Biospecimens are critical in driving health research. There is increased demand for scale and quality of biospecimens that in turn drives biobanking operational costs, influences utilization, and ...threatens the sustainability of individual biobanks. Biospecimen research has begun to inform the details of new biobanking standards and the steps of the biobanking process that are most important to focus on to achieve higher quality. This focus on quality is currently centered mostly on intrinsic features of biospecimens and their annotating data. This review highlights additional quality features that are important to researchers in determining the fit for purpose in their research. First, we define complex qualities as those that are mostly extrinsic to the individual biospecimen and data, and second, we provide data on the growth in demand for biospecimens with this type of quality in cancer research biobanks. Finally, we discuss why biospecimen complexity is a challenge for biobanks and utilization of existing collections, and provide examples of strategies biobanks can consider to improve their focus on this aspect of quality, as we predict that researcher demand for complex biospecimens will continue to expand in the future.
The new global biodiversity framework (GBF) being developed under the Convention on Biological Diversity must drive action to reverse the ongoing decline of the Earth's biodiversity. Explicit, ...measurable goals that specify the outcomes we want to achieve are needed to set the course for this action. However, the current draft goals and targets fail to set out these clear outcomes. We argue that distinct outcome goals for species, ecosystems, and genetic diversity are essential and should specify net outcomes required for each. Net outcome goals such as “no net loss” do, however, have a controversial history, and loose specification can lead to perverse outcomes. We outline seven general principles to underpin net outcome goal setting that minimize risk of such perverse outcomes. Finally, we recommend inclusion of statements of impact in action targets that support biodiversity goals, and we illustrate the importance of this with an example from the draft GBF action targets. These modifications would help reveal the specific contribution each action would make to achieving the outcome goals and provide clarity on whether the successful achievement of action targets would be adequate to achieve the outcome goals and, in turn, the 2050 vision: living in harmony with nature.
Cancers accumulate mutations over time, each of which brings the potential for recognition by the immune system. We evaluated T-cell recognition of the tumor mutanome in patients with ovarian cancer ...undergoing standard treatment.
Tumor-associated T cells from 3 patients with ovarian cancer were assessed by ELISPOT for recognition of nonsynonymous mutations identified by whole exome sequencing of autologous tumor. The relative levels of mutations and responding T cells were monitored in serial tumor samples collected at primary surgery and first and second recurrence.
The vast majority of mutations (78/79) were not recognized by tumor-associated T cells; however, a highly specific CD8(+) T-cell response to the mutation hydroxysteroid dehydrogenase-like protein 1 (HSDL1)(L25V) was detected in one patient. In the primary tumor, the HSDL1(L25V) mutation had low prevalence and expression, and a corresponding T-cell response was undetectable. At first recurrence, there was a striking increase in the abundance of the mutation and corresponding MHC class I epitope, and this was accompanied by the emergence of the HSDL1(L25V)-specific CD8(+) T-cell response. At second recurrence, the HSDL1(L25V) mutation and epitope continued to be expressed; however, the corresponding T-cell response was no longer detectable.
The immune system can respond to the evolving ovarian cancer genome. However, the T-cell response detected here was rare, was transient, and ultimately failed to prevent disease progression. These findings reveal the limitations of spontaneous tumor immunity in the setting of standard treatments and suggest a high degree of ignorance of tumor mutations that could potentially be reversed by immunotherapy.
Biomarkers are critical tools that underpin precision medicine. However there has been slow progress and frequent failure of biomarker development. The root causes are multifactorial. Here, we focus ...on the need for fast, efficient, and reliable access to quality biospecimens as a critical area that impacts biomarker development. We discuss the past history of biobanking and the evolution of biobanking processes relevant to the specific area of cancer biomarker development as an example, and describe some solutions that can improve this area, thus potentially accelerating biomarker research.
Although it is generally accepted that human tissue biobanks are important to facilitate progress in health and medical research, many academic biobanks face sustainability challenges. We propose ...that biobank sustainability is challenged by a lack of available data describing the outputs and benefits that are produced by biobanks, as reflected by a dearth of publications that enumerate biobank outputs. We further propose that boosting the available information on biobank outputs and using a broader range of output metrics will permit economic analyses such as cost-consequence analyses of biobank activity. Output metrics and cost-consequence analyses can allow biobanks to achieve efficiencies, and improve the quality and/or quantity of their outputs. In turn, biobank output measures provide all stakeholders with explicit and accountable data on biobank value, which could contribute to the evolution of biobank operations to best match research needs, and mitigate some threats to biobank sustainability.
•Biobanks play an essential role in facilitating basic and translational health research. In particular, biobanked human specimens are a critical component in personalized medicine approaches to human disease. Nevertheless, it has proved difficult to determine a value for academic biobanks that can be interpreted and used by all stakeholders. A lack of value confers a threat to biobank sustainability, a common challenge for biobanks across the world.•To determine accurate biobank values, we describe an approach for academic biobanks to enumerate a comprehensive range of currently underreported biobank outputs. Using a broader range of output metrics also permits economic analyses such as cost-consequence analyses, providing a more comprehensive and transparent decision-making tool for funders, decision makers, and policy makers.•Consideration is given to the consequences of a lack of biobank output data, and approaches to achieve an output focus are then discussed. This includes efforts from biobanks, funders, policy makers, journal editors, and conference organizers. Finally, the benefits of focusing on biobank outputs are articulated, including operational efficiencies for biobanks and achieving explicit and accountable values for other stakeholders. This is necessary for biobank sustainability, and ultimately for better support of health and medical research.
