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Marine host-associated microbiomes are affected by a combination of species-specific (e.g., host ancestry, genotype) and habitat-specific features (e.g., environmental physiochemistry and microbial biogeography). The stingray epidermis provides a gradient of characteristics from high dermal denticles coverage with low mucus to reduce dermal denticles and high levels of mucus. Here we investigate the effects of host phylogeny and habitat by comparing the epidermal microbiomes of Myliobatis californica (bat rays) with a mucus rich epidermis, and Urobatis halleri (round rays) with a mucus reduced epidermis from two locations, Los Angeles and San Diego, California (a 150 km distance). We found that host microbiomes are species-specific and distinct from the water column, however composition of M. californica microbiomes showed more variability between individuals compared to U. halleri. The variability in the microbiome of M. californica caused the microbial taxa to be similar across locations, while U. halleri microbiomes were distinct across locations. Despite taxonomic differences, Shannon diversity is the same across the two locations in U. halleri microbiomes suggesting the taxonomic composition are locally adapted, but diversity is maintained by the host. Myliobatis californica and U. halleri microbiomes maintain functional similarity across Los Angeles and San Diego and each ray showed several unique functional genes. Myliobatis californica has a greater relative abundance of RNA Polymerase III-like genes in the microbiome than U. halleri, suggesting specific adaptations to a heavy mucus environment. Construction of Metagenome Assembled Genomes (MAGs) identified novel microbial species within Rhodobacteraceae, Moraxellaceae, Caulobacteraceae, Alcanivoracaceae and Gammaproteobacteria. All MAGs had a high abundance of active RNA processing genes, heavy metal, and antibiotic resistant genes, suggesting the stingray mucus supports high microbial growth rates, which may drive high levels of competition within the microbiomes increasing the antimicrobial properties of the microbes.

Characterizations of shark-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (

Characterizations of sharks-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California born and held permanently in captivity), semi-captive (held in captivity for T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as Metagenomes associated genomes revealed a consistent relationship across captive, semi-captive, and wild populations. Since changes in microbial communities is often associated with poor health outcomes, our report illustrates that epidermally-associated microbes belonging to T. semifasciata are not suffering detrimental impacts from long or short-term captivity. Therefore, conservation programs which house sharks in aquariums are providing a healthy environment for the organisms on display. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel associations that are consistent across captive gradients.

Characterizations of shark-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California born and held permanently in captivity), semi-captive (held in captivity for

The epidermal microbiome is a critical element of marine organismal immunity, but the epidermal virome of marine organisms remains largely unexplored. The epidermis of sharks represents a unique viromic ecosystem. Sharks secrete a thin layer of mucus which harbors a diverse microbiome, while their hydrodynamic dermal denticles simultaneously repel environmental microbes. Here, we sampled the virome from the epidermis of three shark species in the family Carcharhinidae: the genetically and morphologically similar Carcharhinus obscurus (n = 6) and Carcharhinus galapagensis (n = 10) and the outgroup Galeocerdo cuvier (n = 15). Virome taxonomy was characterized using shotgun metagenomics and compared with a suite of multivariate analyses. All three sharks retain species-specific but highly similar epidermal viromes dominated by uncharacterized bacteriophages which vary slightly in proportional abundance within and among shark species. Intraspecific variation was lower among C. galapagensis than among C. obscurus and G. cuvier. Using both the annotated and unannotated reads, we were able to determine that the Carcharhinus galapagensis viromes were more similar to that of G. cuvier than they were to that of C. obscurus, suggesting that behavioral niche may be a more prominent driver of virome than host phylogeny.

