be used to analyse human or yeast expression data obtained with DNA microarrays or SAGE. We introduce our metabolic map method and demonstrate how it can be applied to explore DNA microarray data for yeast. ViMAc is freely available for academic institutions on request from the authors.


Chemical diversity in Indian oregano (Origanum vulgare L.).
The terpenoid composition of the essential oils of 17 different populations of Origanum vulgare L., collected from wild populations and subsequently grown under similar conditions in the sub-temperate region of the Western Himalaya, was studied. Analysis by GC (RI) and GC/MS allowed the identification of 51 components, representing 90.15 to 99.94% of the total oil. The two classes of the phenolic compounds and the monoterpenoids were predominant in all the essential oils. On the basis of the major constituents, i.e., marker compounds, and by comparison of the results with previous reports, new chemotypes could be identified. Principal component analysis was performed to determine the chemical variability within the different populations of O. vulgare collected and grown under similar conditions. Based on the marker compounds, six chemotypes with significant variations in their terpenoid profile were noticed within the 17 populations.


Underpotential deposition of Cu on Au(111) from neutral chloride containing electrolyte.
The structure of a chloride terminated copper monolayer electrodeposited onto Au(111) from a CuSO4/KCl electrolyte was investigated ex situ by three complementary experimental techniques (scanning tunneling microscopy (STM), photoelectron spectroscopy (PES), X-ray standing wave (XSW) excitation) and density functional theory (DFT) calculations. STM at atomic resolution reveals a stable, highly ordered layer which exhibits a Moiré structure and is described by a (5 × 5) unit cell. The XSW/PES data yield a well-defined position of the Cu layer and the value of 2.16 Å above the topmost Au layer suggests that the atoms are adsorbed in threefold hollow sites. The chloride exhibits some distribution around a distance of 3.77 Å in agreement with the observed Moiré pattern due to a higher order commensurate lattice. This structure, a high order commensurate Cl overlayer on top of a commensurate (1 × 1) Cu layer with Cu at threefold hollow sites, is corroborated by the DFT calculations.


Postmortem 9.4-T MRI for Fetuses With Congenital Heart Defects Diagnosed in the First Trimester.
To evaluate the feasibility of 9. 4-T postmortem MRI (pm-MRI) for assessment of major congenital heart defects (CHD) cases terminated in the early stage of gestation. Fetuses with CHD detected by the detailed first-trimester ultrasound scan and terminated before 18 gestational weeks were recruited between January 2018 and June 2020. All fetuses were offered 9.4-T pm-MRI examinations and those terminated over 13+6 weeks were offered conventional autopsies simultaneously. Findings of pm-MRI were compared with those of conventional autopsy and prenatal ultrasound. A total of 19 fetuses with major CHD were analyzed, including 6 cases of the atrioventricular septal defect, 5 cases of Tetralogy of Fallot, 3 cases of hypoplastic left heart syndrome, 1 case of tricuspid atresia, 1 case of transposition of the great arteries, 1 case of severe tricuspid regurgitation, and 2 cases of complex CHD. Pm-MRI had concordant findings in 73.7% (14/19) cases, discordant findings in 15.8% (3/19) cases, and additional findings in 10.5% (2/19) cases when compared with prenatal ultrasound. Pm-MRI findings were concordant with autopsy in all 8 CHD cases terminated over 13+6 weeks. It is feasible to exhibit the structure of fetal heart terminated in the first trimester clearly on 9.4-T pm-MRI with an optimized scanning protocol. High-field pm-MRI could provide medical imaging information of CHD for those terminated in the early stage of gestation, especially for those limited by conventional autopsy.


Transient superior vena cava syndrome due to propylthiouracil therapy in intrathoracic goiter.
Intrathoracic goiter is a rare cause of superior vena cava syndrome. We present the findings in a patient in whom the syndrome was precipitated by therapy with propylthiouracil and remitted on withdrawal of the medication. The superior vena cava syndrome did not recur on medical management, suggesting that surgery is not always indicated in this setting.


Paroxysmal nonkinesigenic dyskinesia with tremor.
Introduction. Paroxysmal nonkinesigenic dyskinesia (PNKD) consists of episodes of chorea, athetosis, or dystonia which are not triggered by movement, with complete remission between episodes. A case of genetically confirmed PNKD with simultaneous tremor has not been previously reported. Case Report. The patient is an 86-year-old right-handed female who presented with episodic stiffness, with onset at age 9. Attacks have a prodrome of difficulty in speaking, followed by abnormal sensation in extremities. Episodes consist of dystonia of trunk associated with upper and lower extremity chorea. There is complete resolution between attacks except for persistent mild head tremor and action tremor of both extremities. Attack frequency and duration as well as tremor amplitude escalated two and a half years ago, in correlation with development of breast carcinoma. Episodes improved after successful cancer treatment, but higher amplitude tremor persisted. There is an autosomal dominant family history of similar episodes but not tremor. Genetic diagnosis was confirmed via A7V mutation of the myofibrillogenesis regulator (MR-1) gene. Conclusion. Exacerbation due to another medical or psychiatric condition should be considered if there is unexpected deterioration in episode frequency or length. PNKD due to MR-1 mutation may exist even in the presence of action tremor.


Cinacalcet attenuates the renal endothelial-to-mesenchymal transition in rats with adenine-induced renal failure.
Elevated serum parathyroid hormone (PTH) is an important complicated phenomenon in patients with chronic kidney disease (CKD). Emerging evidence indicates the involvement of PTH in organ fibrosis, and suppression of PTH by cinacalcet (CINA) ameliorates the progression of fibrotic disorders. However, the underlying mechanisms are largely unknown. The endothelial-to-mesenchymal transition (EndMT) has been shown to be an important mechanism involved in renal fibrosis. The present study aimed to investigate whether CINA treatment attenuated renal EndMT in rats with adenine-induced chronic renal failure (CRF). Compared with the control group, serum PTH was significantly higher in the CRF group and was suppressed after CINA treatment. Serum calcium, phosphorus, and calcium × phosphorus product levels were similar in the CRF group and CINA-treated CRF group. Renal collagen accumulation was significantly increased in the CRF group, which was markedly ameliorated by CINA treatment. Expression of the endothelial marker CD31 was significantly downregulated in rats with CRF, whereas expression of the mesenchymal markers fibroblast specific-protein 1 and α-smooth muscle actin was markedly upregulated. These changes were inhibited by CINA treatment. The protein levels of these EndMT-related markers were strongly correlated with serum PTH concentrations. Furthermore, the in vitro study showed that PTH could significantly increase the expression of fibroblast specific-protein 1 and α-smooth muscle actin and decrease CD31 in mRNA and protein levels in a concentration- and time-dependent manner. In conclusion, our study suggests that reducing serum PTH by CINA treatment could attenuate renal fibrosis via suppression of EndMT in the adenine-induced CRF rat model.


Emotional intelligence: painting different paths for low-anxious and high-anxious psychopathic variants.
Psychopathic individuals may be disaggregated into low-anxious (emotionally stable "primary psychopaths") and high-anxious (emotionally disturbed "secondary psychopaths") variants that may differ in their capacity for adaptive behavior. In turn, the skills encompassed by emotional intelligence (EI) predict social and business success. Based on a sample of 188 male undergraduates, we evaluate the performance of low-anxious psychopathic, high-anxious psychopathic, and low psychopathic comparison groups on a measure of EI. High-anxious psychopaths manifested significantly lower EI than the other two groups, particularly with respect to managing emotions and facilitating thoughts. In contrast, low-anxious psychopaths manifested intact EI, with skill in facilitating thoughts. High-anxious (but not low anxious) psychopaths were more likely than low psychopathic comparisons to manifest violence. These results are consistent with the notion that primary psychopaths have greater capacity to attain success in traditional society than secondary psychopaths, and invite a direct test of this hypothesis in future research.


Localization of calcium and microfilament changes in mechanically stressed cells.
We combined fluorescence labeling, digital image processing, and micromanipulation to investigate the intracellular events induced by inflicting a mechanical stress on rat basophilic leukemia cells. Our findings were as follows: 1. Most cells displayed a localized calcium rise in response to micropipet aspiration. This represented an average threefold increase as compared to resting level, and it was observed during the first 10 s following aspiration. A slow return to initial level occurred within about 3 min. Further, this calcium rise involved a mobilization of intracellular stores, since it was not prevented by adding a calcium chelator into the extracellular medium. 2. All micropipet-aspirated cells displayed a local accumulation of microfilaments, with a preferential localization in the cell protrusions or near the pipet tips. 3. No absolute correlation was found between the localization of calcium rise and cytoskeletal accumulation. 4. Cell deformability was decreased when intracellular calcium was maintained at a constant (high or low) level with ionomycin and/or EGTA. It is concluded that cells have a general ability to respond to mechanical stimulation by a coordinated set of events. More parameters must be studied before the mechanisms of cell shape regulation are fully understood.


Transcriptomic analysis of Sur7-mediated response of Beauveria bassiana to different nutritional conditions.
Integrity of the cell wall is requisite for fungal growth and function. Sur7 governs cell wall composition, and affects conidial sporulation and germination in Beauveria bassiana, a filamentous entomopathogenic fungus. The role of Sur7 in fungal growth on various nutrients remains unclear. We have previously reported that Sur7 deletion results in the attenuation of B. bassiana growth on supplemented Sabouraud dextrose agar (SDAY) and minimal Czapek-Dox agar (CDA) compared to wild type (WT). Here, we used transcriptomic analysis to compare WT and Sur7 mutant (ΔSur7) responses to CDA and SDAY. Growth on CDA, compared with that on SDAY, affected the expression of more genes in the WT than in the mutant. Differentially expressed genes were enriched for transportation process terms in the ΔSur7 mutant and metabolic process terms in the WT. Different processes were repressed in the ΔSur7 (metabolic process) and WT (ribosome synthesis) cells. Despite the shared enrichment of nitrogen metabolism genes, differentially expressed genes were enriched in distinct saccharide-energy metabolism terms in each strain. We conclude that Sur7 ensures the growth of B. bassiana in a minimal medium by influencing the expression of genes involved in the consumption of sucrose via specific energy metabolism pathways.


