Primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphomas: reappraisal of a provisional entity in the 2016 WHO classification of cutaneous lymphomas.

Primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma is a rare and poorly characterized variant of cutaneous lymphoma still considered a provisional entity in the latest 2016 World Health Organization Classification of Cutaneous lymphomas. We sought to better characterize and provide diagnostic and therapeutic guidance of this rare cutaneous lymphoma. Thirty-four patients with a median age of 77 years (range 19-89 years) presented primarily with extensive annular necrotic plaques or tumor lesions with frequent mucous membrane involvement. The 5-year survival was 32% with a median survival of 12 months. A subset of 17 patients had a prodrome of chronic patches prior to the development of aggressive ulcerative lesions. We identified cases with lack of CD8 or αβ T-cell receptor expression yet with similar clinical and pathological presentation. Allogeneic stem cell transplantation provided partial or complete remissions in 5/6 patients. We recommend the term primary cutaneous aggressive epidermotropic cytotoxic T-cell lymphoma as this more broad designation better describes this clinical-pathologic presentation, which allows the inclusion of cases with CD8 negative and/or αβ/γδ T-cell receptor chain double-positive or double-negative expression. We have identified early skin signs of chronic patch/plaque lesions that are often misdiagnosed as eczema, psoriasis, or mycosis fungoides. Our experience confirms the poor prognosis of this entity and highlights the inefficacy of our standard therapies with the exception of allogeneic stem cell transplantation in selected cases

Characterization of a Bacterial Contaminant in Loblolly Pine Tissue Culture

Bacterial contamination of immature seed explants can decrease the efficiency in initiating and establishing pine embryogenic cultures. A type of contaminant commonly observed surrounding the megagametophyte explant of immature loblolly pine (Pinus taeda L.) appears as a white to creamy halo on the surface or within the culture medium. This contaminant appears within 24-48 hours after culturing the immature seed. The severity of the contamination varies by year and family. The pattern of contamination among seeds pooled from several cones did not suggest operator technique as the source of contamination. Tests with seeds separated by cone during sterilization and culture suggest that the source of the contamination was from seeds of specific cones. To better understand the causal bacterium and provide insight to help prevent or decrease the occurrence of contamination, several isolates taken from different contaminated explants were identified. This identification was done by PCR amplification of a 500bp sequence of a 16S ribosomal RNA gene. The closest match in terms of sequence similarity was Erwinia amylovora. Erwinia species are the causal agents of several economically important diseases. For example, fire blight (E. amylovora) in the Roseaceae family that affects apple and pear trees, and soft rot (E. carotovora) in several crops including potato. Our results suggest that Erwinia may also infect immature loblolly pine seeds and is a probable causal agent of this type of bacterial contamination in pine tissue culture. We have been able to significantly reduce the negative impact of this contamination and increase culture establishment efficiency by separating seeds by cone for sterilization and culture.Papers and abstracts from the 27th Southern Forest Tree Improvement Conference held at Oklahoma State University in Stillwater, Oklahoma on June 24-27, 2003

The Incidence of Common Respiratory Viruses During the COVID-19 Pandemic: Results From the Louisville COVID-19 Epidemiology Study

Introduction: Social distancing has been utilized during the COVID-19 pandemic to reduce the spread of SARS-CoV-2, which is also expected to reduce the spread of common respiratory viruses. Methods: This retrospective, descriptive study assessed the rate of positivity of common respiratory viruses from commercially available respiratory pathogen panel, across a five-hospital health-system, during four-week periods within March to April of 2019 and 2020. Results: During the four-week period in 2019, the percent positivity of common respiratory viruses from week one to week four decreased from 6 to 32% among the four included viruses. In the comparator period in 2020, a decrease ranging from 74 to 100% was observed from week one to week four. Conclusions: These data indicate that the social distancing efforts implemented in Louisville, Kentucky, may be associated with a decrease in incidence of common respiratory viruses. This decrease in positivity of common respiratory viruses may serve as a surrogate marker for the effect of social distancing on the transmission of SARS-CoV-2

