Modern day zoos and aquariums continuously assess the welfare of their animals and use evidence to make informed management decisions. Historically, many of the indicators of animal welfare used to ...assess the collection are negative indicators of welfare, such as stereotypic behavior. However, a lack of negative indicators of animal welfare does not demonstrate that an individual animal is thriving. There is a need for validated measures of positive animal welfare and there is a growing body of evidence that supports the use of behavioral diversity as a positive indicator of welfare. This includes an inverse relationship with stereotypic behavior as well as fecal glucocorticoid metabolites and is typically higher in situations thought to promote positive welfare. This review article highlights previous research on behavioral diversity as a potential positive indicator of welfare. Details are provided on how to calculate behavioral diversity and how to use it when evaluating animal welfare. Finally, the review will indicate how behavioral diversity can be used to inform an evidence-based management approach to animal care and welfare.
Background
Metaplastic breast cancer (MBC) is a rare disease subtype characterized by an aggressive clinical course. MBC is commonly triple negative (TN), although hormone receptor (HR) positive and ...human epidermal growth receptor 2 (HER2) positive cases do occur. Previous studies have reported similar outcomes for MBC with regard to HR status. Less is known about outcomes for HER2 positive MBC.
Materials and Methods
Surveillance, Epidemiology, and End Results Program data were used to identify women diagnosed 2010–2014 with MBC or invasive ductal carcinoma (IDC). Kaplan‐Meier curves estimated overall survival (OS) and multivariate Cox models were fitted. For survival analyses, only first cancers were included, and 2014 diagnoses were excluded to allow for sufficient follow‐up.
Results
Our MBC sample included 1,516 women. Relative to women with IDC, women with MBC were more likely to be older (63 vs. 61 years), black (16.0% vs. 11.1%), and present with stage III disease (15.6% vs. 10.8%). HER2 positive and HER2 negative/HR positive MBC tumors represented 5.2% and 23.0% of cases. For MBC overall, 3‐year OS was greatest for women with HER2 positive MBC (91.8%), relative to women with TN (75.4%) and HER2 negative/HR positive MBC (77.1%). This difference was more pronounced for stage III MBC, for which 3‐year OS was 92.9%, 47.1%, and 42.2% for women with HER2 positive, TN, and HER2 negative/HR positive MBC, respectively. A multivariate Cox model of MBC demonstrated that HER2 positive tumors (relative to TN) were associated with improved survival (hazard ratio = 0.32, 95% confidence interval CI 0.13–0.79). In a second Cox model of exclusively HER2 positive tumors, OS did not differ between MBC and IDC disease subtypes (hazard ratio = 1.16, 95% CI 0.48–2.81).
Conclusion
In this contemporary, population‐based study of women with MBC, HER2 but not HR status was associated with improved survival. Survival was similar between HER2 positive MBC and HER2 positive IDC. This suggests HER2 positive MBC is responsive to HER2‐directed therapy, a finding that may offer insights for additional therapeutic approaches to MBC.
Implications for Practice
This population‐based study reports recent outcomes, by receptor status, for women with metaplastic breast cancer. Survival in metaplastic breast cancer is not impacted by hormone receptor status. To the authors' knowledge, this is the first report indicating that women with human epidermal growth receptor 2 (HER2) positive metaplastic breast cancer have survival superior to women with HER2 negative metaplastic breast cancer and survival similar to women with HER2 positive invasive ductal carcinoma. This information can be used for counseling patients diagnosed with metaplastic breast cancer. Further understanding of HER2 positive metaplastic breast cancer could offer insights for the development of therapeutic approaches to metaplastic breast cancer more broadly.
