Double blind controlled trial of D-penicillamine in patients with primary biliary cirrhosis.

One hundred and eighty nine patients with primary biliary cirrhosis were entered into a double blind, placebo controlled randomised trial starting in January 1978 to assess the therapeutic value of d-penicillamine 1200 mg daily. Eighteen of the 98 patients receiving d-penicillamine and 22 of the 91 placebo treated patients died during the study. Thirty six per cent of those on d-penicillamine and 8% of those on placebo were withdrawn from the study. No difference in overall survival was noted between the two groups of patients whether the results were analysed for the entire period of observation or only during the period in which the patients were receiving therapy. The mortality rate of those receiving d-penicillamine in histological stage I to II, however, was one third of that of the placebo group although this difference did not reach statistical significance. Using the occurrence rate ratio as the statistical method of analysis, no effect of d-penicillamine was noted on any clinical, biochemical or hist

A comparison of the accuracy of peritoneoscopy and liver biopsy in the diagnosis of cirrhosis

The accuracy of peritoneoscopy and liver biopsy in the diagnosis of hepatic cirrhosis was compared in 473 consecutive patients submitted to both procedures. One hundred and fifty-two of them had cirrhosis diagnosed by one or both methods. There was 73% agreement between the two procedures. `Apparent' false-negative results were 17·7% for peritoneoscopy and 9·3% for liver biopsy. The incidence of false-negative results in the diagnosis of cirrhosis can be reduced by combining both procedures.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

A Novel Homozygous R764H Mutation in CRB1 Causes Autosomal Recessive Retinitis Pigmentosa in a Consanguineous Family

Purpose: Retinitis pigmentosa (RP; MIM 268000) is a hereditary disease characterized by poor night vision and progressive loss of photoreceptors, eventually leading to blindness. This degenerative process primarily affects peripheral vision due to the loss of rods. Autosomal recessive RP (arRP) is clinically and genetically heterogeneous. It has been associated with mutations in different genes, including CRB1 (Crumbs homolog 1). The aim of this study was to determine the causative gene in a Tunisian patient with arRP born to non consanguineous parents.Methods: Four accessible family members were included. They underwent full ophthalmic examination with best corrected Snellen visual acuity, fundus photography and fluoroangiography. Haplotype analyses were used to test linkage in the family to 20 arRP loci, including ABCA4, LRAT, USH2A, RP29, CERKL, CNGA1, CNGB1, CRB1, EYS, RP28, MERTK, NR2E3, PDE6A, PDE6B, RGR, RHO, RLBP1, TULP1. All exons and intron-exon junctions of candidate genes not excluded by haplotype analysis were PCR amplified and directly sequenced.Results: A 39 aged affected member was individualized. Best corrected visual acuity was OR: 20/63, OS: 20/80. Visual loss began at the third decade. Funduscopic examination and FA revealed typical advanced RP changes with bone spicule-shaped pigment deposits in the posterior pole and the mild periphery along with retinal atrophy, narrowing of the vessels and waxy optic discs. Haplotypes analysis revealed homozygosity with microsatellites markers D1S412 and D1S413 on chromosome 1q31.3. These markers flanked the CRB1 gene. Our results excluded linkage of all the other arRP loci/ genes tested. Sequencing of the 12 coding exons and splice sites of CRB1 gene disclosed a homozygous missense mutation in exon 7 at nucleotide c.(2291 G>A), resulting in an Arg to Hist substitution (p.R764H).Conclusions: R764H is a novel mutation associated with CRB1-related arRP. Previously, an R764C mutation was observed. Extending the mutation spectrum of CRB1 with additional families is important for genotype-phenotype correlations.