Leucine zipper dimerized bivalent and bispecific scFv antibodies from a semi-synthetic antibody phage display library.
This report describes the construction of leucine zipper-based dimerization cassettes for the conversion of recombinant monomeric scFv antibody fragments to bivalent and bispecific dimers. A truncated murine IgG3 hinge region and a Fos or Jun leucine zipper were cloned into four scFv fragments previously isolated from a synthetic antibody phage display library. Cysteine residues flanking the zipper region were introduced to covalently link dimerized scFv fragments. The secreted fusion proteins were shown to spontaneously and efficiently form stable Fos-Fos or Jun-Jun homodimers in the Escherichia coli periplasm at levels comparable to their monovalent counterparts. The bivalent (scFv)2 fragments performed well in enzyme-linked immunosorbent assay, flowcytometric, and immunohistochemical analysis. Fos and Jun homodimer (scFv)2 antibodies with different specificities could be reduced, reshuffled, and reoxidized to form preparations of functional bispecific (scFv)2 Fos-Jun heterodimers. These Fos and Jun fusion protein cassettes provide a universal basis for the construction of dimeric scFv antibodies with enhanced avidity or dual specificity.


Efficacy of Tai Chi on Patients With Chronic Kidney Disease.
Previous systematic reviews elucidate the efficacy of Tai Chi on the rehabilitation and treatment for various chronic diseases. Yet, no consensus has been reached on its efficacy and safety from those with chronic kidney disease (CKD). Therefore, we conducted a systematic review to critically summarize what is already known about the prevailing benefits of Tai Chi for CKD patients. There was no evidence that Tai Chi had adverse effects on CKD patients. Long-term Tai Chi exercises could improve quality of life, cardiorespiratory fitness, and physical motor function for the end-stage renal disease (ERSD) patients undergoing dialysis. Regular Tai Chi exercises might exert modest influences in delaying CKD progression for mild-moderate CKD patients. However, there is insufficient evidence to demonstrate positive effects of Tai Chi exercises on bone health of the ESRD patients. Accordingly, rigorously designed, longer-term studies of Tai Chi are warranted to identify its efficacy on CKD patients across different stages, especially targeting potential mechanisms in terms of Tai Chi altering biological gene profile expressions.


Comparative proteomics of ovarian epithelial tumors.
We analyzed 12 ovarian epithelial tumors using 2D PAGE-based comparative proteomics to construct intra- and inter-tumoral distance map trees and to discover surrogate biomarkers indicative of an ovarian tumor. The analysis was performed after laser microdissection of 12 fresh-frozen tissue samples, including 4 serous, 5 mucinous, and 3 endometrioid tumors, with correlation with their histopathological characteristics. Ovarian epithelial tumors and normal tissues showed an apparent separation on the distance map tree. Mucinous carcinomas were closest to the normal group, whereas serous carcinomas were located furthest from the normal group. All mucinous tumors with aggressive histology were separated from the low malignant potential (LMP) group. The benign-looking cysts adjacent to the intraepithelial carcinoma (IEC) showed an expression pattern identical to that of the IEC area. The extent of change on the lineages leading to the mucinous and serous carcinoma was 1.98-fold different. The overall gene expression profiles of serous or endometrioid carcinomas appeared to be less affected by grade or stage than by histologic type. The potential candidate biomarkers screened in ovarian tumors and found to be significantly up-regulated in comparison to normal tissues were as follows: NM23, annexin-1, protein phosphatase-1, ferritin light chain, proteasome alpha-6, and NAGK (N-acetyl glucosamine kinase). In conclusion, ovarian mucinous tumors are distinct from other ovarian epithelial tumors. LMP mucinous tumors showing histologically aggressive features belong to mucinous carcinoma on the proteomic basis.


Developmental basis of sexually dimorphic digit ratios.
Males and females generally have different finger proportions. In males, digit 2 is shorter than digit 4, but in females digit 2 is the same length or longer than digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous sexually dimorphic behavioral and physiological conditions. Although correlational studies suggest that digit ratios reflect prenatal exposure to androgen, the developmental mechanism underlying sexually dimorphic digit development remains unknown. Here we report that the 2D:4D ratio in mice is controlled by the balance of androgen to estrogen signaling during a narrow window of digit development. Androgen receptor (AR) and estrogen receptor α (ER-α) activity is higher in digit 4 than in digit 2. Inactivation of AR decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas inactivation of ER-α increases growth of digit 4, which leads to a lower 2D:4D ratio. We also show that addition of androgen has the same effect as inactivation of ER and that addition of estrogen mimics the reduction of AR. Androgen and estrogen differentially regulate the network of genes that controls chondrocyte proliferation, leading to differential growth of digit 4 in males and females. These studies identify previously undescribed molecular dimorphisms between male and female limb buds and provide experimental evidence that the digit ratio is a lifelong signature of prenatal hormonal exposure. Our results also suggest that the 2D:4D ratio can serve as an indicator of disrupted endocrine signaling during early development, which may aid in the identification of fetal origins of adult diseases.


Magnesium sulphate for pre-eclampsia: care of the neonate.
Whilst the care of women requiring magnesium sulphate for pre-eclampsia and eclampsia is well documented, there is considerably less guidance on the identification and treatment of magnesium toxicity in women and neonates within midwifery literature, particularly in relation to neonatal care. Given the potential risk of magnesium toxicity in the neonate and the ensuing problems that may occur, it is essential that all midwives are knowledgeable about the care and observations required for the fetus and neonate. This paper provides a background to the neonatal anatomy and physiology, recognition of neonatal magnesium toxicity and implications for midwifery practice.


The regulation of prostitution in Beyoğlu (1875-1915).
This study examines the development and nature of the regulation of prostitution in Beyoğlu during the late Ottoman Empire with special emphasis on the way the regulationist regime reinforced existing patterns of class and gender domination. The regulation of prostitution became a matter of urgency in the last decades of the nineteenth century in Istanbul, particularly in Beyoğlu, the cosmopolitan centre of the city. Through this process, the protests of the local residents of the area objecting to the proliferation of prostitution in their neighbourhoods played a crucial role in prompting the governmental authorities to tighten the regulations.


Members of the YjgF/YER057c/UK114 family of proteins inhibit phosphoribosylamine synthesis in vitro.
The YjgF/YER057c/UK114 family of proteins is highly conserved across all three domains of life and currently lacks a consensus biochemical function. Analysis of Salmonella enterica strains lacking yjgF has led to a working model in which YjgF functions to remove potentially toxic secondary products of cellular enzymes. Strains lacking yjgF synthesize the thiamine precursor phosphoribosylamine (PRA) by a TrpD-dependent mechanism that is not present in wild-type strains. Here, PRA synthesis was reconstituted in vitro with anthranilate phosphoribosyltransferase (TrpD), threonine dehydratase (IlvA), threonine, and phosphoribosyl pyrophosphate. TrpD-dependent PRA formation in vitro was inhibited by S. enterica YjgF and the human homolog UK114. Thus, the work herein describes the first biochemical assay for diverse members of the highly conserved YjgF/YER057c/UK114 family of proteins and provides a means to dissect the cellular functions of these proteins.


Ganciclovir treatment of serious cytomegalovirus infection in heart and heart-lung transplant recipients.
Experience with ganciclovir treatment of life- or sight-threatening cytomegalovirus (CMV) infections in 22 heart and heart-lung transplant recipients at six medical centers was reviewed. All six heart-lung recipients and six of 16 heart recipients had CMV pneumonitis; five heart recipients had CMV gastrointestinal disease, three had retinitis, and two had infections in more than one organ system. Of the 18 patients (82%) surviving initial ganciclovir therapy, 16 improved, one stabilized, and one showed no change in clinical status. All cultures positive for CMV before treatment became negative during therapy. Six patients (33% of survivors) had recurrent episodes and received additional therapy. Four patients (18%) died during initial therapy; death was believed to be related to CMV infection in only two cases and to ganciclovir treatment in no case. Adverse reactions possibly attributable to ganciclovir included neutropenia (four patients), impaired renal function (one), thrombocytopenia (one), decreased blood pressure (one), and seizure (one). Ganciclovir appears to be well tolerated and to alter favorably the outcome of serious CMV infection in this patient population.


Reasonable incomplete revascularisation after percutaneous coronary intervention: the SYNTAX Revascularisation Index.
Incomplete revascularisation is common after percutaneous coronary intervention (PCI). While the absolute amount of residual coronary artery disease (CAD) after PCI has been shown to be associated with worse outcomes, whether the proportion of treated CAD is prognostically important remains to be determined. We sought to quantify the proportion of CAD burden treated by PCI and to evaluate its impact on outcomes using a new prognostic instrument - the SYNTAX Revascularisation Index (SRI). The baseline SYNTAX score (bSS) and residual SYNTAX score (rSS) were determined from 2,618 angiograms of patients enrolled in the prospective ACUITY trial. The SRI was then calculated for each patient using the following formula: SRI=(1-[rSS/bSS])×100. Outcomes were examined according to three SRI groups (SRI=100% [complete revascularisation], 50-99%, and <50%). The median bSS was nine (IQR 5, 16), and after PCI the median rSS was one (IQR 0, 6). The median SRI was 85% (IQR 50, 100), and was 100% in 1,079 patients (41.2%), 50-99% in 907 patients (34.6%), and <50% in 632 patients (24.1%). One-year adverse outcomes, including death, were inversely proportional to the SRI. An SRI cut-off of <80% (present in 1,189 [45.4%] patients after PCI) had the best prognostic accuracy for prediction of death (area under the curve 0.60, 95% confidence interval [CI]: 0.53-0.67, p<0.0001). By multivariable analysis, SRI was an independent predictor of one-year mortality (hazard ratio [HR] 2.17, 95% CI: 1.05-4.35, p=0.03). However, when compared to other scores, the rSS showed superior accuracy and predictive capability for one-year mortality. The SRI is a newly described method for quantifying the proportion of CAD burden treated by PCI. Given its correlation with mortality, and pending external validation, the SRI may be useful in assessing the degree of revascularisation after PCI, with SRI ≥80% representing a reasonable goal. However, the rSS showed superior predictive capability for one-year mortality.


