Economic Valuation of PFAS Remediation in New Hampshire Municipal Drinking Water Systems: A Contingent Valuation Approach

In the past two decades there has been an increase in detection and awareness of PFAS (Per- or Polyfluoroalkyl substances) chemicals in groundwater and drinking water in the United States. In stark contrast to other known harmful chemical pollutants, little is known yet about the specific epidemiological and toxicological effects of prolonged intake and consumption of PFAS chemicals in environmentally occurring levels. New Hampshire in particular has encountered two high-profile episodes of PFAS contamination with hotspots in Merrimack, NH due to factory pollution and Pease International Tradeport in Portsmouth, NH due to military activity. These instances have brought increased attention to the issue from both the state legislature and residents.The purpose of this study was to ask New Hampshire residents how much they value the removal of PFAS chemicals from their public drinking water systems to reduce the risk of possible negative health outcomes that come with PFAS intake. Using data from a September 2021 online survey of New Hampshire residents and employing the contingent valuation survey method in the form of Willingness-To-Pay, we used several regression techniques, we determined that NH residents are willing to pay an additional $13.07 to their existing water bill to remove the risk of negative health outcomes stemming from PFAS consumption. Throughout the models, the most important confounding factor influencing higher willingness-to-pay values was the presence of moderate or major existing health concerns about drinking tap water

The Chester 'Command' System c. 71-96 C.E.

This thesis centres on the operations of the Chester ‘command’ system in the region of North Wales, roughly from the first year in which Petilius Cerialis served as the governor of Britain to the death of Emperor Domitian. Despite the several auxiliary forts that were occupied simultaneously during this period, seven military stations have been selected to demonstrate the direct application of Roman rule in the region imposed by a fortified network of defences and communications: the legionary fortress of Chester, the fortress at Wroxeter, the fort at Forden Gaer, along with Caersws II, Pennal, Caernarfon, and Caerhun. After the fortress at Wroxeter was abandoned c. 90 C.E. the fortress of Chester held sole legionary authority and administered control over the auxiliary units stationed in North Wales and the Welsh midlands. Each fort within this group was strategically positioned to ensure the advantages of its location and environment were exploited. The sites of Wroxeter, Forden Gaer, Caersws II, and Pennal were not only placed on the same road (RR64) to maintain a reliable communications system across the Severn valley, but the paths through which indigenous people could travel north or south were limited as each military post controlled access to the preferred land routes over the River Severn and the River Dyfi. The fortress at Chester, and the forts of Caerhun and Caernarfon, however, were northern coastal sites that utilised large ships for transport and for their garrisons to exchange goods between one another. While no naval base has been officially identified on the west coast of Wales, Pennal was accessible to ships and a 17th century description of a potential Roman port facility near the site suggests provisions were also imported by this fort. Each military station described here was designed to preserve Roman political and military supremacy in North Wales beyond the late-1st century C.E

Exploiting satellite-based rainfall for weather index insurance: the challenges of spatial and temporal aggregation

Lack of access to insurance exacerbates the impact of climate variability on smallholder famers in Africa. Unlike traditional insurance, which compensates proven agricultural losses, weather index insurance (WII) pays out in the event that a weather index is breached. In principle, WII could be provided to farmers throughout Africa. There are two data-related hurdles to this. First, most farmers do not live close enough to a rain gauge with sufficiently long record of observations. Second, mismatches between weather indices and yield may expose farmers to uncompensated losses, and insurers to unfair payouts – a phenomenon known as basis risk. In essence, basis risk results from complexities in the progression from meteorological drought (rainfall deficit) to agricultural drought (low soil moisture). In this study, we use a land-surface model to describe the transition from meteorological to agricultural drought. We demonstrate that spatial and temporal aggregation of rainfall results in a clearer link with soil moisture, and hence a reduction in basis risk. We then use an advanced statistical method to show how optimal aggregation of satellite-based rainfall estimates can reduce basis risk, enabling remotely sensed data to be utilized robustly for WII

Hypertension and hand-foot skin reactions related to VEGFR2 genotype and improved clinical outcome following bevacizumab and sorafenib

