GpABC: a Julia package for approximate Bayesian computation with Gaussian process emulation

Motivation Approximate Bayesian computation (ABC) is an important framework within which to infer the structure and parameters of a systems biology model. It is especially suitable for biological systems with stochastic and nonlinear dynamics, for which the likelihood functions are intractable. However, the associated computational cost often limits ABC to models that are relatively quick to simulate in practice. Results We here present a Julia package, GpABC, that implements parameter inference and model selection for deterministic or stochastic models using i) standard rejection ABC or ABC-SMC, or ii) ABC with Gaussian process emulation. The latter significantly reduces the computational cost. Availability and Implementation https://github.com/tanhevg/GpABC.jl Supplementary information Supplementary data are available at Bioinformatics online

Women's perceptions of effects of war on intimate partner violence and gender roles in two post-conflict West African Countries: Consequences and unexpected opportunities

Background The aim of this paper is to explore women's perceptions of the causes of intimate partner violence (IPV) in West Africa, and the ways in which they understand these causes to interact with the experiences of war. Methods The study was conducted in two locations in Sierra Leone and two in Liberia, using focus group discussions (N groups =14) and individual interviews (N-=-20). Results Women perceive the causes of IPV to be linked with other difficulties faced by women in these settings, including their financial dependence on men, traditional gender expectations and social changes that took place during and after the wars in those countries. According to respondents, the wars increased the use of violence by some men, as violence became for them a normal way of responding to frustrations and challenges. However, the war also resulted in women becoming economically active, which was said by some to have decreased IPV, as the pressure on men to provide for their families reduced. Economic independence, together with services provided by NGOs, also gave women the option of leaving a violent relationship. Conclusions IPV was found to be a significant problem for women in Sierra Leone and Liberia. The interactions between war experiences and financial and cultural issues are multi-faceted and not uniformly positive or negative.sch_iih8 [12]pub3561pu

Correlation of tumor PD-L1 expression in different tissue types and outcome of PD-1-based immunotherapy in metastatic melanoma – analysis of the DeCOG prospective multicenter cohort study ADOREG/TRIM

Background PD-1-based immune checkpoint inhibition (ICI) is the major backbone of current melanoma therapy. Tumor PD-L1 expression represents one of few biomarkers predicting ICI therapy outcome. The objective of the present study was to systematically investigate whether the type of tumor tissue examined for PD-L1 expression has an impact on the correlation with ICI therapy outcome. Methods Pre-treatment tumor tissue was collected within the prospective DeCOG cohort study ADOREG/TRIM (CA209-578; NCT05750511) between February 2014 and May 2020 from 448 consecutive patients who received PD-1-based ICI for non-resectable metastatic melanoma. The primary study endpoint was best overall response (BOR), secondary endpoints were progression-free (PFS) and overall survival (OS). All endpoints were correlated with tumor PD-L1 expression (quantified with clone 28–8; cutoff ≥5%) and stratified by tissue type. Findings Tumor PD-L1 was determined in 95 primary tumors (PT; 36.8% positivity), 153 skin/subcutaneous (34.0% positivity), 115 lymph node (LN; 50.4% positivity), and 85 organ (40.8% positivity) metastases. Tumor PD-L1 correlated with BOR if determined in LN (OR = 0.319; 95% CI = 0.138–0.762; P = 0.010), but not in skin/subcutaneous metastases (OR = 0.656; 95% CI = 0.311–1.341; P = 0.26). PD-L1 positivity determined on LN metastases was associated with favorable survival (PFS, HR = 0.490; 95% CI = 0.310–0.775; P = 0.002; OS, HR = 0.519; 95% CI = 0.307–0.880; P = 0.014). PD-L1 positivity determined in PT (PFS, HR = 0.757; 95% CI = 0.467–1.226; P = 0.27; OS; HR = 0.528; 95% CI = 0.305–0.913; P = 0.032) was correlated with survival to a lesser extent. No relevant survival differences were detected by PD-L1 determined in skin/subcutaneous metastases (PFS, HR = 0.825; 95% CI = 0.555–1.226; P = 0.35; OS, HR = 1.083; 95% CI = 0.698–1.681; P = 0.72). Interpretation For PD-1-based immunotherapy in melanoma, tumor PD-L1 determined in LN metastases was stronger correlated with therapy outcome than that assessed in PT or organ metastases. PD-L1 determined in skin/subcutaneous metastases showed no outcome correlation and therefore should be used with caution for clinical decision making. Funding Bristol-Myers Squibb (ADOREG/TRIM, NCT05750511); German Research Foundation (DFG; Clinician Scientist Program UMEA); Else Kröner-Fresenius-Stiftung (EKFS; Medical Scientist Academy UMESciA)

Impact of radiotherapy and sequencing of systemic therapy on survival outcomes in melanoma patients with previously untreated brain metastasis: a multicenter DeCOG study on 450 patients from the prospective skin cancer registry ADOREG