EFSUMB Recommendations and Clinical Guidelines for Intestinal Ultrasound (GIUS) in Inflammatory Bowel Diseases.
The accuracy and usefulness of gastrointestinal ultrasound (GIUS) for detecting activity and complications of inflammatory bowel diseases (IBD), has been reported in studies, promoting this technique as an important tool for the management of IBD patients. Whilst well recognised by international guidelines, standardization and general agreement in the definition of the luminal and extra-intestinal features, still need to be well defined.A task force group of 17 experts in GIUS faced this issue, by developing recommendations and clinical guidelines for the use of GIUS in IBD, under the auspices of EFSUMB. This article presents the consensus on the current data on sonographic features of IBD and summarises the accuracy of different sonographic modalities for the management of IBD patients.


The expression of collagenase 3 (MMP-13) mRNA in the synovial tissue is associated with histopathologic type II synovitis in rheumatoid arthritis.
The histopathologic analysis of the synovial tissue is important to distinguish rheumatoid arthritis (RA) from other forms of synovitis and to provide information about prognosis and therapeutic strategies at early stages of the disease. In this context, the present study was performed to investigate the correlation between immunohistopathological and morphological features of synovitis and the expression of collagenase 3 (MMP-13) known to contribute significantly to cartilage degradation in RA. In the histopathologic scoring system used in this study, type I synovitis is characterized by B lymphocyte infiltration and an intact lining, and is only mild destructive to cartilage and bone. Type II shows marked diffuse infiltrations of macrophages and T lymphocytes, an ulcerated lining, fibrin exudation, and invasive growth into cartilage and bone tissue. Investigating 36 patients with RA, 21 patients (58%) were positive for the expression of collagenase 3 mRNA in the synovial tissue. Among these patients, 19 showed a histopathologic type II synovitis and only 2 patients had undifferentiated synovitis. In contrast, synovial tissue samples from patients without collagenase 3 mRNA expression were characterized in 6 cases by type I, in 5 cases by type II and in 4 cases by undifferentiated synovitis. The analysis of the clinical data revealed that RA patients with a histopathologic type II synovitis and synovial tissue collagenase 3 mRNA expression had elevated levels of systemic markers of inflammation and received stronger therapies. The data suggest, that collagenase 3 expression and the histopathologic type II synovitis are associated with a severe and destructive course of RA.


Molecular Swings as Highly Active Ion Transporters.
Ions are transported across membrane mostly via carrier or channel mechanisms. Herein, a unique class of molecular-machine-inspired membrane transporters, termed molecular swings is reported that utilize a previously unexplored swing mechanism for promoting ion transport in a highly efficient manner. In particular, the molecular swing, which carries a 15-crown-5 unit as the ion-binding and transporting unit, exhibits extremely high ion-transport activities with EC50 values of 46 nm (a channel:lipid molar ratio of 1:4800 or 0.021 mol % relative to lipid) and 110 nm for K+ and Na+ ions, respectively. Remarkably, such ion transport activities remain high in a cholesterol-rich environment, with EC50 values of 130 (0.045 mol % relative to lipid/cholesterol) and 326 nm for K+ and Na+ ions, respectively.


Training issues in emergency psychiatry.
The psychiatric emergency service (PES) is an excellent learning environment that offers trainees a multitude of educational opportunities. PES personnel need to develop training programs to ensure that psychiatry residents obtain knowledge and skills in emergency evaluation, crisis management, and triage of patients, as required by accreditation bodies. Curriculum guidelines can best be achieved through a rotation that offers an orientation, didactic presentations, clinical supervision, and graded responsibilities. Improved training opportunities, senior electives, and fellowships will promote emergency psychiatry as a career choice.


Adaptive extraction of modulation for cavitation noise.
Modulation analysis is an important issue in target classification and identification for ship-radiated noise. However, the modulated cavitation noise sought for analyzing is always submerged under strong ambient noise and difficult to be separated out. In this paper, an approach is proposed to extract the modulated cavitation noise adaptively by combining empirical mode decomposition and singular value decomposition. The results for both synthetical and practical signals demonstrate the practicability and effectivity of the approach.


Mesenchymal Stromal Cells Implantation in Combination with Platelet Lysate Product Is Safe for Reconstruction of Human Long Bone Nonunion.
Nonunion is defined as a minimum of 9 months since injury without any visible progressive signs of healing for 3 months. Recent literature has shown that the application of mesenchymal stromal cells is safe, in vitro and in vivo, for treating long bone nonunion. The present study was performed to investigate the safety of mesenchymal stromal cell (MSC) implantation in combination with platelet lysate (PL) product for treating human long bone nonunion. In this case series clinical trial, orthopedic surgeons visited eighteen patients with long bone nonunion, of whom 7 complied with the eligibility criteria. These patients received mesenchymal stromal cells (20 million cells implanted once into the nonunion site using a fluoroscopic guide) in combination with PL product. For evaluation of the effects of this intervention all the patients were followed up by taking anterior-posterior and lateral X-rays of the affected limb before and 1, 3, 6, and 12 months after the implantation. All side effects (local or systemic, serious or non-serious, related or unrelated) were observed during this time period. From a safety perspective the MSC implantation in combination with PL was very well tolerated during the 12 months of the trial. Four patients were healed; based on the control Xray evidence, bony union had occurred. Results from the present study suggest that the implantation of bone marrow-derived MSCs in combination with PL is safe for the treatment of nonunion. A double blind, controlled clinical trial is required to assess the efficacy of this treatment (Registration Number: NCT01206179).


Immunohistochemical detection of CD5 with monoclonal antibody 4C7 on paraffin sections.
CD5 is useful for the classification of low-grade B-cell lymphomas, because it is aberrantly expressed in B-cell chronic lymphocytic leukemias/small lymphocytic lymphomas (B-CLLs/SLLs) and mantle cell lymphomas (MCLs), but not in the other well-described low-grade B-cell lymphomas. Therefore, we tested the utility of monoclonal antibody (MAb) 4C7 to detect CD5 on paraffin sections of 22 cases with low-grade B-cell lymphomas and 4 cases with high-grade B-cell lymphomas and compared the results with CD5 detection by analysis of fresh tissue with a fluorescent-activated cell sorting (FACS). After heat-induced epitope retrieval we could detect CD5 on paraffin sections in all MCLs and B-CLLs/SLLs, identical to the results of flow cytometry. Eleven of 12 cases that showed no CD5 expression by FACS analysis were also negative on paraffin sections. In only one case of a presumed blastoid MCL, CD5 was detectable by immunohistochemistry but not by FACS analysis. We conclude that MAb 4C7 against CD5 is a useful paraffin-reactive marker, especially to correctly identify MCLs on paraffin sections.


Complications after endoscopic sphincterotomy in liver transplant recipients: A retrospective single-centre study.
Biliary tract complications after liver transplantation are usually treated by endoscopic retrograde cholangiopancreatography. When biliary tract intervention is indicated, endoscopic sphincterotomy is often required. However, data regarding complication rates after endoscopic sphincterotomy in liver transplant recipients are limited. This study therefore investigated complication rates during the first 15 days after endoscopic sphincterotomy in liver transplant recipients. This study retrospectively reviewed 157 consecutive liver transplant recipients who underwent endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy between January 1998 and August 2013 at the University Hospital of Münster, Germany. Complications that occurred within the first 15 days after the procedure were recorded, and complication rates were compared between patients who underwent conventional and precut endoscopic sphincterotomy. A total of 24 complications (15.2%) were recorded, including 9 cases (5.7%) of pancreatitis, 6 cases (3.8%) of bleeding, and 1 case (0.6%) of perforation. There were no procedure-related deaths. There were no significant differences in complication rates between the two sphincterotomy techniques. The rate of post-procedural pancreatitis decreased over time. Endoscopic sphincterotomy is a safe procedure in liver transplant recipients. The procedure-related complication rate is reasonable and most complications can be managed conservatively.


The effects of passive smoking on olfaction in children.
The effect of passive smoking on odor identification was studied in 10 children exposed to passive smoke at home. All had at least one parent who smoked at least one pack of cigarettes a day. The control group consisted of 10 children of nonsmoking parents. Ten odorants were tested: vinegar, ammonia, peppermint, roses, bleach, vanilla, cough drops, turpentine, licorice and mothballs. Each child was presented with five test trays containing all 10 odorants in random order. Of the total of 500 odors presented, the control group correctly identified 396 (79%) and the study group, 356 (71%) (p < 0.005). This work demonstrates that children exposed to passive smoke have difficulty identifying odors in comparison to children raised in relatively smoke-free environments. Since the study group tend to misidentify four of the 10 odorants tested--vanilla, roses, mothballs and cough drops--we suggest that these four odorants should suffice in testing odor identification in children.


A Dyadic Growth Approach to Partner Regulation Attempts on Changes in Drinking and Negative Alcohol-Related Consequences.
Many individuals engage in regulation attempts to manage or reduce their partner's alcohol use. Research on partner social control behaviors has shown that regulation attempts generally factor into negative (i.e., punishing) and positive (i.e., rewarding) dimensions. In the alcohol domain, partner drinking has been associated with poorer relationship functioning through punishment. This research applied a dyadic growth model approach to investigate changes in alcohol consumption and negative alcohol-related consequences over 6 months, and evaluated whether partner regulation attempts (punishment and reward) were influential (i.e., successful) in these changes. Married couples (N = 123 dyads) completed web-based measures of partner regulation attempts, alcohol consumption, and alcohol-related consequences three times over a 6-month period. Results from dyadic growth curve analyses showed that partner punishment was significantly associated with increases in alcohol-related consequences-and marginally associated with increases in alcohol consumption-over the 6-month period. Partner reward was associated with decreases in consumption over the study period. These effects were not different for husbands and wives. Conclusion/Importance: Results support previous research demonstrating deleterious impact of partner punishing control strategies and provide important implications for future interventions and treatment.