A noncanonical function of cGAMP in inflammasome priming and activation

Recognition of pathogen-associated molecular patterns and danger-associated molecular patterns by host cells is an important step in innate immune activation. The DNA sensor cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) synthase (cGAS) binds to DNA and produces cGAMP, which in turn binds to stimulator of interferon genes (STI N G) to activate IFN-I. Here we show that cGAMP has a noncanonical function in inflammasome activation in human and mouse cells. Inflammasome activation requires two signals, both of which are activated by cGAMP. cGAMP alone enhances expression of inflammasome components through IFN-I, providing the priming signal. Additionally, when combined with a priming signal, cGAMP activates the inflammasome through an AIM2, NLRP3, ASC, and caspase-1 dependent process. These two cGAMP-mediated functions, priming and activation, have differential requirements for STI N G. Temporally, cGAMP induction of IFN-I precedes inflammasome activation, which then occurs when IFN-I is waning. In mice, cGAS/cGAMP amplify both inflammasome and IFN-I to control murine cytomegalovirus. Thus, cGAMP activates the inflammasome in addition to IFN-I, and activation of both is needed to control infection by a DNA virus

PhenX RISING: real world implementation and sharing of PhenX measures

Abstract Background The purpose of this manuscript is to describe the PhenX RISING network and the site experiences in the implementation of PhenX measures into ongoing population-based genomic studies. Methods Eighty PhenX measures were implemented across the seven PhenX RISING groups, thirty-three of which were used at more than two sites, allowing for cross-site collaboration. Each site used between four and 37 individual measures and five of the sites are validating the PhenX measures through comparison with other study measures. Self-administered and computer-based administration modes are being evaluated at several sites which required changes to the original PhenX Toolkit protocols. A network-wide data use agreement was developed to facilitate data sharing and collaboration. Results PhenX Toolkit measures have been collected for more than 17,000 participants across the PhenX RISING network. The process of implementation provided information that was used to improve the PhenX Toolkit. The Toolkit was revised to allow researchers to select self- or interviewer administration when creating the data collection worksheets and ranges of specimens necessary to run biological assays has been added to the Toolkit. Conclusions The PhenX RISING network has demonstrated that the PhenX Toolkit measures can be implemented successfully in ongoing genomic studies. The next step will be to conduct gene/environment studies

GLOBAL ASYMPTOTIC STABILIZATION OF THE SPINNING TOP

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57818/1/WanOCAMTop1995.pd

The PhenX Toolkit: Get the Most From Your Measures

The potential for genome-wide association studies to relate phenotypes to specific genetic variation is greatly increased when data can be combined or compared across multiple studies. To facilitate replication and validation across studies, RTI International (Research Triangle Park, North Carolina) and the National Human Genome Research Institute (Bethesda, Maryland) are collaborating on the consensus measures for Phenotypes and eXposures (PhenX) project. The goal of PhenX is to identify 15 high-priority, well-established, and broadly applicable measures for each of 21 research domains. PhenX measures are selected by working groups of domain experts using a consensus process that includes input from the scientific community. The selected measures are then made freely available to the scientific community via the PhenX Toolkit. Thus, the PhenX Toolkit provides the research community with a core set of high-quality, well-established, low-burden measures intended for use in large-scale genomic studies. PhenX measures will have the most impact when included at the experimental design stage. The PhenX Toolkit also includes links to standards and resources in an effort to facilitate data harmonization to legacy data. Broad acceptance and use of PhenX measures will promote cross-study comparisons to increase statistical power for identifying and replicating variants associated with complex diseases and with gene-gene and gene-environment interactions

Clinical Utilities of Peripheral Blood Gene Expression Profiling in the Management of Cardiac Transplant Patients

