Hodgkin's lymphoma in remission after first-line therapy: which patients need FDG-PET/CT for follow-up?

Background: The purpose of the study was to evaluate the impact of 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET)/computed tomography (CT) during follow-up of patients with Hodgkin's lymphoma. Patients and methods: Patients in complete remission or an unconfirmed complete remission after first-line therapy who received FDG-PET/CT during their follow-up were analyzed retrospectively. Confirmatory biopsy was mandatory in case of recurrence. Results: Overall, 134 patients were analyzed. Forty-two (31.3%) patients had a recurrence. The positive predictive value of FDG-PET/CT was 0.98. Single-factor analysis identified morphological residual mass [P = 0.0005, hazard ratio (HR) 3.4, 95% confidence interval (CI) 1.7-6.6] and symptoms (P 24 months). Conclusions: Asymptomatic patients without morphological residues and an early stage of disease do not need a routine FDG-PET/CT for follow-up. Asymptomatic patients with morphological residues should receive routine follow-up FDG-PET/CT for the first 24 months. Only patients with advanced initial stage do need a routine follow-up FDG-PET/CT beyond 24 month

Convergent origination of a Drosophila-like dosage compensation mechanism in a reptile lineage

Sex chromosomes differentiated from different ancestral autosomes in various vertebrate lineages. Here, we trace the functional evolution of the XY Chromosomes of the green anole lizard (Anolis carolinensis), on the basis of extensive high-throughput genome, transcriptome and histone modification sequencing data and revisit dosage compensation evolution in representative mammals and birds with substantial new expression data. Our analyses show that Anolis sex chromosomes represent an ancient XY system that originated at least ≈160 million years ago in the ancestor of Iguania lizards, shortly after the separation from the snake lineage. The age of this system approximately coincides with the ages of the avian and two mammalian sex chromosomes systems. To compensate for the almost complete Y Chromosome degeneration, X-linked genes have become twofold up-regulated, restoring ancestral expression levels. The highly efficient dosage compensation mechanism of Anolis represents the only vertebrate case identified so far to fully support Ohno’s original dosage compensation hypothesis. Further analyses reveal that X up-regulation occurs only in males and is mediated by a male-specific chromatin machinery that leads to global hyperacetylation of histone H4 at lysine 16 specifically on the X Chromosome. The green anole dosage compensation mechanism is highly reminiscent of that of the fruit fly, Drosophila melanogaster. Altogether, our work unveils the convergent emergence of a Drosophila-like dosage compensation mechanism in an ancient reptilian sex chromosome system and highlights that the evolutionary pressures imposed by sex chromosome dosage reductions in different amniotes were resolved in fundamentally different ways

Corporate Social Responsibility/Sustainability Reporting Among the Fortune Global 250: Greenwashing or Green Supply Chain?

The sustainability reporting efforts of MNCs who are members of the Fortune Global 250 (FG250) was investigated. The focus was on sustainability reporting by MNCs of supply chain impacts. The reporting of FG250 MNCs was examined to determine if greenwashing was occurring or whether MNCs had committed to operating a green supply chain. A mixed methodology was used consisting of quantitative analysis of twenty-five MNC CSR/sustainability reports which were randomly selected from the FG250 listing. Qualitative analysis using content analysis was also conducted on the reports. Both methodologies concentrated on the sustainability reporting of the selected MNCs in regard to their supply chain. Findings were mixed as there were great variations among the MNCs in their level of sustainability reporting about their supply chains. Some MNCs did not report on the activities of their supply chain at all (20%), the majority of the MNCs reported on their supply chain impacts at the value and goal level (48%), while the rest reported at the management approach level (32%). A majority of the sampled MNCs could be accused of greenwashing due to the lack of detailed quantitative information provided by the MNCs on the environmental impacts of their supply chai

Feasibility, acceptability and effectiveness of integrated care for COPD patients: a mixed methods evaluation of a pilot community-based programme.

