Demonstrating Agreement between Radio and Fluorescence Measurements of the Depth of Maximum of Extensive Air Showers at the Pierre Auger Observatory.

We show, for the first time, radio measurements of the depth of shower maximum (X_{max}) of air showers induced by cosmic rays that are compared to measurements of the established fluorescence method at the same location. Using measurements at the Pierre Auger Observatory we show full compatibility between our radio and the previously published fluorescence dataset, and between a subset of air showers observed simultaneously with both radio and fluorescence techniques, a measurement setup unique to the Pierre Auger Observatory. Furthermore, we show radio X_{max} resolution as a function of energy and demonstrate the ability to make competitive high-resolution X_{max} measurements with even a sparse radio array. With this, we show that the radio technique is capable of cosmic-ray mass composition studies, both at Auger and at other experiments.

Limits to Gauge Coupling in the Dark Sector Set by the Nonobservation of Instanton-Induced Decay of Super-Heavy Dark Matter in the Pierre Auger Observatory Data.

Instantons, which are nonperturbative solutions to Yang-Mills equations, provide a signal for the occurrence of quantum tunneling between distinct classes of vacua. They can give rise to decays of particles otherwise forbidden. Using data collected at the Pierre Auger Observatory, we search for signatures of such instanton-induced processes that would be suggestive of super-heavy particles decaying in the Galactic halo. These particles could have been produced during the post-inflationary epoch and match the relic abundance of dark matter inferred today. The nonobservation of the signatures searched for allows us to derive a bound on the reduced coupling constant of gauge interactions in the dark sector: α_{X}≲0.09, for 10^{9}≲M_{X}/GeV<10^{19}. Conversely, we obtain that, for instance, a reduced coupling constant α_{X}=0.09 excludes masses M_{X}≳3×10^{13} GeV. In the context of dark matter production from gravitational interactions alone, we illustrate how these bounds are complementary to those obtained on the Hubble rate at the end of inflation from the nonobservation of tensor modes in the cosmological microwave background.

Measurement of the Fluctuations in the Number of Muons in Extensive Air Showers with the Pierre Auger Observatory.

We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Features of the Energy Spectrum of Cosmic Rays above 2.5×10

We report a measurement of the energy spectrum of cosmic rays above 2.5×10^{18} eV based on 215 030 events. New results are presented: at about 1.3×10^{19} eV, the spectral index changes from 2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×10^{19} eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×10^{18} eV is [5.66±0.03(stat)±1.40(syst)]×10^{53} erg Mpc^{-3}.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Testing Hadronic Interactions at Ultrahigh Energies with Air Showers Measured by the Pierre Auger Observatory.

Ultrahigh energy cosmic ray air showers probe particle physics at energies beyond the reach of accelerators. Here we introduce a new method to test hadronic interaction models without relying on the absolute energy calibration, and apply it to events with primary energy 6-16 EeV (E_{CM}=110-170 TeV), whose longitudinal development and lateral distribution were simultaneously measured by the Pierre Auger Observatory. The average hadronic shower is 1.33±0.16 (1.61±0.21) times larger than predicted using the leading LHC-tuned models EPOS-LHC (QGSJetII-04), with a corresponding excess of muons.

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy.

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8±0.7(stat)±6.7(syst) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principles calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.

[Clinical results after implantation of a new segmental refractive multifocal intraocular lens]. / Klinische Ergebnisse nach Implantation einer neuen segmentalen refraktiven Multifokallinse.

BACKGROUND: The aim of the study was a clinical evaluation of an intraocular lens (IOL) with a segmental multifocal optic design and near addition of + 3.0 D as part of a CE approval study. PATIENTS AND METHODS: In a multicenter study the LENTIS Mplus LS-312 MF IOL (Oculentis) was implanted in 134 eyes of 79 patients with a mean age of 68 ± 12 years. The multifocality is achieved by implementation of a distance part and a segmented near sector. Three months after surgery, uncorrected and best corrected distance visual acuity (UCDVA and BCDVA, respectively), near visual acuity (UCNVA and BCNVA, respectively), contrast vision and patient satisfaction (questionnaire) were evaluated. RESULTS: The IOLs were implanted uneventfully either unilaterally or bilaterally and 3 months postoperatively (n = 86 eyes) the following mean visual acuities were obtained (logMAR): UCDVA = 0.05, BCDVA = - 0.01, UCNVA = 0.09 and BCNVA = 0.02. Contrast sensitivity (n = 25 eyes) was within normal limits. Of the 66 questioned patients 10.6% spontaneously reported halos and 3% glare. CONCLUSION: This new innovative multifocal IOL concept showed very good functional results as well as high patient satisfaction.