Cardiac allografts induce host immune responses that lead to endomyocardial tissue injury and progressive graft dysfunction. Inflammatory cell infiltration and myocyte damage characterize acute cellular rejection (ACR) that presents episodically in either a subclinical or symptom-associated manner. Sampling of the endomyocardium by transvenous biopsy enables pathologic grading using light microscopic criteria to distinguish severity based on the focality or diffuseness of inflammation and associated myocyte injury. Monitoring for ACR utilizes endomyocardial biopsy in conjunction with history and physical examination and assessment of allograft function by echocardiography. However, procedural and interpretive issues limit the diagnostic certainty provided by endomyocardial biopsy. The dynamic profiling of genes expressed by peripheral blood mononuclear cells (PBMCs) enables quantitative assessments of intracellular mRNA whose levels fluctuate during systemic alloimmune responses. Gene expression profiling of PBMCs using a multi-gene ACR classifier enables the AlloMap® molecular expression test to distinguish moderate to severe ACR (p = 0.0018) in heart transplant patients. The AlloMap test provides molecular insights into a patient's risk for ACR by distilling the aggregate expression levels of its informative genes into a single score on a scale of 0 to 40. The selection of a score as a threshold value for clinical decision-making is based on its associated negative predictive value (NPV), which ranges from 98 to 99% for values in three post-transplant periods: >2 to ≤6 months, > 6to ≤ 12 months, and >12 months. Scores below the threshold value rule out ACR, while those above suggest increased ACR risk. Incorporating the AlloMap test into immunomonitoring protocols provides an opportunity for clinicians to enhance patient care and to define its role in immunodiagnostic strategies to optimize the clinical outcomes of heart transplant recipients. This summary highlights the concepts presented in an invited presentation at a conference focused on Immunodiagnostics and Immunomonitoring: From Research to Clinic, in San Diego, CA on November 7, 2006

Data compatibility in the addiction sciences: An examination of measure commonality

The need for comprehensive analysis to compare and combine data across multiple studies in order to validate and extend results is widely recognized. This paper aims to assess the extent of data compatibility in the substance abuse and addiction (SAA) sciences through an examination of measure commonality, defined as the use of similar measures, across grants funded by the National Institute on Drug Abuse (NIDA) and the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Data were extracted from applications of funded, active grants involving human-subjects research in four scientific areas (epidemiology, prevention, services, and treatment) and six frequently assessed scientific domains. A total of 548 distinct measures were cited across 141 randomly sampled applications. Commonality, as assessed by density (range of 0–1) of shared measurement, was examined. Results showed that commonality was low and varied by domain/area. Commonality was most prominent for (1) diagnostic interviews (structured and semi-structured) for substance use disorders and psychopathology (density of 0.88), followed by (2) scales to assess dimensions of substance use problems and disorders (0.70), (3) scales to assess dimensions of affect and psychopathology (0.69), (4) measures of substance use quantity and frequency (0.62), (5) measures of personality traits (0.40), and (6) assessments of cognitive/neurologic ability (0.22). The areas of prevention (density of 0.41) and treatment (0.42) had greater commonality than epidemiology (0.36) and services (0.32). To address the lack of measure commonality, NIDA and its scientific partners recommend and provide common measures for SAA researchers within the PhenX Toolkit

Viking Thrust Vector Control Dynamics Using Hybrid Coordinates to Model Vehicle Flexibility and Propellant Slosh

