The Segmented Zambezi Sedimentary System from Source to Sink: 1. Sand Petrology and Heavy Minerals

The Zambezi River rises at the center of southern Africa, flows across the low-relief Kalahari Plateau, meets Karoo basalt, plunges into Victoria Falls, follows along Karoo rifts, and pierces through Precambrian basement to eventually deliver its load onto the Mozambican passive margin. Reflecting its polyphase evolution, the river is subdivided into segments with different geological and geomorphological character, a subdivision finally fixed by man’s construction of large reservoirs and faithfully testified by sharp changes in sediment composition. Pure quartzose sand recycled from Kalahari desert dunes in the uppermost tract is next progressively enriched in basaltic rock fragments and clinopyroxene. Sediment load is renewed first downstream of Lake Kariba and next downstream of Lake Cahora Bassa, documenting a stepwise decrease in quartz and durable heavy minerals. Composition becomes quartzo-feldspathic in the lower tract, where most sediment is supplied by high-grade basements rejuvenated by the southward propagation of the East African rift. Feldspar abundance in Lower Zambezi sand has no equivalent among big rivers on Earth and far exceeds that in sediments of the northern delta, shelf, and slope, revealing that provenance signals from the upper reaches have ceased to be transmitted across the routing system after closure of the big dams. This high-resolution petrologic study of Zambezi sand allows us to critically reconsider several dogmas, such as the supposed increase of mineralogical “maturity” during long-distance fluvial transport, and forges a key to unlock the rich information stored in sedimentary archives, with the ultimate goal to accurately reconstruct the evolution of this mighty river flowing across changing African landscapes since the late Mesozoic

Family members’ perspectives of child protection services, a metasynthesis of the literature

This review is part of a EC research project funded by RDAP-GBW-AG-2018-2 Domestic Violence/European Commission.This metasynthesis brings together what is known about family members’ perspectives of their relationship with social care practitioners as a starting point for developing a pan-European training resource for practitioners. Four databases were searched for qualitative literature with search terms relating to family members and social care practitioners. After the application of inclusion and exclusion criteria, 35 studies were critically appraised and were included in the metasynthesis. Three broad themes were identified through a thematic analysis of the studies’ findings: family members’ perspectives of the system; perceptions of how they were viewed by their worker; and view of their worker. The following aspects are discussed: whether partnership between family and worker is possible within a legal framework; the detrimental effects of cultural bias; and practical foundations for building trust. Recommendations are made for practical support, reflection on cultural practice and broader service provision.Publisher PDFPeer reviewe

Neogene to Quaternary evolution of carbonate and mixed carbonate-siliciclastic systems along New Caledonia's eastern margin (SW Pacific)

Neogene and Quaternary shallow-water carbonate records surrounding New Caledonia main island, Grande Terre, provide a good example for understanding the stratigraphic architecture of tropical mixed carbonate-siliciclastic systems. Due to a southeastern tilt of the eastern margin, the eastern shelf of Grande Terre has been better preserved from erosion than the western part, favouring the development and preservation of shallow-water carbonates. Based on the integration of bathymetric and seismic data, along with paleoenvironmental and biostratigraphic constraints derived from dredged carbonate rocks, a comprehensive geomorphological and architectural characterization of the offshore eastern margin of Grande Terre has been made. During the Mio-Pliocene, a wide, up to 750 m-thick carbonate build-up developed and extended over at least 350 km from north to south. This Mio-Pliocene build-up, currently lying at 300 to 600 m water depths, is overlain by a Pleistocene-Holocene barrier reef-lagoon complex and associated slope deposits. The switch from aggrading Neogene carbonate banks to backstepping Quaternary platforms likely reflects an increase in accommodation due to a high subsidence rate or to relative sea-level rise, and/or results from a switch in carbonate producers associated with global environmental changes. The internal architecture of the Quaternary barrier reef-lagoon complex is highlighted, especially the development of lowstand siliciclastic prisms alternating with transgressive shallow-water carbonate sequences. This pattern agrees with the reciprocal sedimentation model typically invoked for mixed sedimentary systems. This stratigraphic pattern is well developed in front of the Cap Bayes inlet in the north of our study area, yet it is not observed southward along the eastern margin. This difference suggests that other factors than relative sea-level variations directed the architecture of the margin, such as low terrigenous inputs, lagoon paleo-drainage networks or sediment by-pass towards deep basins

Treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for acute leukemia increases the risk of graft-versus-host disease and death

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A pan-European review of good practices in early intervention safeguarding practice with children, young people and families : evidence gathering to inform a multi-disciplinary training programme (the ERICA project) in preventing child abuse and neglect in seven European countries

Funded by the Rights, Equality and Citizenship Programme of the European Commission (European Commission 2019–2021).Child maltreatment has detrimental social and health effects for individuals, families and communities. The ERICA project is a pan-European training programme that equips non-specialist threshold practitioners with knowledge and skills to prevent and detect child maltreatment. This paper describes and presents the findings of a rapid review of good practice examples across seven participating countries including local services, programmes and risk assessment tools used in the detection and prevention of child maltreatment in the family. Learning was applied to the development of the generic training project. A template for mapping the good practice examples was collaboratively developed by the seven participating partner countries. A descriptive data analysis was undertaken organised by an a priori analysis framework. Examples were organised into three areas: programmes tackling child abuse and neglect, local practices in assessment and referral, risk assessment tools. Key findings were identified using a thematic approach. Seventy-two good practice examples were identified and categorised according to area, subcategory and number. A typology was developed as follows: legislative frameworks, child health promotion programmes, national guidance on child maltreatment, local practice guidance, risk assessment tools, local support services, early intervention programmes, telephone or internet-based support services, COVID-19 related good practices. Improved integration of guidance into practice and professional training in child development were highlighted as overarching needs. The impact of COVID-19 on safeguarding issues was apparent. The ERICA training programme formally responded to the learning identified in this international good practice review.Publisher PDFPeer reviewe

Novel SPG11 mutations in Asian kindreds and disruption of spatacsin function in the zebrafish

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum (HSP-TCC) maps to the SPG11 locus in the majority of cases. Mutations in the KIAA1840 gene, encoding spatacsin, have been shown to underlie SPG11-linked HSP-TCC. The aim of this study was to perform candidate gene analysis in HSP-TCC subjects from Asian families and to characterize disruption of spatacsin function during zebrafish development. Homozygosity mapping and direct sequencing were used to assess the ACCPN, SPG11, and SPG21 loci in four inbred kindreds originating from the Indian subcontinent. Four novel homozygous SPG11 mutations (c.442+1G>A, c.2146C>T, c.3602_3603delAT, and c.4846C>T) were identified, predicting a loss of spatacsin function in each case. To investigate the role of spatacsin during development, we additionally ascertained the complete zebrafish spg11 ortholog by reverse transcriptase PCR and 5′ RACE. Analysis of transcript expression through whole-mount in situ hybridization demonstrated ubiquitous distribution, with highest levels detected in the brain. Morpholino antisense oligonucleotide injection was used to knock down spatacsin function in zebrafish embryos. Examination of spg11 morphant embryos revealed a range of developmental defects and CNS abnormalities, and analysis of axon pathway formation demonstrated an overall perturbation of neuronal differentiation. These data confirm loss of spatacsin as the cause of SPG11-linked HSP-TCC in Asian kindreds, expanding the mutation spectrum recognized in this disorder. This study represents the first investigation in zebrafish addressing the function of a causative gene in autosomal recessive HSP and identifies a critical role for spatacsin during early neural development in vivo

High fat diet induces dysregulation of hepatic oxygen gradients and mitochondrial function in vivo

