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The process of magnetic reconnection when studied in Nature or when modeled in 3D simulations differs in one key way from the standard 2D paradigmatic cartoon: it is accompanied by much fluctuations in the electromagnetic fields and plasma properties. We developed a new diagnostics, the topographical fluctuations analysis (TFA) to study the spectrum of fluctuations in the various regions around a reconnection site. We find that fluctuations belong to two very different regimes. The first regime is better known, it develops in the reconnection outflows and is characterized by a strong link between plasma and electromagnetic fluctuations leading to momentum and energy exchanges via anomalous viscosity and resistivity. But there is a second, new, regime: it develops in the inflow and in the region around the separatrix surfaces, including the reconnection diffusion region itself. In this new regime the plasma remains laminar but the electromagnetic fields fluctuates strongly. We present an analogy with the smooth continuous motion of the bow of a violin producing the vibrations of the strings to emit music., Comment: 4 figures, submitted, 3 april 2019

Background Law enforcement officers (LEOs) experience high rates of cardiovascular events compared with the general US population. Metabolic syndrome (MetS) confers an increased risk of cardiovascular disease and all-cause mortality. Data regarding MetS among LEOs are limited. Methods We sought to determine the prevalence of MetS and its associated risk factors as well as gender differences among LEOs who participated in the World Trade Center (WTC) Law Enforcement Cardiovascular Screening (LECS) Program from 2008-2010. We evaluated a total of 2,497 participants, 40 years and older, who responded to the 9/11 WTC attacks. Results The prevalence of MetS was 27%, with abdominal obesity and hypertension being the most frequently occurring risk factors. MetS and its risk factors were significantly higher among male compared to female LEOs, except for reduced HDL-cholesterol levels. Conclusions MetS is a rising epidemic in the United States, and importantly, approximately one in four LEOs who worked at the WTC site after 9/11 are affected.

©2016. American Geophysical Union. All Rights Reserved.We report observations from the Magnetospheric Multiscale satellites of large-amplitude, parallel, electrostatic waves associated with magnetic reconnection at the Earths magnetopause. The observed waves have parallel electric fields (E||) with amplitudes on the order of 100 mV/m and display nonlinear characteristics that suggest a possible net E||. These waves are observed within the ion diffusion region and adjacent to (within several electron skin depths) the electron diffusion region. They are in or near the magnetosphere side current layer. Simulation results support that the strong electrostatic linear and nonlinear wave activities appear to be driven by a two stream instability, which is a consequence of mixing cold (

Questions have arisen regarding the risk of developing symptomatic Histoplasma capsulatum infection among patients who undergo transplant-related immunosuppression in areas endemic for histoplasmosis. Our medical center is located in a hyperendemic area for histoplasmosis, where three large outbreaks occurred since 1978. We undertook a retrospective chart review of 137 patients who received allogeneic bone marrow transplant and of 449 patients who received solid organ transplant from January 1994 to December 1996 in order to assess the incidence of active histoplasmosis. Charts were reviewed before and after transplantation for clinical outcomes, H. capsulatum serologies and antigen results, and microbiological and radiological results. After a mean follow-up duration exceeding 16 months, no patient was diagnosed with histoplasmosis. In the absence of an outbreak, histoplasmosis is a rare infection following the immunosuppression of allogeneic bone marrow or solid organ transplantation even in a hyperendemic area. Pre-transplant serologies or chest radiographs consistent with prior infection were not associated with post-transplant histoplasmosis.

To investigate the role of T cells in drug allergy, we stimulated PBMC from penicillin-allergic patients with reactive penicillin G itself or penicillin G coupled with human serum albumin (BPO-HSA). T cell clones specific for penicillin G or BPO-HSA were established and their phenotype and reactivity to both forms of the beta-lactam were analyzed. T cell clones stimulated by penicillin G were CD4 and CD8 positive, whereas BPO-HSA stimulated the growth of CD4+ T cells. The penicillin G-specific clones were HLA class I or class II restricted and processing was not required as fixed APC could still present penicillin G. In contrast, BPO-HSA has to undergo processing to stimulate BPO-HSA-specific T cell clones. In addition to classical APC, activated MHC class II expressing T cells could also restimulate the penicillin G-specific clones, indicating that various cell types might serve as APC. Penicillin G and BPO-HSA-specific T cell clones produced a heterogeneous cytokine pattern as most clones produced high amounts of IL-2, IFN-gamma, TFN-alpha, and rather variable levels of IL-4 and IL-5. Since no Ag processing was required, penicillin G may stimulate T cells by binding directly to MHC molecules on the cell surface or to their embedded peptide. Alternatively, it may bind to soluble proteins like HSA, which are processed and subsequently presented in an immunogenic form. These different modes of presentation, which elicit a variety of immunological reactivities, may explain the great heterogeneity of the clinical pictures seen in penicillin allergy.