[Pharmacological therapy of keloids in an athymic mouse model]. / Pharmakologische keloidtherapie im tiermodell.

PURPOSE: In spite of the high incidence of dermal fibroproliferative disorders, there is no agreement about the treatment of choice. Due to the inability of animals to produce keloid tissue, a standardised model to study the effects of different treatment modalities in vivo is lacking. Therefore, a comparative study on the effect of three pharmacological agents was conducted with human keloid implants in an athymic mouse model. MATERIAL AND METHODS: Cubic keloid tissue blocks from 10 human volunteers were implanted in 54 male, athymic, homozygotic mice. The animals were divided into 4 groups, including an untreated control group. Members of each section received either colchicine, nicardipine or triamcinolone applied transdermally into the keloid tissue or into the peritoneum. The tissue specimens of 5 mice each were explanted according to a predetermined time schedule on days 28, 42 and 56 post-implantation and examined using various histological techniques including standard dye and immune histochemistry. The freeze-dried and moist weights of the keloid tissue were determined and analysed. RESULTS: Statistically significant changes regarding declining weight parameters were seen in the colchicines-treated group. Moreover, the densities of fibroblasts and endothelial cells were significantly reduced through colchicines treatment when compared to the control group and the groups treated with the other agents. The triamcinolone group also showed partially significant changes of weight compared to the control group, whereas no statistically significant effect of nicardipine on any parameter was found. Any influence of the host organism could be excluded as there were no signs of rejection or lymphocytic infiltration. CONCLUSION: Our study represents a successful attempt to create a standardised model for a comparative investigation on keloid tissue in vivo. The effect of colchicine was demonstrated in the light of an inhibitory effect on fibroblastic proliferative activity. The studied model allows a direct comparison of implanted, vascularised keloid tissue and its reactivity to various agents without being biased by numerous unknown variables in humans.

[Liposuction curettage versus Botox for axillary hyperhidrosis. A prospective study of the quality of life]. / Liposuktionskürettage versus Botox bei axillärer Hyperhidrosis. Eine prospektive Studie der Lebensqualität.

BACKGROUND: Axillary hyperhidrosis is a dysfunction of the secretion of sweat glands. Conservative treatment modalities are mostly ineffective. Liposuction combined with subcutaneous curettage (TLC) destroys the sweat glands, while Botox injections inhibit the cholinergic transmission. MATERIAL AND METHOD: Of a total of 88 patients, TLC was carried out in 47 and 41 patients received intradermal Botox injections. The effect of both forms of treatment on the quality of life was assessed using a specific hyperhidrosis questionnaire and was correlated with sweat volumes measured by gravimetry. RESULTS: Follow-up after 6 months showed significantly changed sweat volumes of 52+/-41 mg/min of TLC patients versus 78+/-87 mg/min in the Botox group. In the TLC group 91% and in the Botox group 98% were satisfied with the result. CONCLUSION: The stress of a single surgical intervention is to be weighed against the necessary repetitive application of multiple Botox injections. Both methods are superior to other, more radical surgical methods in terms of efficacy and complication rates. Botox and TLC lead to a significant improvement of the quality of life.

[Functional bracing after operative treatment of metacarpal fractures]. / Frühfunktionelle Nachbehandlung operativ versorgter Mittelhandfrakturen.

Metacarpal fractures are frequently immobilized for several weeks in forearm plaster cast, even after operative stabilisation. The purpose of this study was to assess the results after early functional treatment using metacarpal braces. 87 patients with 105 metacarpal fractures were included in a prospective study from February 1997 until November 2000. The AO-classification of the fractures was assessed for all patients: n=33 A1,n=9 A2,n=3 A3, n=27 B1,n=6 B2,n=7 B3,n=10 C1,n=7 C2, n=3 C3.Exclusion criteria were tendon or nerve injuries,pathological fractures (tumor or metabolic),additional digital fractures of the same ray,and a patients age of less then 18 years. All fractures were treated operatively. 73 patients (84%) were recruited for follow up after an average period of nine months. Average grip strength reached 96% (Jamar II) for the power grip, 97% for the three finger and 98% for the pinch grip compared to the contra-lateral side in the group where the dominant hand was affected. It was 88% for the power grip, 91% for the three finger grip and 94% for the pinch grip after injury of the non-dominant hand. The mean postoperative pain score on the visual analog scale was 0.2 for resting conditions, 0.8 for motion and 2.2 under stress.A decreased total range of motion was observed in 15 of 73 patients (21%). The average DASH score reached 6.5 points. Physical therapy was required for an average of 6.7 weeks. Only 41% of the patients with early functional treatment required further physical therapy after removal of the brace. The metacarpal brace used in this series protects from direct trauma,and provides a high patients comfort.It has no disadvantages considering fracture retention compared to conventional plaster casts or splints. The need for physical therapy is reduced after functional fracture bracing.Thus, the metacarpal brace has proven to be a suitable tool for early functional treatment after operative stabilisation of metacarpal fractures.