The aim of this study was to assess the feasibility, acceptability and effectiveness of a pilot COPD integrated care programme implemented in Valais, Switzerland. The programme was adapted from the self-management programme Living Well with COPD, and included the following elements: self-management patient-education group sessions, telephone and medical follow-ups, multidisciplinary teams, training of healthcare professionals, and evidence-based COPD care. A process and outcome evaluation of the pilot phase of the programme was conducted by means of qualitative and quantitative methods. Reach (coverage, participation rates), dosage (interventions carried out), fidelity (delivered as intended) and stakeholders' acceptance of the programme were evaluated through data monitoring and conduct of focus groups with patients and healthcare professionals. Effectiveness was assessed with pre-post analyses (before and after the intervention). The primary outcome measures were; (1) generic and disease-specific quality of life (36-Item Short Form Health Survey, Chronic Respiratory Questionnaire); and (2) hospitalisations (all-cause and for acute exacerbations) in the past 12 months. Secondary outcomes included self-efficacy, number of exacerbations and exercise capacity. Finally, controlled pre-post comparisons were also made with patients from the Swiss COPD Cohort for three common outcome measures (dyspnoea [mMRC score], number of exacerbations and smoking status). During the first 2 years of the programme, eight series of group-based education sessions were delivered to 57 patients with COPD in three different locations of the canton of Valais. Coverage objectives were achieved and attendance rate at the education sessions was high (83.6%). Patients' and healthcare professionals' reported a high degree of satisfaction, except for multidisciplinarity and transfer of information. Exploration of the effectiveness of this pilot programme suggested positive pre-post results at 12 months, with improvements in terms of health-related quality of life, self-efficacy, exercise capacity, immunisation coverage and Patient Assessment of Chronic Illness Care score. No other outcome, including the number of hospital admissions, differed significantly after 12 months. We observed no differences from the control group. The evaluation demonstrated the feasibility and acceptability of the programme and confirmed the relevance of mixed method process evaluation to adjust and improve programme implementation. The introduction of multidisciplinary teams in a context characterised by fragmentation of care was identified as the main challenge in the programme implementation and could not be achieved as expected. Despite this area for improvement, patients' feedback and early effectiveness results confirmed the benefits of COPD integrated care programmes emphasising self-management education

Molecular evolution of HoxA13 and the multiple origins of limbless morphologies in amphibians and reptiles

Developmental processes and their results, morphological characters, are inherited through transmission of genes regulating development. While there is ample evidence that cis-regulatory elements tend to be modular, with sequence segments dedicated to different roles, the situation for proteins is less clear, being particularly complex for transcription factors with multiple functions. Some motifs mediating protein-protein interactions may be exclusive to particular developmental roles, but it is also possible that motifs are mostly shared among different processes. Here we focus on HoxA13, a protein essential for limb development. We asked whether the HoxA13 amino acid sequence evolved similarly in three limbless clades: Gymnophiona, Amphisbaenia and Serpentes. We explored variation in ω (dN/dS) using a maximum-likelihood framework and HoxA13sequences from 47 species. Comparisons of evolutionary models provided low ω global values and no evidence that HoxA13 experienced relaxed selection in limbless clades. Branch-site models failed to detect evidence for positive selection acting on any site along branches of Amphisbaena and Gymnophiona, while three sites were identified in Serpentes. Examination of alignments did not reveal consistent sequence differences between limbed and limbless species. We conclude that HoxA13 has no modules exclusive to limb development, which may be explained by its involvement in multiple developmental processes

Divergence of Mammalian Higher Order Chromatin Structure Is Associated with Developmental Loci

Several recent studies have examined different aspects of mammalian higher order chromatin structure - replication timing, lamina association and Hi-C inter-locus interactions - and have suggested that most of these features of genome organisation are conserved over evolution. However, the extent of evolutionary divergence in higher order structure has not been rigorously measured across the mammalian genome, and until now little has been known about the characteristics of any divergent loci present. Here, we generate a dataset combining multiple measurements of chromatin structure and organisation over many embryonic cell types for both human and mouse that, for the first time, allows a comprehensive assessment of the extent of structural divergence between mammalian genomes. Comparison of orthologous regions confirms that all measurable facets of higher order structure are conserved between human and mouse, across the vast majority of the detectably orthologous genome. This broad similarity is observed in spite of many loci possessing cell type specific structures. However, we also identify hundreds of regions (from 100 Kb to 2.7 Mb in size) showing consistent evidence of divergence between these species, constituting at least 10% of the orthologous mammalian genome and encompassing many hundreds of human and mouse genes. These regions show unusual shifts in human GC content, are unevenly distributed across both genomes, and are enriched in human subtelomeric regions. Divergent regions are also relatively enriched for genes showing divergent expression patterns between human and mouse ES cells, implying these regions cause divergent regulation. Particular divergent loci are strikingly enriched in genes implicated in vertebrate development, suggesting important roles for structural divergence in the evolution of mammalian developmental programmes. These data suggest that, though relatively rare in the mammalian genome, divergence in higher order chromatin structure has played important roles during evolution

