Place of Light' : what cultural villages can tell us about 'culture', 'ethnicity' and tourism in post-apartheid South Africa

Includes abstract. Includes bibliographical references (leaves 99-106).The 'new' South Africa is abuzz with keywords. There is much talk within academic discourse and beyond of 'ethnicity', 'culture' and the 'rainbow nation' among others. They are a national obsession at this crucial time when South Africa is still struggling to negotiate its identity. The usage of these words is rapidly evolving and today they their use extends far past their original meanings. However, their use has persisted and has done so largely unchallenged. This has meant that the words are now highly problematic. In order to critically examine these concepts, I use the space of the cultural village as an analytical tool. Cultural villages have faced criticism in recent years - accusations that they 'stage' their 'authenticity', and freeze cultures in order to package them for international consumption. While this paper does devote space to these criticisms, it focuses its attention on 'what cultural villages can tell us about the nature of post-apartheid South Africa', specifically about the keywords, 'culture' and 'ethnicity'. Research is based at Lesedi Cultural Village in the North West Province. I use the landscape of the surrounding area and the signs and symbols in the village itself as entry points to map and frame my discussions. The Cradle ofHumankind where Lesedi is situated is saturated with an evolutionary narrative that visitors to Lesedi will bring with them to the site. Evolutionary notions of the 'primitive' have been re-appropriated by the tourist industry to draw visitors back 'home' to Africa, while South Africa owes much of its difficult history to the same evolutionary narratives. Through ethnographic fieldwork, the space of the cultural village is deconstructed to see what it can tell us about 'culture' and 'ethnicity' in the country beyond its fences. I interrogate the concept of 'culture', by closely analyzing the meaning of a proverb on Lesedi's shebeen wall which reads, 'a man without culture is like a zebra without stripes'. It transpires that the humble zebra can tell us a great deal about the nature of 'culture' in South Africa and the current debates which surround the use of the word

Law versus Action: How Five Cape Town Organizations Are Combating High Rates of Sexual Assault and the Failure of Progressive Sexual Offences Legislation

This Independent Study Project (ISP) seeks to understand the work various Cape Town organizations are doing to help survivors of sexual assault gain access to justice. Previous research finds that social norms defining masculinity as well as rape myths and stereotypes lead to the high levels of gender-based violence (GBV) in South Africa. This research led to my hypothesis that organizations fighting GBV would target these norms to help survivors access the justice system that so frequently ignores them. Eight organizations were contacted requesting an interview to discuss their work and two agreed to participate. Participants were asked to discuss the goals, successes, and failures of their organizations work. Three additional organizations are included in this report using information from annual reports published on their websites. From the information gleaned from these interviews and annual reports, this ISP finds that while targeting social norms is an objective of some organizations, many directly support survivors in court and other post-trauma processes and still others research and analyze policy and legislation to determine how the law can be changed to support survivors. This report concludes that while progressive legislation is in place, there is still policy that must be changed for survivors to truly be able to access justice. Thus, organizations focus on law as well as social norms within communities to create real change for survivors. This report suggests future research investigating intersectional approaches to organization work to understand how they address the unequal realities of rape survivors

Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial

Antitumor activity; Monotherapy; Solid tumorsActividad antitumoral; Monoterapia; Tumores sólidosActivitat antitumoral; Monoteràpia; Tumors sòlidsImportance Mismatch repair deficiency (dMMR) occurs in various cancers, and these tumors are attractive candidates for anti–programmed cell death 1 therapies, such as dostarlimab, a recently approved immune checkpoint inhibitor. Objective To assess the antitumor activity and safety of dostarlimab in patients with advanced or recurrent dMMR solid tumors. Design, Setting, And Participants The GARNET trial was a phase 1, open-label, single-group, multicenter study that began enrolling May 8, 2017. Participants had advanced or recurrent dMMR and microsatellite instability–high (MSI-H) or polymerase epsilon (POLE)–altered solid tumors. The data cut for this interim analysis was from November 1, 2021, with median follow-up of 27.7 months. Interventions Patients received 500 mg of dostarlimab intravenously every 3 weeks for 4 doses, then 1000 mg every 6 weeks until disease progression, discontinuation, or withdrawal. Main Outcomes and Measures The primary objective was to evaluate objective response rate and duration of response in patients with dMMR solid tumors by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1. Results The efficacy population included 327 patients (median [range] age, 63 [24-85] years; 235 [71.9%] female; 7 [2.1%] Asian, 6 [1.8%] Black, and 206 [63.0%] White patients), with 141 patients (43.1%) with dMMR endometrial cancer, 105 patients (32.1%) with dMMR colorectal cancer, and 81 patients (24.8%) with other dMMR tumor types. All patients had at least 1 previous line of therapy. Objective response rate assessed per blinded independent central review for dMMR solid tumors was 44.0% (95% CI, 38.6% to 49.6%). Median duration of response was not reached (range, ≥1.18 to ≥47.21 months); 72.2% of responders (104 of 144) had a response lasting 12 or more months. Median progression-free survival was 6.9 months (95% CI, 4.2 to 13.6 months); probability of progression-free survival at 24 months was 40.6% (95% CI, 35.0% to 46.1%). Median overall survival was not reached (95% CI, 31.6 months to not reached). The most frequent immune-related adverse events were hypothyroidism (25 [6.9%]), alanine aminotransferase increase (21 [5.8%]), and arthralgia (17 [4.7%]). No new safety concerns were identified. Conclusions And Relevance In this nonrandomized controlled trial, dostarlimab was a well-tolerated treatment option with rapid, robust, and durable antitumor activity in patients with diverse dMMR solid tumors. These findings suggest that dostarlimab provides meaningful long-term benefit in a population with high unmet need. Trial Registration ClinicalTrials.gov Identifier: NCT02715284This study was funded by GSK