摘要
背景。化生性乳腺癌 (MBC) 是一种以侵袭性临床病程为特征的罕见疾病亚型。MBC 通常呈三阴性 (TN), 但会发生激素受体 (HR) 阳性和人类表皮生长受体 2 (HER2) 阳性病例。既往研究已报告了 MBC 在 HR 状态方面的相似预后。对 HER2 阳性 MBC 的预后知之较少。
材料和方法。使用监测、流行病学和最终结果项目数据识别在 2010 至 2014 年期间诊断出 MBC 或浸润性导管癌 (IDC) 的女性。采用 Kaplan‐Meier 曲线估算总生存率 (OS), 并拟合多变量 Cox 模型。对于生存率分析, 仅将先发癌症包括在内, 并排除了 2014 年的诊断以便进行充分随访。
结果。我们的 MBC 样本包括 1 516 名女性。与 IDC 女性相比, MBC 女性更可能如下所述：年龄较大（63 岁 vs. 61 岁）、黑色人种 (16.0% vs. 11.1%) 以及患有 III 期疾病 (15.6% vs. 10.8%)。HER2 阳性和 HER2 阴性/HR 阳性 MBC 肿瘤占病例的 5.2% 和 23.0%。对于 MBC 总体, 相对于 TN (75.4%) 和 HER2 阴性/HR 阳性 MBC (77.1%) 女性, HER2 阳性 MBC 女性的 3 年 OS 最高 (91.8%)。对于 III 期 MBC, 此差异更为明显, 其中 HER2 阳性、TN 以及 HER2 阴性/HR 阳性 MBC 女性的 3 年 OS 分别为 92.9%、47.1% 和 42.2%。MBC 的多变量 Cox 模型表明, HER2 阳性肿瘤（相对于 TN）与生存率改善有关风险比=0.32, 95% 置信区间（CI）0.13‐0.79。在另一个仅针对 HER2 阳性肿瘤的 Cox 模型中, OS 在 MBC 与 IDC 疾病亚型之间无差异（风险比=1.16, 95% CI 0.48‐2.81）。
结论。在 MBC 女性的本项同期人群研究中, HER2 状态（而非 HR 状态）与生存率改善有关。HER2 阳性 MBC 与 HER2 阳性 IDC 的生存率相似。这表明 HER2 阳性 MBC 对 HER2 导向治疗有反应, 这一发现可为其他 MBC 治疗方法提供见解。
对临床实践的启示：本项人群研究按受体状态报告了化生性乳腺癌女性的近期预后。化生性乳腺癌的生存率不受激素受体状态的影响。据作者所知, 这是第一份指出人类表皮生长受体 2 (HER2) 阳性化生性乳腺癌女性的生存率高于 HER2 阴性化生性乳腺癌女性, 而与 HER2 阳性浸润性导管癌女性生存率相似的报告。这些信息可用于为诊断出化生性乳腺癌的患者提供建议。对 HER2 阳性化生性乳腺癌的进一步了解可更为广泛地为化生性乳腺癌的治疗方法开发提供见解
Metaplastic breast cancer (MBC) is a rare subtype of breast cancer that is generally associated with poor outcomes. This article reports outcomes by receptor status for a large group of women with metaplastic breast cancer.
Accredited zoological facilities are committed to fully understanding the behavioral, mental, and physical needs of each species to continuously improve the welfare of the animals under their ...professional care and detect when welfare has diminished. In order to accomplish this goal, internally consistent and externally valid indicators of animal welfare are necessary to advance our understanding of the current welfare status of individual animals. Historically, efforts have focused on monitoring visible or observable signs of poor health or problem behavior, but lack of signs or problems does not necessarily demonstrate that an individual animal is thriving. The current study examined fecal hormone metabolite levels and behavior for two species of bottlenose dolphins (Tursiops truncatus and Tursiops aduncus) from 25 different accredited zoological facilities. At the time of the study, all facilities were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. This was part of the multi-institutional study 'Towards understanding of the welfare of cetaceans in zoos and aquariums" commonly referred to as the Cetacean Welfare Study. Behavioral diversity was calculated using the Shannon Diversity Index on species-appropriate behavioral events. Behavioral diversity was compared to the fecal metabolites of cortisol, aldosterone, and the ratio of cortisol to dehydroepiandrosterone (DHEA) as well as the stereotypic behavior of route tracing. Similar to previous studies on other species, there was a significant inverse relationship between behavioral diversity and both fecal cortisol metabolites and route tracing. Additionally, a significant inverse relationship also exists between behavioral diversity and the ratio of fecal cortisol to DHEA metabolites. Behavioral diversity and fecal aldosterone metabolites were not associated. Additional research is still needed to validate behavioral diversity as an indicator of positive animal welfare for bottlenose dolphins and across species. However, based on current results, facilities could utilize behavioral diversity combined with other measures of welfare to more comprehensively evaluate the welfare of bottlenose dolphins.
Cetaceans are long-lived, social species that are valued as ambassadors inspiring the public to engage in conservation action. Under professional care, they are critical partners with the scientific ...community to understanding the biology, behavior, physiology, health, and welfare requirements of this taxonomic group. The Cetacean Welfare Study was a highly collaborative research effort among zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and/or the Association of Zoos & Aquariums that provided important empirical and comparative information on the care and management of cetaceans. The goal was to identify factors that were related to the welfare of bottlenose dolphins and to develop reference intervals and values for common and novel indicators of health and welfare for common bottlenose dolphins (Tursiops truncatus), Indo-Pacific bottlenose dolphins (Tursiops aduncus), beluga whales (Delphinapterus leucas), and Pacific white-sided dolphins (Lagenorhynchus obliquidens). Data were collected from cetaceans at 43 accredited zoos and aquariums in seven countries in 2018 and 2019. This overview presents a summary of findings from the initial research articles that resulted from the study titled "Towards understanding the welfare of cetaceans in zoos and aquariums." With multiple related objectives, animal-based metrics were used to advance frameworks of clinical care and target key conditions that were associated with good welfare of cetaceans in zoo and aquarium environments. As a result of this collaboration, species-specific reference intervals and values for blood variables and fecal hormone metabolites were developed and are freely available in an iOS application called ZooPhysioTrak. The results suggested that environmental enrichment programs and social management factors were more strongly related to behaviors likely indicative of positive welfare than habitat characteristics for common and Indo-Pacific bottlenose dolphins. These findings can be widely applied to optimize care and future science-based welfare practice.
