Curbing the hepatitis C virus epidemic in Pakistan: The impact of scaling up treatment and prevention for achieving elimination

Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide.Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets.Results: With no further treatment (currently ∼150 000 treated annually) during 2016-30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually.Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan\u27s HCV burden will increase markedly

Go home?: The politics of immigration controversies

The 2013 Go Home vans marked a turning point in government-sponsored communication designed to demonstrate control and toughness on immigration. In this study, the authors explore the effects of this toughness: on policy, public debate, pro-migrant and anti-racist activism, and on the everyday lives of people in Britain. Bringing together an authorial team of eight respected social researchers, alongside the voices of community organisations, policy makers, migrants and citizens, and with an afterword by journalist Kiri Kankhwende, this is an important intervention in one of the most heated social issues of our time

Missing the full story: First estimates of carbon deposition rates for the European flat oyster, Ostrea edulis

Globally, momentum to restore damaged habitats has been increasing. For example, the number of European shellfish restoration projects has quadrupled in the past 3 years. In line with the increasing focus on both restoration and climate change mitigation efforts, this study highlights how these two practices can complement each other.This experimental study quantifies the active and passive sediment deposition associated with the European flat oyster (Ostrea edulis) and the organic and inorganic carbon fractions of the deposits. Treatments included ‘dead’, ‘live’, and control to account for (i) passive deposition, (ii) biodeposition and passive deposition, and (iii) background deposition respectively. By utilizing these data, the expected carbon deposition associated with a restored flat oyster bed was investigated.The experiment was conducted ex situ, with natural seawater input. Covariate data on temperature, suspended particulate influx, salinity, and oxygen availability were recorded. Enhanced sedimentation (2.9 times) and organic carbon deposition (three times) were observed in the presence of living oysters, compared with the control. The shell structure of the oysters had no influence on passive sedimentation in this study.By developing a full understanding of the ecosystem services (functioning, supporting, regulating, and cultural) provided by a habitat, it becomes possible to quantify overall ecosystem function. This evidence is key in advising policymakers, restoration funders, and marine spatial planners on the connection between keystone species restoration, ecosystem service restoration, and conservation management.The enhancement of benthopelagic coupling by the European flat oyster, evidenced here for the first time, is contextualized from the perspective of quantification of ecosystem service provision for both restoration practices and blue carbon store management. The data produced in this study are discussed comparatively with work that has focused on other species from both Europe and the US

A blue carbon model for the European flat oyster (Ostrea edulis) and its application in environmental restoration

1. Historically, considerations of the carbon budget of bivalve shellfish have disproportionately focused on the cycling of carbon in shell alone, overlooking respiratory release and the potential role of bivalve shellfish habitats in the stabilization of sediment, and therefore of carbon. 2. Data on carbon cycling are key to providing essential evidence to inform evaluation of management strategies and the business case for restoration of European flat oyster (Ostrea edulis) habitats. The purpose of this study was to examine the flat oyster carbon budget at the scale of the individual and to set out a framework to enable future comparisons of carbon budgets between ecosystems. 3. Through the combination of previously established work with measurements of calcification and respiration both in situ and ex situ, a carbon budget at the scale of a single oyster was determined. 4. In consideration of the flat oyster carbon budget, the inclusion of the deposition of sedimentary carbon, as well as carbon stored in shell, balanced with the release of carbon through respiration and calcification suggests that these habitats are unlikely to be significant carbon sinks in the context of global climate change mitigation. However, the recovery of flat oyster beds is likely to facilitate the accretion of substantial carbon stocks that are nevertheless important in conservation management

Granular discharge and clogging for tilted hoppers

We measure the flux of spherical glass beads through a hole as a systematic function of both tilt angle and hole diameter, for two different size beads. The discharge increases with hole diameter in accord with the Beverloo relation for both horizontal and vertical holes, but in the latter case with a larger small-hole cutoff. For large holes the flux decreases linearly in cosine of the tilt angle, vanishing smoothly somewhat below the angle of repose. For small holes it vanishes abruptly at a smaller angle. The conditions for zero flux are discussed in the context of a {\it clogging phase diagram} of flow state vs tilt angle and ratio of hole to grain size

Internet Facilitated Rape: A Multivariate Model of Offense Behavior

In recent years there has been a significant increase in individuals reporting they have been raped by someone they have met through the internet (IFR). Previous literature has primarily focused on child victims, hence, the overriding aim of this study is to further our understanding of IFR in terms of overt crime scene behaviour. The sample consisted of 144 single IFR cases and two comparative samples of age-matched non-IFR offenders (confidence approach and surprise approach). Thirty-eight crime scene actions were coded as either present or absent for each offence. Findings suggest that the platforms IFR offenders use to meet their victims were not suggestive of the behaviour they were likely to display. In terms of specific offence behaviours, the IFR and confidence approach samples were considerably similar and both samples were comparatively different from the surprise approach cases. A smallest space analysis of the IFR sample revealed three distinct themes of behaviour with 71% of cases being assigned to a dominant behavioural theme. The practical and theoretical implications of the findings will be discussed