We have previously demonstrated that IL-9 induction in human T cells stimulated with PMA and anti-CD3 Ab is mediated by IL-2, as it was blocked by anti-IL-2R Ab. The experiments reported here indicate that anti-IL-2R Ab also inhibited the expression of IL-4, IL-6, and IL-10, thereby raising the possibility that the blockade of IL-9 production by anti-IL-2R mAb could be secondary to the blockade of these cytokines. We found that the inhibition caused by anti-IL-2R Ab on IL-9 production could be reversed by the addition of a combination of IL-4 and IL-10. Moreover, IL-9 production by T cells stimulated with PMA and anti-CD3 Ab was blocked by the addition of anti-IL-4 and anti-IL-10 Abs. Similar results were obtained with T cells cultured on B7-1/Fc gamma RII-transfected fibroblasts in the presence of anti-CD3 Ab. Analysis of cytokine production by different T cell subsets revealed that IL-4, IL-9, and IL-10 were produced only by CD45 Ro+ T cells. Importantly, CD45 Ra+ T cells were capable of producing IL-9 provided that both IL-4 and IL-10 were added to the cultures. The possible relationship between IL-4 production and IL-10 production was clarified by experiments indicating that IL-10 production was inhibited by anti-IL-4 Ab. However, IL-4 was not sufficient to trigger IL-10 production, which required both IL-2 and IL-4. Taken together, our results demonstrate the existence of a cascade of cytokines responsible for IL-9 expression, with IL-2 being required for IL-4 production, a combination of IL-2 and IL-4 for IL-10 production, and a combination of IL-4 and IL-10 for IL-9 production. Kinetics studies of cytokine gene expression in T cells further validated this model.

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that induces the production of several pro-inflammatory cytokines, leading to a self-limited shock. In the present study, we show that SEB also triggers the systemic release of IL-10, an anti-inflammatory and immunosuppressive cytokine. Serum IL-10 was undetectable (< 1000 pg/ml) in control BALB/c mice and rose to 8500 +/- 2850 pg/ml (mean +/- SEM) 4 h after injection of 100 micrograms SEB. Cell depletion experiments and analysis of IL-10 mRNA expression indicated that CD4+ cells played a major role in SEB-induced IL-10 production. Pretreatment of mice with neutralizing anti-IL-10 mAb before SEB challenge did not modify the release of TNF but led to increased and sustained IL-2 and IFN-gamma serum levels. Furthermore, although no lethality occurred in mice injected with SEB and control mAb, injection of anti-IL-10 mAb before SEB resulted in a 30% lethality (p < 0.05). This lethality was completely prevented by anti-IFN-gamma mAb injection, indicating that IFN-gamma plays a crucial role in the increased toxicity of SEB in anti-IL-10 mAb-injected mice. We conclude that SEB induces the production of IL-10 by CD4+ cells in vivo and that endogenous IL-10 plays an important immunoregulatory role in this model by down-regulating IL-2 and IFN-gamma production.