BACKGROUND: Hypertension (HT) and hand-foot skin reactions (HFSR) may be related to the activity of bevacizumab and sorafenib. We hypothesized that these toxicities would correspond to favorable outcome in these drugs, that HT and HFSR would coincide, and that VEGFR2 genotypic variation would be related to toxicity and clinical outcomes. METHODS: Toxicities (≥ grade 2 HT or HFSR), progression-free survival (PFS), and overall survival (OS) following treatment initiation were evaluated. Toxicity incidence and VEGFR2 H472Q and V297I status were compared to clinical outcomes. RESULTS: Individuals experiencing HT had longer PFS following bevacizumab therapy than those without this toxicity in trials utilizing bevacizumab in patients with prostate cancer (31.5 vs 14.9 months, n = 60, P = 0.0009), and bevacizumab and sorafenib in patients with solid tumors (11.9 vs. 3.7 months, n = 27, P = 0.052). HT was also linked to a > 5-fold OS benefit after sorafenib and bevacizumab cotherapy (5.7 versus 29.0 months, P = 0.0068). HFSR was a marker for prolonged PFS during sorafenib therapy (6.1 versus 3.7 months respectively, n = 113, P = 0.0003). HT was a risk factor for HFSR in patients treated with bevacizumab and/or sorafenib (OR(95%CI) = 3.2(1.5-6.8), P = 0.0024). Carriers of variant alleles at VEGFR2 H472Q experienced greater risk of developing HT (OR(95%CI) = 2.3(1.2 - 4.6), n = 170, P = 0.0154) and HFSR (OR(95%CI) = 2.7(1.3 - 5.6), n = 170, P = 0.0136). CONCLUSIONS: This study suggests that HT and HFSR may be markers for favorable clinical outcome, HT development may be a marker for HFSR, and VEGFR2 alleles may be related to the development of toxicities during therapy with bevacizumab and/or sorafenib

The International Landscape of Medical Licensing Examinations: A Typology Derived From a Systematic Review

Abstract Background: National licensing examinations (NLEs) are large-scale examinations usually taken by medical doctors close to the point of graduation from medical school. Where NLEs are used, success is usually required to obtain a license for full practice. Approaches to national licensing, and the evidence that supports their use, varies significantly across the globe. This paper aims to develop a typology of NLEs, based on candidacy, to explore the implications of different examination types for workforce planning. Methods: A systematic review of the published literature and medical licensing body websites, an electronic survey of all medical licensing bodies in highly developed nations, and a survey of medical regulators. Results: The evidence gleaned through this systematic review highlights four approaches to NLEs: where graduating medical students wishing to practice in their national jurisdiction must pass a national licensing exam before they are granted a license to practice; where all prospective doctors, whether from the national jurisdiction or international medical graduates, are required to pass a national licensing exam in order to practice within that jurisdiction; where international medical graduates are required to pass a licensing exam if their qualifications are not acknowledged to be comparable with those students from the national jurisdiction; and where there are no NLEs in operation. This typology facilitates comparison across systems and highlights the implications of different licensing systems for workforce planning. Conclusion: The issue of national licensing cannot be viewed in isolation from workforce planning; future research on the efficacy of national licensing systems to drive up standards should be integrated with research on the implications of such systems for the mobility of doctors to cross borders

Collaborative patch-based super-resolution for diffusion-weighted images

In this paper, a new single image acquisition super-resolution method is proposed to increase image resolution of diffusion weighted (DW) images. Based on a nonlocal patch-based strategy, the proposed method uses a non-diffusion image (b0) to constrain the reconstruction of DW images. An extensive validation is presented with a gold standard built on averaging 10 high-resolution DW acquis itions. A comparison with classical interpo- lation methods such as trilinear and B-spline demonstrates the competitive results of our proposed approach in termsofimprovementsonimagereconstruction,fractiona lanisotropy(FA)estimation,generalizedFAandangular reconstruction for tensor and high angular resolut ion diffusion imaging (HARDI) models. Besides, fi rst results of reconstructed ultra high resolution DW images are presented at 0.6 × 0.6 × 0.6 mm 3 and0.4×0.4×0.4mm 3 using our gold standard based on the average of 10 acquisitions, and on a single acquisition. Finally, fi ber tracking results show the potential of the proposed super-resolution approach to accurately analyze white matter brain architecture.We thank the reviewers for their useful comments that helped improve the paper. We also want to thank the Pr Louis Collins for proofreading this paper and his fruitful comments. Finally, we want to thank Martine Bordessoules for her help during image acquisition of DWI used to build the phantom. This work has been supported by the French grant "HR-DTI" ANR-10-LABX-57 funded by the TRAIL from the French Agence Nationale de la Recherche within the context of the Investments for the Future program. This work has been also partially supported by the French National Agency for Research (Project MultImAD; ANR-09-MNPS-015-01) and by the Spanish grant TIN2011-26727 from the Ministerio de Ciencia e Innovacion. This work benefited from the use of FSL (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/), FiberNavigator (code.google.com/p/fibernavigator/), MRtrix software (http://www. brain.org.au/software/mrtrix/) and ITKsnap (www.itk.org).Coupé, P.; Manjón Herrera, JV.; Chamberland, M.; Descoteaux, M.; Hiba, B. (2013). Collaborative patch-based super-resolution for diffusion-weighted images. NeuroImage. 83:245-261. https://doi.org/10.1016/j.neuroimage.2013.06.030S2452618

