Assessing the effects of mining projects on child health in sub-Saharan Africa: a multi-country analysis

BACKGROUND: The African continent hosts many industrial mining projects, and many more are planned due to recent prospecting discoveries and increasing demand for various minerals to promote a low-carbon future. The extraction of natural resources in sub-Saharan Africa (SSA) represents an opportunity for economic development but also poses a threat to population health through rapid urbanisation and environmental degradation. Children could benefit from improved economic growth through various channels such as access to high-quality food, better sanitation, and clean water. However, mining can increase food insecurity and trigger local competition over safe drinking water. Child health can be threatened by exposure to mining-related air, noise, and water pollution. To assess the impact of mines on child health, we analyse socio-demographic, health, and mining data before and after several mining projects were commissioned in SSA. RESULTS: Data of 90,951 children living around 81 mining sites in 23 countries in SSA were analysed for child mortality indicators, and 79,962 children from 59 mining areas in 18 SSA countries were analysed for diarrhoea, cough, and anthropometric indicators. No effects of the launch of new mining projects on overall under-five mortality were found (adjusted Odds Ratio (aOR): 0.88; 95% Confidence Interval (CI): 0.68-1.14). However, activation of mining projects reduced the mortality risk among neonates (0-30 days) by 45% (aOR: 0.55; 95% CI: 0.37-0.83) and risk for a child to develop diarrhoeal diseases by 32% (aOR: 0.68; 95% CI: 0,51-0.90). The timing analysis of observed changes showed that there is a significant decline in the risk for childhood diarrhoea (aOR: 0.69; 95% CI: 0.49-0.97), and the mean height-for-age z-scores by 28 percentage points, during the prospection and construction phase; i.e., within four years to the initiation of extraction activity. No effects were found for cough and weight-for-height. CONCLUSION: The results presented suggest that the impacts of mining on child health vary throughout the mine's life cycle. Mining development likely contributes positively to the income and livelihoods of the impacted communities in the initial years of mining operations, particularly the prospection and construction phase; these potential benefits are likely to be at least partially offset by food insecurity and environmental pollution during early and later mining stages, respectively. Further research is warranted to better understand these health impacts and to identify policies that can help sustain the positive initial health impacts of mining projects in the long term

Morphometric analysis of hepatocellular nodular lesions in HCV cirrhosis

Background and aims. We generated a computerized morphometric model to evaluate and quantify the morphological features in large regenerative nodules (LRN), high-grade dysplastic nodules (HGDN) and hepatocellular carcinoma (HCC). Methods. Sixteen LRN, 10 HGDN and 16 HCC in HCV-cirrhotic livers, were stained with H&E, smooth muscle actin, CD34, CD31 and reticulin to evaluate volume and surface fractions. Results. On H&E stains, the features most discriminatory between LRN, HGDN and HCC were volume fraction and number of hepatocytes nuclei in unit volume, and hepatocyte nuclear/cytoplasmic ratio. On immunohistochemistry, volume fractions of capillarised sinusoids, capillary units and isolated arteries were significantly different among all groups and highest in HCC; surface fraction of reticulin was markedly decreased in HCC. Conclusions. Our morphometric model is an objective method of quantification of the morphological changes of the nodular lesions and it could be applied in studies involving histological evaluation of the spectrum of nodular lesions arising in the cirrhotic liver

Obstructive sleep apnoea: a cause of chronic cough

Chronic cough is a common reason for presentation to both general practice and respiratory clinics. In up to 25% of cases, the cause remains unclear after extensive investigations. We report 4 patients presenting with an isolated chronic cough who were subsequently found to have obstructive sleep apnoea. The cough improved rapidly with nocturnal continuous positive airway pressure therapy. Further studies are required to investigate the prevalence of coexistence of these common conditions

Localized inhibition of protein phosphatase 1 by NUAK1 promotes spliceosome activity and reveals a MYC-sensitive feedback control of transcription.