Injection of anti-CD3 is accompanied by an increase in systemic TNF, a mediator of the physiologic changes induced by anti-CD3 injection. Various mechanisms have been reported to be responsible for TNF inactivation and clearance. Recently, it has become evident that circulating soluble TNFRs (P55 and P75), which are known to increase in response to TNF inducers such as LPS, represent a natural protection mechanism against circulating TNF. Here we show that triggering the TCR by anti-CD3 injection results in a strong induction of both systemic TNF and soluble TNFR release. Maximal levels of TNF were reached after 2 h (10 ng/ml). Maximum levels of P55 (450 pg/ml) were reached between 0.5 and 8 h, whereas the highest levels of P75 were reached after 2 h (28 ng/ml). Because TNF and IFN-gamma are supposed to be involved in the pathophysiology of the anti-CD3 response, we investigated the influence of in vivo neutralization of TNF and IFN-gamma. Injection of mAb to TNF and IFN-gamma significantly reduced systemic TNF levels and both soluble TNFR levels. Two inhibitors of anti-CD3 induced TNF release; steroids and pentoxifylline both reduced TNF levels and P75 levels without affecting P55 levels. The results show that T cell activation induces both systemic TNF release and release of both soluble TNFRs. Although TNF and IFN-gamma are involved in this mechanism, their role does not seem to be crucial.

In preparation for the MMS mission we ask the question: how common are bipolar signatures linked to the presence of electron holes along separatrices emanating from reconnection regions? To answer this question, we conduct massively parallel simulations for realistic conditions and for the hydrogen mass ratio in boxes larger than considered in similar previous studies. The magnetic field configuration includes both a field reversal and a out of plane guide field, as typical of many space situations. The guide field is varied in strength from low values (typical of the Earth magnetotail) to high values comparable to the in plane reconnecting field (as in the magnetopause). In all cases, along the separatrices a strong electron flow is observed, sufficient to lead to the onset of streaming instabilities and to form bipolar parallel electric field signatures. The presence of bipolar structures at all guide fields allows the control of the MMS mission to consider the presence of bipolar signatures as a general flag of the presence of a nearby reconnection site both in the nightside and in the dayside of the magnetosphere., Comment: 3 figures, To appear Geophys Res Lett

We developed a “continual engagement†model to better integrate knowledge from policy makers, communities, and researchers with the goal of promoting more effective action to balance poverty alleviation and wildlife conservation in 4 pastoral ecosystems of East Africa. The model involved the creation of a core boundary-spanning team, including community facilitators, a policy facilitator, and transdisciplinary researchers, responsible for linking with a wide range of actors from local to global scales. Collaborative researcher–facilitator community teams integrated local and scientific knowledge to help communities and policy makers improve herd quality and health, expand biodiversity payment schemes, develop land-use plans, and fully engage together in pastoral and wildlife policy development. This model focused on the creation of hybrid scientific–local knowledge highly relevant to community and policy maker needs. The facilitation team learned to be more effective by focusing on noncontroversial livelihood issues before addressing more difficult wildlife issues, using strategic and periodic engagement with most partners instead of continual engagement, and reducing costs by providing new scientific information only when deemed essential. We conclude by examining the role of facilitation in redressing asymmetries in power in researcher–community–policy maker teams, the role of individual values and character in establishing trust, and how to sustain knowledge-action links when project funding ends.

Recently, functional heterogeneity among Th cells has been recognized. Based on pattern of lymphokine secretion, two mutually exclusive subsets of CD4+ cells have been defined and designated Th1 (secreting IL-2 and IFN-gamma) and Th2 (secreting IL-4 and IL-5). Identification of these subsets was mostly based on the study of long term cultured T cell lines and clones, and little is known about the Th heterogeneity in vivo. In particular, it has been suggested that IL-4 producing cells cannot be detected in vivo or in primary stimulations in vitro unless responder cells had been previously primed. Our data however, indicate that anti-CD3 mediated stimulation can induce T cells isolated from unprimed animals to IL-4 production. An assay system based on the ability of IL-4 to increase Ia expression of B cells present in the environment of activated T cells was found to be more sensitive than detection of secreted IL-4 in the supernatant by conventional bioassays and was used to study IL-4 production by unprimed lymphocytes polyclonally stimulated in vivo and in vitro by anti-CD3 mAb. The results obtained indicate that CD4+ CD8- T cells able to produce IL-4 upon receptor-specific stimulation exist in the preimmune pool of adult animals. Remarkably, these cells can also be stimulated in vivo by treating animals with anti-CD3 mAb, as indicated by the in vivo induction of IL-4 specific mRNA and hyper-Ia expression on B cells. These results indicate that the inability to detect IL-4 in primary cultures is not due to different activation requirements of Th2 cells but may simply result from their lower frequency in unprimed animals.

