Randomized trial of FK 506/prednisone vs FK 506/azathioprine/prednisone after renal transplantation: preliminary report.

FK 506 was used as a primary immunosuppressive agent in 125 cases of renal transplantation in a randomized trial comparing FK 506/prednisone with FK 506/azathioprine/prednisone. With a mean follow-up of 5.5 +/- 2.5 months, there has been a 6-month actuarial patient survival of 99% and graft survival of 88%. There is no difference thus far between the two-drug and three-drug groups, although there may be less rejection and diabetes in the three-drug group. These results suggest that FK 506 is a useful immunosuppressive agent in kidney transplantation

Uterocervical angle measurement improves prediction of preterm birth in twin gestation

Objective An obtuse uterocervical angle (UCA) has been associated with increased risk of preterm birth in singleton gestations. Our objective was to compare the performance of UCA to cervical length (CL) as sonographic predictors of spontaneous preterm birth (sPTB) in patients with twin gestation. Study Design We conducted a retrospective cohort study of twin gestations at a single academic center from May 2008-2016 who received a transvaginal ultrasound for the evaluation of the cervix between 16 0/7 - 22 6/7 weeks. An investigator blinded to clinical outcomes reviewed images of cervical morphology and measured UCA and CL parameters. Data on obstetrical outcomes was extracted from the medical record. The primary outcome was prediction of preterm birth <28 weeks and <32 weeks by UCA and CL. Receiver operator characteristic (ROC) curves and binary logistic regression were used for statistical analysis. Statistical significance was defined as p <0.05. Results Among 259 women with twin gestation, the mean gestational age at birth was 34.83 +/- 3.48 weeks, and 44.7% (n=116) delivered prior to 36 weeks. ROC curves demonstrated optimal prediction of sPTB prior to 32 weeks at a UCA > 110o (80% sensitivity, 82% specificity) vs. CL 114o (80% sensitivity, 84% specificity) vs. CL 110o conferred an OR 15.7 (95% CI 7.2-34.4) for delivery prior to 32 weeks, and UCA > 114o an OR 24.3 (95% CI 6.7-88.5) for delivery prior to 28 weeks. In comparison, CL<25mm had an OR 5.2 (95% CI 2.2-12.2) and OR 6.0 (95% CI 2.0-18.1) prior to 32 and 28 weeks respectively. Conclusion Uterocervical angles >110o performed better than the traditional cervical length threshold (25mm) for the prediction of sPTB in a cohort of twin gestations. Measurement of the UCA during the mid-trimester may improve identification of twin gestations at risk for sPTB

Relative performance of antimicrobial susceptibility assays on clinical Escherichia coli isolates from animals

The assessment of antimicrobial resistance in bacteria derived from animals is often performed using the disc diffusion assay. However broth-microdilution is the preferred assay for national antimicrobial resistance surveillance programs. This study aimed to evaluate the accuracy of disc diffusion relative to broth-microdilution across a panel of 12 antimicrobials using data from a collection of 994 clinical Escherichia coli isolates from animals. Disc diffusion performance was evaluated by diagnostic sensitivity, specificity, likelihood ratio pairs and receive-operating characteristic (ROC) analysis. Data was dichotomised using CLSI susceptible and resistant clinical breakpoints. In addition, disc diffusion breakpoints produced using diffusion Breakpoint Estimation Testing Software (dBETS) were evaluated. Analysis revealed considerable variability in performance estimates for disc diffusion susceptible and resistant breakpoints (AUC ranges: 0.78–0.99 and 0.92–1.0, respectively) across the panel of antimicrobials. Ciprofloxacin, tetracycline, and ampicillin estimates were robust across both breakpoints, whereas estimates for several antimicrobials including amoxicillin-clavulanic acid, cefoxitin and gentamicin were less favourable using susceptible breakpoints. Overall performance estimates were moderately improved when dBETS susceptible breakpoints were applied. For most antimicrobials, disc diffusion was accurate at predicting resistance of clinical E. coli from animals that could otherwise be determined by broth-microdilution. While disc diffusion is suboptimal for assessing the proportion of fully susceptible isolates for some drugs, sensitivity and specificity estimates provided here allow for the use of standard formula to correct this. For this reason, disc diffusion has applicability in national surveillance provided the performance of the assay is taken into account