Trade and trade-offs: shipping in changing climates

This paper addresses the evolution of maritime transport demand in response to global climate change mitigation and adaptation efforts. The complexity of the global shipping system makes predicting volumes and patterns of long-term future international maritime trade a challenging task which is best explored by building scenarios rather than ‘precise’ forecasts. We present four contrasting scenarios of international maritime trade out to 2050, available in high resolution in terms of the dimensions studied (regions, countries, commodities, decades), which are consistent with high and low levels of global CO2 mitigation and associated climate impacts. The scenarios project trade increasing to between two and four times the 2010 value by 2050. Scenarios characterised by low temperature increases and material intensity lead to the lower bound trade increase with high trade growth in bioenergy commodities. Unfettered production growth across countries, high temperature increases and material intensity lead to a quadrupling of trade across energy, containerised, dry and wet commodities. The estimated range is lower than those in existing scenarios and forecasts in which globalisation is assumed to continue apace. The scenarios which project the highest growth presupposes both limited decarbonisation (in contrast to the Paris Agreement) and continued growth in expanding markets. The scenarios therefore become a valuable policy and decision-making tool to address technological and operational change required of the shipping sector, if it is to deliver mitigation in line with the Paris Agreement

Expression of OATP Family Members in Hormone-Related Cancers: Potential Markers of Progression

The organic anion transporting polypeptide (OATP) family of transporters has been implicated in prostate cancer disease progression probably by transporting hormones or drugs. In this study, we aimed to elucidate the expression, frequency, and relevance of OATPs as a biomarker in hormone-dependent cancers. We completed a study examining SLCO1B3, SLCO1B1 and SLCO2B1 mRNA expression in 381 primary, independent patient samples representing 21 cancers and normal tissues. From a separate cohort, protein expression of OATP1B3 was examined in prostate, colon, and bladder tissue. Based on expression frequency, SLCO2B1 was lower in liver cancer (P = 0.04) which also trended lower with decreasing differentiation (P = 0.004) and lower magnitude in pancreatic cancer (P = 0.05). SLCO2B1 also had a higher frequency in thyroid cancer (67%) than normal (0%) and expression increased with stage (P = 0.04). SLCO1B3 was expressed in 52% of cancerous prostate samples and increased SLCO1B3 expression trended with higher Gleason score (P = 0.03). SLCO1B3 expression was also higher in testicular cancer (P = 0.02). SLCO1B1 expression was lower in liver cancer (P = 0.04) which trended lower with liver cancer grade (P = 0.0004) and higher with colon cancer grade (P = 0.05). Protein expression of OATP1B3 was examined in normal and cancerous prostate, colon, and bladder tissue samples from an independent cohort. The results were similar to the transcription data, but showed distinct localization. OATPs correlate to differentiation in certain hormone-dependent cancers, thus may be useful as biomarkers for assessing clinical treatment and stage of disease

Origin and Evolution of European Community-Acquired Methicillin- Resistant Staphylococcus aureus

ABSTRACT Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) was recognized in Europe and worldwide in the late 1990s. Within a decade, several genetically and geographically distinct CA-MRSA lineages carrying the small SCCmec type IV and V genetic elements and the Panton-Valentine leukocidin (PVL) emerged around the world. In Europe, the predominant CA-MRSA strain belongs to clonal complex 80 (CC80) and is resistant to kanamycin/amikacin and fusidic acid. CC80 was first reported in 1993 but was relatively rare until the late 1990s. It has since been identified throughout North Africa, the Middle East, and Europe, with recent sporadic reports in sub-Saharan Africa. While strongly associated with skin and soft tissue infections, it is rarely found among asymptomatic carriers. Methicillin-sensitive S. aureus (MSSA) CC80 strains are extremely rare except in sub-Saharan Africa. In the current study, we applied whole-genome sequencing to a global collection of both MSSA and MRSA CC80 isolates. Phylogenetic analyses strongly suggest that the European epidemic CA-MRSA lineage is derived from a PVL-positive MSSA ancestor from sub-Saharan Africa. Moreover, the tree topology suggests a single acquisition of both the SCCmec element and a plasmid encoding the fusidic acid resistance determinant. Four canonical SNPs distinguish the derived CA-MRSA lineage and include a nonsynonymous mutation in accessory gene regulator C (agrC). These changes were associated with a star-like expansion into Europe, the Middle East, and North Africa in the early 1990s, including multiple cases of cross-continent imports likely driven by human migrations. IMPORTANCE With increasing levels of CA-MRSA reported from most parts of the Western world, there is a great interest in understanding the origin and factors associated with the emergence of these epidemic lineages. To trace the origin, evolution, and dissemination pattern of the European CA-MRSA clone (CC80), we sequenced a global collection of strains of the S. aureus CC80 lineage. Our study determined that a single descendant of a PVL-positive methicillin-sensitive ancestor circulating in sub-Saharan Africa rose to become the dominant CA-MRSA clone in Europe, the Middle East, and North Africa. In the transition from a methicillin-susceptible lineage to a successful CA-MRSA clone, it simultaneously became resistant to fusidic acid, a widely used antibiotic for skin and soft tissue infections, thus demonstrating the importance of antibiotic selection in the success of this clone. This finding furthermore highlights the significance of horizontal gene acquisitions and underscores the combined importance of these factors for the success of CA-MRSA