Longer delays in diagnosis and treatment ofpulmonary tuberculosis in pastoralist setting, Eastern Ethiopia

Purpose: This study aimed to assess the extent of patient, health system and total delays in diagnosis and treatment of pulmonary tuberculosis (TB) in Somali pastoralist setting, Ethiopia. Patients and Methods: A cross-sectional study among 444 confirmed new pulmonary TB patients aged ≥15 years in 5 TB care units was conducted between December 2017 and October 2018. Data were collected using a structured questionnaire and record review. We measured delays from symptom onset to provider visit, provider visit to diagnosis and diagnosis to treatment initiation. Delays were summarized using median days. Mann- Whitney and Kruskal-Wallis tests were used to compare delays between categories of explanatory variables. The Log-binomial regression model was used to reveal factors associated with health system delay ≥15 days, presented in adjusted prevalence ratio (APR) with 95% confidence interval (CI). Results: The median age of patients was 30 years, ranged from 15 to 82. The majority (62.4%) were male, and nearly half (46.4%) were pastoralists. The median patient, health system and total delays were 30 (19-48.5), 14 (4.5-29.5) and 50 (35-73.5) days, respec-tively. The median patient delay (35.5 days) and total delay (58.5 days) among pastoralists were substantially higher than the equivalent delays among non-pastoralists [p<0.001]. Of all, 3.8% of patients (16 of 18 were pastoralists) delayed longer than 6 months without initiating treatment. Factors associated with health system delay ≥15 days were mild symptoms [APR (95% CI) = 1.4 (1.1-1.7)], smear-negativity [APR (95% CI) = 1.2 (1.01- 1.5)], first visit to health centers [APR (95% CI) = 1.6 (1.3-2.0)] and multiple provider contacts [APR (95% CI) = 5.8 (3.5-9.6)]. Conclusion: Delay in diagnosis and treatment remains a major challenge of tuberculosis control targets in pastoralist settings of Ethiopia. Efforts to expand services tailored to transhumance patterns and diagnostic capacity of primary healthcare units need to be prioritized. © 2020 Getnet et al.Purpose: This study aimed to assess the extent of patient, health system and total delays in diagnosis and treatment of pulmonary tuberculosis (TB) in Somali pastoralist setting, Ethiopia. Patients and Methods: A cross-sectional study among 444 confirmed new pulmonary TB patients aged ≥15 years in 5 TB care units was conducted between December 2017 and October 2018. Data were collected using a structured questionnaire and record review. We measured delays from symptom onset to provider visit, provider visit to diagnosis and diagnosis to treatment initiation. Delays were summarized using median days. Mann- Whitney and Kruskal-Wallis tests were used to compare delays between categories of explanatory variables. The Log-binomial regression model was used to reveal factors associated with health system delay ≥15 days, presented in adjusted prevalence ratio (APR) with 95% confidence interval (CI). Results: The median age of patients was 30 years, ranged from 15 to 82. The majority (62.4%) were male, and nearly half (46.4%) were pastoralists. The median patient, health system and total delays were 30 (19-48.5), 14 (4.5-29.5) and 50 (35-73.5) days, respec-tively. The median patient delay (35.5 days) and total delay (58.5 days) among pastoralists were substantially higher than the equivalent delays among non-pastoralists [p<0.001]. Of all, 3.8% of patients (16 of 18 were pastoralists) delayed longer than 6 months without initiating treatment. Factors associated with health system delay ≥15 days were mild symptoms [APR (95% CI) = 1.4 (1.1-1.7)], smear-negativity [APR (95% CI) = 1.2 (1.01- 1.5)], first visit to health centers [APR (95% CI) = 1.6 (1.3-2.0)] and multiple provider contacts [APR (95% CI) = 5.8 (3.5-9.6)]. Conclusion: Delay in diagnosis and treatment remains a major challenge of tuberculosis control targets in pastoralist settings of Ethiopia. Efforts to expand services tailored to transhumance patterns and diagnostic capacity of primary healthcare units need to be prioritized. © 2020 Getnet et al