Steroid-free liver transplantation using rabbit antithymocyte globulin induction: results of a prospective randomized trial.

Steroids have been 1 of the primary modes of immunosuppression since the inception of transplantation and have been credited with both the prevention and treatment of rejection. Steroids also have been held responsible for increased infections, posttransplantation diabetes, and recurrent hepatitis after orthotopic liver transplantation (OLT). The purpose of this ongoing prospective randomized trial is to eliminate steroid use in OLT through induction with rabbit antithymocyte globulin (RATG). This is the first report of a prospective randomized trial in OLT achieving complete absence of steroids. Seventy-one adult patients were prospectively randomized to administration of RATG or steroids. Thirty-six patients were randomized to the administration of RATG induction at a dose of 1.5 mg/kg intravenously (IV) beginning during the anhepatic phase. No steroids were administered. Patients were administered a second 1.5-mg/kg dose of RATG post-OLT day 1. Thirty-five patients were randomized to the administration of methylprednisolone, which had been our standard immunosuppressive protocol. These patients were administered methylprednisolone, 1,000 mg IV, initiated during the anhepatic phase and followed by steroid taper. Maintenance immunosuppression consisted of tacrolimus and mycophenolate, with or without prednisone. Three patients died in each group, for an overall survival rate of 91% in each group. One patient in each group required re-OLT, for a graft survival rate of 89% in each group. Seven patients administered RATG had biopsy-proven rejection (20.5%), all of whom were successfully treated by increasing tacrolimus doses. Eleven patients administered steroid had biopsy-proven rejection (32%), 7 (64%) of whom required additional steroids for treatment, whereas 4 patients (36%) were successfully treated by increasing tacrolimus doses. The incidence of rejection was not statistically significant; however, there was a significant difference in the incidence of steroid-requiring rejection (P =.01). The incidence of recurrent hepatitis C was 50% in RATG patients and 71% in steroid patients (P = not significant). The incidence and severity of infectious complications were slightly lower in RATG patients, accounted for by a greater incidence of cytomegalovirus (CMV) infection in the steroid patients. RATG induction enables complete avoidance of steroid use in OLT with a trend toward a lower rejection rate, decreased incidence of post-OLT diabetes and recurrent hepatitis C, and decreased CMV infection. This prospective randomized trial gives encouraging support that steroids can be safely eliminated in OLT.

Transplantation of livers from hbc Ab positive donors into HBc Ab negative recipients: a strategy and preliminary results.

Here we describe a strategy for using livers from hepatitis B core antibody (anti-HBc) positive donors in anti-HBc negative recipients and report our preliminary results. Adult anti-HBc negative recipients were immunized against hepatitis B virus (HBV) prior to transplantation. Liver biopsies from anti-HBc positive, HBs Ag negative donors were performed at the time of procurement to rule out acute hepatitis or chronic liver disease. Donor serum and liver samples were collected for HBV DNA analysis by PCR. Recipients were given HBIG (10000 units, i.v.) during the anhepatic phase of transplantation. Patients were treated with lamivudine (150 mg) beginning on postoperative day (POD) 1. If HBV DNA was not detected in either donor liver or serum by PCR, recipient antiviral therapy was stopped. If donor liver and serum were positive for HBV DNA by PCR, the recipient was maintained on combination lamivudine and HBIG therapy. If HBV DNA was detected in donor liver but not in donor serum, the patient was managed on lamivudine therapy alone. Between February 1999 and June 2000, six anti-HBc negative recipients received liver transplants from anti-HBc positive donors. PCR analysis of serum from the six donors was negative for HBV DNA in each, while donor liver PCR analysis was positive in five of six for HBV DNA. Accordingly, all patients were given HBIG in the anhepatic phase of transplantation and five of six were maintained on daily lamivudine therapy. Follow-up periods have ranged from 2 to 18 months. There has been no emergence of de novo hepatitis B. Serial serum HBs Ag and HBV DNA assays have all proven negative. Moreover, while on lamivudine therapy, 2 patients now have undetectable HBV DNA in hepatic allograft biopsies by PCR analysis. Our strategy for using livers from anti-HBc donors has yielded promising initial results. De novo hepatitis B has not occurred and our data suggest residual hepatitis B virus may be eradicated in recipients maintained on lamivudine therapy.