A prospective randomized trial of FK506-based immunosuppression after renal transplantation

A group of 204 adult patients was entered into a prospective, randomized trial comparing FK506/pred-nisone with FK506/azathioprine/prednisone after renal transplantation between August 1, 1991 and October 11,1992. The purpose of the study was to see if the addition of azathioprine would reduce the incidence of rejection and improve graft survival. The recipient population was unselected, with 61 (30%) patients undergoing retransplantation, 37 (18%) having a panel-reactive antibody greater than 40%, and 33 (16%) over 60 years of age. The mean recipient age was 43.8±13.7 years (range 17.6-78). The mean donor age was 34.0±20.1 years (range 0.3-75); 13% of the cadaveric kidneys were from pediatric donors less than 3 years of age and were transplanted en bloc. The mean cold ischemia time was 31.4±8.4 hr. Living donors were the source of 13% of the kidneys. The mean follow-up was 22±4 months (range 12-29). Overall one-year actual patient survival was 94%. Overall one-year actual graft survival was 87%. Patients starting on double therapy had a one-year actual patient survival of 96% and a one-year actual graft survival of 92%. Patients starting on triple therapy had a one-year actual patient survival of 91% (P=ns compared with double therapy), and a one-year actual graft survival of 82% (P<0.02, compared with double therapy). Overall results with first cadaver transplants included a one-year actual patient survival of 94% and one-year actual graft survival of 88%, with no differences between double and triple therapy. The overall incidence of rejection was 48%, with 54% in the double therapy group and 41% in the triple therapy group (P<.07). The incidence of steroid-resistant rejection requiring antilymphocyte therapy (OKT3 or ATGAM) was 13%, and was not different between the double and triple therapy groups. The mean serum creatinine was 1.8±0.8 mg/dl. The mean BUN was 33±21 mg/dl, with no significant difference between the therapy groups. The mean serum cholesterol was 192 ±49 mg/dl. A total of 56% of the patients are off prednisone, and 35% of the patients are not taking any antihypertensive medications. Other complications included cytomegalovirus—14%; new-onset diabetes—16% (half of which was reversible); and posttransplant lymphoproliferative disorder—1%. There was a high incidence of crossover between the two groups, 27% of the patients in the double therapy group requiring the addition of azathioprine, and 45% of the patients in the triple therapy group requiring its discontinuation (usually tempoгагу). These results show that FK506 is an excellent immunosuppressive agent after renal transplantation and that azathioprine is not routinely effective as a third agent. A high quality of life resulted from the ability to use no (56%) or low-dose maintenance steroids. © 1995 by Williams and Wilkins

Addressing Food Insecurity in College: Mapping a Shared Conceptual Framework for Campus Pantries in Michigan

The first known university food pantry started at Michigan State University in 1993. Since then, campus food pantries are more widespread, although little is known about them. The current study examined how college pantries best serve students and foster their success. Twentyâ eight food pantry directors and staff from across sixteen Michigan college campuses engaged in concept mapping, a technique used to examine the interrelationships among concepts understood by stakeholders. Analyses identified six concepts, examined importance of each concept as assigned by participants, and evaluated variation among institutions. Implications for findings and future research directions are discussed.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/1/asap12161_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147046/2/asap12161.pd