This paper highlights results from a collaborative study performed by The University of Tennessee Space Institute (UTSI) and NASA Langley Research Center on the Shockwave/Boundary-Layer Interaction (SWBLI) generated by a cylindrical protuberance on a flat plate in a Mach 6 flow. The study was performed in the 20-Inch Mach 6 Air Tunnel at NASA Langley Research Center and consisted of two separate entries. In the first entry, simultaneous high-speed schlieren and high-speed pressure-sensitive paint (PSP) imaging – which was performed for the first time in the 20-Inch Mach 6 facility at NASA Langley – were performed as well as simultaneous high-speed schlieren and oil-flow imaging. In the second entry, the model configuration was modified to increase the size of the interaction region. High-speed schlieren and infrared thermography (IR) surface imaging were performed in this second entry. The goal of these tests was to characterize the SBLI in the presence of a laminar, transitional, and turbulent boundary layer using high-speed optical imaging techniques. AoA = sting angle-of-attack (°) dcylinder = cylinder diameter (mm) dtrip = cylindrical tripping element diameter (mm) Δshock = shock stand-off distance (mm) hcylinder = cylinder height (mm) htrip = cylindrical tripping element height (mm) HSS = high-speed schlieren M∞ = freestream Mach number PSP = pressure-sensitive paint Re∞ = freestream unit Reynolds number (m-1) SWBLI = shockwave/boundary-layer interaction θplate = model plate angle (°) Introduction his paper highlights two experimental entries performed in the 20-Inch Mach 6 Air Blowdown Tunnel at NASA Langley Research Center in collaboration with The University of Tennessee Space Institute (UTSI). The purpose of these entries was to characterize the dynamic shockwave/boundary-layer interaction (SWBLI) between a vertical cylinder on a flat plate and laminar, transitional (XSWBLI), and turbulent (SWTBLI) boundary layers with a freestream Mach number of 6 using non-intrusive optical diagnostics. Experiments performed by Murphree et al.1,2 were among the first to specifically characterize XSWBLI induced by a vertical cylinder on a flat plate geometry using several optical measurement techniques. Recent optical studies of XSWBLI phenomenon have been performed by UTSI at Mach 2 in their low-enthalpy blow wind tunnel3-8 and by Texas A&M University and UTSI at Mach numbers of 6 and 7 in their Adjustable Contour Expansion wind tunnel.9 The experiments described in this paper were intended to complement previous studies by expanding the freestream unit Reynolds number range, Re∞, over which the XSWBLI phenomena has been observed. Additionally these experiments, made possible under NASA’s new facility funding model under the Aeronautics Evaluation and Test Capabilities (AETC) project, promoted collaboration between university and NASA researchers. The initial entry in the 20-Inch Mach 6 Air Tunnel at NASA Langley occurred in December of 2016. Originally, testing was to occur in November of 2016 in the 31-Inch Mach 10 Air Tunnel at NASA Langley. This facility was chosen so that the XSWBLI phenomenon could be observed at much higher Mach numbers than had previously been attempted in ground test experiments. The model selected for this experiment, a 10° half-angle wedge with a sharp leading edge (described in detail in section II.B), had previously been used by Danehy et al. [10] for boundary layer transition studies using the nitric oxide planar laser-induced fluorescence (NO PLIF) flow visualization technique. In that work, it was determined that transition could be induced downstream of a single htrip = 1-mm tall, dtrip = 4-mm diameter cylindrical tripping element and that the streamwise location of the transition could be changed for a single Re∞ by changing the model angle-of-attack (AoA) (see Fig. A3 in Ref. [10] for more details). Based on the findings of that work, a decision was made to use the wedge model with the cylindrical tripping element to trip the boundary layer flow ahead of a cylindrical protuberance in order to achieve a XSWBLI. Unfortunately, the 31-Inch Mach 10 facility had been taken offline for repairs in October of 2016 and a decision was made to move the test to the 20-Inch Mach 6 facility. Since the behavior of the boundary layer with the chosen model configuration had not been studied before in that facility and the available test time was limited, the entry was considered to be exploratory and was used to collect spatially-resolved and time-resolved flow and surface visualization data that would be used to inform a second entry. Test techniques included simultaneous high-speed schlieren (HSS) captured at 160 kHz and high-speed pressure sensitive paint captured at 10 kHz as well as oil flow visualization, captured at 750 Hz. The second entry in the 20-Inch Mach 6 