Importance of using comparative genomic hybridization to improve detection of chromosomal changes in childhood acute lymphoblastic leukemia.

We used comparative genomic hybridization (CGH) and conventional cytogenetics (CC) to define chromosomal changes and to evaluate the usefulness of CGH in 65 patients having childhood acute lymphoblastic leukemia (ALL). Subsequently, fluorescence in situ hybridization (FISH) was used to evaluate the CGH and cytogenetic results. Comparative genomic hybridization revealed DNA copy number changes in 49 (75%) patients (including 7 patients with unsuccessful cytogenetics and 2 patients with normal karyotype). A total of 85 losses and 195 gains were detected. The most commonly gained chromosomes were 21 (35%), X (31%), 18 (27%), 10 (26%), 6 (25%), 17 (25%), 4 (23%), and 14 (22%). Losses were most frequently observed on chromosomes 9p (18%) and 12p (11%). Other losses were detected on chromosomes 13q (9%), 6q (9%), 7p (8%), and chromosome X (6%). Conventional cytogenetics revealed chromosomal changes in 53 (82%) patients. The employment of CGH and FISH together with CC analysis revealed chromosomal changes in 62 (95%) of the childhood ALL patients investigated. The CGH completed CC results in 36 patients; in 9 patients, the changes escaped detection without using CGH. The results of our study were compared to 6 other CGH studies previously reported. Our observations underline the benefits of supplementing routine cytogenetic investigation in childhood ALL by FISH and CGH, because small unbalanced changes may escape detection when conventional cytogenetics is the only diagnostic method used.

Liver transplantation: perspectives after 250 liver transplants at the Ochsner Clinic.

At the Ochsner Clinic we recently performed our 250th liver transplant. Reaching this milestone has led us to reflect back on the history of liver transplant, both at our own institution and nationally, noting the many achievements and improvements in liver transplantation during the relatively brief history of this therapeutic modality. Furthermore, there are a number of issues both medical and political which will likely be affecting how liver transplantation is performed in the future.

Liver transplantation for hepatocellular carcinoma: one center's experience, 1987-1994.

A retrospective review was done to evaluate the detection of hepatocellular carcinoma preoperatively, using ultrasonography and alpha-fetoprotein in patients awaiting orthotopic liver transplantation. Sixteen of the 187 patients who underwent 209 orthotopic liver transplantations at the Ochsner Transplant Center from 1987 to 1994 were diagnosed with hepatocellular carcinoma, 3 preoperatively and 11 at the time of pathological inspection of the liver explant. Two developed metastatic hepatocellular carcinoma while awaiting orthotopic liver transplantation. Ultrasonography detected abnormalities in the region where hepatoma was identified in 5 of 11 (45%) patients with incidental hepatocellular carcinoma, in all 3 with overt hepatocellular carcinoma, and in neither of the 2 who developed metastatic hepatocellular carcinoma while awaiting orthotopic liver transplantation. Hepatocellular carcinoma was present in 5 of 23 (22%) patients with an alpha-fetoprotein greater than 20 ng/mL and in 3 of 10 (30%) with an alpha-fetoprotein greater than 50 ng/mL.

Diffusion of antibiotics across tissue expanders: an in vitro study.

Local infection remains a significant complication of tissue expansion. Subclinical infection of pockets with permanent prosthesis used in breast reconstruction has also been associated with capsular contracture around the implant. In an in vitro model, we used four groups of eighteen 50-ml tissue expanders, each containing Bactrim, Ancef, Nafcil, or saline only, in beakers containing fresh frozen plasma, placed in a rotary shaker for 48 hours. Inoculums of Staphylococcus aureus and Staphylococcus epidermidis were then selectively added to the medium external to the expanders in each group. The growth of such strains was found to be variably inhibited. We thus determined that antibiotics can diffuse through a tissue expander's Silastic membrane and establish an efficient bacteriostatic level in the surrounding fluid. This information could have potential clinical application in reducing infections associated with the use of expanders.