Combined embolization and surgical resection of a giant mediastinal tumor.
Large mediastinal tumors typically have a rich blood supply derived from multiple arteries, and surgical resection can be associated with a large blood loss. Embolization is used to treat a variety of malignant and benign conditions preoperatively, as well as an alternative to surgery, however, the use of preoperative embolization of large mediastinal tumors has not been extensive. Herein, we report a case of a giant mediastinal tumor measuring >15 cm and extending into both chest cavities in which preoperative embolization was used to reduce the surgical blood loss and facilitate excision of the lesion.


White variants of Trichophyton violaceum isolated in Ethiopia.
Certain dermatophytes are geographically restricted and endemic in particular parts of the world, while other species may have a sporadic but worldwide distribution. Trichophyton violaceum is one of the most common dermatophytes causing tinea capitis, and is the predominant cause of tinea in Africa, South America and the Indian subcontinent. Among 1187 dermatophyte isolates collected from Ethiopian patients with various types of tinea, 32 isolates had uncharacteristic phenotypic features. Based on conventional methods complemented by sequence analysis of the rDNA ITS2 region, these isolates were identified as white variants of T. violaceum. This is the first time that white isolates of T. violaceum have been identified in Ethiopia.


Antioxidative Effect of Quetiapine on Acute Ultraviolet-B-Induced Skin and HaCaT Cell Damage.
Quetiapine is a new type of antipsychotic drug, with effective protection of pheochromocytoma PC12 cells from oxidative stress-induced apoptosis. Ultraviolet-B radiation can increase reactive oxygen species (ROS) production, resulting in significant inflammatory responses in damaged skin. Thus, the purpose of this study is to explore whether quetiapine protects the skin from intermediate-wave ultraviolet (UVB)-induced damage through antioxidant stress. In vivo, we found quetiapine treatment was able to significantly decrease skin thickness, erythema, and edema, as well as inflammation compared to control group. Moreover, quetiapine treatment increased the activities of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In addition, it reduced the production of malondialdehyde (MDA), a kind of oxidized lipid. In vitro, we found that quetiapine blocked UVB-induced intracellular ROS generation and maintained the cell activity at a normal level. Furthermore, we tested the phosphorylation of p38 both in vivo and in vitro, and we found that quetiapine could inhibit phosphorylation of p38, which is caused by UVB irradiation. We concluded that quetiapine was able to relieve UVB-induced skin damage through its antioxidative properties. These effects might be associated with p38 MAPK signaling pathway.


Indoxyl sulfate is a nephro-vascular toxin.
Indoxyl sulfate is markedly accumulated in the serum of patients with chronic kidney disease (CKD). The oral sorbent AST-120 reduces the serum levels of indoxyl sulfate in CKD patients by adsorbing indole, a precursor of indoxyl sulfate, in the intestine, and thereby stimulating its excretion in feces. AST-120 is used for the treatment of patients with CKD to slow down the progression of CKD. Indoxyl sulfate is taken up by the cells through organic anion transporters (OAT1 and/or OAT3), and induces cellular production of free radicals such as superoxide by activating nicotinamide adenine dinucleotide phosphate oxidase, especially Nox4, thereby impairing the cellular antioxidative system. Indoxyl sulfate induces free radicals in renal tubular cells and glomerular mesangial cells, and stimulates the progression of CKD. I proposed the protein metabolite theory, which states that endogenous protein metabolites such as indoxyl sulfate play a significant role in the progression of CKD by increasing expressions of transforming growth factor-beta1, tissue inhibitor of metalloproteinase-1, and proalpha1(I)collagen. Indoxyl sulfate also induces free radicals in vascular smooth muscle cells and vascular endothelial cells. Indoxyl sulfate stimulates proliferation and osteoblastic transdifferentiation of vascular smooth muscle cells, and inhibits viability and nitric oxide production of vascular endothelial cells. Indoxyl sulfate promotes aortic calcification and aortic wall thickening in hypertensive rats with expression of osteoblast-specific proteins. In conclusion, indoxyl sulfate is a nephro-vascular toxin that is involved in the progression of not only CKD, but also of cardiovascular disease in CKD patients. Therefore, AST-120 may ameliorate the progression of cardiovascular disease as well as of CKD by removing indoxyl sulfate.


How stroke survivors and primary support persons experience nurses in rehabilitation.
The role of nursing in rehabilitation has been studied from various perspectives. This study explored experiences with nursing care in rehabilitation from the perspective of stroke survivors and their primary support persons (PSP). The sample consisted of six stroke survivors and seven primary support persons. Through in-depth phenomenological interviews, participants related the experiences with nursing care that stood out for them. The experience was conceptualized as a two-dimensional continuum from helpful to adversarial, with none of the participants articulating a therapeutic presence from nurses. Implications for nursing are explored.


Maintenance of a computerized medical record form.
Structured entry forms for clinical records should be updated to take into account the physicians' needs during consultation and advances in medical knowledge and practice. We updated the computerized medical record form of a hypertension clinic, based on its previous use and clinical guidelines. A statistical analysis of previously completed forms identified several unnecessary items rarely used by clinicians. A terminological analysis of guidelines and of free-text answers on completed forms identified several new topics relevant to current clinical practice. We therefore added new items to the form and some topics previously recorded as free text were itemized. We collaborated with clinicians in interpretation of the results of the statistical and terminological analyses used as the starting point and guide for this updating process.


A tribute to Dr. Frank I Tovey on his 90th birthday.
This paper pays a tribute to Dr. Frank I Tovey on his 90th birthday which happens on September 1, 2011, and briefly describes the major findings in his research career and contributions as follows. The geographical prevalence of duodenal ulceration is related to staple diets. Unrefined wheat and maize, soya, certain pulses and millets are associated with a low prevalence while refined wheat, maize and rice, yams, cassava and green banana with a high prevalence. Predominant foodstuffs from low prevalence areas are ulceroprotective in rat peptic ulcer models. The protective activity lies in the lipid fraction present in these foodstuffs. The lipid fraction also promotes ulcer healing, is active both orally and intramuscularly and is ulceroprotective against non-steroidal anti-inflammatory drugs (NSAIDs). The phospholipids and phytosterols present in the lipid have been identified to be responsible for this protective activity. The combination of phospholipids and phytosterols may be of value in the prevention and treatment of duodenal ulceration and protection against the ulcerogenic effect of NSAIDs.


Split support and split conflict randomization tests in phylogenetic inference.
Randomization tests allow the formulation and statistical testing of null hypotheses about the quality of entire data sets or the quality of fit between the data and particular phylogenetic hypotheses. Randomization tests of phylogenetic hypotheses based on the concepts of split support and split conflict are described here, as are tests where splits, rather than the data, are randomly permuted. These tree-independent randomization tests are explored through their application to phylogenetic data for caecilian amphibians. Of these tests, split support randomization tests appear to be the most promising tools for phylogeneticists. These tests seem quite conservative, are applicable to nonpolar data and unordered multistate characters, and do not have the problems of nonindependence that affect split conflict and hierarchy tests. Unlike split conflict tests, their power does not appear to be correlated with split size. However, all tests are sensitive to taxonomic scope. Split support tests may help discern data that are likely to be affected by the problems of long-branches effects. Comparison of test results for mutually incompatible splits may help identify the presence of strong misleading signals in phylogenetic data. Significant split support could be a prerequisite for considering phylogenetic hypotheses to be well supported by the data, and split support randomization tests might be usefully applied prior to or as part of tree construction.


Risk factors for repeated cerebrospinal shunt failures in pediatric patients with hydrocephalus.
Repeated cerebrospinal fluid (CSF) shunt failures in pediatric patients are common, and they are a significant cause of morbidity and, occasionally, of death. To date, the risk factors for repeated failure have not been established. By performing survival analysis for repeated events, the authors examined the effects of patient characteristics, shunt hardware, and surgical details in a large cohort of patients. During a 10-year period all pediatric patients with hydrocephalus requiring CSF diversion procedures were included in a prospective single-institution observational study. Patient characteristics were defined as age, gender, weight, head circumference, American Society of Anesthesiology class, and cause of hydrocephalus. Surgical details included whether the procedure was performed on an emergency or nonemergency basis, use of antibiotic agents, concurrent surgical procedures, and duration of the surgical procedure. Details on shunt hardware included: the type of shunt, the valve system, whether the shunt system included multiple or complex components, the type of distal catheter, the site of the shunt, and the side on which the shunt was placed. Repeated shunt failures were assessed using multivariable time-to-event analysis (by using the Cox regression model). Conditional models (as established by Prentice, et al.) were formulated for gap times (that is, times between successive shunt failures). There were 1183 shunt failures in 839 patients. Failure time from the first shunt procedure was an important predictor for the second and third episodes of failure, thus establishing an association between the times to failure within individual patients. An age younger than 40 weeks gestation at the time of the first shunt implantation carried a hazard ratio (HR) of 2.49 (95% confidence interval [CI] 1.68-3.68) for the first failure, which remained high for subsequent episodes of failure. An age from 40 weeks gestation to 1 year (at the time of the initial surgery) also proved to be an important predictor of first shunt malfunctions (HR 1.77, 95% CI 1.29-2.44). The cause of hydrocephalus was significantly associated with the risk of initial failure and, to a lesser extent, later failures. Concurrent other surgical procedures were associated with an increased risk of failure. The patient's age at the time of initial shunt placement and the time interval since previous surgical revision are important predictors of repeated shunt failures in the multivariable model. Even after adjusting for age at first shunt insertion as well as the cause of hydrocephalus, there is significant association between repeated failure times for individual patients.


Olive: a key gene required for chlorophyll biosynthesis in Antirrhinum majus.
Olive (oli) is a recessive nuclear mutation of Antirrhinum majus which reduces the level of chlorophyll pigmentation and affects the ultrastructure of chloroplasts. The oli-605 allele carries a Tam3 transposon insertion which has allowed the locus to be isolated. The oli gene encodes a large putative protein of 153 kDa which shows homology to the products of two bacterial genes necessary for tetrapyrrole-metal chelation during the synthesis of bacteriochlorophyll or cobyrinic acid. We therefore propose that the product of the oli gene is necessary for a key step of chlorophyll synthesis: the chelation of magnesium by protoporphyrin IX. Somatic reversion of the oli-605 allele produces chimeric plants which indicate that the oli gene functions cell-autonomously. Expression of oli is restricted to photosynthetic cells and repressed by light, suggesting that it may be involved in regulating the rate of chlorophyll synthesis in green tissues.