Accredited zoos and aquariums continually strive to ensure high levels of animal welfare for the animals under their professional care. Best management practices include conducting research to better ...understand factors that lead to optimal welfare and then turning findings into practice. The current study is part of the larger Cetacean Welfare Study or more formally, "Towards understanding the welfare of cetaceans in zoos and aquariums." Facilities participating in the study were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. Animal management factors and habitat characteristics were examined in relation to two potential indicators of welfare for common (Tursiops truncatus) and Indo-Pacific (Tursiops aduncus) bottlenose dolphins. Specifically, we examined environmental enrichment, animal training, and habitat characteristics that were significantly related to behavioral diversity and route tracing, a form of stereotypic behavior. Behavior was recorded from 47 animals at 25 facilities around the world. Overall, the rate of route tracing behavior observed during the study was very low and few animal management factors or habitat characteristics were found to be related to this behavior. One factor, enrichment diversity, had a significant positive relationship with route tracing and an inverse relationship with behavioral diversity. This finding may be a product of a response mounted by animal care specialists to the behavior as opposed to a cause. Animals that engaged in this behavior were likely provided more diverse enrichment in attempts to ameliorate the stereotypic behavior. However, multiple factors were found to significantly relate to behavioral diversity, a potential positive indicator of welfare for bottlenose dolphins. Dolphins that were trained on a predictable schedule had higher behavioral diversity than those on a semi-predictable schedule. There was a positive significant relationship between behavioral diversity and the number of habitats to which an animal had access, and a significant inverse relationship with the maximum depth of the habitat. Finally, animals that were split into groups and reunited or rotated between subgroups had higher behavioral diversity than animals managed in the same group. Information gained from the current study suggested that animal management techniques may be more important in ensuring good welfare for bottlenose dolphins than focusing on habitat size.
As the animal welfare community strives to empirically assess how care and management practices can help maintain or even enhance welfare, the development of tools for non-invasively measuring ...physiological biomarkers is essential. Of the suite of physiological biomarkers, Immunoglobulin A (IgA), particularly the secretory form (Secretory IgA or SIgA), is at the forefront because of its crucial role in mucosal immunity and links to physical health, stress, and overall psychological well-being. While interpretation of changes in SIgA concentrations on short time scales is complex, long-term SIgA patterns are consistent: conditions that create chronic stress lead to suppression of SIgA. In contrast, when welfare is enhanced, SIgA is predicted to stabilize at higher concentrations. In this review, we examine how SIgA concentrations are reflective of both physiological stress and immune function. We then review the literature associating SIgA concentrations with various metrics of animal welfare and provide detailed methodological considerations for SIgA monitoring. Overall, our aim is to provide an in-depth discussion regarding the value of SIgA as physiological biomarker to studies aiming to understand the links between stress and immunity.
•Secretory Immunoglobulin A (SIgA) plays a crucial role in mucosal immunity.•SIgA monitoring provides a non-invasive means to assess stress-immune interactions.•Animal welfare studies can provide context for observed SIgA patterns.•SIgA sampling schemes should account for species characteristics and sample type.•SIgA can help shift animal welfare research towards focusing on positive outcomes.
In recent decades, animal welfare science has evolved to utilize a multidisciplinary approach to assess the welfare of animals in accredited zoos and aquariums. Science-based animal welfare ...assessments have become an essential component of management programs and widespread application is expected by animal care professionals. Management practices for bottlenose dolphins in accredited facilities incorporate several programs that potentially impact animal welfare including environmental enrichment and animal training. Additionally, habitat characteristics, such as the dimensions of the habitat, have been proposed to affect welfare. While accredited facilities are required to meet high standards of care, habitat characteristics and management practices are not standardized across locations. Knowledge and subsequent application of these practices and habitat characteristics can enhance our understanding of factors associated with positive welfare. As part of a larger study of dolphin welfare titled "Towards understanding the welfare of cetaceans in zoos and aquariums" (colloquially called the Cetacean Welfare Study), survey data were collected from 86 bottlenose dolphins in 40 habitats at 38 facilities in seven countries. The major aims of this paper are to provide general descriptive information regarding dolphin management in accredited zoos and aquariums and to provide supplemental context to the other research published from the Cetacean Welfare Study data set. This paper provides a review of current habitat characteristics and management practices at those 38 accredited zoos and aquariums. These data enabled the identification and quantification of how cetacean management practices differed between participating facilities accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Variables were selected based on their potential association with welfare including the physical habitat, environmental enrichment, and training programs. The variables were also used for subsequent research in this collection of related papers to investigate important connections between potential indicators of welfare and habitat characteristics, environmental enrichment, and training programs.
