Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis

Ross-Konno and Endocardial Fibroelastosis Resection After Hybrid Stage I Palliation in Infancy: Successful Staged Left-Ventricular Rehabilitation and Conversion to Biventricular Circulation After Fetal Diagnosis of Aortic Stenosis

We report a patient who presented during fetal life with severe aortic stenosis, left-ventricular dysfunction, and endocardial fibroelastosis (evolving hypoplastic left heart syndrome). Management involved in utero and postnatal balloon aortic valvuloplasty for partial relief of obstruction and early postnatal hybrid stage I palliation until recovery of left-ventricular systolic function had occurred. The infant subsequently had successful conversion to a biventricular circulation by combining resection of endocardial fibroelastosis with single-stage Ross-Konno, aortic arch reconstruction, hybrid takedown, and pulmonary artery reconstruction

Directed self-organization of graphene nanoribbons on SiC

Realization of post-CMOS graphene electronics requires production of semiconducting graphene, which has been a labor-intensive process. We present tailoring of silicon carbide crystals via conventional photolithography and microelectronics processing to enable templated graphene growth on 4H-SiC{1-10n} (n = 8) crystal facets rather than the customary {0001} planes. This allows self-organized growth of graphene nanoribbons with dimensions defined by those of the facet. Preferential growth is confirmed by Raman spectroscopy and high-resolution transmission electron microscopy (HRTEM) measurements, and electrical characterization of prototypic graphene devices is presented. Fabrication of > 10,000 top-gated graphene transistors on a 0.24 cm2 SiC chip demonstrates scalability of this process and represents the highest density of graphene devices reported to date.Comment: 13 pages, 5 figure

Visceral Artery Aneurysms in Liver Transplant Candidates and in Patients after Liver Transplantation

There are only few reviews concerning visceral aneurysms in cirrhotics, and a small number of papers on visceral aneurysms in liver transplant patients. The present paper investigates this condition in both groups of patients in a 10-year-retrospective study

Prospective randomized comparison of open versus laparoscopic management of splenic artery aneurysms: a 10-year study

Abstract BACKGROUND: The literature does not support the choice between open and laparoscopic management of splenic artery aneurysms (SAA). METHODS: We designed a prospective, randomized comparison between open and laparoscopic surgery for SAA. Primary end points were types of surgical procedures performed and clinical outcomes. Analysis was developed on an intention-to-treat basis. RESULTS: Fourteen patients were allocated to laparotomy (group A) and 15 to laparoscopy (group B). Groups displayed similar patient- and aneurysm-related characteristics. The conversion rate to open surgery was 13.3 %. The type of surgical procedure performed on the splenic artery was similar in the two groups: aneurysmectomy with splenic artery ligature or direct anastomosis was performed in 51 % and 21 % of patients in group A and in 60 % and 20 % in group B, respectively. The splenectomy rate was similar (14 % vs. 20 %). Postoperative splenic infarction was observed in one case in each group. Laparoscopy was associated with shorter procedures (p = 0.0003) and lower morbidity (25 % vs. 64 %, p = 0.045). Major morbidity requiring interventional procedures and blood transfusion was observed only in group A. Laparoscopy was associated with quicker resumption of oral diet (p < 0.001), earlier drain removal (p = 0.046), and shorter hospital stay (p < 0.01). During a mean follow-up of 50 months, two patients in group A required hospital readmission. In group B, two patients developed a late thrombosis of arterial anastomoses. CONCLUSIONS: Our study demonstrates that laparoscopy permits multiple technical options, does not increase the splenectomy rate, and reduces postoperative complications. It confirms the supposed clinical benefits of laparoscopy when ablative procedures are required but laparoscopic anastomoses show poor long-term results

Non-specific interstitial pneumonia in cigarette smokers: a CT study

The goal of this study was to seek indirect evidence that smoking is an aetiological factor in some patients with non-specific interstitial pneumonia (NSIP). Ten current and eight ex-smokers with NSIP were compared to controls including 137 current smokers with no known interstitial lung disease and 11 non-smokers with NSIP. Prevalence and extent of emphysema in 18 smokers with NSIP were compared with subjects meeting GOLD criteria for chronic obstructive pulmonary disease (COPD; group A; n = 34) and healthy smokers (normal FEV1; group B; n = 103), respectively. Emphysema was present in 14/18 (77.8%) smokers with NSIP. Emphysema did not differ in prevalence between NSIP patients and group A controls (25/34, 73.5%), but was strikingly more prevalent in NSIP patients than in group B controls (18/103, 17.5%, P < 0.0005). On multiple logistic regression, the likelihood of emphysema increased when NSIP was present (OR = 18.8; 95% CI = 5.3–66.3; P < 0.0005) and with increasing age (OR = 1.04; 95% CI = 0.99–1.11; P = 0.08). Emphysema is as prevalent in smokers with NSIP as in smokers with COPD, and is strikingly more prevalent in these two groups than in healthy smoking controls. The association between NSIP and emphysema provides indirect support for a smoking pathogenesis hypothesis in some NSIP patients

ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism

BACKGROUND: The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1). OBJECTIVE: We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain. DESIGN: We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex. RESULTS: Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001). CONCLUSIONS: Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study

Measurement of CP-violation asymmetries in D0 to Ks pi+ pi-

We report a measurement of time-integrated CP-violation asymmetries in the resonant substructure of the three-body decay D0 to Ks pi+ pi- using CDF II data corresponding to 6.0 invfb of integrated luminosity from Tevatron ppbar collisions at sqrt(s) = 1.96 TeV. The charm mesons used in this analysis come from D*+(2010) to D0 pi+ and D*-(2010) to D0bar pi-, where the production flavor of the charm meson is determined by the charge of the accompanying pion. We apply a Dalitz-amplitude analysis for the description of the dynamic decay structure and use two complementary approaches, namely a full Dalitz-plot fit employing the isobar model for the contributing resonances and a model-independent bin-by-bin comparison of the D0 and D0bar Dalitz plots. We find no CP-violation effects and measure an asymmetry of ACP = (-0.05 +- 0.57 (stat) +- 0.54 (syst))% for the overall integrated CP-violation asymmetry, consistent with the standard model prediction.Comment: 15 page

Effective Rheology of Bubbles Moving in a Capillary Tube

We calculate the average volumetric flux versus pressure drop of bubbles moving in a single capillary tube with varying diameter, finding a square-root relation from mapping the flow equations onto that of a driven overdamped pendulum. The calculation is based on a derivation of the equation of motion of a bubble train from considering the capillary forces and the entropy production associated with the viscous flow. We also calculate the configurational probability of the positions of the bubbles.Comment: 4 pages, 1 figur