Body of evidence: forensic use of baseline health assessments to convict wildlife poachers

CONTEXT. Given the immense impact of wildlife trade, disease and repatriations on populations, health assessments can" "provide powerful forensic material to help convict wildlife poachers and minimise risks of releasing unhealthy wildlife." AIMS. We aimed to use reference ranges to assess the health of confiscated tortoises, to illustrate forensic application of these ranges, and to advance analyses for future applications." METHODS. We used analyses of variance (ANOVA) and covariance (ANCOVA), and composite indices, to compare wild and confiscate tortoise body condition, haematocrit and haemoglobin concentration of males and females of three tortoise species. Subsequently, we used multivariate statistics (e.g. discriminant analyses) to evaluate the relative importance of species, sex and group (wild or confiscate) on tortoise condition and haematology." KEY RESULTS. Our initial statistical tests demonstrated, at P < 0.05 to P < 0.0005, that confiscate body condition and haematology were compromised compared with that of wild tortoises. Subsequently, discriminant analyses strongly discriminated between most wild and confiscate groups (P < 0.0001), correctly classified individual health as wild or confiscate 80–90% of the time, indicated that species and sex effects were stronger than was the wild-confiscate category, and provided discriminant functions for use on other taxa and studies." CONCLUSIONS. The health assessments discriminated well between wild and confiscate tortoises. The results had considerable forensic value, being relevant, quickly generated using portable field equipment, reliable, accurate, easy to explain and convey in terms of likelihood in a court of law, synergistically consistent among variables and groups, a strong rebuttal to the poachers’ specific statements, and consistent with other types of evidence. Multivariate analyses were consistent with, and more prudent and powerful than, the original statistical analyses. Discriminant functions can be applied in future studies and on other chelonian species, and should be developed for other wildlife species." IMPLICATIONS. Reference ranges provide considerable value for forensics, diagnostics and treatment. Given the disease risks resulting from the massive scale of wildlife trade and release, reference ranges should be developed for more species."Web of Scienc

Switching to bedaquiline for treatment of rifampicin-resistant tuberculosis in South Africa: A retrospective cohort analysis.

South Africa led the world with guidelines on bedaquiline (BDQ) use as a single drug substitution to manage rifampin resistant tuberculosis regimen toxicity. We examined reasons for giving BDQ in a retrospective cohort: >75% of patients were switched to BDQ for toxicity (ototoxicity or renal dysfunction) rather than drug resistance

Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma

T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B-cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbored PD-L1/PD-L2 copy gain or amplification in 64% of cases, which was associated with increased PD-L1 expression (P = .0111). By directed and unsupervised spatial analyses of multiparametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune “neighborhoods” in which malignant B cells are surrounded by exceptionally high numbers of PD-L1–expressing TAMs and PD-1+ T cells. Furthermore, unbiased clustering of spatially resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in 3 of 5 patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies (NCT03316573; NCT01953692), including 2 complete responses and 1 partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL and also support the potential utility of spatially resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types. Key Points: • Spatially resolved signatures of PD-1/PD-L1 signaling in the tumor microenvironment define T-cell/histiocyte-rich large B-cell lymphoma. • Three of 5 patients with relapsed/refractory TCRLBCL showed objective clinical responses to single-agent PD-1 blockade (pembrolizumab)