Curbing the hepatitis C virus epidemic in Pakistan: the impact of scaling up treatment and prevention for achieving elimination

Background: The World Health Organization (WHO) has developed a global health strategy to eliminate viral hepatitis. We project the treatment and prevention requirements to achieve the WHO HCV elimination target of reducing HCV incidence by 80% and HCV-related mortality by 65% by 2030 in Pakistan, which has the second largest HCV burden worldwide. Methods: We developed an HCV transmission model for Pakistan, and calibrated it to epidemiological data from a national survey (2007), surveys among people who inject drugs (PWID), and blood donor data. Current treatment coverage data came from expert opinion and published reports. The model projected the HCV burden, including incidence, prevalence and deaths through 2030, and estimated the impact of varying prevention and direct-acting antiviral (DAA) treatment interventions necessary for achieving the WHO HCV elimination targets. Results: With no further treatment (currently ?150 000 treated annually) during 2016�30, chronic HCV prevalence will increase from 3.9% to 5.1%, estimated annual incident infections will increase from 700 000 to 1 100 000, and 1 400 000 HCV-associated deaths will occur. To reach the WHO HCV elimination targets by 2030, 880 000 annual DAA treatments are required if prevention is not scaled up and no treatment prioritization occurs. By targeting treatment toward persons with cirrhosis (80% treated annually) and PWIDs (double the treatment rate of non-PWIDs), the required annual treatment number decreases to 750 000. If prevention activities also halve transmission risk, this treatment number reduces to 525 000 annually. Conclusions: Substantial HCV prevention and treatment interventions are required to reach the WHO HCV elimination targets in Pakistan, without which Pakistan�s HCV burden will increase markedly

DNA barcoding the native flowering plants and conifers of Wales

We present the first national DNA barcode resource that covers the native flowering plants and conifers for the nation of Wales (1143 species). Using the plant DNA barcode markers rbcL and matK, we have assembled 97.7% coverage for rbcL, 90.2% for matK, and a dual-locus barcode for 89.7% of the native Welsh flora. We have sampled multiple individuals for each species, resulting in 3304 rbcL and 2419 matK sequences. The majority of our samples (85%) are from DNA extracted from herbarium specimens. Recoverability of DNA barcodes is lower using herbarium specimens, compared to freshly collected material, mostly due to lower amplification success, but this is balanced by the increased efficiency of sampling species that have already been collected, identified, and verified by taxonomic experts. The effectiveness of the DNA barcodes for identification (level of discrimination) is assessed using four approaches: the presence of a barcode gap (using pairwise and multiple alignments), formation of monophyletic groups using Neighbour-Joining trees, and sequence similarity in BLASTn searches. These approaches yield similar results, providing relative discrimination levels of 69.4 to 74.9% of all species and 98.6 to 99.8% of genera using both markers. Species discrimination can be further improved using spatially explicit sampling. Mean species discrimination using barcode gap analysis (with a multiple alignment) is 81.6% within 10×10 km squares and 93.3% for 2×2 km squares. Our database of DNA barcodes for Welsh native flowering plants and conifers represents the most complete coverage of any national flora, and offers a valuable platform for a wide range of applications that require accurate species identification

Inhibiting ERK Activation with CI-1040 Leads to Compensatory Upregulation of Alternate MAPKs and Plasminogen Activator Inhibitor-1 following Subtotal Nephrectomy with No Impact on Kidney Fibrosis

Extracellular-signal regulated kinase (ERK) activation by MEK plays a key role in many of the cellular processes that underlie progressive kidney fibrosis including cell proliferation, apoptosis and transforming growth factor β1-mediated epithelial to mesenchymal transition. We therefore assessed the therapeutic impact of ERK1/2 inhibition using a MEK inhibitor in the rat 5/6 subtotal nephrectomy (SNx) model of kidney fibrosis. There was a twentyfold upregulation in phospho-ERK1/2 expression in the kidney after SNx in Male Wistar rats. Rats undergoing SNx became hypertensive, proteinuric and developed progressive kidney failure with reduced creatinine clearance. Treatment with the MEK inhibitor, CI-1040 abolished phospho- ERK1/2 expression in kidney tissue and prevented phospho-ERK1/2 expression in peripheral lymphocytes during the entire course of therapy. CI-1040 had no impact on creatinine clearance, proteinuria, glomerular and tubular fibrosis, and α-smooth muscle actin expression. However, inhibition of ERK1/2 activation led to significant compensatory upregulation of the MAP kinases, p38 and JNK in kidney tissue. CI-1040 also increased the expression of plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasmin-dependent matrix metalloproteinases. Thus inhibition of ERK1/2 activation has no therapeutic effect on kidney fibrosis in SNx possibly due to increased compensatory activation of the p38 and JNK signalling pathways with subsequent upregulation of PAI-1