FK506 IN PEDIATRIC KIDNEY-TRANSPLANTATION - PRIMARY AND RESCUE EXPERIENCE

Between December 14, 1989, and December 17, 1993,43 patients undergoing kidney transplantation alone at the Children’s Hospital of Pittsburgh received FK506 as the primary immunosuppressive agent. The mean recipient age was 10.2 ± 4.8 years (range 0.7–17.4), with 7 (16%) children under 5 years of age and 2 (5%) under 2 years of age. Fifteen (35%) children underwent retransplantation, and 5 (12%) had a panel reactive antibody level greater than 40%. Twenty-two (51%) cases were with cadaveric donors, and 21 (49%) were with living donors. The mean follow-up is 25 ± 14 months. There were no deaths. One and three year actuarial graft survival was 98% and 85%. The mean serum creatinine and BUN were 1.2 ± 0.6 mg/dl and 26 ± 11 mg/dl; the calculated creatinine clearance was 75 ± 23 ml/min/1.73 m(2). Twenty-four (62%) patients have been successfully withdrawn from steroids, and 24 (62%) require no anti-hypertensive medication. Improved growth was seen, particularly in pre-adolescent children off steroids. Between July 28, 1990, and December 2, 1993, 24 children were referred for rescue therapy with FK506, 14.6 ± 16.4 months (range 1.1–53.2) after transplantation. Nineteen (79%) were referred because of resistant rejection; 4 (17%) were referred because of proteinuria; 1 (4%) was switched because of steroid-related obesity. There were no deaths. One and two year graft survival was 75% and 68%. Seventeen (71%) patients were successfully rescued, including 1 of 2 patients who arrived on dialysis. Four (24%) of the successfully rescued patients were weaned off steroids. While not without side effects, which include nephrotoxicity, neurotoxicity, diabetogenicity, and viral complications, FK506 appears to be an effective immunosuppressive agent for both primary and rescue therapy after kidney transplantation. Its steroid-sparing qualities may be of particular importance in the pediatric population

Nucleotide Frequencies in Human Genome and Fibonacci Numbers

This work presents a mathematical model that establishes an interesting connection between nucleotide frequencies in human single-stranded DNA and the famous Fibonacci's numbers. The model relies on two assumptions. First, Chargaff's second parity rule should be valid, and, second, the nucleotide frequencies should approach limit values when the number of bases is sufficiently large. Under these two hypotheses, it is possible to predict the human nucleotide frequencies with accuracy. It is noteworthy, that the predicted values are solutions of an optimization problem, which is commonplace in many nature's phenomena.Comment: 12 pages, 2 figure

Sparkling extreme-ultraviolet bright dots observed with Hi-C

Observing the Sun at high time and spatial scales is a step toward understanding the finest and fundamental scales of heating events in the solar corona. The high-resolution coronal (Hi-C) instrument has provided the highest spatial and temporal resolution images of the solar corona in the EUV wavelength range to date. Hi-C observed an active region on 2012 July 11 that exhibits several interesting features in the EUV line at 193 Å. One of them is the existence of short, small brightenings "sparkling" at the edge of the active region; we call these EUV bright dots (EBDs). Individual EBDs have a characteristic duration of 25 s with a characteristic length of 680 km. These brightenings are not fully resolved by the SDO/AIA instrument at the same wavelength; however, they can be identified with respect to the Hi-C location of the EBDs. In addition, EBDs are seen in other chromospheric/coronal channels of SDO/AIA, which suggests a temperature between 0.5 and 1.5 MK. Based on their frequency in the Hi-C time series, we define four different categories of EBDs: single peak, double peak, long duration, and bursty. Based on a potential field extrapolation from an SDO/HMI magnetogram, the EBDs appear at the footpoints of large-scale, trans-equatorial coronal loops. The Hi-C observations provide the first evidence of small-scale EUV heating events at the base of these coronal loops, which have a free magnetic energy of the order of 1026 erg. © 2014. The American Astronomical Society. All rights reserved

Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates.

The efficient production of biofuels from cellulosic feedstocks will require the efficient fermentation of the sugars in hydrolyzed plant material. Unfortunately, plant hydrolysates also contain many compounds that inhibit microbial growth and fermentation. We used DNA-barcoded mutant libraries to identify genes that are important for hydrolysate tolerance in both Zymomonas mobilis (44 genes) and Saccharomyces cerevisiae (99 genes). Overexpression of a Z. mobilis tolerance gene of unknown function (ZMO1875) improved its specific ethanol productivity 2.4-fold in the presence of miscanthus hydrolysate. However, a mixture of 37 hydrolysate-derived inhibitors was not sufficient to explain the fitness profile of plant hydrolysate. To deconstruct the fitness profile of hydrolysate, we profiled the 37 inhibitors against a library of Z. mobilis mutants and we modeled fitness in hydrolysate as a mixture of fitness in its components. By examining outliers in this model, we identified methylglyoxal as a previously unknown component of hydrolysate. Our work provides a general strategy to dissect how microbes respond to a complex chemical stress and should enable further engineering of hydrolysate tolerance