Control System Design Implementation of the linear feedback control system with time varying feedback gains and command forces may be accomplished with a fairly simple analog controller. The feedback gains and command forces consist of well behaved sinusoidal functions, constants, and simple ramp functions. The difficulty caused by the gain fluctuation near the simulation final time may be overcome by cycling the control gain functions back to the beginning before the fluctuations take place. Cycling the control gain functions is not a problem because the control is in a feedback form. The effect of cycling the control gain functions may be interpreted in the analysis as restarting the nonlinear simulation with an initial state closer to the final state. Simulation of the nonlinear system within the region of operation always resulted in a stable response so the effect of restarting the simulation when the system state has moved closer to the final state is valid. A consequence of cycling the control is that the functional in Eq. Conclusions This study has shown that the dynamic instability caused by sloshing fluid stores carried in the main rigid body of a spacecraft may be controlled by use of a linear quadratic regulator with the fluid modeled as an equivalent spherical pendulum and only the first mode of fluid oscillation included. The control system presented stabilized a highly nonlinear system for a large deviation from the nominal operating point and uses easily measured state variables (only main body fixed angular rates and attitude) and was shown to be stable for a wide variation in fluid level. It was shown that sensing the dynamic state of the fluid was not necessary for the specific spacecraft under study. A pointing maneuver was also successfully accomplished by this control system and a control design based on the analysis was outlined for the specific spacecraft. Acknowledgments This study was completed under partial support of contract no. AFOSR-86-0080 and subcontract 83RIP33, U.S. Air Force. The authors wish to acknowledge the support of Iowa State University in accomplishing the lengthy digital computer simulation required in this study. References Introduction An interesting problem in robotics is cloth handling. Applications include composite lay-up and apparel and upholstery manufacturing. Rebman (1986) describes an application of a tactile sensor to assembly of a flexible diaphram and a plastic cap. Hertzanu and Tabak (1986) described an adaptive controller for an industrial sewing machine. For most applications, cloth must be held taut and unwrinkled. It was postulated that this requires multi-axis force control, and a suitable control system was designed and constructed. The system chosen is an adaptive force feedback loop with position accommodation. Non-adaptive force feedback control schemes have been described and tested by many researchers, such as Whitney (1977). An adaptive force feedback loop for coordination of two robot arms was described by Because cloth stiffness varies depending on whether the individual cloth fibers are taut or slack, a nonadaptive loop is unsuitable for cloth handling. An adaptive control loop was designed with cloth stiffness as the adaptive variable. The system design was constructed and tested using a PUMA 560 robot with a LORD 15/50 force/torque sensor mounted on its wrist. Control System Description The parameter estimator is a least mean square (LMS) estimator. Let y=KH(z)u = K a x z ' + + a"z~ -r-"u, \+b x z + ... +b"z~ where a it ..., a" and b\ b" axe found from the ordinary least squares plant identification, y is the error in the force, and u is the position command. Then the LMS estimator for A-is K* =K*^i+r{y-y*)w-l , where K* is the estimated stiffness, +a"u""), and Vf_ 1 =ff 1 «_ 1 + The position control law is where u, is the change in the position of the /th degree of freedom (DOF), y t is the force (or torque) error of the ith DOF, and K* is the stiffness of the rth DOF. end of a cloth of dimensions 36 by 36 in., the other end of which was attached to a table. Both ends of the cloth were stapled to wooden rods; proper robot end effectors would eliminate the need for these rods. Two 8086 microprocessor cards were also built. The 1st microprocessor calculated the cloth stiffness and end effector position changes; the 2nd microprocessor was used for communication with the robot and the force/torque sensor. Experimental Procedure The experiments were run with one end of the cloth fixed. The initial slack and misalignments of the cloth were as follows: Stretch (x) direction Lateral (y) direction 6 direction 6 to 10 in. of slack 2 to 4 in. of misalignment 5° to 20° of misalignment The robot straightened out the misalignments and pulled 4 lb of tension on the cloth. After it had done so the end effector was moved inward to produce 6 in. of slack in the x-direction. This movement draped the cloth over 2 boxes without wrinkling. Test Setup Experimental Results The visual results showed consistency between the experiments. In all of them, the cloth was successfully draped over the boxes without wrinkles, the motion was smooth, and the times were approximately the same. Transactions of the ASME position, the robot pulls a 4 lb tension on the cloth and adjusts the lateral (y) force and the moment to zero. This requires approximately 12 s. At 14 s the robot drapes the cloth; at this point the tension (x-force) falls to zero. This experiment was successfully repeated several times. Conclusions A force feedback control loop implemented on a robot has been used successfully to straighten and draw a tension on a cloth. Further work will include using more sophisticated end effectors to grip the cloth, and applications in upholstery and composite manufacture. Reference