The immaturity of the neonatal immune system in mice is associated with defective IFN-gamma production and Th2-biased immune responses. In this study, infants vaccinated at birth with BCG produced similar concentrations of IFN-gamma in response to PPD and showed similar frequencies of IFN-gamma-producing lymphocytes as compared to immune adults. Infants and adults produced only low concentrations of IL-4 and IL-5. CD4+ T lymphocytes were the main source of IFN-gamma. Similar proportions of Th1 and Th0 PPD-specific T cell clones were observed in infants and adults. This study demonstrates that the human neonatal immune response to BCG is not biased towards Th2 and is characterized by the predominant production of IFN-gamma by CD4+ T lymphocytes.

N-acetyl-L-cysteine (NAC) is an antioxidant molecule endowed with immunomodulatory properties. To investigate the effect of NAC on the induction phase of T cell responses, we analyzed its action on human dendritic cells (DC) derived from adherent PBMC cultured with IL-4 and granulocyte-macrophage CSF. We first found that NAC inhibited the constitutive as well as the LPS-induced activity of the transcription factor NF-kappaB. In parallel, NAC was shown to down-regulate the production of cytokines by DC as well as their surface expression of HLA-DR, CD86 (B7-2), and CD40 molecules both at the basal state and upon LPS activation. NAC also inhibited DC responses induced by CD40 engagement. The inhibitory effects of NAC were not due to nonspecific toxicity as neither the viability of DC nor their mannose receptor-mediated endocytosis were modified by NAC. Finally, we found that the addition of NAC to MLR between naive T cells and allogeneic DC resulted in a profound inhibition of alloreactive responses, which could be attributed to a defect of DC as APC-independent T cell responses were not inhibited by NAC. Altogether, our results suggest that NAC might impair the generation of primary immune responses in humans through its inhibitory action on DC.

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In order to launch a new transplantation program for Parkinson's disease (PD), we evaluated the safety and efficacy of fetal ventral mesencephalic grafts in 3 patients with advanced PD. Inclusion criteria and clinical evaluation followed strictly the Core Assessment Program for Intracerebral Transplantation. The transplantation procedure was based on the technique previously described by the groups in Lund (Sweden) and Créteil (France). The putamen contralateral to the site of predominant symptoms was unilaterally grafted in all patients. Magnetic resonance (MR)-based stereotactic guidance with multiplanar correlation was used to define 3 implantation trajectories in the precommissural, commissural, and postcommissural putamen. Fetal ventral mesencephalon was prepared from 6- to 8-week-old human embryos obtained from same-day abortions. Under general anesthesia, 8 deposits of 3 microliters of the fetal tissue were placed 1 mm apart along each implantation trajectory using a customized microsyringe and needle attached to the stereotactic frame. The patients recovered uneventfully from the neurosurgical procedure. Early postoperative MR clearly showed the implantation trajectories reaching the putamen in all patients. The follow-up period was of 12, 9 and 6 months, for each of the 3 patients, respectively. Clinical changes appeared between 3 and 6 months after transplantation and consisted of an increase in the 'on' periods and in quantitative bilateral improvement in the motor timed tests. There was an improvement of the Unified Parkinson's Disease Rating Scale score and an improvement of rigidity. Tremor was unchanged, and there was a slight and transient increase in dyskinesias. Neuropsychological follow-up revealed slight frontal alterations in 2 patients. Positron emission tomography demonstrated an increase of 18F-fluorodopa uptake in the grafted site. Adverse events include a reversible Cushing syndrome secondary to immunosuppression in 1 patient and a transient episode of confusion in another. The results of this study, designed as a prerequisite for a wider transplantation program, are in accordance with those previously reported by others and show that, using standardized neurosurgical techniques and methods of evaluation, transplantation is a reproducible and safe therapeutic approach which provides clinical benefits to patients with advanced PD.

