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"Campbell, Mary"
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The secret of the mansion
Thirteen-year-old Trixie Belden and her friends search for hidden treasure in a mysterious mansion owned by an old miser.
Book
Enfortumab Vedotin in Previously Treated Advanced Urothelial Carcinoma
Patients who had had a relapse after receiving platinum-containing chemotherapy and a PD-1 or PD-L1 immune checkpoint inhibitor were assigned to receive enfortumab vedotin or one of three chemotherapy agents chosen by their doctor. Enfortumab vedotin prolonged progression-free and overall survival.
Journal Article
Enfortumab vedotin after PD-1 or PD-L1 inhibitors in cisplatin-ineligible patients with advanced urothelial carcinoma (EV‑201): a multicentre, single-arm, phase 2 trial
Locally advanced or metastatic urothelial carcinoma is generally incurable and has scarce treatment options, especially for cisplatin-ineligible patients previously treated with PD-1 or PD-L1 therapy. Enfortumab vedotin is an antibody–drug conjugate directed at Nectin-4, a protein highly expressed in urothelial carcinoma. We aimed to evaluate the efficacy and safety of enfortumab vedotin in the post-immunotherapy setting in cisplatin-ineligible patients.
EV-201 is a multicentre, single-arm, phase 2 study of enfortumab vedotin in patients with locally advanced or metastatic urothelial carcinoma previously treated with PD-1 or PD-L1 inhibitors. Cohort 2 included adults (aged ≥18 years) with an Eastern Cooperative Oncology Group performance status score of 2 or less who were considered ineligible for cisplatin at enrolment and who had not received platinum-containing chemotherapy in the locally advanced or metastatic setting. Enfortumab vedotin was given intravenously at a dose of 1·25 mg/kg on days 1, 8, and 15 of every 28-day cycle. The primary endpoint was confirmed objective response rate per Response Evaluation Criteria in Solid Tumours version 1.1 assessed by blinded independent central review. Efficacy and safety were analysed in all patients who received at least one dose of enfortumab vedotin. EV-201 is an ongoing study and the primary analysis is complete. This study is registered with Clinicaltrials.gov, NCT03219333.
Between Oct 8, 2017, and Feb 11, 2020, 91 patients were enrolled at 40 sites globally, of whom 89 received treatment. Median follow-up was 13·4 months (IQR 11·3–18·9). At data cutoff (Sept 8, 2020), the confirmed objective response rate was 52% (46 of 89 patients; 95% CI 41–62), with 18 (20%) of 89 patients achieving a complete response and 28 (31%) achieving a partial response. 49 (55%) of 89 patients had grade 3 or worse treatment-related adverse events. The most common grade 3 or 4 treatment-related adverse events were neutropenia (eight [9%] patients), maculopapular rash (seven [8%] patients), and fatigue (six [7%] patients). Treatment-related serious adverse events occurred in 15 (17%) patients. Three (3%) patients died due to acute kidney injury, metabolic acidosis, and multiple organ dysfunction syndrome (one [1%] each) within 30 days of first dose and these deaths were considered by the investigator to be related to treatment; a fourth death from pneumonitis occurred more than 30 days after the last dose and was also considered to be related to treatment.
Treatment with enfortumab vedotin was tolerable and confirmed responses were seen in 52% of cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma who were previously treated with PD-1 or PD-L1 inhibitors. These patients have few treatment options, and enfortumab vedotin could be a promising new therapy for a patient population with a high unmet need.
Astellas Pharma Global Development and Seagen.
Journal Article
The therapeutic efficacy of azithromycin and nitazoxanide in the acute pig model of Cryptosporidium hominis
Recent reports highlighting the global significance of cryptosporidiosis among children, have renewed efforts to develop control measures. We have optimized the gnotobiotic piglet model of acute diarrhea to evaluate azithromycin (AZR), nitazoxanide (NTZ), or treatment with both against Cryptosporidium hominis, the species responsible for most human cases. Piglets, animals reproducibly clinically susceptible to C. hominis, when inoculated with 106 oocysts, developed acute diarrhea with oocyst excretion in feces within 3 days. Ten day-treatment with recommended doses for children, commencing at onset of diarrhea, showed that treatment with AZR or NTZ relieved symptoms early in the treatment compared with untreated animals. Piglets treated with AZR exhibited no reduction of oocyst excretion whereas treatment with NTZ significantly reduced oocyst shedding early, increasing however after 5 days. While treatment with AZR+NTZ led to considerable symptomatic improvement, it had a modest effect on reducing mucosal injury, and did not completely eliminate oocyst excretion. Doubling the dose of AZR and/or NTZ did not improve the clinical outcome, confirming clinical observations that NTZ is only partially effective in reducing duration of diarrhea in children. This investigation confirms the gnotobiotic piglet as a useful tool for drug evaluation for the treatment of cryptosporidiosis in children.