facility occurred in June and July of 2017. In this follow-on test, modifications to the wind tunnel model were made based on observations made during the first entry and included removing the cylindrical tripping element, increasing the size of the cylinder used to induce the SWBLI to increase the size of the interaction while simultaneously improving spatial resolution, and using a swept ramp array, similar to that described in Ref. [11], to trip the flow to turbulence. Simultaneous HSS (captured at 140 kHz, 100 kHz, and 40 kHz) and conventional IR thermography (captured at 30 Hz) imaging were performed simultaneously in this follow-on entry. This paper is intended to serve as a summary of the work performed during these two entries, to detail lessons learned from each entry, and to highlight some of the datasets acquired. Details on the experimental setup, model configuration, and techniques used are provided. Papers providing a more rigorous analysis of data acquired during the second entry, including statistical, spectral, and modal decomposition methods, can be found in Refs. [12,13]. An entry examining XSWBLI in the 31-Inch Mach 10 Blowdown Wind Tunnel facility is currently planned for mid-to-late calendar year 2019, pending the success of facility repairs. The work performed and described in this paper and the upcoming entry in the 31-Inch Mach 10 facility at NASA Langley have been made possible by NASA’s new facility funding model under the Aeronautics Evaluation and Test Capabilities (AETC) project. Wind Tunnel Facility All experiments discussed in this paper were performed in the 20-Inch Mach 6 Air Tunnel at NASA Langley Research Center. Specific details pertaining to this facility can be found in Refs. [14,15], with only a brief description of the facility provided here. For both entries, the nominal freestream unit Reynolds number was varied between 1.8×106 m-1 (0.5×106 ft-1) and 26.3×106 m-1 (8×106 ft-1). The nominal stagnation pressure was varied between 0.21 MPa and 3.33 MPa and the nominal stagnation temperature was varied between 480 K and 520 K to achieve the desired Re∞ condition. For all runs, the nominal freestream Mach number was 6. The nearly square test section is 520.7-mm (20.5-inches) wide by 508-mm (20-inches) high. Two 431.8-mm (17-inch) diameter windows made of Corning 7940, Grade 5F schlieren-quality glass serve as the side walls of the tunnel and provide optical access for the high-speed schlieren measurements. A rectangular window made of the same material as the side windows served as the top wall of the test section and provided optical access for the high-speed PSP and oil flow measurements. For the second entry, this top window was replaced with a Zinc Selenide (ZnSe) window with an anti-reflection coating capable of passing IR wavelengths between 8μm and 12μm with greater than 98% transmittance. The model was sting supported by a strut attached to a hydraulic system that allows for the model pitch angle to be adjusted between -5° to +55°. For the first entry, an initial pitch/pause sweep of the model AoA was performed to observe the resulting SWBLI. Ultimately, however, the sting pitch angle for this entry was fixed at +10.0° so that the angle of the top surface of the wedge relative to the streamwise axis of the tunnel (referred to herein as the plate angle, θplate), was θplate = 0°. For the second entry, θplate = 0° and θplate = -13.25° were initially tested with the swept ramp array (discussed in the following section) to determine which orientation produced conditions most favorable for XSWBLI to occur based on the heating signatures observed over the top surface of the model in the IR thermography images. Based on these initial tests, θplate = -13.25° was set for the remainder of the runs in the second entry. For both entries, any model changes were performed in a housing located beneath the closed test section. Prior to performing a run of the tunnel, the housing was sealed and the tunnel started. Once the appropriate freestream conditions were achieved, the model was injected into the test section using a hydraulic injection system. B. Model Geometry For all runs, a 10° half-angle (20° full-angle) wedge model with a sharp leading edge was used. The model is described in detail in Refs. [10,16]. The top surface of the sharp leading edge of the model extended 47.8 mm from its upstream-most edge to a junction with the upstream edge of a stainless steel top plate that then extended an (a) (c) (b) Fig. 1 (a) Schematic of top surface of wedge model with gas seeding insert, (b) perspective view of the model in the 20-Inch Mach 6 tunnel with centerline pressure orifices on sharp leading edge, and (c) a perspective view of the model with stainless steel (top) and SLA middle insert (bottom) during the first entry. Flow occurs from left to right.