A plain language summary of results from the GARNET study of dostarlimab in patients with endometrial cancer

Endometrial cancer; Gynecologic cancer; ImmunotherapyCàncer d'endometri; Càncer ginecològic; ImmunoteràpiaCáncer de endometrio; Cáncer ginecológico; InmunoterapiaWhat is this summary about? Dostarlimab, also known by the brand name JEMPERLI, is a medicine that can be used to treat certain types of endometrial cancer. GARNET is an ongoing phase 1 clinical study that is testing the safety and side effects of dostarlimab and the best way to administer it to patients. The results presented in this summary are from a time point in the middle of the study. What were the results? The results from the GARNET study published in 2022 showed how well dostarlimab worked for people participating in the study. Dostarlimab was found to reduce the size of tumors in patients with certain types of endometrial cancer. The patients treated with dostarlimab had side effects that could be managed and few severe side effects. What do the results mean? The results of the GARNET study led to dostarlimab being approved to treat patients with certain types of endometrial cancer. For patients with advanced-stage endometrial cancer, or endometrial cancer that has come back after chemotherapy (recurrent), there are few treatment options. The results suggest that dostarlimab may provide long-term benefits for these patients.This study (NCT02715284) was funded by GSK. Trademarks are owned by or licensed to the GSK group of companies. Full author disclosure information can be found in the original article

Safety and antitumor activity of dostarlimab in patients with advanced or recurrent DNA mismatch repair deficient/microsatellite instability-high (dMMR/MSI-H) or proficient/stable (MMRp/MSS) endometrial cancer: interim results from GARNET—a phase I, single-arm study

Immunotherapy; Programmed cell death 1 receptorImmunoteràpia; Receptor de mort cel·lular programada 1Inmunoterapia; Receptor de muerte celular programada 1Background Dostarlimab is a humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. We report interim data from patients with endometrial cancer (EC) participating in a phase I trial of single-agent dostarlimab. Methods GARNET, an ongoing, single-arm, open-label, phase I trial of intravenous dostarlimab in advanced solid tumors, is being undertaken at 123 sites. Two cohorts of patients with EC were recruited: those with dMMR/MSI-H disease (cohort A1) and those with proficient/stable (MMRp/MSS) disease (cohort A2). Patients received dostarlimab 500 mg every 3 weeks for 4 cycles, then dostarlimab 1000 mg every 6 weeks until disease progression. The primary endpoints were objective response rate (ORR) and duration of response (DOR) per RECIST V.1.1, as assessed by blinded independent central review. Results Screening began on April 10, 2017, and 129 and 161 patients with advanced EC were enrolled in cohorts A1 and A2, respectively. The median follow-up duration was 16.3 months (IQR 9.5–22.1) for cohort A1 and 11.5 months (IQR 11.0–25.1) for cohort A2. In cohort A1, ORR was 43.5% (95% CI 34.0% to 53.4%) with 11 complete responses and 36 partial responses. In cohort A2, ORR was 14.1% (95% CI 9.1% to 20.6%) with three complete responses and 19 partial responses. Median DOR was not reached in either cohort. In the combined cohorts, the majority of treatment-related adverse events (TRAEs) were grade 1–2 (75.5%), most commonly fatigue (17.6%), diarrhea (13.8%), and nausea (13.8%). Grade≥3 TRAEs occurred in 16.6% of patients, and 5.5% discontinued dostarlimab because of TRAEs. No deaths were attributable to dostarlimab. Conclusion Dostarlimab demonstrated durable antitumor activity in both dMMR/MSI-H (ORR 43.5%) and MMRp/MSS EC (ORR 14.1%) with a manageable safety profile

The spatial and velocity bias of linear density peaks and proto-haloes in the Lambda cold dark matter cosmology

