A public health approach to modern slavery in the United Kingdom: a codeveloped framework.

OBJECTIVES: Modern slavery is a public health challenge. The objective of this research was to build and refine a public health approach to addressing it. STUDY DESIGN: This was a participatory qualitative study with a proof-of-concept exercise. METHODS: Nine deliberative workshops with 65 people working across the antislavery sector. Thematic analysis of qualitative data. Of the nine workshops, two were proof of concept. These explored and tested the public health framework devised. RESULTS: Participants contributed to the development of a public health framework to modern slavery that included multiple elements across national, local, and service levels. There were six 'C's to national components: policy that was coherent, co-ordinated, consistent, comprehensive, co-operative and compliant with international law. Local components centred on effective local multiagency partnerships and service design and delivery focussed on trauma-informed, flexible, person-centred care. CONCLUSIONS: A public health approach to modern slavery is a promising development in the antislavery field in the United Kingdom and globally. It was well supported by workshop participants and appeared to be operable. Barriers to its implementation exist, however, including the challenge of intersectoral working and an incongruent policy environment.

Incidence and prognostic impact of U2AF1 mutations and other gene alterations in myelodysplastic neoplasms with isolated 20q deletion.

BACKGROUND: In myelodysplastic neoplasms (MDS), the 20q deletion [del(20q)] is a recurrent chromosomal abnormality that it has a high co-occurrence with U2AF1 mutations. Nevertheless, the prognostic impact of U2AF1 in these MDS patients is uncertain and the possible clinical and/or prognostic differences between the mutation type and the mutational burden are also unknown. METHODS: Our study analyzes different molecular variables in 100 MDS patients with isolated del(20q). RESULTS & CONCLUSIONS: We describe the high incidence and negative prognostic impact of U2AF1 mutations and other alterations such as in ASXL1 gene to identify prognostic markers that would benefit patients to receive earlier treatment.

Modern slavery and public health: a rapid evidence assessment and an emergent public health approach.

OBJECTIVES: Modern slavery is a human rights violation and a global public health concern. To date, criminal justice approaches have dominated attempts to address it. Modern slavery has severe consequences for people's mental and physical health, and there is a pressing need to identify and implement effective preventative measures. As such, a public health approach to modern slavery requires elucidation. The objectives of this study were to explore the case for public health involvement in addressing modern slavery and the components of a public health approach and to develop a globally relevant framework for public health action. STUDY DESIGN: A Rapid Evidence Assessment. METHODS: This study is a rapid systematic review of published literature and stakeholder consultation. RESULTS: The accounts of 32 consultees and evidence from 17 papers including reviews, commentaries and primary studies were included in the evidence assessment. A strong ethical rationale for public health engagement in addressing modern slavery was evident. Multilevel and multicomponent interventional strategies were identified across global, national, regional, local and service levels. Although public health could add value to existing approaches, multiple barriers and tensions exist. CONCLUSION: Published literature and stakeholder opinion indicate an emergent public health approach to modern slavery. It involves intervention at multiple levels and is guided by a rights-based, survivor-centred and trauma-informed approach. This synthesis offers an important early step in the construction of a globally relevant public health approach to modern slavery.

Public health practitioners' perspectives of migrant health in an English region.

OBJECTIVES: Migration is a complex and contested topic of public debate. Professionals working in public health must negotiate this politicised complexity, yet few studies examine the perspectives and practices of public health professionals in relation to migrant health. This study seeks to redress this by exploring how migrant health is conceptualised and addressed by public health professionals after a key transitional point in the reorganisation of public health in England and the public vote for the UK to leave the EU. STUDY DESIGN: This is a qualitative in-depth exploratory study. METHODS: Ten interviews and one focus group were conducted with 14 public health professionals working at Public Health England or local authorities in an English region. Recordings were transcribed, and thematic analysis was conducted. RESULTS: Professionals viewed migrant health mainly through a health inequalities lens; migrants were considered vulnerable, and their health was often determined by wider social issues. This influenced public health professionals' perceived ability to affect change. Public health professionals were greatly influenced by the societal, policy and institutional, post-Brexit vote context in England, describing nervousness around addressing migrant health. At an institutional level, public health professionals described a sense that migrant health was not prioritised. It was considered 'too hard' and complex, especially with shrinking resources and highly politicised social narratives. Consequently, migrant health was often not directly addressed in current practice. The gaps identified by public health professionals were as follows: lack of knowledge of health needs and cultural difference; lack of access to appropriate training; lack of cultural diversity within the public health workforce; and concerns about meaningful community engagement. CONCLUSIONS: These findings raise concerns about public health professionals' ability to address the health needs of migrants living in England. The gaps highlighted require further and deeper examination across relevant organisations including the broader public health infrastructure in the UK.