Journal Article
The Implications of Racial Misclassification by Observers
We hypothesize that individuals who self-identify with one racial group but are routinely perceived by observers as \"looking like\" another racial group may experience negative outcomes associated with this stressful situation. Since American Indians experience very high rates of misclassification, we use them as our case in point. Drawing from the National Longitudinal Survey of Adolescent Health, our analyses compare young American Indian adults who are perceived as another race by an observer to those who are correctly classified, using several indicators of psychological distress: depression, suicidal thoughts, use of psychological counseling services, suicide attempts, and fatalism. We also investigate differences in racial attitudes and behaviors, such as belonging to an ethnic solidarity organization or believing it is important to have a committed relationship with someone of the same race. The evidence suggests that, on the whole, misclassified American Indians have higher rates of psychological distress. We conclude by discussing our findings and their wider implications, especially in the context of an increasingly heterogeneous and multiracial society.
Journal Article
Clinical and microbiologic efficacy of the piperazine-based drug lead MMV665917 in the dairy calf cryptosporidiosis model
Cryptosporidiosis causes life-threatening diarrhea in infants, but the best available treatment is only modestly efficacious. Rodents infected with relevant Cryptosporidium species do not develop diarrhea, which complicates drug development. Cryptosporidium parvum infection of dairy calves, however, causes an illness like that seen in infants. Here, the clinical and microbiologic anti-Cryptosporidium efficacy of the piperazine-based compound MMV665917 was demonstrated in neonatal calves. Oral administration of MMV665917 (22 mg/kg once daily) was begun two days after the onset of severe diarrhea and continued for seven days. Treatment resulted in prompt resolution of diarrhea, and reduced total fecal oocyst shedding by ~94%. MMV665917 was useful for treatment, rather than just prophylaxis, since it was safe and effective when administered well after the onset of diarrhea. Furthermore, even though all animals received intensive supportive care, there was a strong trend towards improved secondary health outcomes, including general health, appetite, and dehydration measures amongst treated animals. These data establish MMV665917 as an outstanding lead compound for Cryptosporidium drug development.
Journal Article
Becoming a Citizen in the Age of Trump: Citizenship as Social Rights for Latines in Texas
In the anti-immigrant national context of the first Trump administration, what motivated Latine immigrants in Texas to pursue naturalization? Based on 31 Spanish and English semi-structured interviews conducted during 2017–2019, we examine how lawful permanent residents’ (LPRs’) perceptions of contemporary immigration policy and their social rights affect their motivations to naturalize. Surprisingly, we find that although fear of deportation was an extremely common motivation, it was rarely the residents’ primary motivation. When asked why they wanted to naturalize, our respondents expressed four primary motivations grounded in their claims for social rights: proactive (gain the right to vote, benefit the group), pragmatic (expedite family reunification, access better jobs, benefit the individual), defensive (protect against deportation), and emotional (formalize a sense of belonging). Although 60 percent of interview subjects mentioned some defensive motivations, citing the current national and state political climate as hostile to immigrants, it was the least common primary motivation for naturalization; that is, they named another motivation first as their most important reason for naturalizing. The need to naturalize to protect their social rights in a shifting political context is a strong subtext to subjects’ narratives about why they choose to become citizens. Defensive motivations undergird all other motivations, but the national hostile climate is moderated by relatively positive local interactions with law enforcement and the larger community.
Journal Article
Ethnoracial Transformations? Linking Administrative Data to Explain Changes in Identification
We link the 2010 Census microdata to the 2010–2020 American Community Surveys and Social Security Administration records to test patterns of ethnoracial identification change across this decade. After documenting substantial ethnoracial stability in some categories, we find substantial flows between many racial categories, more movement into Hispanic identification than movement out of the Hispanic category, foreign-born Hispanic multiracial respondents are 14 percentage points (40 percent) more likely to identify later as Hispanic White than their native-born counterparts, and foreign-born non-Hispanic multiracial respondents are 19 percentage points (90 percent) less likely to identify later as non-Hispanic White than native-born. Higher income and education are both associated with less racial identification change. Change also varies by household type.
Journal Article
Do White People See Variation in Black Skin Tones? Reexamining a Purported Outgroup Homogeneity Effect
Previous research has reported that white survey interviewers remember black respondents’ skin tones in a much narrower range than recollections by black interviewers. This finding has been used to suggest that, in line with the one-drop rule, whites do not perceive meaningful differences between light- and dark-skinned black people. The authors reanalyze evidence thought to demonstrate relative homogeneity in white interviewers’ evaluation of black skin tones. In contrast to previous studies, this examination of several data sources reveals significant heterogeneity in the ratings assigned by white interviewers when taking into account the ordinal nature of the skin tone measures. The results are consistent with theories of social cognition that emphasize that beyond formal racial classification schemes, skin tone is used to implicitly categorize others along a continuum of “blackness.” The findings also align with research suggesting that rather than nullifying within-race skin tone, increases in white racism intensify white colorism.
Journal Article