Staphylococcus aureus has been implicated in the pathophysiology of eczema, allergic rhinitis, asthma, and food allergy. S aureus is a marker of more severe eczema, which is a risk factor for food ...sensitization/allergy. Therefore it might be that the association between S aureus and food allergy in eczematous patients is related to eczema severity.
We sought to investigate the association of S aureus colonization with specific IgE (sIgE) production to common food allergens and allergies in early childhood independent of eczema severity. We additionally determined the association of S aureus colonization with eczema severity and persistence.
In Learning Early About Peanut Allergy (LEAP) study participants eczema severity was assessed, and skin/nasal swabs were cultured for S aureus. Sensitization was identified by measuring sIgE levels. Peanut allergy was primarily determined by means of oral food challenge, and persistent egg allergy was primarily determined by using skin prick tests.
Skin S aureus colonization was significantly associated with eczema severity across the LEAP study, whereas at 12 and 60 months of age, it was related to subsequent eczema deterioration. Skin S aureus colonization at any time point was associated with increased levels of hen's egg white and peanut sIgE independent of eczema severity. Participants with S aureus were more likely to have persistent egg allergy and peanut allergy at 60 and 72 months of age independent of eczema severity. All but one of the 9 LEAP study consumers with peanut allergy (9/312) were colonized at least once with S aureus.
S aureus, independent of eczema severity, is associated with food sensitization and allergy and can impair tolerance to foods. This could be an important consideration in future interventions aimed at inducing and maintaining tolerance to food allergens in eczematous infants.
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Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical ...archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for individual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.
CD74 (invariant chain) plays a role in MHC class II antigen presentation. We assessed CD74 and MHCII expression in tumor cells, as well as CD8, CD4, and CD68 tumor infiltrating leucocyte (TIL) ...density by immunohistochemistry in a cohort of 492 breast cancer patients. CD74 expression was associated with poor prognostic markers including patient age, tumor grade, ER status, non-Luminal A subtypes, and with MHCII expression and higher TIL densities, particularly in the Basal-like subgroup. Univariate analysis showed a favorable prognostic effect of CD74 (Hazard ratio = 0.46, 95% CI = 0.26-0.89, p = 0.022) and for combined CD74/MHCII (Hazard ratio = 0.26, 95% CI = 0.17-0.81, p = 0.014) positive status for overall survival that was only manifested in the Basal-like subgroup. CD74 and MHCII expression is associated with patient survival in Basal-like breast cancer, and the association with TIL may reflect an effective intratumoral immune response.
PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic ...significance.
Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype.
Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16.5%) cases and associated with known indicators of poor prognosis, including low patient age, high tumor grade, ER/PR negative status, but not with outcome. However, in the Triple Negative breast cancer subset PD-L1 was associated with better recurrence free survival (RFS) especially within the Basal-like subset (Hazard ratio = 0.39, 95% CI = 0.22 - 0.86,
= 0.018). Combined PD-L1/epithelial CD8 positive status was also strongly associated with better RFS and OS (Hazard ratio = 0.12, 95% CI = 0.10 - 0.71,
= 0.010 and Hazard ratio = 0.11, 95% CI = 0.11 - 0.68,
= 0.006 respectively) in the Basal-like subgroup.
PD-L1 expression is associated with better patient survival in Basal-like breast cancer.
In the United States, the Bald and Golden Eagle Protection Act prohibits take of golden eagles (Aquila chrysaetos) unless authorized by permit, and stipulates that all permitted take must be ...sustainable. Golden eagles are unintentionally killed in conjunction with many lawful activities (e.g., electrocution on power poles, collision with wind turbines). Managers who issue permits for incidental take of golden eagles must determine allowable take levels and manage permitted take accordingly. To aid managers in making these decisions in the western United States, we used an integrated population model to obtain estimates of golden eagle vital rates and population size, and then used those estimates in a prescribed take level (PTL) model to estimate the allowable take level. Estimated mean annual survival rates for golden eagles ranged from 0.70 (95% credible interval = 0.66–0.74) for first‐year birds to 0.90 (0.88–0.91) for adults. Models suggested a high proportion of adult female golden eagles attempted to breed and breeding pairs fledged a mean of 0.53 (0.39–0.72) young annually. Population size in the coterminous western United States has averaged ~31,800 individuals for several decades, with λ = 1.0 (0.96–1.05). The PTL model estimated a median allowable take limit of ~2227 (708–4182) individuals annually given a management objective of maintaining a stable population. We estimate that take averaged 2572 out of 4373 (59%) deaths annually, based on a representative sample of transmitter‐tagged golden eagles. For the subset of golden eagles that were recovered and a cause of death determined, anthropogenic mortality accounted for an average of 74% of deaths after their first year; leading forms of take over all age classes were shooting (~670 per year), collisions (~611), electrocutions (~506), and poisoning (~427). Although observed take overlapped the credible interval of our allowable take estimate and the population overall has been stable, our findings indicate that additional take, unless mitigated for, may not be sustainable. Our analysis demonstrates the utility of the joint application of integrated population and prescribed take level models to management of incidental take of a protected species.
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