A polymeric nanomedicine diminishes inflammatory events in renal tubular cells

The polyglutamic acid/peptoid 1 (QM56) nanoconjugate inhibits apoptosis by interfering with Apaf-1 binding to procaspase-9. We now describe anti-inflammatory properties of QM56 in mouse kidney and renal cell models. In cultured murine tubular cells, QM56 inhibited the inflammatory response to Tweak, a non-apoptotic stimulus. Tweak induced MCP-1 and Rantes synthesis through JAK2 kinase and NF-kB activation. Similar to JAK2 kinase inhibitors, QM56 inhibited Tweak-induced NF-kB transcriptional activity and chemokine expression, despite failing to inhibit NF-kB-p65 nuclear translocation and NF-kB DNA binding. QM56 prevented JAK2 activation and NF-kB-p65(Ser536) phosphorylation. The anti-inflammatory effect and JAK2 inhibition by QM56 were observed in Apaf-12/2 cells. In murine acute kidney injury, QM56 decreased tubular cell apoptosis and kidney inflammation as measured by downmodulations of MCP-1 and Rantes mRNA expression, immune cell infiltration and activation of the JAK2-dependent inflammatory pathway. In conclusion, QM56 has an anti-inflammatory activity which is independent from its role as inhibitor of Apaf-1 and apoptosis and may have potential therapeutic relevance.This work was supported by grants from the Instituto de Salud Carlos III (www.isciii.es), FIS: PI07/0020, CP08/1083, PS09/00447 and ISCIII-RETICS REDINREN RD 06/0016; Sociedad Española de Nefrología (www.senefro.org). Álvaro Ucero, Sergio Berzal and Carlos Ocaña supported by Fundacion Conchita Rabago (www.fundacionconchitarabago.net), Alberto Ortiz by the Programa de Intensificación de la Actividad Investigadora in the Sistema Nacional de Salud of the Instituto de Salud Carlos III and the Agencia ‘‘Pedro Lain Entralgo’’ of the Comunidad de Madrid and CIFRA S-BIO 0283/2006 www.madrid.org/lainentralgo) and Adrián Ramos, by FIS (Programa Miguel Servet)

Employment of ex-prisoners with mental health problems, a realistic evaluation protocol

Background Offenders with a mental illness are routinely excluded from vocational services due to their mental health. Employment has shown to be very important in improving mental health, reducing recidivism, and connecting people to society. This study examines the effectiveness of an established intervention which is relatively untested in this population, Individual Placement and Support (IPS), to help offenders with mental health problems into competitive employment. The overall research question is whether IPS is effective in gaining and sustaining competitive employment for offenders with a Severe Mental Illness (SMI). The context is an English criminal justice setting across different populations. The study will also measure non-vocational outcomes such as recidivism, mental health and social stability. Methods/Design A Realistic Evaluation (RE) design will address the questions “What works, for whom, and in what circumstances?” This study includes pre and post comparisons for a cohort of approximately 20 people taking part in IPS, and a similar number of controls, over a one year period. The RE also consists of interviews with practitioners and offenders in order to understand how IPS works and develops within the criminal justice system (CJS). By applying this framework the research can go from discovering whether IPS works, to how and why (or why not) IPS works. This is achieved by examining where the intervention is occurring (Context (C)), the mechanisms (M) that create particular behaviours, and how the outcomes (O) from the intervention all come together (CMOs). Employment outcomes will also be examined for all participants. Discussion By applying RE the research will permit inferences to be drawn about how and why (or why not) IPS works, by examining context, mechanisms and outcomes. IPS has never been implemented within the CJS in the United Kingdom. As a result, this evaluative research will not only provide a novel insight into the core research areas, but also how the intervention can be improved for others in the future