Situational and sociodemographic characteristics of children infected with human immunodeficiency virus from pediatric sexual abuse.
This study assessed the situational and sociodemographic characteristics of children infected with human immunodeficiency virus (HIV) from pediatric sexual abuse. A letter of inquiry was sent to 2147 professionals across health and social service disciplines involved with child abuse assessment, treatment, and prevention. Respondents working in programs where HIV antibody testing of abuse victims occurs and who had identified HIV infection in one or more abused children were sent a survey to assess the demographics of victims, the family/living situation where abuse occurred, alternative risks for HIV infection, bases for diagnosis of sexual abuse and for HIV antibody testing, and profiles of the perpetrator and type of abuse. Of 5622 estimated HIV antibody tests conducted during 113,198 sex abuse assessments, 28 children were infected with HIV and lacked any alternative transmission route to that of sexual abuse. A total of 41 HIV-infected children with a history of sexual abuse were identified. Thirteen cases had alternative risk factors and were excluded from analysis. Sixty-four percent of the 28 victims with sexual abuse as the sole risk factor were female and 71% were African-American. The mean age was 9 years. Coinfection with another sexually transmitted disease (STD) occurred in 9 (33%) cases. Sexual abuse was diagnosed on the basis of a victim disclosure in 21 (75%) cases. The basis for HIV antibody testing was physical findings suggestive of HIV infection in 9 (32%) cases, HIV-seropositive or high-risk perpetrator in 6 (21%) and 2 (7%) cases, respectively, and the presence of another STD in the victim in 4 (14%) cases. Perpetrators were a child's parent in 10 (42%) cases and another relative in 6 (25%) cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Self-sorting organization of two heteroditopic monomers to supramolecular alternating copolymers.
Self-sorting organization of two AB-type heteroditopic monomers led to the formation of linear supramolecular alternating copolymers driven by host-guest noncovalent interactions based on the bis(p-phenylene)-34-crown-10/paraquat derivative and dibenzo-24-crown-8/dibenzylammonium salt recognition motifs as confirmed by 1H NMR, cyclic voltammetry, dynamic light scattering, viscosity measurements, and scanning electron microscopy.


Empirical research to evaluate ethics committees' burdensome and perhaps unproductive policies and practices: a proposal.
THE U.S. SYSTEM FOR THE PROTECTION of human research subjects, particularly its ethics committee or Institutional Review Board (IRB) component, is excessively burdened. Many commentators, myself included, are concerned that, as a consequence of these excessive burdens, the IRB is losing its effectiveness in safeguarding the rights and welfare of human subjects. I believe that IRBs devote too much time doing work that simply does not need to be done. Several routine practices of IRBs are highly time consuming and, in my opinion, not sufficiently productive to warrant their continuation in their present form. Empirical research can and should be done to evaluate the consequences of these practices. If they are found to be insufficiently cost-effective, they should be modified or abandoned. This would result in reducing the burdens on IRBs, freeing up reviewers' time and energy to concentrate on more important and productive pursuits. I suggest we begin by evaluating two routine practices: (1) The practice of conducting all continuing reviews of ongoing research at convened meetings of the IRB. (2) The practice of referring all adverse events to the IRB for its review.


The reduced responsiveness of reticulospinal neurones to paired stimuli in cats.
In anaesthetized cats, the reactions of reticulospinal (RS) neurones were tested to paired stimuli applied at the periphery and in central structures (spinal cord funiculi, the reticular formation). This resulted in depression or disappearance of polysynaptic responses to the electrical testing stimuli. The intensity and duration of depression in the same animal after stimulation of peripheral and central structures was comparable, indicating that the responsible mechanisms act chiefly in the reticular formation itself. Polysynaptic discharges from RS neurones could be evoked from one source even when their responses to frequent stimulation of another source was depressed; this shows that attenuation affects reticular formation neurones before RS neurone level. Interposition of this mechanism between receptors and the RS system is very effective from the functional aspect: when the transmission and processing of a signal which does not bring any new information is minimized, the responses of the efferent RS system are minimized at the same instant.


Development and validation of a self-management scale of type 1 diabetes for Chinese adults.
Self-management is beneficial for improving health outcomes in adults with type 1 diabetes. However, there are no validated instruments to assess self-management in Chinese adults with type 1 diabetes. The aim of this study was to develop and validate the Self-Management of Type 1 Diabetes for Chinese Adults (SMOD-CA) scale. Qualitative and quantitative methods were used to develop the SMOD-CA.We conducted a literature review and semi-structured interviews to generate an initial item pool. An expert panel examined the content validity. We conducted a cross-sectional survey to evaluate scale reliability and validity. A total of 243 participants were recruited. Exploratory factor analyses were used to test the construct validity, and internal consistency and test-retest reliability were assessed. The expert panel determined that the SMOD-CA content validity index was satisfactory. The final 30-item scale consisted of four factors explaining 49.50% of the total variance in the data. Cronbach's α was 0.901 for the total scale and 0.911 for test-retest reliability. The SMOD-CA demonstrated good reliability and validity. The scale is a credible and effective instrument that can be used by social workers and health care professionals to assess self-management in Chinese adults with type 1 diabetes.Trial registration number NCT03610984.


Open-system nonequilibrium steady state: statistical thermodynamics, fluctuations, and chemical oscillations.
Gibbsian equilibrium statistical thermodynamics is the theoretical foundation for isothermal, closed chemical, and biochemical reaction systems. This theory, however, is not applicable to most biochemical reactions in living cells, which exhibit a range of interesting phenomena such as free energy transduction, temporal and spatial complexity, and kinetic proofreading. In this article, a nonequilibrium statistical thermodynamic theory based on stochastic kinetics is introduced, mainly through a series of examples: single-molecule enzyme kinetics, nonlinear chemical oscillation, molecular motor, biochemical switch, and specificity amplification. The case studies illustrate an emerging theory for the isothermal nonequilibrium steady state of open systems.


Deep-sequencing analysis of the mouse transcriptome response to infection with Brucella melitensis strains of differing virulence.
Brucella melitensis is an important zoonotic pathogen that causes brucellosis, a disease that affects sheep, cattle and occasionally humans. B. melitensis strain M5-90, a live attenuated vaccine cultured from B. melitensis strain M28, has been used as an effective tool in the control of brucellosis in goats and sheep in China. However, the molecular changes leading to attenuated virulence and pathogenicity in B. melitensis remain poorly understood. In this study we employed the Illumina Genome Analyzer platform to perform genome-wide digital gene expression (DGE) analysis of mouse peritoneal macrophage responses to B. melitensis infection. Many parallel changes in gene expression profiles were observed in M28- and M5-90-infected macrophages, suggesting that they employ similar survival strategies, notably the induction of anti-inflammatory and antiapoptotic factors. Moreover, 1019 differentially expressed macrophage transcripts were identified 4 h after infection with the different B. melitensis strains, and these differential transcripts notably identified genes involved in the lysosome and mitogen-activated protein kinase (MAPK) pathways. Further analysis employed gene ontology (GO) analysis: high-enrichment GOs identified endocytosis, inflammatory, apoptosis, and transport pathways. Path-Net and Signal-Net analysis highlighted the MAPK pathway as the key regulatory pathway. Moreover, the key differentially expressed genes of the significant pathways were apoptosis-related. These findings demonstrate previously unrecognized changes in gene transcription that are associated with B. melitensis infection of macrophages, and the central signaling pathways identified here merit further investigation. Our data provide new insights into the molecular attenuation mechanism of strain M5-90 and will facilitate the generation of new attenuated vaccine strains with enhanced efficacy.


Nasolacrimal polyurethane stent placement: preliminary results.
To present our initial results in the treatment of nasolacrimal obstruction by placing a polyurethane stent. 74 nasolacrimal stents were implanted under fluoroscopic guidance in obstructed nasolacrimal systems of 64 patients. Dacryocystography and CT were used to verify the position and patency of the stents. Mean follow-up was 15 months. Clinical examinations were done at the first week, first month, third month and sixth month after stent placement. Polyurethane stents were successfully inserted and permeable in 59 patients (92.1%), but could not be inserted in 5 patients (7.8%). Epiphora was solved and permeable in 53 cases (82.8%), it was not permeable but asymptomatic in 2 cases (3.1%), and was not permeable but symptomatic in 4 (6.2%). In 5 cases (7.8%) stents remained permeable although patients complained of epiphora. Polyurethane stent placement is a non-invasive technique that can replace dacryocystorhinostomy, giving better results and tolerance.


Lercanidipine in type II diabetic patients with mild to moderate arterial hypertension.
This study evaluates the effects of lercanidipine antihypertensive treatment on glucose homeostasis in patients with type II diabetes mellitus with mild to moderate hypertension. Forty patients were enrolled. After a 2-week wash-out period, they were randomly allocated to receive in double-blind manner either 10 mg or 20 mg in single daily administration for 8 weeks. Nonresponding patients after the initial 4 weeks, were titrated up to 20 mg and 30 mg lercanidipine, respectively. At the end of the double-blind treatment, all patients entered in single-blind 4 weeks placebo follow-up. Systolic and diastolic blood pressure significantly decreased in both groups of patients after 4 weeks of treatment, and decreased further during the following 4 weeks. In both groups, progressive and significant decrease in fasting blood glucose, glycosylated hemoglobin and area under the curve of the oral glucose tolerance test were detected during lercanidipine treatment. Similarly, a decrease in serum fructosamine values were also observed. All variables returned to towards baseline values during the placebo follow-up period. Adverse events (headache and mild asthenia) were limited to two patients and resolved spontaneously. These data indicate that lercanidipine is effective in lowering high blood pressure in hypertensive patients with type II diabetes mellitus and does not exert negative effects on glucose homeostasis.