Non-Corrosive Tie Reinforcing and Dowel Bars for Highway Pavement Slabs, HR-343, 1993

The use of non-metallic load transfer and reinforcement devices for concrete highway pavements is a possible alternative to avoid corrosion problems related to the current practice of steel materials. Laboratory and field testing of highway pavement dowel bars, made of both steel and fiber composite materials, and fiber composite tie rods were carried out in this research investigation. Fatigue, static, and dynamic testing was performed on full-scale concrete pavement slabs which were supported by a simulated subgrade and which included a single transverse joint. The bahavior of the full-scale specimens with both steel and fiber composite dowels placed in the test joints was monitored during several million load cycles which simulated truck traffic at a transverse joint. Static bond tests were conducted on fiber composite tie rods to determine the required embedment length. These tests took the form of bending tests which included curvature and shear in the embedment zone and pullout tests which subjected the test specimen to axial tension only. Fiber composite dowel bars were placed at two transverse joints during construction of a new concrete highway pavement in order to evaluate their performance under actual field conditions. Fiber composite tie rods were also placed in the longitudinal joint between the two fiber composite doweled transverse joints.

The biogenic origin of needle fibre calcite

Needle fibre calcite is one of the most ubiquitous habits of calcite in vadose environments (caves deposits, soil pores, etc.). Its origin, either through inorganic, indirect or direct biological processes, has long been debated. In this study, investigations at 11 sites in Europe, Africa and Central America support arguments for its biogenic origin. The wide range of needle morphologies is the result of a gradual evolution of the simplest type, a rod. This rod is the elementary brick which, by aggregation and welding, builds more complex needles. The absence of cross-welded needles implies that they are welded in a mould, or under a longitudinal and unidirectional constraint, before being released inside the soil pores. The difference between the lengthening of the needles and the c axis can be explained by the existence of needles observed under a scanning electron microscope in organic sleeves, which can act as a mould during rod growth. Complex morphologies with epitaxial outgrowths on straight rods cannot have grown entirely inside organic microtubes; they must result from soil diagenesis after the release of straight rods in a soil-free medium. Whisker crystals are interpreted as the result of growth and coalescence of euhedral crystals on a rod. Rhomb chains are considered to be the consequence of successive epitaxial growth steps on a needle during variations in growth conditions. Isotopic signatures for needle fibre calcite vary from -16.63[per mille] to +1.10[per mille] and from -8.63[per mille] to -2.25[per mille] for Delta13C and Delta18O, respectively. The absence of high Delta18O values for needle fibre calcite precludes a purely physicochemical origin (evaporative) for this particular habit of calcite. As epitaxial growth cannot precipitate in the same conditions as initial needles, needle fibre calcite stable isotopic signatures should be used with caution as a proxy for palaeoenvironmental reconstructions. In addition, it is suggested that the term needle fibre calcite should be kept for the original biogenic form. The other habit should be referred to as epitaxial forms of needle fibre calcite.

Standards for Single Span Prefabricated Bridges, Phase I - Concept Development, TR-663, 2014

In coordination with a Technical Advisory Committee (TAC) consisting of County Engineers and Iowa DOT representatives, the Iowa DOT has proposed to develop a set of standards for a single span prefabricated bridge system for use on the local road system. The purpose of the bridge system is to improve bridge construction, accelerate project delivery, improve worker safety, be cost effective, reduce impacts to the travelling public by reducing traffic disruptions and the duration of detours, and allow local forces to construct the bridges. HDR Inc. was selected by the Iowa DOT to perform the initial concept screening of the bridge system. This Final Report summarizes the initial conceptual effort to investigate potential systems, make recommendations for a preferred system and propose initial details to be tested in the laboratory in Phase 2 of the project. The prefabricated bridge components were to be based on the following preliminary criteria set forth by the TAC. The criteria were to be verified and/ or modified as part of the conceptual development. - 24’ and 30’ roadway widths - Skews of 0o, 15o, and 30o - Span lengths of 30’ – 70’ in 10’ increments using precast concrete beams - Voided box beams could be considered - Limit precast element weight to 45,000 pounds for movement and placement of beams - Beams could be joined transversely with threaded rods - Abutment concepts may included precast as well as an option for cast-in-place abutments with pile foundations In addition to the above criteria, there was an interest to use a single-width prefabricated bridge component to simplify fabrication as well as a desire to utilize non-prestressed concrete systems where possible to allow for precasting of the beam modules by local forces or local precast plants. The SL-1 modular steel bridge rail was identified for use with this single span prefabricated bridge system.