This study reports comprehensive clinical pathology data for hematology, serum, and plasma biochemistry reference intervals for 174 apparently healthy common bottlenose dolphins (
Tursiops truncatus
...) and reference values for 27 Indo-Pacific bottlenose dolphins (
Tursiops aduncus
), 13 beluga whales (
Delphinapterus leucas
), and 6 Pacific white-sided dolphins (
Lagenorhynchus obliquidens
) in zoos and aquariums accredited by the Alliance for Marine Mammal Parks and Aquariums and the Association of Zoos & Aquariums. Blood samples were collected as part of a larger study titled “Towards understanding the welfare of cetaceans in zoos and aquariums” (colloquially called the Cetacean Welfare Study). Two blood samples were collected following a standardized protocol, and two veterinarian examinations were conducted approximately six months apart between July to November 2018 and January to April 2019. Least square means, standard deviations, and 95% confidence intervals were calculated for hematology, serum, and plasma biochemical variables. Comparisons by age, gender, and month revealed statistically significant differences (
p
< 0.01) for several variables. Reference intervals and values were generated for samples tested at two laboratories for up to 56 hematologic, serum, and plasma biochemical variables. To apply these data, ZooPhysioTrak, an iOS mobile software application, was developed to provide a new resource for cetacean management. ZooPhysioTrak provides species-specific reference intervals and values based on user inputs of individual demographic and sample information. These data provide a baseline from which to compare hematological, serum, and plasma biochemical values in cetaceans in zoos and aquariums.
Bottlenose dolphins are a behaviorally complex, social species that display a variety of social behaviors. Because of this, it is important for zoological facilities to strive to ensure animals ...display species-appropriate levels of social behavior. The current study is part of the multi-institutional study entitled "Towards understanding the welfare of cetaceans in zoos and aquariums" commonly referred to as the Cetacean Welfare Study. All participating facilities were accredited by the Alliance of Marine Mammal Parks and Aquariums and/or the Association of Zoos and Aquariums. Behavioral data were collected on 47 bottlenose dolphins representing two subspecies, Tursiops truncatus and Tursiops aduncus, at 25 facilities. The social behaviors of group related activity (group active) as well as interacting with conspecifics (interact with conspecific) were examined for their relationships to both animal management factors and habitat characteristics. The behavioral state of group active and the rate of interact with conspecific were both positively related to the frequency of receiving new forms of environmental enrichment. Both were inversely related to the random scheduling of environmental enrichment. Additional results suggested interact with conspecific was inversely related with daytime spatial experience and that males displayed group active more than females. Overall, the results suggested that animal management techniques such as the type and timing of enrichment may be more important to enhance social behavior than habitat characteristics or the size of the habitat. Information gained from this study can help facilities with bottlenose dolphins manage their enrichment programs in relation to social behaviors.
Resting behaviors are an essential component of animal welfare but have received little attention in zoological research. African savanna elephant (Loxodonta africana) and Asian elephant (Elephas ...maximus) rest includes recumbent postures, but no large-scale investigation of African and Asian zoo elephant recumbence has been previously conducted. We used anklets equipped with accelerometers to measure recumbence in 72 adult female African (n = 44) and Asian (n = 28) elephants housed in 40 North American zoos. We collected 344 days of data and determined associations between recumbence and social, housing, management, and demographic factors. African elephants were recumbent less (2.1 hours/day, S.D. = 1.1) than Asian elephants (3.2 hours/day, S.D. = 1.5; P < 0.001). Nearly one-third of elephants were non-recumbent on at least one night, suggesting this is a common behavior. Multi-variable regression models for each species showed that substrate, space, and social variables had the strongest associations with recumbence. In the African model, elephants who spent any amount of time housed on all-hard substrate were recumbent 0.6 hours less per day than those who were never on all-hard substrate, and elephants who experienced an additional acre of outdoor space at night increased their recumbence by 0.48 hours per day. In the Asian model, elephants who spent any amount of time housed on all-soft substrate were recumbent 1.1 hours more per day more than those who were never on all-soft substrate, and elephants who spent any amount of time housed alone were recumbent 0.77 hours more per day than elephants who were never housed alone. Our results draw attention to the significant interspecific difference in the amount of recumbent rest and in the factors affecting recumbence; however, in both species, the influence of flooring substrate is notably important to recumbent rest, and by extension, zoo elephant welfare.
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