Full-Scale Wind-Tunnel Tests of a PCA-2 Autogiro Rotor

This report presents the results of force tests on and air-flow surveys near PCA-2 autogiro rotor in the NACA full-scale wind tunnel. The force tests were made at three pitch settings and several rotor speeds; the effect of fairing protuberances on the rotor blade was determined. Induced downwash and yaw angles were determined at low tip-speed ratios in a plane 1 1/2 feet above the path of the blade tips. The results show that the maximum l/d of the rotor cannot be appreciably increased by increasing the blade pitch angle above about 4.5 degrees at the blade tip; that the protuberances on the blades cause more than 5 percent of the total rotor drag; and that the rotor center-of-pressure travel is very small

Physical properties and radius variations in the HAT-P-5 planetary system from simultaneous four-colour photometry

The radii of giant planets, as measured from transit observations, may vary with wavelength due to Rayleigh scattering or variations in opacity. Such an effect is predicted to be large enough to detect using ground-based observations at multiple wavelengths. We present defocussed photometry of a transit in the HAT-P-5 system, obtained simultaneously through Stromgren u, Gunn g and r, and Johnson I filters. Two more transit events were observed through a Gunn r filter. We detect a substantially larger planetary radius in u, but the effect is greater than predicted using theoretical model atmospheres of gaseous planets. This phenomenon is most likely to be due to systematic errors present in the u-band photometry, stemming from variations in the transparency of Earth's atmosphere at these short wavelengths. We use our data to calculate an improved orbital ephemeris and to refine the measured physical properties of the system. The planet HAT-P-5b has a mass of 1.06 +/- 0.11 +/- 0.01 Mjup and a radius of 1.252 +/- 0.042 +/- 0.008 Rjup (statistical and systematic errors respectively), making it slightly larger than expected according to standard models of coreless gas-giant planets. Its equilibrium temperature of 1517 +/- 29 K is within 60K of that of the extensively-studied planet HD 209458b.Comment: Version 2 corrects the accidental omission of one author in the arXiv metadata. Accepted for publication in MNRAS. 9 pages, 4 figures, 7 tables. The properties of HAT-P-5 have been added to the Transiting Extrasolar Planet Catalogue at http://www.astro.keele.ac.uk/~jkt/tepcat

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Long-term follow-up of brain-damaged children requiring feeding gastrostomy: Should an antireflux procedure always be performed?

Due to the frequent presence of latent gastroesophageal reflux (GER) in mentally impaired children, it is now standard to perform upper gastrointestinal contrast (UGI) and pH probe studies in all children referred for feeding gastrostomy, even if they are without clinical evidence for GER. For patients with documented GER, an antireflux operation performed in conjunction with gastrostomy is usually considered mandatory. Some authors have suggested that a "protective" antireflux operation be performed at the time of gastrostomy placement in all brain-damaged children, citing a high incidence of postoperative GER in this group of patients following gastrostomy, even with a negative preoperative evaluation for GER. To evaluate this theory, we prospectively studied, over the past 6 years, all mentally retarded children referred for feeding gastrostomy with UGI contrast and esophageal pH probe studies. In total, 148 children were studied; 105 had a positive evaluation for GER and underwent gastrostomy and antireflux surgery. Of the 43 children with a negative preoperative evaluation for GER, 37 are doing well following gastrostomy alone without clinical reflux at an average follow-up of 21 months. Six of the 43 (14%) developed symptomatic GER occurring at an average of 10 months following gastrostomy placement. Five of these children have been successfully treated with an antireflux operation and the sixth patient has been successfully man-aged nonoperatively. Given the significant morbidity and mortality that has been documented with antireflux operations in mentally retarded children, we conclude that a protective antireflux operation at the time of gastrostomy placement is not indicated because the data suggest that 86% of children with a negative preoperative evaluation for GER would undergo the operation needlessly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29436/1/0000517.pd

Hirschsprung's disease in adolescents and adults

Hirschsprung's disease in the adolescent and adult is a rare and often misdiagnosed cause of lifelong refractory constipation. Two adolescent and three adult patients with Hirschsprung's disease treated between 1973 and 1987 at the University of Michigan Medical Center are reported. Each patient presented with chronic constipation requiring enemas, cathartics, and multiple hospital admissions for management. Diagnosis in each case was made with barium enema and full-thickness rectal biopsy. Four patients underwent endorectal pull-through procedures, all with good long-term results. The fifth patient, initially treated with a Duhamel retrorectal pull-through procedure, required reoperation for constipation secondary to a retained rectal septum. Review of 199 cases of adult Hirschsprung's disease enables comparison of the various operative procedures for this disorder with respect to postoperative complications and functional outcomes. Anorectal myectomy with low anterior resection, the Duhamel-Martin procedure, and the Soave endorectal pull-through procedure are the most acceptable methods for surgical management .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41392/1/10350_2005_Article_BF02052222.pd