Para-arterial sparing phenotype in Leber congenital amaurosis associated with homozygous p.R108X SPATA-7 mutation

Purpose: To describe the genotype/phenotype correlation associated with homozygous p.R108X mutation in the SPATA7 gene. Methods: A consanguineous nuclear family of Ethiopian origin was ascertained for genotypic and phenotypic characterization, including fundus photography, fundus autofluorescence (FAF), and full-field ERG. Molecular diagnosis was performed using a microarray. Results: Two of the 5 family members were affected with LCA. A homozygous c.322C>T (p.R108X) mutation in exon 5 of SPATA-7 was identified in both of them. The patients were 4 and 11 years old, respectively. Fundus examination revealed an unremarkable macular area, but optic nerve pallor, attenuated vascular calibre and deep retinal nummular deposits with para-arterial sparing predominant in the midperiphery. FAF showed multiples areas of hyperautofluorescence, corresponding to the deep retinal deposits. ERG was not recordable in the young patient, and showed severe rods/cones dysfunction in the older one. Conclusions: The literature describing genotype/phenotype correlation of SPATA-7 mutations in Leber congenital amaurosis (LCA) is still limited. We report the occurrence of para-arterial sparing in two sibs with SPATA7-linked LCA which may represent a clinical marker of this condition.

Photoreceptor types and distributions in the retinae of insectivores.

The retinae of insectivores have been rarely studied, and their photoreceptor arrangements and expression patterns of visual pigments are largely unknown. We have determined the presence and distribution of cones in three species of shrews (common shrew Sorex araneus, greater white-toothed shrew Crocidura russula, dark forest shrew Crocidura poensis; Soricidae) and in the lesser hedgehog tenrec Echinops telfairi (Tenrecidae). Special cone types were identified and quantified in flattened whole retinae by antisera/antibodies recognizing the middle-to-long-wavelength-sensitive (M/L-)cone opsin and the short-wavelength-sensitive (S-)cone opsin, respectively. A combination of immunocytochemistry with conventional histology was used to assess rod densities and cone/rod ratios. In all four species the rods dominate at densities of about 230,000-260,000/mm2. M/L- and S-cones are present, comprising between 2% of the photoreceptors in the nocturnal Echinops telfairi and 13% in Sorex araneus that has equal diurnal and nocturnal activity phases. This suggests dichromatic color vision like in many other mammals. A striking feature in all four species are dramatically higher S-cone proportions in ventral than in dorsal retina (0.5% vs. 2.5-12% in Sorex, 5-15% vs. 30-45% in Crocidura poensis, 3-12% vs. 20-50% in Crocidura russula, 10-30% vs. 40-70% in Echinops). The functional and comparative aspects of these structural findings are discussed.

Iron mining in Goa (India) : an interdisciplinary study

En aquest article es presenten breument els diferents capítols d’un treball interdisciplinari per tal d’entendre el context de prohibició de la mineria de ferro a Goa a finals del 2012 i proporcionar la informació necessària per tal d’orientar i gestionar la presa de decisions sobre l’activitat minera en un futur. Els sis primers capítols consisteixen en l’estudi del medi abiòtic, medi biòtic, fluxos de materials, aspectes socials, aspectes econòmics i finalment aspectes polítics. En canvi, en els dos últims capítols s'avaluen i es gestionen els impactes ambientals de la mineria mitjançant, per una banda, una anàlisi DPSIR i, d'altra banda, es proposen tres escenaris per integrar les diferents variables i fomentar la participació en la presa de decisions. S’ha dut a terme una extensa recerca mitjançant la recopilació de dades, entrevistes i visites a les zones d’estudi d’interès per tal d’entendre el conflicte de la mineria a Goa.

Bax-induced apoptosis in Leber's congenital amaurosis: a dual role in rod and cone degeneration.

Pathogenesis in the Rpe65(-/-) mouse model of Leber's congenital amaurosis (LCA) is characterized by a slow and progressive degeneration of the rod photoreceptors. On the opposite, cones degenerate rapidly at early ages. Retinal degeneration in Rpe65(-/-) mice, showing a null mutation in the gene encoding the retinal pigment epithelium 65-kDa protein (Rpe65), was previously reported to depend on continuous activation of a residual transduction cascade by unliganded opsin. However, the mechanisms of apoptotic signals triggered by abnormal phototransduction remain elusive. We previously reported that activation of a Bcl-2-dependent pathway was associated with apoptosis of rod photoreceptors in Rpe65(-/-) mice during the course of the disease. In this study we first assessed whether activation of Bcl-2-mediated apoptotic pathway was dependent on constitutive activation of the visual cascade through opsin apoprotein. We then challenged the direct role of pro-apoptotic Bax protein in triggering apoptosis of rod and cone photoreceptors.Quantitative PCR analysis showed that increased expression of pro-apoptotic Bax and decreased level of anti-apoptotic Bcl-2 were restored in Rpe65(-/-)/Gnat1(-/-) mice lacking the Gnat1 gene encoding rod transducin. Moreover, photoreceptor apoptosis was prevented as assessed by TUNEL assay. These data indicate that abnormal activity of opsin apoprotein induces retinal cell apoptosis through the Bcl-2-mediated pathway. Following immunohistological and real-time PCR analyses, we further observed that decreased expression of rod genes in Rpe65-deficient mice was rescued in Rpe65(-/-)/Bax(-/-) mice. Histological and TUNEL studies confirmed that rod cell demise and apoptosis in diseased Rpe65(-/-) mice were dependent on Bax-induced pathway. Surprisingly, early loss of cones was not prevented in Rpe65(-/-)/Bax(-/-) mice, indicating that pro-apoptotic Bax was not involved in the pathogenesis of cone cell death in Rpe65-deficient mice.This is the first report, to our knowledge, that a single genetic mutation can trigger two independent apoptotic pathways in rod and cone photoreceptors in Rpe65-dependent LCA disease. These results highlight the necessity to investigate and understand the specific death signaling pathways committed in rods and cones to develop effective therapeutic approaches to treat RP diseases.

Remaining rod activity mediates visual behavior in adult Rpe65-/- mice.

Purpose: C57/Bl6, Cpfl1-/- (Cone photoreceptors function loss 1; pure rod function), Gnat1alpha-/- (rod alpha-transducin; pure cone function) and Rpe65-/-;Rho-/- double knock-out mice were studied in order to distinguish the respective contributions of the different photoreceptor (PR) systems that enable light perception and mediate a visual reflex in adult Rpe65-/- mice using a simple behavioural procedure. Methods: Visual function was estimated using a rotating automatized optomotor drum covered with vertical black and white stripes at spatial frequencies of 0.025 to 0.5 cycles per degree (cpd) in both photopic and scotopic conditions. To evaluate the contribution as well as the light intensity threshold of each PR system, we tested the mouse strains with different luminances. Results: Stripe rotation elicits head movements in wild-type (WT) animals in photopic and scotopic conditions depending on the spatial frequency, whereas Cpfl1-/- mice show a reduced activity in the photopic condition and Gnat1alpha-/- mice an almost absent response in the scotopic condition. Interestingly, a robust visual response is obtained with Rpe65-/- knockout mice at 0.075 cpd and 0.1 cpd in the photopic condition. The residual rod function in the Rpe65-/- animals was demonstrated by testing Rpe65-/-;Rho-/- mice that present no response in photopic conditions. Conclusions: The optomotor test is a simple method to estimate the visual function, and to evaluate the respective contributions of rod and cone systems. Using this test, we demonstrate that in Rpe65-/- mice, devoid of functional cones and of detectable 11-cis-retinal protein, rods mimic in part the cone function by mediating vision in photopic conditions.