Infrared atmospheric sounder interferometer radiometric noise assessment from spectral residuals.
The problem of characterizing and estimating the radiometric noise of satellite high spectral resolution infrared spectrometers from Earth views is addressed in this paper. A methodology has been devised which is based on the common concept of spectral residuals (Observations-Calculations) obtained after spectral radiance inversion for atmospheric and surface parameters. An in-depth analytical assessment of the statistical covariance matrix of the spectral residuals has been performed which is based on the optimal estimation theory. It has been mathematically demonstrated that the use of spectral residuals to assess instrument noise leads to an effective estimator, which is largely independent of possible departures of the observational covariance matrix from the true covariances. Application to the Infrared Atmospheric Sounder Interferometer has been considered. It is shown that Earth-view-derived observation errors agree with blackbody in-flight calibration. The spectral residuals approach also proved to be effective in characterizing noise features due to mechanical microvibrations of the beam splitter of the IASI instrument.


Genetic epidemiological study of schizophrenia in Palau, Micronesia: prevalence and familiality.
We are studying the genetic etiology of schizophrenia in the Republic of Palau, a remote island nation in Micronesia that has been geographically and ethnically isolated for approximately 2,000 years. The first epidemiological phase sought to estimate the lifetime prevalence of schizophrenia and evaluate the familiality of the illness based on complete ascertainment of cases and families segregating schizophrenia. A total of 160 strictly defined cases of schizophrenia were ascertained in a population of 13,750 adults who were 15 years of age and older. The lifetime prevalence of strictly defined schizophrenia in Palau was 1.99% overall and 2.77% in males vs. 1.24% in females. This greater than 2:1 male-to-female risk ratio for schizophrenia was accompanied by an earlier mean age of onset for males (23.3 years) than for females (27.5 years). These 160 cases of strict schizophrenia represent 59 separate families each identified by a single common founder. Eleven of these families have 5 to 14 cases and represent nearly half of the strict schizophrenia cases in Palau. Although schizophrenia is clearly aggregating in these 11 families, cases are distributed sparsely throughout the large sibships. In the entire sample of 160 cases of strict schizophrenia, there were only 11 sib-pairs and 2 sib-trios. When a family was defined to include third-degree relatives, only 11 cases (6.9%) were nonfamilial. The majority of the ascertained cases can be linked together into extended pedigrees with complex multilineal inheritance patterns. These intricately interconnected families may pose challenges for traditional linkage techniques. However, these Palauan families represent a valuable resource for studying the genetic etiology of schizophrenia because there may be fewer susceptibility genes for schizophrenia in this genetic isolate than in the heterogeneous populations that are common throughout the world today.


Dental approach to erosive tooth wear in gastroesophageal reflux disease.
The duration of gastro-esophageal reflux disease (GERD), the frequency of reflux, the pH and type of acid, and the quality and quantity of saliva affect the severity of dental erosion due to GERD. To summarize the diagnostic protocol and treatment of dental erosion due to GERD. A Medline literature search was performed to identify articles associated with a dental approach to GERD. The dental professional must carry out a diagnostic protocol, which includes collecting data on the patient's medical and dietary history, occupational/recreational history, dental history, and oral hygiene methods. Intraoral, head and neck, and salivary function examinations should be performed to expose the dental implications of GERD symptoms. Diagnosing the cause of erosive tooth wear can help prevent further damage. Patients must be informed about how to prevent GERD.


Extrinsic parameter calibration of stereo vision sensors using spot laser projector.
The on-site calibration of stereo vision sensors plays an important role in the measurement field. Image coordinate extraction of feature points of existing targets is difficult under complex light conditions in outdoor environments, such as strong light and backlight. This paper proposes an on-site calibration method for stereo vision sensors based on a spot laser projector for solving the above-mentioned problem. The proposed method is used to mediate the laser spots on the parallel planes for the purpose of calibrating the coordinate transformation matrix between two cameras. The optimal solution of a coordinate transformation matrix is then solved by nonlinear optimization. Simulation experiments and physical experiments are conducted to validate the performance of the proposed method. Under the condition that the field of view is approximately 400 mm×300 mm, the proposed method can reach a calibration accuracy of 0.02 mm. This accuracy value is comparable to that of the method using a planar target.


UDP-glucuronosyltransferase (UGT) 1A1*28 polymorphism-directed phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer.
We performed a phase II study of irinotecan with 5'-deoxy-5-fluorouridine (5'-DFUR) for metastatic colorectal cancer based on UDP-glucuronosyltransferase (UGT) 1A1 polymorphism. A total of 28 patients were enrolled. The dose of irinotecan was 150 mg/m(2) for patients with the *1/*1 wild-type genotype, and 70 mg/m(2) for those with the *1/*28 mutated genotype. The primary end-point was the response rate (RR); secondary end-points were safety, time to treatment failure (TTF), and overall survival (OS). In 28 patients total, genotype was wild-type in 22 and mutated in six. The RR was *1/*1 (22.7%; wild-type) vs. *1/*28 (16.7%; mutated); the median TTF was 5 months vs. 4.5 months, and the median OS was 13 months vs. 17.5 months, respectively. None of these differences were significant. Toxicities of grade 3 or higher were neutropenia (9.0% vs. 0%, respectively) and diarrhea (13.6% vs. 0%, respectively). This genotype-oriented therapy was effective and safe, and thus appears useful for patients who have complications or advanced age.


Automatic analysis of the aggressive behavior of laboratory animals using thermal video processing.
The bite detection is very important but difficult element of the social interaction analysis. Standard observation methods like human observer or a camcorder of visible light frequencies fail in this case. However, it is possible to discern cooler spots on the rodent's body that appear after body contact with another individual, and vanish after short time. These spots are assumed to be a saliva trace left on fur after bite. In this paper we have described a result of saliva trace detection by the most popular corner detectors. The analysis of traces and their parameters is also presented. The dynamic characteristic of the temperature change of the saliva trace enables the automatic discrimination of the related characteristic point from other corner points. This can be very useful for the automatic analysis of social behavior of animals in many pharmacological studies.


Biogenic Synthesis and Characterization of Antioxidant and Antimicrobial Silver Nanoparticles Using Flower Extract of Couroupita guianensis Aubl.
Couroupita guianensis Aubl. is an important medicinal tree. This tree is rich in various phytochemicals, and is therefore used as a potent antioxidant and antibacterial agent. This plant is also used for the treatment of various diseases. Here, we have improved its medicinal usage with the biosynthesis of silver nanoparticles (AgNPs) using Couroupita guianensis Aubl. flower extract as a reducing and capping agent. The biosynthesis of the AgNPs reaction was carried out using 1 mM of silver nitrate and flower extract. The effect of the temperature on the biosynthesis of AgNPs was premeditated by room temperature (25 °C) and 60 °C. The continuous stirring of the reaction mixture at room temperature for approximately one hour resulted in the successful formation of AgNPs. A development of a yellowish brown color confirmed the formation of AgNPs. The efficacious development of AgNPs was confirmed by the characteristic peaks of UV-Vis, X-ray diffraction (XRD) and Fourier transform infrared (FT-IR) spectroscopy spectra. The biosynthesized AgNPs exhibited significant free radical scavenging activity through a DPPH antioxidant assay. These AgNPs also showed potent antibacterial activity against many pathogenic bacterial species. The results of molecular dynamics simulations also proved the average size of NPs and antibacterial potential of the flower extract. The observations clearly recommended that the green biosynthesized AgNPs can serve as effective antioxidants and antibacterial agents over the plant extract.


Nucleolar organizer regions in aggressive and nonaggressive basal cell carcinoma of the skin.
Nucleolar organizer regions (NOR) were investigated on routine paraffin-embedded histologic sections of 11 aggressive basal cell carcinomas that recurred and/or metastasized (BCC2) and 11 nonaggressive basal cell carcinomas (BCC1). The absolute number of NOR per nucleus was higher in BCC2 than in BCC1, and their distribution pattern was also different. In fact, the means of argyrophilic staining of NOR (AgNOR) counts in the two groups of tumors by two observers were 6.56 with a SD of 1.98 for the nonaggressive and 9.48 with a SD of 2.12 for the aggressive basal cell carcinomas. A statistical analysis of these data using the Student's t test confirmed these observations (t = 64.49). Problems in the evaluation of NOR and possible comparison with other experiences are also discussed. The authors conclude that a quantitative assay of AgNOR and perhaps their distribution pattern may provide information useful to recognize BCC2 and hence may be of help in their prognostic prediction.


Identifying potential recommendation domains for conservation agriculture in Ethiopia, Kenya, and Malawi.
Conservation agriculture (CA) is being promoted as an option for reducing soil degradation, conserving water, enhancing crop productivity, and maintaining yield stability. However, CA is a knowledge- and technology-intensive practice, and may not be feasible or may not perform better than conventional agriculture under all conditions and farming systems. Using high resolution (≈1 km(2)) biophysical and socioeconomic geospatial data, this study identified potential recommendation domains (RDs) for CA in Ethiopia, Kenya, and Malawi. The biophysical variables used were soil texture, surface slope, and rainfall while the socioeconomic variables were market access and human and livestock population densities. Based on feasibility and comparative performance of CA over conventional agriculture, the biophysical and socioeconomic factors were first used to classify cultivated areas into three biophysical and three socioeconomic potential domains, respectively. Combinations of biophysical and socioeconomic domains were then used to develop potential RDs for CA based on adoption potential within the cultivated areas. About 39, 12, and 5% of the cultivated areas showed high biophysical and socioeconomic potential while 50, 39, and 21% of the cultivated areas showed high biophysical and medium socioeconomic potential for CA in Malawi, Kenya, and Ethiopia, respectively. The results indicate considerable acreages of land with high CA adoption potential in the mixed crop-livestock systems of the studied countries. However, there are large differences among countries depending on biophysical and socio-economic conditions. The information generated in this study could be used for targeting CA and prioritizing CA-related agricultural research and investment priorities in the three countries.