This paper will highlight the development and application of a carbon-based resistive heating layer for use in transition detection at cryogenic temperatures at the National Transonic Facility (NTF) for full-flight Reynolds number testing. This study builds upon previous work that was successfully demonstrated at the 0.3-m Transonic Cryogenic Tunnel on a smaller-scale airfoil shape of regular geometry. However, the test performed at the NTF involved a semispan wing with complex geometry and significantly larger than previous tests. This required the development of new coatings to provide suitable resistances to provide adequate heating rates for transition detection. Successful implementation of this technology has the ability to greatly enhance transition detection experiments at cryogenic temperatures as well as reducing perturbation in the tunnel caused by more traditional transition detection methods.

This paper will present details of a pressure-sensitive paint system for measuring global surface pressures on rotor blades in simulated forward flight at the 14×22 ft subsonic tunnel at the NASA Langley Research Center. The system was designed to use a pulsed laser as an excitation source and pressure-sensitive paint data were collected using the lifetime-based approach. The higher intensity of the laser allowed pressure-sensitive paint images to be acquired using a single laser pulse, resulting in a collection of images that can be used to determine blade pressure at a specific instant in time. This is extremely important in rotorcraft applications because the blades experience dramatically different flowfields depending on their position. In addition, there can be fluctuations on the blade that vary every cycle due to factors such as lead/lag, flapping, and twisting of the blade. These effects generally preclude the use of phase averaging and thus the need for acquiring the data in a single image pair...

(68)Ga-PSMA-11 PET is used to stage patients with prostate cancer. We performed an updated metaanalysis that separates imaging at the time of diagnosis and at the time of biochemical recurrence and focuses on pathology correlation in both populations. Methods: We searched the MEDLINE and EMBASE databases using the PRISMA statement. Quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool 2. In total, 1,811 studies were screened, 58 were analyzed, 41 were included for qualitative synthesis, and 29 were included for quantitative analysis. A random-effect model and a hierarchical summary receiver-operating-characteristic model were used to summarize the sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy for pelvic lymph nodes in initial staging compared with pathology at prostatectomy and the PPV for lesions with pathologic correlation in those with biochemical recurrence. We also summarized the detection rate of (68)Ga-PSMA-11 in those with biochemical recurrence stratified by prostate-specific antigen (PSA) at the time of imaging. Results: The metaanalysis of (68)Ga-PSMA-11 at initial staging demonstrated a sensitivity and specificity of 0.74 (95% confidence interval [95% CI], 0.51–0.89) and 0.96 (95% CI, 0.85–0.99), respectively, using nodal pathology at prostatectomy as a gold standard. At biochemical recurrence, the PPV was 0.99 (95% CI, 0.96–1.00). The detection rate was 0.63 (95% CI, 0.55–0.70), with a PSA of less than 2.0 and 0.94 (95% CI, 0.91–0.96) with a PSA of more than 2.0. Conclusion: (68)Ga-PSMA-11 performed well for the localization of metastatic prostate cancer at initial staging and at the time of biochemical recurrence.

Background and Purpose— Stroke is the leading cause of long-term disability in the United States, yet no drugs are available that are proven to improve recovery. Brain-derived neurotrophic factor stimulates neurogenesis and plasticity, processes that are implicated in stroke recovery. It binds to both the tropomyosin-related kinase B and p75 neurotrophin receptors. However, brain-derived neurotrophic factor is not a feasible therapeutic agent, and no small molecule exists that can reproduce its binding to both receptors. We tested the hypothesis that a small molecule (LM22A-4) that selectively targets tropomyosin-related kinase B would promote neurogenesis and functional recovery after stroke. Methods— Four-month-old mice were trained on motor tasks before stroke. After stroke, functional test results were used to randomize mice into 2 equally, and severely, impaired groups. Beginning 3 days after stroke, mice received LM22A-4 or saline vehicle daily for 10 weeks. Results— LM22A-4 treatment significantly improved limb swing speed and accelerated the return to normal gait accuracy after stroke. LM22A-4 treatment also doubled both the number of new mature neurons and immature neurons adjacent to the stroke. Drug-induced differences were not observed in angiogenesis, dendritic arborization, axonal sprouting, glial scar formation, or neuroinflammation. Conclusions— A small molecule agonist of tropomyosin-related kinase B improves functional recovery from stroke and increases neurogenesis when administered beginning 3 days after stroke. These findings provide proof-of-concept that targeting of tropomyosin-related kinase B alone is capable of promoting one or more mechanisms relevant to stroke recovery. LM22A-4 or its derivatives might therefore serve as “pro-recovery” therapeutic agents for stroke.