NAFLD (non-alcoholic fatty liver disease), associated with obesity and the cardiometabolic syndrome, is an important medical problem affecting up to 20% of western populations. Evidence indicates that mitochondrial dysfunction plays a critical role in NAFLD initiation and progression to the more serious condition of NASH (non-alcoholic steatohepatitis). Herein we hypothesize that mitochondrial defects induced by exposure to a HFD (high fat diet) contribute to a hypoxic state in liver and this is associated with increased protein modification by RNS (reactive nitrogen species). To test this concept, C57BL/6 mice were pair-fed a control diet and HFD containing 35% and 71% total calories (1 cal≈4.184 J) from fat respectively, for 8 or 16 weeks and liver hypoxia, mitochondrial bioenergetics, NO (nitric oxide)-dependent control of respiration, and 3-NT (3-nitrotyrosine), a marker of protein modification by RNS, were examined. Feeding a HFD for 16 weeks induced NASH-like pathology accompanied by elevated triacylglycerols, increased CYP2E1 (cytochrome P450 2E1) and iNOS (inducible nitric oxide synthase) protein, and significantly enhanced hypoxia in the pericentral region of the liver. Mitochondria from the HFD group showed increased sensitivity to NO-dependent inhibition of respiration compared with controls. In addition, accumulation of 3-NT paralleled the hypoxia gradient in vivo and 3-NT levels were increased in mitochondrial proteins. Liver mitochondria from mice fed the HFD for 16 weeks exhibited depressed state 3 respiration, uncoupled respiration, cytochrome c oxidase activity, and mitochondrial membrane potential. These findings indicate that chronic exposure to a HFD negatively affects the bioenergetics of liver mitochondria and this probably contributes to hypoxic stress and deleterious NO-dependent modification of mitochondrial proteins

Full-Length L1CAM and Not Its Δ2Δ27 Splice Variant Promotes Metastasis through Induction of Gelatinase Expression

Tumour-specific splicing is known to contribute to cancer progression. In the case of the L1 cell adhesion molecule (L1CAM), which is expressed in many human tumours and often linked to bad prognosis, alternative splicing results in a full-length form (FL-L1CAM) and a splice variant lacking exons 2 and 27 (SV-L1CAM). It has not been elucidated so far whether SV-L1CAM, classically considered as tumour-associated, or whether FL-L1CAM is the metastasis-promoting isoform. Here, we show that both variants were expressed in human ovarian carcinoma and that exposure of tumour cells to pro-metastatic factors led to an exclusive increase of FL-L1CAM expression. Selective overexpression of one isoform in different tumour cells revealed that only FL-L1CAM promoted experimental lung and/or liver metastasis in mice. In addition, metastasis formation upon up-regulation of FL-L1CAM correlated with increased invasive potential and elevated Matrix metalloproteinase (MMP)-2 and -9 expression and activity in vitro as well as enhanced gelatinolytic activity in vivo. In conclusion, we identified FL-L1CAM as the metastasis-promoting isoform, thereby exemplifying that high expression of a so-called tumour-associated variant, here SV-L1CAM, is not per se equivalent to a decisive role of this isoform in tumour progression

Genetics of human hydrocephalus

Human hydrocephalus is a common medical condition that is characterized by abnormalities in the flow or resorption of cerebrospinal fluid (CSF), resulting in ventricular dilatation. Human hydrocephalus can be classified into two clinical forms, congenital and acquired. Hydrocephalus is one of the complex and multifactorial neurological disorders. A growing body of evidence indicates that genetic factors play a major role in the pathogenesis of hydrocephalus. An understanding of the genetic components and mechanism of this complex disorder may offer us significant insights into the molecular etiology of impaired brain development and an accumulation of the cerebrospinal fluid in cerebral compartments during the pathogenesis of hydrocephalus. Genetic studies in animal models have started to open the way for understanding the underlying pathology of hydrocephalus. At least 43 mutants/loci linked to hereditary hydrocephalus have been identified in animal models and humans. Up to date, 9 genes associated with hydrocephalus have been identified in animal models. In contrast, only one such gene has been identified in humans. Most of known hydrocephalus gene products are the important cytokines, growth factors or related molecules in the cellular signal pathways during early brain development. The current molecular genetic evidence from animal models indicate that in the early development stage, impaired and abnormal brain development caused by abnormal cellular signaling and functioning, all these cellular and developmental events would eventually lead to the congenital hydrocephalus. Owing to our very primitive knowledge of the genetics and molecular pathogenesis of human hydrocephalus, it is difficult to evaluate whether data gained from animal models can be extrapolated to humans. Initiation of a large population genetics study in humans will certainly provide invaluable information about the molecular and cellular etiology and the developmental mechanisms of human hydrocephalus. This review summarizes the recent findings on this issue among human and animal models, especially with reference to the molecular genetics, pathological, physiological and cellular studies, and identifies future research directions