Metastatic clear-cell hidradenocarcinoma of the vulva.
Clear-cell hidradenocarcinoma is a malignant tumor of sweat gland origin. It is most often found on the trunk, head, and extremities. This case report describes a rare occurrence of this tumor on the vulva of a young woman. The discovery of metastatic disease reflects the potentially aggressive nature of this tumor.


Thumb function without the abductor pollicis longus and extensor pollicis brevis.
Two patients are reported in which one thumb has lost the abductor pollicis longus and extensor pollicis brevis tendons. This is an uncommon injury in isolation, and these cases provide an opportunity to assess the functional importance of these musculotendinous units.


The magnitude of acute tolerance to morphine analgesia: concentration-dependent or time-dependent?
We evaluated the relationship of either the infusion time or the plasma morphine concentrations on the magnitude of acute tolerance to morphine analgesia. Male New Zealand White rabbits were randomly allocated to one of four groups. Group 1 received an IV bolus of morphine 40 mg followed by an infusion at 20 mg/h for 8 h. Group 2 received a 20-mg morphine bolus followed by an infusion at 10 mg/h. Group 3 received a 10-mg morphine bolus followed by an infusion at 5 mg/h. Group 4 received a saline bolus and infusion. Analgesia was determined by the paw-pressure test, and the plasma concentrations of morphine were measured by high-performance liquid chromatography. We found that the plasma concentrations of morphine were maintained at a steady-state between 2 and 8 h after the morphine administration. However, from 2 to 8 h after the morphine infusion, the longer the infusion time was, the less the analgesic effect remained. Furthermore, the magnitude of acute tolerance was significantly correlated to the duration of morphine infusion (r = 0.93; P < 0.01) but not the different steady-state plasma morphine concentrations. We conclude that the magnitude of morphine tolerance is significantly correlated to the duration of infusion but not the different steady-state plasma morphine concentrations. We evaluated the relationship of either the infusion time or the plasma morphine concentrations on the magnitude of acute tolerance to morphine analgesia in rabbits. We found that the magnitude of morphine tolerance is significantly correlated to the duration of infusion but not to the different steady-state plasma morphine concentrations.


Management of the wide nasal dorsum.
The literature is replete with discussions outlining surgical techniques for managing nasal tip deformities. In contrast, articles devoted to specific dorsal nasal abnormalities are rare. Surgical management of the nasal dorsum has traditionally been relegated to either augmentation or reduction followed by osteotomy. Contemporary rhinoplasty demands attention to the creation of an ideal profile line, which may require dorsal reduction in some areas and augmentation in others. Treatment of the patient with an appropriate projection of the profile but with a wide nasal dorsum presents a special challenge: to narrow the nasal bridge without altering its projection. We discuss several surgical techniques to narrow the nasal dorsum, while maintaining dorsal height. Selected cases are presented to illustrate these techniques and to clarify surgical options.


Modeling spatial survival data using semiparametric frailty models.
We propose a new class of semiparametric frailty models for spatially correlated survival data. Specifically, we extend the ordinary frailty models by allowing random effects accommodating spatial correlations to enter into the baseline hazard function multiplicatively. We prove identifiability of the models and give sufficient regularity conditions. We propose drawing inference based on a marginal rank likelihood. No parametric forms of the baseline hazard need to be assumed in this semiparametric approach. Monte Carlo simulations and the Laplace approach are used to tackle the intractable integral in the likelihood function. Different spatial covariance structures are explored in simulations and the proposed methods are applied to the East Boston Asthma Study to detect prognostic factors leading to childhood asthma.


[Immunosuppressive substance derived from choriocarcinoma (author's transl)].
Addition of choriocarcinoma culture fluid (CCF) inhibited mixed lymphocyte reaction (MLR) in vitro antibody production and in vitro allo-killer induction. This suppression was not mediated by HCG, and predominant when CCF was added at the initial phase of culture. The suppression of antibody production was observed when stimulated by T cell-dependent antigen but not by T cell-independent antigens. This suppression was mediated by suppressor T cell, since CSF induced antigen-nonspecific suppressor T cell during 24 hr-incubation. The suppressor T cell once induced was X-ray resistant, but sensitive at precursor level before incubation with CCF. The specific antiserum was raised in rabbit by immunization with a fraction of CCF. After appropriate absorbtion, the obtained antiserum reacted with choriocarcinoma cell lines and normal human chorionic trophoblast, but not with other human cells as tested by immunofluorescent antibody technique. Interestingly, this antiserum effectively neutralized the immunosuppressive activity of CCF, but this neutralizing activity was absorbed out with normal human chorionic villi. Thus, the trophoblasts of choriocarcinoma released them from maternal attack.


Bitumen Binders Modified with Sulfur/Organic Copolymers.
With the continuing growth of waste sulfur production from the petroleum industry processes, its utilization for the production of useful, low-cost, and environmentally beneficial materials is of primary interest. Elemental sulfur has a significant and established history in the modification of bitumen binders, while the sulfur-containing high-molecular compounds are limited in this field. Herein, we report a novel possibility to utilize the sulfur/organic copolymers obtained via the inverse vulcanization process as modifiers for bitumen binders. Synthesis and thermal characterization (TGA-DSC) of polysulfides derived from elemental sulfur (S8) and unsaturated organic species (dicyclopentadiene, styrene, and limonene) have been carried out. The performance of modified bitumen binders has been studied by several mechanical measurements (softening point, ductility, penetration at 25 °C, frass breaking point, adhesion to glass and gravel) and compared to the unmodified bitumen from the perspective of normalized requirements concerning polymer-modified bitumen. The interaction of bitumen binder with sulfur/organic modifier has been studied by means of FTIR spectroscopy and DSC measurements. The impact of the modification on the performance properties of bitumen has been demonstrated. The bitumen binders modified with sulfur/organic copolymers are in general less sensitive to higher temperatures (higher softening point up to 7 °C), more resistant to permanent deformations (lower penetration depth), and more resistant to aging processes without intrusive deterioration of parameters at lower temperatures. What is more, the modification resulted in significantly higher adhesion of bitumen binders to both glass (from 25% up to 87%) and gravel surfaces in combination with a lower tendency to form permanent deformations (more elastic behavior of the modified materials).


Structural integrity of corticospinal motor fibers predicts motor impairment in chronic stroke.
Motor impairment after stroke has been related to infarct size, infarct location, and integrity of motor tracts. To determine the value of diffusion tensor imaging (DTI) as a predictor of motor outcome and its role as a structural surrogate marker of impairment in chronic stroke, we tested correlations between motor impairment and DTI-derived measures of motor tract integrity. Thirty-five chronic stroke patients with varying degrees of recovery underwent DTI and motor impairment assessments. Fibers originating from the precentral gyrus were traced and separated into pyramidal tract (PT) and alternate motor fibers (aMF). Asymmetry indices of fiber number and regional fractional anisotropy (FA) values comparing lesional with nonlesional hemispheres were correlated with motor impairment scores and compared to an age-matched control group. Fiber number and regional FA value asymmetry significantly differed between the groups with lower values in the patients' lesional hemispheres. Both measures significantly predicted motor impairment with stronger predictions when all motor tracts were combined as compared to predictions using only the PT. The pattern of motor tract damage (PT only vs PT and aMF) led to a classification of mild, moderate, or severe impairment with significant between-group differences in motor impairment scores. Diffusion tensor imaging-derived measures are valid structural markers of motor impairment. The integrity of all descending motor tracts, not merely the pyramidal tract, appears to account for stroke recovery. A 3-tier, hierarchical classification of impairment categories based on the pattern of motor tract damage is proposed that might be helpful in predicting recovery potential.


Protein turnover in the kidney and the whole body in humans.
For a better understanding of protein synthesis and degradation in the human kidney, the arteriovenous difference technique across the kidney, splanchnic organs, and leg muscle was combined with labeled leucine and phenylalanine isotope dilution models. Results indicate that in the postabsorptive state, the protein balance across the human kidney is negative because the rate of leucine release from protein degradation is greater than the amount used for protein synthesis. In the splanchnic bed, net protein balance is neutral since the amount of leucine deriving from protein degradation is similar to the amount utilized for protein synthesis. In the leg muscle, protein degradation exceeds protein synthesis. The kidney exhibits the highest leucine metabolic activity when expressed in terms of total organ leucine content. The estimated fractional protein synthesis rate in the human kidney is about 40% per day (vs. about 2% in muscle and 12% in the splanchnic bed). The human kidney presents high rates of protein turnover and accounts for a significant fraction of whole-body protein degradation, protein synthesis, and leucine oxidation.


Repression of the Plastidic Isoenzymes of Aldolase, 3-Phosphoglycerate Kinase, and Triosephosphate Isomerase in the Barley Mutant "albostrians".
White leaves of the mutant line albostrians and green leaves of the wild-type cultivar Salome of barley (Hordeum vulgare L.) were screened for the presence of plastidic and cytosolic isoenzymes of sugar-phosphate metabolism. Isoenzyme separation was achieved by anion-exchange chromatography on Fractogel TSK DEAE-650(S). The mutant tissue had a markedly reduced level of plastidic 3-phosphoglycerate kinase, triosephosphate isomerase, and aldolase activity. In contrast, the activity of plastidic glucosephosphate isomerase, fructose 1,6-bisphosphatase, 6-phosphogluconate dehydrogenase, starch phosphorylase, and ADP-glucose pyrophosphorylase was in the same range as in wild-type leaf tissue. The activity of the corresponding cytosolic isoenzymes (including UDP-glucose pyrophosphorylase) showed essentially no differences in mutant and wild type. The same trend was observed in dark-grown mutant and wild-type leaves. Interestingly, the total activity levels of all isoenzymes were about the same when comparing dark-grown and light-grown mutant or wild-type plants. From these data, it is concluded that mutant leaves exhibit a selective decrease of a subgroup of plastidic isoenzymes associated with the Calvin cycle.