A formative review of physical activity interventions for minority ethnic populations in England.

Background: Physical activity (PA) levels are lower among some UK Black and minority ethnic (BME) groups than the majority White British population and a variety of tailored interventions have emerged. This study documents the characteristics and logic of local adaptations, a vital first step in evaluating such innovations. Methods: An English PA data set was examined to identify and characterize PA programmes focussed on BME populations. Three case studies were conducted, employing documentary analysis and qualitative interviews. Netto et al.'s principles of adapting health promotion interventions for BME populations guided the analysis. Results: Out of 861 PA interventions, 57 focussed on BME populations. These were typically aimed to engage the most inactive groups, improve both health and social outcomes and were largely publically/charitably funded. Tailored approaches matched Netto et al.'s five principles: using community resources for publicity, identifying and addressing barriers, developing sensitive communication strategies, working with values and accommodating cultural identification. Another common principle was identified: building community capacity for sustainability. Conclusions: PA interventions tailored to the needs of BME groups reflect their largely disadvantaged position in society and focus on inactivity. The six principles could be used as a framework for developing, designing and evaluating tailored interventions for BME populations.

The relationship of TP53 R72P polymorphism to disease outcome and TP53 mutation in myelodysplastic syndromes.

Nonsynonymous TP53 exon 4 single-nucleotide polymorphism (SNP), R72P, is linked to cancer and mutagen susceptibility. R72P associations with specific cancer risk, particularly hematological malignancies, have been conflicting. Myelodysplastic syndrome (MDS) with chromosome 5q deletion is characterized by erythroid hypoplasia arising from lineage-specific p53 accumulation resulting from ribosomal insufficiency. We hypothesized that apoptotically diminished R72P C-allele may influence predisposition to del(5q) MDS. Bone marrow and blood DNA was sequenced from 705 MDS cases (333 del(5q), 372 non-del(5q)) and 157 controls. Genotype distribution did not significantly differ between del(5q) cases (12.6% CC, 38.1% CG, 49.2% GG), non-del(5q) cases (9.7% CC, 44.6% CG, 45.7% GG) and controls (7.6% CC, 37.6% CG, 54.8% GG) (P=0.13). Allele frequency did not differ between non-del(5q) and del(5q) cases (P=0.91) but trended towards increased C-allele frequency comparing non-del(5q) (P=0.08) and del(5q) (P=0.10) cases with controls. Median lenalidomide response duration increased proportionate to C-allele dosage in del(5q) patients (2.2 (CC), 1.3 (CG) and 0.89 years (GG)). Furthermore, C-allele homozygosity in del(5q) was associated with prolonged overall and progression-free survival and non-terminal interstitial deletions that excluded 5q34, whereas G-allele homozygozity was associated with inferior outcome and terminal deletions involving 5q34 (P=0.05). These findings comprise the largest MDS R72P SNP analysis.

The degree of neutropenia has a prognostic impact in low risk myelodysplastic syndrome.