BACKGROUND: Despite of various therapeutic strategies, treatment of patients with melanoma brain metastasis (MBM) still is a major challenge. This study aimed at investigating the impact of type and sequence of immune checkpoint blockade (ICB) and targeted therapy (TT), radiotherapy, and surgery on the survival outcome of patients with MBM. METHOD: We assessed data of 450 patients collected within the prospective multicenter real-world skin cancer registry ADOREG who were diagnosed with MBM before start of the first non-adjuvant systemic therapy. Study endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Of 450 MBM patients, 175 (38.9%) received CTLA-4+PD-1 ICB, 161 (35.8%) PD-1 ICB, and 114 (25.3%) BRAF+MEK TT as first-line treatment. Additional to systemic therapy, 67.3% of the patients received radiotherapy (stereotactic radiosurgery (SRS); conventional radiotherapy (CRT)) and 24.4% had surgery of MBM. 199 patients (42.2%) received a second-line systemic therapy. Multivariate Cox regression analysis revealed the application of radiotherapy (HR for SRS: 0.213, 95% CI 0.094 to 0.485, p1 cm: 1.977, 95% CI 1.117 to 3.500, p=0.019), age (HR for age >65 years: 1.802, 95% CI 1.016 to 3.197, p=0.044), and ECOG performance status (HR for ECOG ≥2: HR: 2.615, 95% CI 1.024 to 6.676, p=0.044) as independent prognostic factors of OS on first-line therapy. The type of first-line therapy (ICB vs TT) was not independently prognostic. As second-line therapy BRAF+MEK showed the best survival outcome compared with ICB and other therapies (HR for CTLA-4+PD-1 compared with BRAF+MEK: 13.964, 95% CI 3.6 to 54.4, p<0.001; for PD-1 vs BRAF+MEK: 4.587 95% CI 1.3 to 16.8, p=0.022 for OS). Regarding therapy sequencing, patients treated with ICB as first-line therapy and BRAF+MEK as second-line therapy showed an improved OS (HR for CTLA-4+PD-1 followed by BRAF+MEK: 0.370, 95% CI 0.157 to 0.934, p=0.035; HR for PD-1 followed by BRAF+MEK: 0.290, 95% CI 0.092 to 0.918, p=0.035) compared with patients starting with BRAF+MEK in first-line therapy. There was no significant survival difference when comparing first-line therapy with CTLA-4+PD-1 ICB with PD-1 ICB. CONCLUSIONS: In patients with MBM, the addition of radiotherapy resulted in a favorable OS on systemic therapy. In BRAF-mutated MBM patients, ICB as first-line therapy and BRAF+MEK as second-line therapy were associated with a significantly prolonged OS

Psychological Interventions for Survivors of Intimate Partner Violence in Humanitarian Settings: An Overview of the Evidence and Implementation Considerations

This paper provides an analytical overview of different types of psychological interventions that have demonstrated efficacy in low-income and/or humanitarian settings and points to special considerations that may be needed if used with women who have been subjected to gender-based violence (GBV). This paper reviews diverse therapeutic modalities and contrasts them across several domains, including their conventional use and principles; their documented use and efficacy in humanitarian settings; any special considerations or modifications necessary for GBV-affected clients; and any additional resources or implementation concerns when working in low-income contexts. By examining the evidence base of multiple interventions, we hope to provide clinicians and GBV-prevention advocates with an overview of tools/approaches to provide survivor-centered, trauma-informed responses to GBV survivors. This analysis responds to the growing recognition that gender-based violence, in particular intimate partner violence and sexual violence, is strongly associated with mental health problems, including anxiety, depression, and post-traumatic stress. This is likely to be exacerbated in humanitarian contexts, where people often experience multiple and intersecting traumatic experiences. The need for mental health services in these settings is increasingly recognized, and a growing number of psychological interventions have been shown to be effective when delivered by lay providers and in humanitarian settings

'I don't need an eye for an eye': Women's responses to intimate partner violence in Sierra Leone and Liberia

This paper explores the possibilities for agency in intimate partner violence (IPV) situations from the perspective of women in Sierra Leone and Liberia using focus group discussions (N groups = 14, N participants = 110) and individual interviews (N = 20). Findings identify multiple interrelated factors influencing the decisionmaking of women experiencing IPV. At the individual level, emotional factors and women's knowledge of their rights and options influence their decision-making. At the relational level, the role of neighbours, family and friends is crucial, both for emotional support and practical assistance. At the community level, more formal structures play a role, such as chiefs and women's groups, though their effectiveness varies. At the structural level are barriers to effective responses, including a poorly functioning criminal justice system and a social system in which children often stay with fathers following separation or divorce. Strong cultural beliefs operate to keep women in abusive relationships. We identify implications for prevention and response services and make practice recommendations. Since the desire of most women experiencing IPV was to live in peace with their husbands, interventions should respect women's priorities by focusing more on prevention and interventions to end the violence, rather than solely assisting women to leave violent relationships.sch_iih11pub3966pub1-