Detection of flow transition on aircraft surfaces and models can be vital to the development of future vehicles and computational methods for evaluating vehicle concepts. In testing at ambient conditions, IR thermography is ideal for this measurement. However, for higher Reynolds number testing, cryogenic facilities are often used, in which IR thermography is difficult to employ. In these facilities, temperature sensitive paint is an alternative with a temperature step introduced to enhance the natural temperature change from transition. Traditional methods for inducing the temperature step by changing the liquid nitrogen injection rate often change the tunnel conditions. Recent work has shown that adding a layer consisting of carbon nanotubes to the surface can be used to impart a temperature step on the model surface with little change in the operating conditions. Unfortunately, this system physically degraded at 130 K and lost heating capability. This paper describes a modification of this technique enabling operation down to at least 77 K, well below the temperature reached in cryogenic facilities. This is possible because the CNT layer is in a polyurethane binder. This was tested on a Natural Laminar Flow model in a cryogenic facility and transition detection was successfully visualized at conditions from 200 K to 110 K. Results were also compared with the traditional temperature step method.

This paper will present details of a Pressure Sensitive Paint (PSP) system for measuring global surface pressures on the tips of rotorcraft blades in simulated forward flight at the 14- x 22-Foot Subsonic Tunnel at the NASA Langley Research Center. The system was designed to use a pulsed laser as an excitation source and PSP data was collected using the lifetime-based approach. With the higher intensity of the laser, this allowed PSP images to be acquired during a single laser pulse, resulting in the collection of crisp images that can be used to determine blade pressure at a specific instant in time. This is extremely important in rotorcraft applications as the blades experience dramatically different flow fields depending on their position in the rotor disk. Testing of the system was performed using the U.S. Army General Rotor Model System equipped with four identical blades. Two of the blades were instrumented with pressure transducers to allow for comparison of the results obtained from the PSP. Preliminary results show that the PSP agrees both qualitatively and quantitatively with both the expected results as well as with the pressure taps. Several areas of improvement have been indentified and are currently being developed.

This paper reports a series of wind tunnel tests simulating the near-field behavior of the Space Shuttle Orbiter Boundary Layer Transition Detailed Test Objective (BLT DTO) flight experiment. Hypersonic flow over a flat plate with an attached BLT DTO-shaped trip was tested in a Mach 10 wind tunnel. The sharp-leading-edge flat plate was oriented at an angle of 20 degrees with respect to the freestream flow, resulting in post-shock edge Mach number of approximately 4. The flowfield was visualized using nitric oxide (NO) planar laser-induced fluorescence (PLIF). Flow visualizations were performed at 10 Hz using a wide-field of view and high-resolution NO PLIF system. A lower spatial resolution and smaller field of view NO PLIF system visualized the flow at 500 kHz, which was fast enough to resolve unsteady flow features. At the lowest Reynolds number studied, the flow was observed to be laminar and mostly steady. At the highest Reynolds number, flow visualizations showed streak instabilities generated immediately downstream of the trip. These instabilities transitioned to unsteady periodic and spatially irregular structures downstream. Quantitative surface heating imagery was obtained using the Temperature Sensitive Paint (TSP) technique. Comparisons between the PLIF flow visualizations and TSP heating measurements show a strong correlation between flow patterns and surface heating trends.

The Pressure Sensitive Paint (PSP) method was used to measure global surface pressures on a model at full-scale flight Reynolds numbers. In order to achieve these conditions, the test was carried out at the National Transonic Facility (NTF) operating under cryogenic conditions in a nitrogen environment. The upper surface of a wing on a full-span 0.027 scale commercial transport was painted with a porous PSP formulation and tested at 120K. Data was acquired at Mach 0.8 with a total pressure of 200 kPa, resulting in a Reynolds number of 65 x 106/m. Oxygen, which is required for PSP operation, was injected using dry air so that the oxygen concentration in the flow was approximately 1535 ppm. Results show qualitative agreement with expected results. This preliminary test is the first time that PSP has been successfully deployed to measure global surface pressures at cryogenic condition in the NTF. This paper will describe the system as installed, the results obtained from the test, as well as proposed upgrades and future tests.