We have previously shown that chlorpromazine (CPZ) inhibits tumour necrosis factor (TNF) production and protects against endotoxic shock in mice. In this paper we investigated the effect of pretreatment with CPZ, 4 mg/kg i.p. 30 min before, compared with dexamethasone (DEX; 3 mg/kg) on the induction of other endotoxin (lipopolysaccharide; LPS)-induced cytokines in the serum of mice, i.e. interleukin-1 alpha (IL-1 alpha), IL-6 and IL-10, and TNF. We also studied the effect of CPZ on serum and spleen-associated TNF. Both DEX and CPZ inhibited TNF production, whereas induction of IL-1 and IL-6 was inhibited by DEX but not by CPZ. DEX did not affect IL-10, while CPZ potentiated its induction. CPZ also inhibited spleen-associated TNF induction in LPS-treated mice, suggesting an effect on the synthesis of TNF. CPZ inhibited TNF induction by Gram-positive bacteria (heat-killed Staphylococcus epidermidis) and by anti-CD3 monoclonal antibodies. Intraperitoneal administration of CPZ also inhibited the induction of brain-associated TNF induced by intra-cerebroventricular injection of LPS. Therefore, CPZ is a more specific inhibitor of TNF production than DEX; in particular, CPZ increased the induction of IL-10, which is a 'protective' cytokine known to inhibit LPS toxicity and TNF production. CPZ inhibited TNF production in vivo, irrespective of the TNF stimulus used to induce TNF. Finally, CPZ did not induce the 'rebound' effect of DEX that, when given 24 hr before LPS, potentiates TNF production, but it did inhibit TNF production after 24 hr.

We measured separate volume-pressure (V-P) relationships or rib cage anddiaphragm-abdomen in seven human subjects during voluntary relaxation of the respiratory muscles, breathing at rest, during exercise, and rebreathingexpired air. Estimates of separate volume displacements of the two parallelchest wall pathways were based on analysis of rib cage and abdominal anteroposterior diameter changes. The pressure developed across each pathway (transthoracic pressure) was partitioned into two serial pressure drops: transdiaphragmatic pressure and transabdominal pressure. We develop the concept that the relationship of volume displacements of structures to pressures developed by the structures during breathing, as compared to the relaxed state,reflects action of respiratory muscles in the structure. We interpret therelationship of rib cage volume displacements to transabdominal pressure(during breathing vs. relaxation) as indicating action of intercostal and accessory muscles only, the separate action of diaphragm on rib cage being measured by transdiaphragmatic pressure. At rest, the diaphragm is the only importantly active respiratory muscle. During increased ventilation activityofother respiratory muscles appears coordinated to assist the optimize diaphragmatic function.

Bombesin found in neuroepithelial bodies and oat cell carcinoma of the lung, is thought to play an important role in normally developing and malignant lung. Monocytes-macrophages and human small cell lung carcinoma cells share several features, including macrophage-specific surface markers and the expression of functional receptors for bombesin-like neuropeptides and growth factors. Because small cell lung carcinoma cells synthesize immunoreactive bombesin, we investigated the possibility that alveolar macrophages also contain bombesin, a plausible hypothesis considering the many reports of neuropeptide production by immune cells and cells of bone marrow origin. Adherent human peripheral blood mononuclear cells as well as human and guinea pig alveolar macrophages were found to contain bombesin. The peptide was detected by radioimmunoassay, immunohistochemistry, high-pressure liquid chromatography with the use of different monospecific antibodies.

Continuous production of organic wastes from a large dog colony on a diet containing various amounts of Sr/sup 90/ required the design and construction of a moderate-size waste treatment plant. The contaminated wastes contain in excess of approximates x 10/sup -5/ mu c Sr/sup 90//ml and are produced at approximately 200-500 gal/day. Decontamination depends upon efficient utilization of the principles of primary sedimentation, aeration, chemical clarification and filtration prior to passage of the waste through 5 fta of cation exchange resin. The expended resins are disposed of by offsite burial. Treatment of over 115,000 gal of waste has produced final effluents whose average annual concentration does not exceed the current permissible limit for Sr/sup 90/ in drinking water. The treated waste stream is discharged into an underground leaching field. Decontamination factors up to approximates x 10/sup 4/ have been achieved. The current cost of treatment is estimated at less than 15 cents/ gal including material, (resin costs 1.2 cents/gal), labor and plant amortization. (auth) H03 H0238583 Separate abstracts were prepared for 29 of the 38 papers; seven papers were previously abstracted in NSA. (D.C.W.)