Deregulated expression of MYC induces a dependence on the NUAK1 kinase, but the molecular mechanisms underlying this dependence have not been fully clarified. Here, we show that NUAK1 is a predominantly nuclear protein that associates with a network of nuclear protein phosphatase 1 (PP1) interactors and that PNUTS, a nuclear regulatory subunit of PP1, is phosphorylated by NUAK1. Both NUAK1 and PNUTS associate with the splicing machinery. Inhibition of NUAK1 abolishes chromatin association of PNUTS, reduces spliceosome activity, and suppresses nascent RNA synthesis. Activation of MYC does not bypass the requirement for NUAK1 for spliceosome activity but significantly attenuates transcription inhibition. Consequently, NUAK1 inhibition in MYC-transformed cells induces global accumulation of RNAPII both at the pause site and at the first exon-intron boundary but does not increase mRNA synthesis. We suggest that NUAK1 inhibition in the presence of deregulated MYC traps non-productive RNAPII because of the absence of correctly assembled spliceosomes

Unusual skin toxicity associated with sustained disease response induced by nivolumab in a patient with non-small cell lung cancer

Introduction: Immunotherapy has shown efficacy in the treatment of different malignancies. Nivolumab, an immune checkpoint inhibitor directed against programmed death-1, has been approved for non-small cell lung cancer (NSCLC) in pretreated patients. Although it is generally well-tolerated, immunotherapy may be complicated by a wide range of immune-mediated adverse events. We describe the case of an uncommon skin toxicity arising as alopecia universalis induced by nivolumab in a patient with NSCLC. Case description: A 58-year-old man received nivolumab for metastatic NSCLC after progression to 3 lines of chemotherapy. The treatment was prescribed in June 2016, and induced a rapid and significant disease response. Nivolumab was well-tolerated until May 2017, when partial alopecia at hair and eyelashes appeared. In the next months, alopecia became complete and extended to the whole body surface. The dermatologic picture was compatible with alopecia areata. A topical steroid therapy was attempted, without benefit. The patient refused systemic treatments and is still undergoing nivolumab without new toxicities and with persistent disease response. Conclusions: This case suggests that alopecia areata may be a rare immune-related adverse event of immune checkpoint agents. Its late onset in our patient is uncommon and unexpected, underlining that the risk of nivolumab-induced toxicity is not limited to the beginning of treatment. Despite its rarity, alopecia areata should be considered in the range of adverse events potentially induced by immune checkpoint inhibitors even in the long term. Potential association between toxicity and efficacy of immunotherapy in NSCLC warrants further investigation

Balancing act : competition and cooperation in US Asia-Pacific regionalism

While the United States is an important Asia-Pacific actor, its engagement with the region is complex and often difficult. Not only must US regionalism balance the diverse requirements of an ambitious policy agenda, but also US policy norms and priorities often clash with those of other regional actors. This has important implications for the capacity of the United States to provide regional leadership. Recent years have seen growing policy convergence between the United States and other Asia-Pacific actors, particularly in economic terms, but US regionalism continues to feature competition alongside collaboration

Epidemiology and clinical presentation of community-acquired Staphylococcus aureus bacteraemia in children under 5 years of age admitted to the Manhica District Hospital, Mozambique, 2001-2019

Staphylococcus aureus bacteraemia (SAB) is one of the most common bloodstream infections globally. Data on the burden and epidemiology of community-acquired SAB in low-income countries are scarce but needed to defne preventive and management strategies. Blood samples were collected from children<5 years of age with fever or severe disease admitted to the Manhiça District Hospital for bacterial isolation, including S. aureus. Between 2001 and 2019, 7.6% (3,197/41,891) of children had bacteraemia, of which 12.3% corresponded to SAB. The overall incidence of SAB was 56.1 episodes/100,000 children-years at risk (CYAR), being highest among neonates (589.8 episodes/100,000 CYAR). SAB declined signifcantly between 2001 and 2019 (322.1 to 12.5 episodes/100,000 CYAR). In-hospital mortality by SAB was 9.3% (31/332), and signifcantly associated with infections by multidrugresistant (MDR) strains (14.7%, 11/75 vs. 6.9%, 14/204 among non-MDR, p=0.043) and methicillin-resistant S. aureus (33.3%, 5/15 vs. 7.6%, 20/264 among methicillin-susceptible S. aureus, p=0.006). Despite the declining rates of SAB, this disease remains an important cause of death among children admitted to MDH, possibly in relation to the resistance to the frst line of empirical treatment in use in our setting, suggesting an urgent need to review current policy recommendationspublishersversionpublishe