Ciprofloxacin, a commonly prescribed fluoroquinolone antibiotic, has generally been well-tolerated; however, there are rare reports of associated hepatic failure or renal failure. We describe a case of a 65 year-old man with a history of ischemic cardiomyopathy who was treated with ciprofloxacin 500 mg twice daily for cellulitis. Six days into his treatment course, he developed acute cholestatic jaundice and acute anuric renal failure. Clinical, laboratory, and pathologic data suggest that the patient had developed reversible, severe ciprofloxacin-induced cholestatic liver injury and acute tubular necrosis requiring hemodialysis. Within two months of stopping the ciprofloxacin, the patient was off dialysis and back to his baseline creatinine in three months. Liver tests normalized by five months. This report illustrates a case of cholestatic liver injury and renal failure involving ciprofloxacin use. We review the literature regarding hepatic and renal injury as it relates to ciprofloxacin. To our knowledge, this represents the first case report of simultaneous acute cholestatic liver injury and renal failure secondary to ciprofloxacin.

Several adipocytokines have been implicated in the pathogenesis non-alcoholic fatty liver disease (NAFLD).To assess adipocytokines in NAFLD patients and controls.A total of 95 patients (26 non-alcoholic steatohepatitis (NASH), 19 simple steatosis (SS), 38 obese controls and 12 non-obese controls) were included. Fasting serum insulin, glucose, visfatin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8) and IL-6 were determined. Univariate and multivariate analyses were used to compare groups and determine associations.Serum TNF-alpha and IL-8 were higher in NAFLD patients when compared with both obese and non-obese controls. Analysis involving all patients revealed a significant correlation between serum TNF-alpha and IL-8 (P6.319e-08), and between IL-6 and IL-8 (P5.271e-15). Homeostatic model assessment scores negatively correlated with adiponectin in NAFLD (P0.0032). Serum visfatin was higher in all three obese groups than in non-obese controls (P0.02, P0.002 and P0.008). Visfatin in NASH patients was lower than SS and obese controls. Although TNF-alpha was associated with NAFLD (P0.02), it was interdependent on visfatin. In comparison to SS, four factors were independently associated with NASH: age, alanine aminotransferase, IL-8 and adiponectin (P0.05). Multivariate analysis indicated that TNF-alpha was the only independent predictor of fibrosis in NASH (P0.0004).These findings support a complex interaction between adipocytokines and the pathogenesis of NAFLD.

We developed a short questionnaire—Parental PTSD Questionnaire–(PPQ), designed to assess the presence of posttraumatic stress disorder (PTSD) symptoms in parents. Fifty-eight adult offspring of Holocaust survivors (23 men and 35 women) completed the questionnaire about a parent who was independently evaluated by a trained clinician using the Clinician Administered PTSD Scale (CAPS). Only 5.2% of the offspring reported, “not knowing” if their parent had experienced 10 or fewer symptoms, while 56.9% provided estimates for all 17 items. There were no significant differences between lifetime frequencies of the individual symptoms as endorsed on the PPQ compared to the CAPS when subjects with completed PPQs were compared with CAPS. Interrater reliability between offspring and clinician was highly significant for each of the items when evaluated separately so as to include data for subjects who endorsed not knowing if a certain symptom had been present. Further studies are warranted to examine the psychometric properties of this measure.

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.