We use high resolution N-body simulations to investigate the Lagrangian bias of cold dark matter haloes within the LCDM cosmology. Our analysis focuses on "proto-haloes", which we identify in the simulation initial conditions with the subsets of particles belonging to individual redshift-zero haloes. We then calculate the number-density and velocity-divergence fields of proto-haloes and estimate their auto spectral densities. We also measure the corresponding cross spectral densities with the linear matter distribution. We use our results to test a Lagrangian-bias model presented by Desjacques and Sheth which is based on the assumption that haloes form out of local density maxima of a specific height. Our comparison validates the predicted functional form for the scale-dependence of the bias for both the density and velocity fields. We also show that the bias coefficients are accurately predicted for the velocity divergence. On the contrary, the theoretical values for the density bias parameters do not accurately match the numerical results as a function of halo mass. This is likely due to the simplistic assumptions that relate virialized haloes to density peaks of a given height in the model. We also detect appreciable stochasticity for the Lagrangian density bias, even on very large scales. These are not included in the model at leading order but correspond to higher order corrections.Comment: 10 pages, 4 figures. Matches version accepted for publication in MNRA

Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)

Càncer d'ovaris; Biomarcadors tumoralsCáncer de ovarios; Biomarcadores tumoralesOvarian cancer; Tumour biomarkersARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity

Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients

ObjectivePatients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors.Materials/methodsPatients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses.Results261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS.ConclusionIn stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection

Probing star formation across cosmic time with absorption line systems

We present an empirical connection between cold gas in galactic halos and star formation. Using a sample of more than 8,500 MgII absorbers from SDSS quasar spectra, we report the detection of a 15 sigma correlation between the rest equivalent width W0 of MgII absorbers and the associated OII luminosity, an estimator of star formation rate. This correlation has interesting implications: using only observable quantities we show that MgII absorbers trace a substantial fraction of the global OII luminosity density and recover the overall star formation history of the Universe derived from classical emission estimators up to z~2. We then show that the distribution function of MgII rest equivalent widths, dN/dW0 inherits both its shape and amplitude from the OII luminosity function Phi(L). These distributions can be naturally connected, without any free parameter. Our results imply a high covering factor of cold gas around star forming galaxies: C>0.5, favoring outflows as the mechanism responsible for MgII absorption. We then argue that intervening MgII absorbers and blue-shifted MgII absorption seen in the spectra of star forming galaxies are essentially the same systems. These results not only shed light on the nature of MgII absorbers but also provide us with a new probe of star formation, in absorption, i.e. in a way which does not suffer from dust extinction and with a redshift-independent sensitivity. As shown in this analysis, such a tool can be applied in a noise-dominated regime, i.e. using a dataset for which emission lines are not detected in individual objects. This is of particular interest for high redshift studies.Comment: 13 pages, 7 figures, submitted to MNRA

Antitumor activity and safety of the PARP inhibitor rucaparib in patients with high grade ovarian carcinoma and a germline or somatic BRCA1 or BRCA2 mutation: integrated analysis of data from Study 10 and ARIEL2

Objective: An integrated analysis was undertaken to characterize the antitumor activity and safety profile of the oral poly(ADP-ribose) polymerase inhibitor rucaparib in patients with relapsed high-grade ovarian carcinoma (HGOC). Methods: Eligible patients from Study 10 (NCT01482715) and ARIEL2 (NCT01891344) who received a starting dose of oral rucaparib 600 mg twice daily (BID) with or without food were included in these analyses. The integrated efficacy population included patients with HGOC and a deleterious germline or somatic BRCA1 or BRCA2 (BRCA1/2) mutation who received at least two prior chemotherapies and were sensitive, resistant, or refractory to platinum-based chemotherapy. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR) and progression-free survival (PFS). The integrated safety population included patients with HGOC who received at least one dose of rucaparib 600 mg BID, irrespective of BRCA1/2 mutation status and prior treatments. Results: In the efficacy population (n = 106), ORR was 53.8% (95% confidence interval [CI], 43.8–63.5); 8.5% and 45.3% of patients achieved complete and partial responses, respectively. Median DOR was 9.2 months (95% CI, 6.6–11.6). In the safety population (n = 377), the most frequent treatment-emergent adverse events (AEs) were nausea, asthenia/fatigue, vomiting, and anemia/hemoglobin decreased. The most common grade ≥ 3 treatment-emergent AE was anemia/hemoglobin decreased. Treatment-emergent AEs led to treatment interruption, dose reduction, and treatment discontinuation in 58.6%, 45.9%, and 9.8% of patients, respectively. No treatment-related deaths occurred. Conclusions: Rucaparib has antitumor activity in advanced BRCA1/2-mutated HGOC and a manageable safety profile