X-ray film chamber with carbon target of Tien-Shan complex array

X-ray films were exposed inside the ionization calorimeter under 74g/sq cm of carbon and 5 cm of lead. The X-ray film chamber area is 35 sq. m. Moving X-ray films were used, 50% of the events, which succeeded to determine incidence time, were identified with corresponding extensive air showers (EAS). For such events the size spectrum of associated EAS was derived. Two methods of energy measurement using X-ray films and ionization calorimeter were compared. The energy transfer from selected hadron to electromagnetic component is illustrated. It is found that in cascades with high energy release into electromagnetic components the hadron component is practically absent

High energy hadrons in EAS at mountain altitude

An extensive simulation has been carried out to estimate the physical interpretation of dynamical factors such as , in terms of high energy interaction features, concentrated in the present analysis on the average transverse momentum. It appears that the large enhancement observed for versus primary energy, suggesting in earliest analysis a significant rise of with energy, is only the result of the limited resolution of the detectors and remains in agreement with a wide range of models used in simulations.Comment: 13 pages, 6 PostScript figures, LaTeX Subm. to JPhys

Efficacy and safety of trimodulin, a novel polyclonal antibody preparation, in patients with severe community-acquired pneumonia: a randomized, placebo-controlled, double-blind, multicenter, phase II trial (CIGMA study)

Purpose The CIGMA study investigated a novel human polyclonal antibody preparation (trimodulin) containing ~ 23% immunoglobulin (Ig) M, ~ 21% IgA, and ~ 56% IgG as add-on therapy for patients with severe community-acquired pneumonia (sCAP). Methods In this double-blind, phase II study (NCT01420744), 160 patients with sCAP requiring invasive mechanical ventilation were randomized (1:1) to trimodulin (42 mg IgM/kg/day) or placebo for five consecutive days. Primary endpoint was ventilator-free days (VFDs). Secondary endpoints included 28-day all-cause and pneumonia-related mortality. Safety and tolerability were monitored. Exploratory post hoc analyses were performed in subsets stratified by baseline C-reactive protein (CRP; ≥ 70 mg/L) and/or IgM (≤ 0.8 g/L). Results Overall, there was no statistically significant difference in VFDs between trimodulin (mean 11.0, median 11 [n = 81]) and placebo (mean 9.6; median 8 [n = 79]; p = 0.173). Twenty-eight-day all-cause mortality was 22.2% vs. 27.8%, respectively (p = 0.465). Time to discharge from intensive care unit and mean duration of hospitalization were comparable between groups. Adverse-event incidences were comparable. Post hoc subset analyses, which included the majority of patients (58–78%), showed significant reductions in all-cause mortality (trimodulin vs. placebo) in patients with high CRP, low IgM, and high CRP/low IgM at baseline. Conclusions No significant differences were found in VFDs and mortality between trimodulin and placebo groups. Post hoc analyses supported improved outcome regarding mortality with trimodulin in subsets of patients with elevated CRP, reduced IgM, or both. These findings warrant further investigation

The role of the immune response in the pathogenesis of thyroid eye disease: a reassessment

BACKGROUND: Although thyroid eye disease is a common complication of Graves' disease, the pathogenesis of the orbital disease is poorly understood. Most authorities implicate the immune response as an important causal factor. We sought to clarify pathogenesis by using gene expression microarray. METHODS: An international consortium of ocular pathologists and orbital surgeons contributed formalin fixed orbital biopsies. RNA was extracted from orbital tissue from 20 healthy controls, 25 patients with thyroid eye disease (TED), 25 patients with nonspecific orbital inflammation (NSOI), 7 patients with sarcoidosis and 6 patients with granulomatosis with polyangiitis (GPA). Tissue was divided into a discovery set and a validation set. Gene expression was quantified using Affymetrix U133 Plus 2.0 microarrays which include 54,000 probe sets. RESULTS: Principal component analysis showed that gene expression from tissue from patients with TED more closely resembled gene expression from healthy control tissue in comparison to gene expression characteristic of sarcoidosis, NSOI, or granulomatosis with polyangiitis. Unsupervised cluster dendrograms further indicated the similarity between TED and healthy controls. Heat maps based on gene expression for cytokines, chemokines, or their receptors showed that these inflammatory markers were associated with NSOI, sarcoidosis, or GPA much more frequently than with TED. CONCLUSION: This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos. The juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.James T. Rosenbaum ... Dinesh Selva ... et al

Hemorrhage as a sign of treatment failure after intra-arterial chemotherapy in retinoblastoma

Intra-arterial melphalan chemotherapy (IAC) continues to demonstrate excellent utility in the treatment of retinoblastoma. We present the case of a 3-month-old boy diagnosed with with unilateral, advanced stage 5B retinoblastoma and a Coats' response in the right eye. After laser therapy he received 3 doses of IAC. Intraretinal hemorrhaging, first noted after the second dose and worsening after the third, preceded complex exudative retinal detachment. With little visual potential and evidence of atropy, the eye was enucleated. This case illustrates that intraretinal hemorrhage may serve as an early predictor of treatment failure

Retinoblastoma with Coats' response

Although it is well known that a variety of pediatric ocular diseases may clinically resemble retinoblastoma, perhaps of more concern is when the actual tumor mimics seemingly benign ocular lesions. The authors present two cases of retinoblastoma with a Coats' response as evidence of the challenge often encountered in evaluating intraocular malignancies. The cases further emphasize the need for retaining a high level of clinical suspicion for more malicious diseases, often using repeated fundus evaluations when a diagnosis remains ambiguous

Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study

To describe the clinical and pathologic characteristics of a case of retinal vasculitis and vitritis following brolucizumab administration and subsequent ranibizumab treatment. A 76-year old Caucasian woman experienced pain, decreased vision and floaters one week after receiving her third monthly intravitreal brolucizumab injection in the right eye for exudative age-related macular degeneration. Examination was significant for 0.5+ anterior chamber cells, vitritis, mild peripheral vascular sheathing, and decreased vision from 20/70 to 20/200. She was started on topical 1% prednisolone acetate with improvement in her examination. She was switched to ranibizumab one month after her last brolucizumab injection of the right eye. Three weeks after her ranibizumab injection, she noticed photophobia, pain and decreased vision. Examination revealed worsening uveitis, vitritis, vascular sheathing, and decreased vision to count fingers. Despite starting on 0.05% difluprednate drops every 2 hours and oral high-dose methylprednisolone, the patient did not have any significant improvement in her symptoms or examination. She underwent pars plana vitrectomy and vitreous biopsy with intravitreal triamcinolone injection to the right eye. Vitreous biopsy and culture ruled out infectious endophthalmitis, and further cytopathologic analysis revealed chronic inflammatory infiltrate. Treatment with brolucizumab can result in intraocular inflammation and retinal vasculitis likely due to a delayed hypersensitivity reaction to the drug, supported by cytopathologic analysis of a vitreous sample. We demonstrate a case where retreatment with an alternative anti-VEGF agent resulted in worsening vision and vasculitis