A novel DNA virus, TT virus (TTV), was recently identified in patients with post-transfusion non-A-G hepatitis. The aim of this study was to determine the prevalence and clinical significance of TTV infection in patients with chronic hepatitis C virus (HCV) infection.We analyzed pretreatment serum samples from 171 United States and European patients who relapsed after interferon-alpha treatment and were recruited into an interferon-alpha-2b/ribavirin combination treatment trial. TTV DNA was detected by PCR using two different set of primers (TTV-A and TTV-B) derived from open reading frames 1 and 2, respectively.TTV was detected in 29.2% of the patients with the TTV-A primer set, 70.8% with the TTV-B primer-set, and 72.5% if positive by either/both sets of the primers. The amplicons generated by primer set A were sequenced and a phylogenetic tree was constructed. The 50 isolates belonged to group la (n=8), 1b (n=17), 2a (n=21), 2b (n=3), and 4 (n=1). There was no difference in demographic (age, sex distribution, estimated duration of HCV infection), biochemical (serum ALT levels), virologic (serum HCV RNA levels, HCV genotype distribution), or histologic scores, and their subsequent response to either interferon-alpha-2b or interferon-alpha-2b/ribavirin combination treatment.The prevalence of TTV infection reported previously may have been significantly underestimated, based on the primers originally described and used by most studies. Although TTV infection is very common in patients with chronic HCV infection, it has no identifiable clinical significance.

Pruritus is a common symptom in cholestatic liver disease but is rare in chronic hepatitis C. Eight patients with chronic hepatitis C and severe pruritus were compared with regard to biochemical, serological, and histological features to eight disease controls with primary biliary cirrhosis and seven with cirrhosis due to hepatitis C. Among those with severe pruritus associated with chronic hepatitis C, serum aminotransferases were raised in all, alkaline phosphatase in four, and gamma-glutamyl-transpeptidase levels in all except one. Serum cholylglycine levels were elevated in seven of eight patients. Liver biopsies showed moderate to severe fibrosis in all patients and cirrhosis in five. Compared to control subjects with cirrhosis due to hepatitis C but no pruritus, ductopenia, and cholestatic changes were prominent, although less so than in controls with primary biliary cirrhosis. Chronic hepatitis C with moderate to severe fibrosis may result in low-grade cholestasis with pruritus, possibly in association with bile duct disappearance.

To evaluate response rates to 3, 5, or 10 million units (MU) of interferon alfa-2b, given thrice weekly, and to determine whether higher doses of interferon increase the likelihood or durability of the response, a multicenter, randomized trial was performed at nine academic medical centers in the United States. Two hundred forty eight patients with chronic hepatitis C were randomized to receive 3, 5, or 10 MU of interferon alfa-2b thrice weekly for 12 weeks. Based on the alanine aminotransferase (ALT) response at treatment-week 12, the patients were rerandomized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks; in the case of no response to the highest dose, the patients were discontinued from the study. Serum ALT concentrations and liver histology were measured. The overall complete response rates to 3, 5, or 10 MU were not different at treatment-week 12 (31% vs. 42% vs. 40%, not significant). The majority of week-12 responders continued to respond during additional treatment. When the treatment was discontinued, 15.4% to 19.0% of patients maintained their response. Of the nonresponders to 3 MU at week 12, who were continued on 3 MU for an additional 12 weeks, none responded. However, response to additional therapy occurred in 12% of week-12 nonresponders, whose dose was escalated from 3 or 5 MU to 10 MU. The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype. We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug. Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose; however, a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses. Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week, the side effects are difficult to tolerate. The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis C.

Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment e...

Blood glucose level, urea concentration, and total white blood cell count were determined both before and 10-15 minutes after lumbar puncture (LP) procedure in 26 infants suspected of having meningitis. There was a significant (p less than 0.001) increase in the peripheral white blood cell (WBC) count (mean +/- standard deviation) from 10,960 +/- 3,500 cells/microliter before to 13,300 +/- 3,970 cells/microliter following the LP procedure, due to relative rise in the neutrophils and lymphocytes. Blood glucose levels did not change significantly following this procedure (85.3 +/- 13.4 mg/dl and 84.1 +/- 12.6 mg/dl respectively). An LP procedure does not impair correct cerebrospinal fluid glucose/blood glucose determination but may cause elevation of peripheral WBC count.