Chromatin structural elements and chromosomal translocations in leukemia.
Recurring chromosome abnormalities are strongly associated with certain subtypes of leukemia, lymphoma and sarcomas. More recently, their potential involvement in carcinomas, i.e. prostate cancer, has been recognized. They are among the most important factors in determining disease prognosis, and in many cases, identification of these chromosome abnormalities is crucial in selecting appropriate treatment protocols. Chromosome translocations are frequently observed in both de novo and therapy-related acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The mechanisms that result in such chromosome translocations in leukemia and other cancers are largely unknown. Genomic breakpoints in all the common chromosome translocations in leukemia, including t(4;11), t(9;11), t(8;21), inv(16), t(15;17), t(12;21), t(1;19) and t(9;22), have been cloned. Genomic breakpoints tend to cluster in certain intronic regions of the relevant genes including MLL, AF4, AF9, AML1, ETO, CBFB, MYHI1, PML, RARA, TEL, E2A, PBX1, BCR and ABL. However, whereas the genomic breakpoints in MLL tend to cluster in the 5' portion of the 8.3 kb breakpoint cluster region (BCR) in de novo and adult patients and in the 3' portion in infant leukemia patients and t-AML patients, those in both the AML1 and ETO genes occur in the same clustered regions in both de novo and t-AML patients. These differences may reflect differences in the mechanisms involved in the formation of the translocations. Specific chromatin structural elements, such as in vivo topoisomerase II (topo II) cleavage sites, DNase I hypersensitive sites and scaffold attachment regions (SARs) have been mapped in the breakpoint regions of the relevant genes. Strong in vivo topo II cleavage sites and DNase I hypersensitive sites often co-localize with each other and also with many of the BCRs in most of these genes, whereas SARs are associated with BCRs in MLL, AF4, AF9, AML1, ETO and ABL, but not in the BCR gene. In addition, the BCRs in MLL, AML1 and ETO have the lowest free energy level for unwinding double strand DNA. Virtually all chromosome translocations in leukemia that have been analyzed to date show no consistent homologous sequences at the breakpoints, whereas a strong non-homologous end joining (NHEJ) repair signature exists at all of these chromosome translocation breakpoint junctions; this includes small deletions and duplications in each breakpoint, and micro-homologies and non-template insertions at genomic junctions of each chromosome translocation. Surprisingly, the size of these deletions and duplications in the same translocation is much larger in de novo leukemia than in therapy-related leukemia. We propose a non-homologous chromosome recombination model as one of the mechanisms that results in chromosome translocations in leukemia. The topo II cleavage sites at open chromatin regions (DNase I hypersensitive sites), SARs or the regions with low energy level are vulnerable to certain genotoxic or other agents and become the initial breakage sites, which are followed by an excision end joining repair process.


Phase shifting the hamster circadian clock by 15-minute dark pulses.
The mammalian circadian pacemaker can be phase shifted by exposure to a period of darkness interrupting otherwise continuous light. Circadian phase shifting by dark pulses was interpreted originally as reflecting a photic mirror-image mechanism, but more recent observations suggest that dark pulse-induced phase shifting may be mediated by a nonphotic, behavioral state-dependent mechanism. The authors recently presented evidence indicating that the dark-pulse phase response curve (PRC) is in fact a complex function, reflecting both photic mirror image and nonphotic mechanisms at different phases of the circadian cycle. Previous studies of dark pulse-induced phase shifting have universally employed relatively long (2 to 6 h) pulses, which complicates PRC analysis due to the extended segment of the underlying PRC spanned by such a long pulse. The present study was therefore designed to examine the phase-shifting effects of brief 15-min dark pulses presented at both mid-subjective day and subjective dusk, and to explore the possible activity dependence of these effects by using physical restraint to prevent evoked locomotor activity. The results indicate that 15-min dark pulses are effective phase-shifting stimuli at both midday and dusk. Furthermore, as with longer dark pulses, phase shifting by 15-min dark pulses is completely blocked by physical restraint during subjective day but combines in a simple additive manner with the independent phase-shifting effect of restraint at subjective dusk.


SmI(2)-promoted oxidation of aldehydes in the presence of electron-rich heteroatoms.
[reaction: see text] The Evans-Tishchenko reaction provides an efficient and practical solution for the oxidation of aldehydes possessing sensitive electron-rich heteroatoms to the corresponding esters. Careful selection of the sacrificial beta-hydroxy ketone provides considerable subsequent flexibility to access the desired carboxylic acid.


Multivariate emulation of computer simulators: model selection and diagnostics with application to a humanitarian relief model.
We present a common framework for Bayesian emulation methodologies for multivariate output simulators, or computer models, that employ either parametric linear models or non-parametric Gaussian processes. Novel diagnostics suitable for multivariate covariance separable emulators are developed and techniques to improve the adequacy of an emulator are discussed and implemented. A variety of emulators are compared for a humanitarian relief simulator, modelling aid missions to Sicily after a volcanic eruption and earthquake, and a sensitivity analysis is conducted to determine the sensitivity of the simulator output to changes in the input variables. The results from parametric and non-parametric emulators are compared in terms of prediction accuracy, uncertainty quantification and scientific interpretability.


Reducing adolescent use of harmful legal products: intermediate effects of a community prevention intervention.
Preliminary results are presented from a feasibility study of a comprehensive community prevention intervention to reduce the use of inhalants and other harmful legal products (HLPs) among adolescents in three Alaskan frontier communities conducted in 2004-2007. The legal products used to get high include over-the-counter drugs, prescription drugs, and common household products. Community mobilization, environmental and school-based strategies were implemented to reduce access, enhance knowledge of risks, and improve assertiveness and refusal skills. Pre- and post-intervention survey data were collected from 5-7th grade students from schools in three communities using standardized instruments to assess knowledge, assertiveness, refusal skills, perceived availability, and intent to use. The intervention consisted of community mobilization and environmental strategies to reduce access to HLPs in the home, at school, and through retail establishments. In addition, the ThinkSmart curriculum was implemented in classrooms among 5th grade students to increase the knowledge of harmful effects of HLPs and improve the refusal skills. Data were analyzed using hierarchical linear models that enable corrections for correlated measurement error. Significant increases in knowledge of harms related to HLP use and decreases in perceived availability of HLP products were observed. The environmental strategies were particularly effective in reducing the perceived availability of HLPs among 6th and 7th graders. Although limited by the absence of randomized control groups in this preliminary study design, the results of this study provide encouragement to pursue mixed strategies for the reduction of HLP use among young people in Alaskan frontier communities.


Using the Hough transform for HOLZ line identification in convergent beam electron diffraction.
The Hough transform as a means for automatic line detection is applied for higher order Laue zone (HOLZ) line identification in convergent beam electron diffraction. The HOLZ line positions are commonly used to measure the strain state in the investigated material. Besides the automation, a very important aspect is the accuracy of the detected line positions. The limits are determined by the amount of noise in the pattern relative to the contrast of the HOLZ lines and the line width. Our investigations show that sub-pixel resolution can be achieved routinely. We have also developed a new strain analysis procedure in which the dynamical shift of each individual line can be taken into account using a model based on several Ewald spheres with different radii. In comparison to the effective high voltage method, finer details of the dispersion surface can be considered, which increases the accuracy of the strain analysis. A measurement of the thermal expansion of aluminium is presented as a model experiment. The lattice constants were determined with an accuracy of about 10-4.


Species differences in the disposition and metabolism of camazepam.
After i.v. injection of camazepam, plasma camazepan concn. declined biexponentially. The half-life of the elimination phase (t1/2, beta) increased in the order: mice (0.73 h), rats (1.3 h), dogs (5.3 h). After oral dosing of camazepam, absorption was almost complete whereas systemic availability varied eight-fold, i.e., rats and mice (10-15%) less than dogs and monkeys (about 60%) less than humans (greater than 90%), indicating species difference in the first-pass effect. Camazepam was metabolized extensively in all species investigated to more than 10 metabolites, which were desmethyl, descarbamoyl and/or hydroxy products. In comparison with camazepam, plasma concn. of pharmacologically active metabolites, temazepam, oxazepan and hydroxy camazepam, were much higher in rats and mice than in dogs and monkeys.


Physical and chemical processing for a human dura mater substitute.
Allogenic human fascia lata used in neurosurgery, as dura mater substitute, can be associated with a risk of viral and bacterial transmission. Chemical and physical procedures, developed to inactivate virus and bacteria, have been applied to fascia lata. The aim of this study consists in the evaluation of the biological properties of this treated graft. Grafts were treated with solvent detergents, freeze-dried for conservation and gamma irradiated (25,000 Gy) for sterilization. The indirect toxicity evaluation was performed by extraction method, according to the International Standard Organization (ISO). First, the cytotoxic effect of each extracts incubated in the presence of human fibroblasts (WI38) was quantitatively assessed by measuring the cell growth, the viability (succinate dehydrogenase activity, MTT), the membrane integrity (uptake of the neutral red by viable cells, NR) as well as the release of lactate dehydrogenase in the culture medium. Second, confocal laser scanning microscopy (CLSM) was used to assess the direct contact between human primary fibroblasts and graft. CLSM was performed at days 3 and 7 after cells loading. No acute cytotoxicity was observed for chemically processed allografts. Cells loaded on the graft have demonstrated a good growth and spreading. Human fascia lata secured against conventional and non-conventional agents is a fully biocompatible alternative to the available dural graft materials.


Absorption of NO and NO2 in caprolactam tetrabutyl ammonium halide ionic liquids.
To explore environmentally benign solvents for the absorption of NO and NO2, a series of caprolactam tetrabutyl ammonium halide ionic liquids were synthesized. The solubility of NO and NO2 was measured at temperatures ranging from 298.2 to 363.2 K and atmospheric pressure, and the following trend in the solubility of NO and NO2 in ionic liquids with various halide anions was observed, respectively: F > Br > Cl and Br > Cl > F. Moreover, as the temperature increased from 308.15 to 363.15 K and the mole ratio of caprolactam increased from 2:1 to 6:1, the solubility of NO increased. Alternatively, the solubility of NO2 decreased as the temperature increased from 298.15 to 363.15 K, and the mole ratio of caprolactam increased from 2:1 to 6:1. The absorption and desorption of NO and NO2 was practically reversible in the ionic liquids, which was characterized by nuclear magnetic resonance. The method, which is at least partially reversible, offers interesting possibilities for the removal of NO and NO2.