A circuit modification that improves mammographic phototimer performance

The typical mammographic phototimer does not track with breast thickness. For four common, relatively new mammographic units, phototimed density decreases markedly as breast thickness increases. This trend is attributed to three factors: beam hardening, film reciprocity law failure (RFL), and photosensor dark or leakage current. The contributions of these three factors were experimentally quantitated for the phototimer of a Senographé 500T mammography unit. For a phototimed 28-kVp nongrid technique, the density varied from 2.0 for a 2.5-cm-thick phantom to 0.3 for one 7.6 cm thick. Of the 1.7 difference in film density, 1.1 was attributed to beam hardening, 0.2 to RFL, and 0.4 to photomultiplier tube dark current. A circuit modification was installed in the phototimer that offsets the photomultiplier dark current and has a nonlinear response to compensate for beam hardening and RFL effects. The modified phototimer tracked to within +/- 0.06 density for a 28-kVp grid technique as phantom thickness was varied from 2.0 to 6.0 cm. Similar results were obtained for nongrid techniques.     

Retrospective geometric correlation of MR, CT, and PET images

Magnetic resonance imaging, computed tomographic, and positron emission tomographic studies of the brain provide complementary information, and many patients undergo more than one of these studies during the course of their diagnostic workup and treatment. A new technique for quantitative geometric correlation of such studies makes it possible to create integrated multimodality images by mapping features from one image onto an image obtained with another modality. The coordinate transformation between any pair of images is found by a semiautomatic algorithm for matching models of the patient's external surface as depicted in the two data sets. The resultant hybrid images, which combine complementary features of different studies, are often more useful for diagnosis and treatment planning than are the original single-modality images. The algorithm can also be used for spatial registration of baseline studies with follow-up images created with the same modality, which allows tracking of a lesion to detect subtle interval changes in size and shape. This technique can be applied to images acquired in routine clinical practice, since it is completely retrospective and does not necessitate special positioning or landmarking of the patient.     

Workplace monitoring of occupational exposure to refractory ceramic fiber--a 17-year retrospective

This article presents a 17-year (1990-2006) retrospective summary of ongoing studies of occupational exposure to refractory ceramic fiber (RCF) in the United States. Beginning in 1990, RCF producers integrated and harmonized individual workplace monitoring programs to provide data useful for various longitudinal and cross-sectional analyses, benchmarking, and various technical analyses. For 10 of these 17 years, the program has been conducted in partnership with government agencies, first a 5-year (1993-1998) program with the U.S. Environmental Protection Agency and later another 5-year (2002-2006) program with the Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health. This article updates earlier published studies and provides lessons to be learned in the design of industrial hygiene monitoring and control programs.     

Immune cytolytic activity is associated with reduced intra-tumoral genetic heterogeneity and with better clinical outcomes in triple negative breast cancer

Evaluation of the functional aspects if the tumor immune microenvironment (TIME), such as the recently introduced cytolytic activity score (CYT) index have been under the spotlight in cancer research; however, clinical relevance of immune cell killing activity in breast cancer has never been analyzed in large patient cohorts. We hypothesized that CYT reflects the immune activity of TIME and can predict patient survival. A total of 7533 breast cancer patients were analyzed as both discovery and validation cohorts. We found that high CYT was associated with advanced histological grade and triple-negative breast cancer (TNBC). High CYT in tumors was significantly associated with better survival in TNBC, but unexpectedly, not in other breast cancer subtypes. High CYT TNBC included both favorable immune-related, as well as unfavorable (suppressive) inflammation-related gene sets, and characterized by high infiltration with T cells and B cells. High CYT TNBC was associated with high homologous recombination deficiency and low somatic copy number alteration score and less mutant allele tumor heterogeneity, but not with tumor mutation burden (TMB). Although CYT was not associated with pathological complete response after neoadjuvant chemotherapy, it was significantly associated with high expression of multiple immune checkpoint molecules. In conclusion, CYT of TNBC is associated with enhanced anti-cancer immunity, less intra-tumoral heterogeneity, and with better survival.     

M1 polarization and the effect of PGE2 on TNF‐α production by lymph node cells from dogs with visceral leishmaniasis

Canine visceral leishmaniasis (CVL) is caused by the intracellular parasite Leishmania infantum. Increased levels of arginase, nitric oxide (NO₂) and prostaglandin E2 (PGE₂) can play a regulatory role regarding the immune response in CVL cases. This study aimed to evaluate the arginase activity in adherent macrophages cultured from the lymph nodes of healthy and naturally infected dogs and to examine the NO₂ and PGE₂ levels in the supernatant of these cultures. In addition, the regulatory effect of PGE₂ on the production of tumour necrosis factor (TNF‐α) and interleukin‐10 (IL‐10) in supernatants from the total lymph node was observed in leucocyte cultures. The arginase activity was lower in the adherent macrophages cultured from the lymph nodes of naturally infected dogs and there were higher concentrations of NO₂ and PGE₂ in the supernatants of these cultures. Higher TNF‐α and IL‐10 concentrations were observed in supernatants from total lymph node leucocytes cultures, from infected dogs, and the presence of indomethacin only decreased TNF‐α in the supernatant of these cultures. We conclude that the low arginase activity in macrophages suggested that M1 polarization and PGE₂ were participating in the immune response and were increasing TNF‐α in CVL.