Infection with the hepatitis C virus may result in chronic liver disease for which no effective therapy is now available. We studied the effects of recombinant human interferon alfa in a prospective, randomized, double-blind, placebo-controlled trial in patients with well-documented chronic hepatitis C. Forty-one patients were enrolled in the trial, 37 of whom were later found to have antibody to hepatitis C virus. Twenty-one patients received interferon alfa (2 million units) subcutaneously three times weekly for six months, and 20 received placebo. The mean serum aminotransferase levels and the histologic features of the liver improved significantly in the patients treated with interferon but not in the patients given placebo. Ten patients treated with interferon (48 percent) had a complete response, defined as a decline in mean serum aminotransferase levels to the normal range during therapy; three others had a decrease in mean aminotransferase levels of more than 50 percent. After treatment ended, however, serum aminotransferases usually returned to pretreatment levels; 6 to 12 months after the discontinuation of interferon therapy, only two patients (10 percent) still had normal values. We conclude that interferon alfa therapy is beneficial in reducing disease activity in chronic hepatitis C; however, the beneficial responses are often transient.

Individuals who deny alcohol consumption may develop liver injury that histologically resembles the liver injury found in alcoholic patients. To determine whether any clinical or histologic features distinguish alcoholic and nonalcoholic subjects with "alcohollike" liver injury, the clinical records and liver biopsy specimens of 68 alcoholic and 39 nonalcoholic patients with alcohollike injury on liver biopsy were compared. The clinical and biochemical features of the two groups differed significantly. Alcoholism was associated with more severe clinical and biochemical manifestations of liver disease. However, there was considerable overlap among histologic features of the two clinically defined groups. Based on histology alone, alcoholic and nonalcoholic patients were often indistinguishable. The observations suggest that the clinical differences between the alcoholic and non-alcoholic patients cannot be attributed to qualitative or quantitative differences in liver histology. On the other hand, histologic similarities between the two groups raise the possibility that a shared condition, perhaps nutritional or hormonal, is responsible for the histologic expression of alcohollike injury in both groups.

Fibrolamellar hepatocellular carcinoma (HCC) has recently been separated as a distinct clinicopathologic entity with a better prognosis than the usual HCC associated with cirrhosis. The mean age of our 17 patients was 20 years. Alpha fetoprotein levels were normal, and none of the risk factors for HCC was present. Distinctive histologic features included deeply eosinophilic polygonal hepatocytes and abundant fibrous stroma. Calcification was present on plain films of five of 13 cases. Sonography usually showed a homogeneous, echogenic mass. Computed tomography (CT) demonstrated small, central calcification in four of ten cases. A central echodensity, hypodense on CT scans, was seen in two cases and corresponded to a central scar. By combining clinical and laboratory data with radiologic tests, a correct diagnosis can often be suggested before biopsy is performed.

Previous research indicates that noise is likely to produce decrements in performance (not due to masking) only if task loads are high. We hypothesize that noise acts to increase task load such that noise and tasks may be interchangeable. This hypothesis was confirmed in an experiment involving two tasks—math problem solving M and auditory tracking T—performed individually and simultaneously with, and without, noise N. Equal numbers of male and female undergraduates participated in all conditions. A significant (p < 0.01) decrement in math performance was found only under the M + T + N condition, and the contributions of T and N to this decrement were not found to be different. Similarly, the largest significant (p < 0.01) decrement in tracking performance was obtained under the M + T + N condition. A small, but significant (p < 0.01), tracking decrement also was found under the T + N condition, probably the result of masking. Otherwise, the contributions of M and N to the tracking decrement were not diff...

Loudness of sounds heard outdoors may be influenced by visual features of the listener's environment. Aylor and Marks [J. Acoust. Soc. Am. 59, 397–400 (1976)] found that estimated loudness magnitudes of noise diminished at visibility of sound sources in an outdoor environment improved. The present study sought to determine whether the visibility of vegetation and man‐made structures would exert any influence on estimated loudness magnitudes of tones presented to listeners through headphones under outdoor conditions. Data were collected within five sites that differed systematically in visible vegetation (trees, shrubs, etc.) ranging from a site with no visible man‐made structures (woods) to a site with no visible vegetation (city street). Equal numbers of male and female listeners generated loudness functions for each site. Trend analysis indicated that the obtained functions differed significantly across sites both in overall means (p < 0.01) and slopes (p < 0.01). None of the functions departed signific...