Estimates of the mechanical work of breathing derived from measurements of separate rib cage and abdominal volume displacements, each plotted against transthoracic pressure, include the elastic cost of chest wall distortion which may occur during breathing. Inspiratory work is partitioned between the diaphragm and the rib cage musculature by adding measurements of transabdominal pressure. The mechanical work of breathing derived from separate rib cage and abdominal volume-pressure (V-P) tracings (the sum of work done by the diaphragm, rib cage, and abdominal musculature) is compared with ventilatory work estimated from the Campbell diagram (which does not include any distortional work). During resting breathing the two estimates are closely comparable, consistent with little or no distortion of the chest wall during quiet breathing. As ventilation increases, the estimate developed from rib cage and abdominal tracings reveals systematically greater mechanical work than is estimated from the Campbell diagram, consistent with distortion of the chest wall from the relaxed thoracoabdominal configuration at higher levels of ventilation. At ventilations achieved during exercise, the Campbell diagram may underestimate the work of breathing by up to 25%.

THE advent of thiopental-succinylcholine anesthesia for electroshock therapy has broadened considerably the indications for this mode of treatment. Patients with cardiovascular disease, recent unhealed fractures, pulmonary tuberculosis or hyper-insulinism were formerly considered major risks for shock treatment. These are not taken as positive contraindications at present. Saltzman et al.1 reported 38,000 treatments without serious complications. In view of this therapeutic achievement we are presenting a case illustrating the development of circulatory collapse after shock treatment. Case Report W.G. (C.H. 59–3144), a 51-year-old man with recurrent depressions since the age of 18, had received a series of electroshock treatments since 1948 . . .

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The injection of DBA/2 parental lymphocytes into adult, immunologically intact (C57BL/6 x DBA/2) F1 hybrid mice results in a chronic graft-vs-host reaction (GVHR) characterized by a deficiency in CD4+ T cell functions and a B cell activation leading to autoantibody production. The discovery that distinct subpopulations of Th cells may regulate the effector immune functions led us to investigate whether the chronic GVHR differentially affects Th subsets. Data are presented indicating that mice undergoing a GVHR spontaneously produced lymphokines of Th2 origin. IL-4 and IL-10 mRNA were detected in the spleens of GVH mice, and IL-4 was shown to be responsible for the increased expression of class II Ag on B cells. Moreover, upon polyclonal activation in vitro, GVH T cells exhibited defective IL-2 and IFN-gamma production but elevated IL-4 production. We conclude that the chronic GVHR is characterized by a selective deficiency in cells secreting IL-2 and IFN-gamma and a hyperactivation of Th2 cells. The simultaneous production of IL-4 and IL-10 might explain the association between B cell hyperactivity and impairment of Th1-like activities in various models that associate autoimmunity and immunosuppression, such as GVHR and HIV infection.

Many cancer survivors experience physical and/or psychosocial side effects, which can be severe, debilitating, and sometimes permanent. These NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for common consequences of cancer and cancer treatment for health care professionals who work with survivors of adult-onset cancer in the posttreatment period. These introductory sections of the guidelines include the panel's definition of cancer survivors, a discussion of the effects of cancer and its treatment, general principles and standards for survivorship care, and guidance regarding screening for problems that require further assessment.

To investigate the consequences of CD40 engagement on the neonatal induction of transplantation tolerance, BALB/c mice were injected at birth with (A/J × BALB/c) F1 spleen cells together with activating anti-CD40 mAb and grafted 4 wk later with A/J skin. Whereas A/J allografts were accepted in mice neonatally injected with F1 cells and control Ab, they were acutely rejected in mice injected with F1 cells and anti-CD40 mAb. Neonatal administration of anti-CD40 mAb resulted in enhanced anti-A/J CTL activity, increased IFN-γ, and decreased IL-4 production by donor-specific T cells in vitro. Experiments using anti-cytokine mAb and IFN-γ-deficient mice demonstrated that CD40 ligation prevents neonatal allotolerance through an IFN-γ- and IL-12-dependent pathway. Finally, we found that newborn T cells express less CD40L than adult T cells upon TCR engagement. Taken together these data indicate that insufficiency of CD40/CD40L interactions contribute to neonatal transplantation tolerance.