Redo fundoplication in infants and children with recurrent gastroesophageal reflux

The Nissen fundoplication is well established as the surgical treatment for medically refractory gastroesophageal reflux (GER) in childhood. Recurrent GER following fundoplication is a challenging problem with a reported incidence ranging from 0% to 12%. From January 1974 to January 1989, 286 children have been treated for GER with Nissen fundoplication and gastrostomy tube placement at the University of Michigan C.S. Mott Children's Hospital; 242 of these children have been followed for an average of 30 months, the remaining 44 have been lost to follow-up. Twenty-nine children (12%) have developed recurrent reflux following fundoplication. Medical management with thickened upright feelings, gastrostomy feedings, or gastrojejunostomy tube feedings has been successful for 11 children with control of reflux symptoms. Five additional children who were treated nonoperatively died of coexistant medical problems within 2 months following documentation or recurrent reflux. The remaining 13 children have required redo fundoplication for wrap disruption or herniation, and an additional six children, initially treated at other institutions, have also undergone redo fundoplications. One other child treated at this hospital required redo fundoplication for a postoperative partial gastric volvulus causing gastric outlet obstruction. Of the 20 children who have undergone a second Nissen fundoplication, 16 (80%) are doing well without recurrent GER. Four children have developed recurrent GER with wrap disruption; 1 is doing well following a third fundoplication, 2 have been managed successfully with continuous feedings via gastrojejunostomy feeding tubes, and a fourth child died of complications related to a recurrent tracheoesophageal fistula. Conservative management with gastrojejunal tube feedings should be considered in the initial management of children with recurrent GER following fundoplication. If necessary, redo Nissen fundoplication, although technically difficult, is associated with a good outcome in the majority of children and is indicated for refractory recurrent GER following a failed antireflux procedure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29266/1/0000324.pd

Ligand-induced conformational changes in a SMALP-encapsulated GPCR.

The adenosine 2A receptor (A2AR), a G-protein-coupled receptor (GPCR), was solubilised and purified encapsulated in styrene maleic acid lipid particles (SMALPs). The purified A2AR-SMALP was associated with phospholipids characteristic of the plasma membrane of Pichia pastoris, the host used for its expression, confirming that the A2AR-SMALP encapsulated native lipids. The fluorescence spectrum of the A2AR-SMALP showed a characteristic broad emission peak at 330 nm, produced by endogenous Trp residues. The inverse agonist ZM241385 caused 30% increase in fluorescence emission, unusually accompanied by a red-shift in the emission wavelength. The emission spectrum also showed sub-peaks at 321 nm, 335 nm and 350 nm, indicating that individual Trp inhabited different environments following ZM241385 addition. There was no effect of the agonist NECA on the A2AR-SMALP fluorescence spectrum. Substitution of two Trp residues by Tyr suggested that ZM241385 affected the environment and mobility of Trp2466.48 in TM6 and Trp2687.33 at the extracellular face of TM7, causing transition to a more hydrophobic environment. The fluorescent moiety IAEDANS was site-specifically introduced at the intracellular end of TM6 (residue 2316.33) to report on the dynamic cytoplasmic face of the A2AR. The inverse agonist ZM241385 caused a concentration-dependent increase in fluorescence emission as the IAEDANS moved to a more hydrophobic environment, consistent with closing the G-protein binding crevice. NECA generated only 30% of the effect of ZM241385. This study provides insight into the SMALP environment; encapsulation supported constitutive activity of the A2AR and ZM241385-induced conformational transitions but the agonist NECA generated only small effects

Treatment of renal transplant stones byextracorporeal shock-wave lithotripsy in the prone position

Two patients with renal transplant lithiasis were successfully treated with extracorporealshock-wave lithotripsy (ESWL) in the prone position. Pathogenesis and treatment of transplant lithiasis are discussed. Performing ESWL on renal transplant patients in the prone position has advantages over standard positioning techniques.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29533/1/0000620.pd

Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation

Activation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed