Hepatocellular carcinoma: Review of disease and tumor biomarkers.

© The Author(s) 2016.Hepatocellular carcinoma (HCC) is a common malignancy and now the second commonest global cause of cancer death. HCC tumorigenesis is relatively silent and patients experience late symptomatic presentation. As the option for curative treatments is limited to early stage cancers, diagnosis in non-symptomatic individuals is crucial. International guidelines advise regular surveillance of high-risk populations but the current tools lack sufficient sensitivity for early stage tumors on the background of a cirrhotic nodular liver. A number of novel biomarkers have now been suggested in the literature, which may reinforce the current surveillance methods. In addition, recent metabonomic and proteomic discoveries have established specific metabolite expressions in HCC, according to Warburgs phenomenon of altered energy metabolism. With clinical validation, a simple and non-invasive test from the serum or urine may be performed to diagnose HCC, particularly benefiting low resource regions where the burden of HCC is highest

Natural trace element salinization of the Jemez River, New Mexico by geothermal springs and major tributaries

The Jemez River (JR), a tributary of the Rio Grande, is in north-central New Mexico within the Jemez Mountains, which houses the active, high-temperature (≤ 300 oC), liquid-dominated Valles Caldera geothermal system (VC). This work focuses on the northern portion of the JR, spanning a reach from the East Fork JR to the town of San Ysidro. Previous decadal work during low-flow or baseflow conditions (~10-20 cfs) has identified and characterized significant major-solute contributions from two outflow expressions of the VC, Soda Dam Springs and Jemez Hot Springs, and two major tributaries, Rio San Antonio and Rio Guadalupe. There is generally a net ~500-ppm increase from below Soda Dam to the end of the study segment. The distribution of concentrations of twenty-four trace metals from recent Fall 2017 sampling are defined by range from \u27ultra-trace\u27 levels (0.1-1 ppb) to measurements as much as 1 ppm. A set of elements (e.g., As, Li, Rb, Ba, Ti) follows the same downstream behavior of major ions, which is characterized by an increase in concentrations at each inflow and the observed greatest contribution (as much as an order of magnitude) is at Soda Dam. Another group (e.g., U, Al, Fe, Mn, Se) shows complex downstream patterns, which may be a result of non-conservative processes, such as precipitation/dissolution, sorption, and complexation. We attempt to resolve these potential in-stream processes with high-resolution (regular 1-km spacing with interspersed 50-m intervals around sites with complete chemistry) spatial surveys of temperature, dissolved oxygen, pH, oxidation-reduction potential, and turbidity

Stakeholder perspectives on intensive support teams for adults with intellectual disabilities who display behaviour that challenges in England

BACKGROUND: Adults with intellectual disabilities often display behaviour that challenges that is a result of biological differences, psychological challenges, and lack of appropriate social support. Intensive Support Teams (IST) are recommended to support the care needs of this group and avoid hospitalisation. However, little attention has been paid to the perspectives of stakeholders who manage, work in, or use ISTs. METHOD: Interviews and focus groups were conducted with 50 stakeholders (IST service managers and professionals, adults with intellectual disabilities, and family and paid carers) of ISTs. Services operated according to one of two service models previously identified in ISTs in England (enhanced or independent). RESULTS: Thematic analysis identified accessible and flexible support, individualised care, and the involvement of carers and other relevant agencies in management plans and reviews as features of good IST care highlighted by all stakeholder groups. IST managers and professionals described the key challenges of current IST provision as unclear referral criteria, limited interfaces with other local services, and perceived threats associated with funding and staff retention. Findings were similar between the two IST models. CONCLUSIONS: ISTs are able to offer care and specialist support that is valued by families, service users and other care providers. However, they face several operational challenges that should be addressed if ISTs are to reach their potential along with community intellectual disability services in supporting adults with intellectual disabilities who display behaviour that challenges in the community

Evaluating the Shinumo-Sespe drainage connection: Arguments against the “old” (70–17 Ma) Grand Canyon models for Colorado Plateau drainage evolution

The provocative hypothesis that the Shinumo Sandstone in the depths of Grand Canyon was the source for clasts of orthoquartzite in conglomerate of the Sespe Formation of coastal California, if verified, would indicate that a major river system flowed southwest from the Colorado Plateau to the Pacific Ocean prior to opening of the Gulf of California, and would imply that Grand Canyon had been carved to within a few hundred meters of its modern depth at the time of this drainage connection. The proposed Eocene Shinumo-Sespe connection, however, is not supported by detrital zircon nor paleomagnetic-inclination data and is refuted by thermochronology that shows that the Shinumo Sandstone of eastern Grand Canyon was \u3e60 °C (∼1.8 km deep) and hence not incised at this time. A proposed 20 Ma (Miocene) Shinumo-Sespe drainage connection based on clasts in the Sespe Formation is also refuted. We point out numerous caveats and non-unique interpretations of paleomagnetic data from clasts. Further, our detrital zircon analysis requires diverse sources for Sespe clasts, with better statistical matches for the four “most-Shinumo-like” Sespe clasts with quartzites of the Big Bear Group and Ontario Ridge metasedimentary succession of the Transverse Ranges, Horse Thief Springs Formation from Death Valley, and Troy Quartzite of central Arizona. Diverse thermochronologic and geologic data also refute a Miocene river pathway through western Grand Canyon and Grand Wash trough. Thus, Sespe clasts do not require a drainage connection from Grand Canyon or the Colorado Plateau and provide no constraints for the history of carving of Grand Canyon. Instead, abundant evidence refutes the “old” (70–17 Ma) Grand Canyon models and supports a \u3c6 Ma Grand Canyon

Clinical and cost evaluation of two models of specialist intensive support teams for adults with intellectual disabilities who display behaviours that challenge: the IST-ID mixed-methods study

Background: Intensive support teams (ISTs) are recommended for individuals with intellectual disabilities who display behaviours that challenge. However, there is currently little evidence about the clinical and cost-effectiveness of IST models operating in England.// Aims: To investigate the clinical and cost-effectiveness of IST models.// Method: We carried out a cohort study to evaluate the clinical and cost-effectiveness of two previously identified IST models (independent and enhanced) in England. Adult participants (n = 226) from 21 ISTs (ten independent and 11 enhanced) were enrolled. The primary outcome was change in challenging behaviour between baseline and 9 months as measured by the Aberrant Behaviour Checklist-Community version 2.// Results: We found no statistically significant differences between models for the primary outcome (adjusted β = 4.27; 95% CI −6.34 to 14.87; P = 0.430) or any secondary outcomes. Quality-adjusted life-years (0.0158; 95% CI: −0.0088 to 0.0508) and costs (£3409.95; 95% CI −£9957.92 to £4039.89) of the two models were comparable. Conclusions The study provides evidence that both models were associated with clinical improvement for similar costs at follow-up. We recommend that the choice of service model should rest with local services. Further research should investigate the critical components of IST care to inform the development of fidelity criteria, and policy makers should consider whether roll out of such teams should be mandated

Bacterial and metabolic phenotypes associated with inadequate response to ursodeoxycholic acid treatment in primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease with ursodeoxycholic acid (UDCA) as first-line treatment. Poor response to UDCA is associated with a higher risk of progressing to cirrhosis, but the underlying mechanisms are unclear. UDCA modulates the composition of primary and bacterial-derived bile acids (BAs). We characterized the phenotypic response to UDCA based on BA and bacterial profiles of PBC patients treated with UDCA. Patients from the UK-PBC cohort (n = 419) treated with UDCA for a minimum of 12-months were assessed using the Barcelona dynamic response criteria. BAs from serum, urine, and feces were analyzed using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry and fecal bacterial composition measured using 16S rRNA gene sequencing. We identified 191 non-responders, 212 responders, and a subgroup of responders with persistently elevated liver biomarkers (n = 16). Responders had higher fecal secondary and tertiary BAs than non-responders and lower urinary bile acid abundances, with the exception of 12-dehydrocholic acid, which was higher in responders. The sub-group of responders with poor liver function showed lower alpha-diversity evenness, lower abundance of fecal secondary and tertiary BAs than the other groups and lower levels of phyla with BA-deconjugation capacity (Actinobacteriota/Actinomycetota, Desulfobacterota, Verrucomicrobiota) compared to responders. UDCA dynamic response was associated with an increased capacity to generate oxo-/epimerized secondary BAs. 12-dehydrocholic acid is a potential biomarker of treatment response. Lower alpha-diversity and lower abundance of bacteria with BA deconjugation capacity might be associated with an incomplete response to treatment in some patients

Prevention of Liver Fibrosis and Cancer in Africa: The PROLIFICA project – a collaborative study of hepatitis B-related liver disease in West Africa

Hepatitis B virus (HBV) infection causes a spectrum of acute and chronic liver disease ranging from inactive chronic carrier status to progressive chronic hepatitis, culminating in end-stage cirrhosis and liver cancer. In sub-Saharan Africa, HBV infection is endemic and the HBV-related disease burden is high, making HBV a signficant threat to health in the African continent. The European Union-funded Prevention of Liver Fibrosis and Cancer in Africa (PROLIFICA) project was established in 2011, with the central directive to reduce the incidence of HBV-related liver cancer in West Africa. In this editorial, we outline some of the achievements and challenges of the PROLIFICA platform in West Africa, highlighting the the importance of collaborative studies in Africa

Stakeholder perspectives on intensive support teams for adults with intellectual disabilities who display behaviour that challenges in England

Background Adults with intellectual disabilities often display behaviour that challenges that is a result of biological differences, psychological challenges, and lack of appropriate social support. Intensive Support Teams (IST) are recommended to support the care needs of this group and avoid hospitalisation. However, little attention has been paid to the perspectives of stakeholders who manage, work in, or use ISTs. Method Interviews and focus groups were conducted with 50 stakeholders (IST service managers and professionals, adults with intellectual disabilities, and family and paid carers) of ISTs. Services operated according to one of two service models previously identified in ISTs in England (enhanced or independent). Results Thematic analysis identified accessible and flexible support, individualised care, and the involvement of carers and other relevant agencies in management plans and reviews as features of good IST care highlighted by all stakeholder groups. IST managers and professionals described the key challenges of current IST provision as unclear referral criteria, limited interfaces with other local services, and perceived threats associated with funding and staff retention. Findings were similar between the two IST models. Conclusions ISTs are able to offer care and specialist support that is valued by families, service users and other care providers. However, they face several operational challenges that should be addressed if ISTs are to reach their potential along with community intellectual disability services in supporting adults with intellectual disabilities who display behaviour that challenges in the community

Clinical and cost evaluation of two models of specialist intensive support teams for adults with intellectual disabilities who display behaviours that challenge: the IST-ID mixed-methods study

Background Intensive support teams (ISTs) are recommended for individuals with intellectual disabilities who display behaviours that challenge. However, there is currently little evidence about the clinical and cost-effectiveness of IST models operating in England. Aims To investigate the clinical and cost-effectiveness of IST models. Method We carried out a cohort study to evaluate the clinical and cost-effectiveness of two previously identified IST models (independent and enhanced) in England. Adult participants (n = 226) from 21 ISTs (ten independent and 11 enhanced) were enrolled. The primary outcome was change in challenging behaviour between baseline and 9 months as measured by the Aberrant Behaviour Checklist-Community version 2. Results We found no statistically significant differences between models for the primary outcome (adjusted β = 4.27; 95% CI −6.34 to 14.87; P = 0.430) or any secondary outcomes. Quality-adjusted life-years (0.0158; 95% CI: −0.0088 to 0.0508) and costs (£3409.95; 95% CI −£9957.92 to £4039.89) of the two models were comparable. Conclusions The study provides evidence that both models were associated with clinical improvement for similar costs at follow-up. We recommend that the choice of service model should rest with local services. Further research should investigate the critical components of IST care to inform the development of fidelity criteria, and policy makers should consider whether roll out of such teams should be mandated