The severity of neutropenia in myelodysplastic syndrome (MDS) has not been completely studied. We analyzed the prognostic significance of severe neutropenia (neutrophils count <0.5×10(9)/L) at diagnosis in 1109 patients with de novo MDS and low/intermediate-1 IPSS included in the Spanish MDS Registry. Severe neutropenia was present at diagnosis in 48 of 1109 (4%). Patients with severe neutropenia were most strongly represented within the groups of refractory cytopenia with multilineage dysplasia (40%) and refractory anemia with excess of blast type 1 (29%). Severe neutropenia had negative effects on the low/intermediate-1 risk group. A significant difference in overall survival was observed between patients with severe neutropenia (28 months) and patients with a neutrophil count higher than 0.5×10(9)/L (66 months) (p<0.0001). Also, severe neutropenia predicted a significantly reduced on leukemia-free survival (p<0.0001). In the multivariate analysis, severe neutropenia retained its independent prognostic influence on overall survival [HR: 2.19, 95% CI (1.41-3.10), p<0.0001] and leukemia free survival [HR: 3.51, 95% CI (1.97-6.26), p<0.0001]. The degree of neutropenia should be considered as additional prognostic factor in low/intermediate-1 IPSS MDS.

Impact of adjunct cytogenetic abnormalities for prognostic stratification in patients with myelodysplastic syndrome and deletion 5q.

This cooperative study assessed prognostic factors for overall survival (OS) and risk of transformation to acute myeloid leukemia (AML) in 541 patients with de novo myelodysplastic syndrome (MDS) and deletion 5q. Additional chromosomal abnormalities were strongly related to different patients' characteristics. In multivariate analysis, the most important predictors of both OS and AML transformation risk were number of chromosomal abnormalities (P<0.001 for both outcomes), platelet count (P<0.001 and P=0.001, respectively) and proportion of bone marrow blasts (P<0.001 and P=0.016, respectively). The number of chromosomal abnormalities defined three risk categories for AML transformation (del(5q), del(5q)+1 and del(5q)+ ≥ 2 abnormalities) and two for OS (one group: del(5q) and del(5q)+1; and del(5q)+ ≥ 2 abnormalities, as the other one); with a median survival time of 58.0 and 6.8 months, respectively. Platelet count (P=0.001) and age (P=0.034) predicted OS in patients with '5q-syndrome'. This study demonstrates the importance of additional chromosomal abnormalities in MDS patients with deletion 5q, challenges the current '5q-syndrome' definition and constitutes a useful reference series to properly analyze the results of clinical trials in these patients.

Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia.

Activation of the Wnt signaling pathway has been implicated recently in the pathogenesis of leukemia. We studied the function of epigenetic regulation of the Wnt pathway and its prognostic relevance in acute myelogenous leukemia (AML). We used a methylation-specific polymerase chain reaction approach to analyze the promoter methylation status of a panel of Wnt antagonists including sFRP1, sFRP2, sFRP4, sFRP5, DKK1 and DKK3. Aberrant methylation of Wnt antagonists was detected in four AML cell lines and in up to 64% of AML marrow samples. Treatment of the cell lines with 5-aza-2'-deoxycytidine induced reexpression of methylated Wnt antagonists and inactivation of the Wnt pathway by downregulating the Wnt pathway genes cyclin D1, TCF1 and LEF1 and reducing nuclear localization of beta-catenin. In a subgroup of patients 60 years and younger with newly diagnosed AML and intermediate-risk cytogenetics, abnormal methylation of Wnt antagonists was associated with decreased 4-year relapse-free survival (28 vs 61%, respectively, P=0.03). Our results indicate a function of the epigenetic regulation of the Wnt pathway in predicting relapse in a subgroup of AML patients.

[Biological activity of Bacteroides fragilis]. / Biologiczna aktywnosc Bacteroides fragilis.

The investigation was performed with 9 strains of B. fragilis isolated from pregnant women in their 38th week of pregnancy, strain IPLE 323 obtained from France, strains BE17 and BE61 obtained from Netherlands and a strain 210 isolated from a case of appendicitis. The strains were identified by indirect immunofluorescence method and by API 32 ATB test. Ability to adhere to epithelium of oral cavity and vaginal mucosa and sheep and human erythrocytes was investigated. Susceptibility to antibiotics was also measured. It was found that strains isolated from vagina easier adhere to epithelial cells of vagina than to cheek epithelium and erythrocytes.