Does case misclassification threaten the validity of studies investigating the relationship between neck manipulation and vertebral artery dissection stroke? No

Background: The purported relationship between cervical manipulative therapy (CMT) and stroke related to vertebral artery dissection (VAD) has been debated for several decades. A large number of publications, from case reports to case–control studies, have investigated this relationship. A recent article suggested that case misclassification in the case–control studies on this topic resulted in biased odds ratios in those studies. Discussion: Given its rarity, the best epidemiologic research design for investigating the relationship between CMT and VAD is the case–control study. The addition of a case-crossover aspect further strengthens the scientific rigor of such studies by reducing bias. The most recent studies investigating the relationship between CMT and VAD indicate that the relationship is not causal. In fact, a comparable relationship between vertebral artery-related stroke and visits to a primary care physician has been observed. The statistical association between visits to chiropractors and VAD can best be explained as resulting from a patient with early manifestation of VAD (neck pain with or without headache) seeking the services of a chiropractor for relief of this pain. Sometime after the visit the patient experiences VAD-related stroke that would have occurred regardless of the care received. This explanation has been challenged by a recent article putting forth the argument that case misclassification is likely to have biased the odds ratios of the case–control studies that have investigated the association between CMT and vertebral artery related stroke. The challenge particularly focused on one of the case–control studies, which had concluded that the association between CMT and vertebral artery related stroke was not causal. It was suggested by the authors of the recent article that misclassification led to an underestimation of risk. We argue that the information presented in that article does not support the authors’ claim for a variety of reasons, including the fact that the assumptions upon which their analysis is based lack substantiation and the fact that any possible misclassification would not have changed the conclusion of the study in question. Conclusion: Current evidence does not support the notion that misclassification threatens the validity of recent case–control studies investigating the relationship between CMT and VAD. Hence, the recent re-analysis cannot refute the conclusion from previous studies that CMT is not a cause of VAD.https://doi.org/10.1186/s12998-016-0124-

Monoclonal antibodies against human astrocytomas and their reactivity pattern

The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 × 106 chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner

Adipose Tissue Serves as a Reservoir for Recrudescent Rickettsia prowazekii Infection in a Mouse Model

Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of β-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii

Towards sustainable mixed reality simulation for the mining industry

© 2019 Institute of Materials, Minerals and Mining and The AusIMM Published by Taylor & Francis on behalf of the Institute and The AusIMM. Twenty-first-century mining is a complex pursuit. Stakeholders must manage many interconnected processes and data sets to ensure an operation is sustainable. Mixed Reality (MR) simulation may present an opportunity to improve knowledge and understanding of mine operations via a digital twin. Current and future personnel can model and make predictions using past, current and future data sets. However, MR is still an uncommon tool in the mining industry. This paper asks why that is the case, what some common barriers may be to MR adoption, and presents a possible collaborative solution to make MR sustainable as the technology gains hold and becomes commonplace in mine operations and elsewhere