Introduction: Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC.Methods: One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk  2; cohort 1; n ¼ 4); Rova-T induction (0.3 mg/kg, q6 wk  2) followed by CE every 21 days (q21)  4 (cohort 2; n ¼ 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk  2) overlapping with CE q21  4 (cohort 3; n ¼ 14); and Rova-T maintenance (0.3 mg/kg, q6 wk  2) after CE q21  4 (cohort 4; n ¼ 3).Results: A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had

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The measurement of faecal glucocorticoid metabolites is used as a non-invasive technique to study stress in animal populations. They have been used most widely in mammals, and mammalian studies have also treated issues such as sample stability and storage methods. In birds, faecal corticosterone metabolite (CM) assays have been validated for a small number of species, and adequate storage under field conditions has not been addressed explicitly in previous studies. Furthermore, while it is well-established that baseline plasma corticosterone levels in birds rise with declining body condition, no study so far investigated if this relationship is also reflected in faecal samples. We here present data of a field study in wild Upland geese Chloephaga picta leucoptera on the Falkland Islands, testing different storage methods and investigating the relationship of faecal CM concentrations to body condition and reproductive parameters. We found that faecal CM measures are significantly repeatable within individuals, higher in individuals with lower body condition in both male and female wild Upland geese and higher in later breeding females with smaller broods. These results suggest that measuring faecal CM values may be a valuable non-invasive tool to monitor the relative condition or health of individuals and populations, especially in areas where there still is intense hunting practice.

Glucocorticoid (GC) hormones rise in response to stressors, including natural events including weather or predator presence, and human activities, such as hunting, scientiWc research or recreational visits. However, because blood sampling itself causes stress and is dangerous or even impossible in some wildlife species, feedback-free methods for GC determination are needed to assess stress in these animals. Faecal GC analyses have thus gained interest. Here, we validate a non-invasive method to estimate the physiological stress in the Upland goose Chloephaga picta. An adrenocorticotropin hormone (ACTH) challenge was conducted in captive adults (female and male), and droppings were collected before, during and after the experiment. Corticosterone metabolite (CM) secretion in response to the ACTH challenge was measured with several enzyme immunoassays (EIA) to Wnd the most appropriate test. We used CM levels during the periods before and after the experiment as control data. An EIA for 11-oxoetiocholanolone achieved the highest response to the ACTH challenge and also reXected a stress response to unfamiliar environment. Furthermore, CM concentrations of dry samples were highly correlated with the corresponding non-dried (frozen) samples. The data suggest that this method is appropriate to measure the stress in Upland geese, and that samples can be stored either frozen or dry form.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium’s possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response — defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10−12, R2 = 1.9%) and continuous (P = 6.4 × 10−9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22–5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10−4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.