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While there is a widely shared sense that policy action is required for the electricity system in the United States to decarbonize, most climate policy courses focus only on a handful of federal and state policies. In reality, however, there is a web of state- and local-government-level policy choices that can serve to facilitate or hinder an energy transition, which is less discussed and researched in higher education. A new graduate course, first taught in Winter 2019 at the University of Michigan in the Ford School of Public Policy, employs a range of unique course design elements to introduce the idea of a complex web of policies and actors in the energy transition, and to provide students with practical skills to prepare them to be leaders in the transition. By interviewing students 18 months after finishing the Winter 2019 iteration of the course, in addition to surveying students enrolled in the second interaction of the course in the Fall 2020 semester, this study finds that student experiential learning and applied projects, in tandem with the instructor’s focus on local, real-world implications, was found to be effective in preparing students to be climate leaders.

Austrian economists have debated issues of monetary theory and inflation extensively, but there is still no agreement on the definition of inflation. Mises (1953, 240) defined inflation as an increase in the supply of money not offset by an increase in the demand for money, leading to a fall in the purchasing power of money (PPM). Rothbard (2009, 990) defined it as an increase of fiduciary media, explicitly excluding increases in the stock of specie. This article will argue that Rothbard’s definition is the most suitable for economic discourse and analysis and can be generalized to any market-selected money. By consistently applying the method of counterfactual reasoning (Hülsmann 2003), it is shown that the processes of money creation lead to very different outcomes depending on the conditions of money production. The term “inflation” is therefore best reserved for money production in the form of bank credit expansion or fiat money creation. These phenomena are external to the market, and the process of redistribution they bring about runs counter to the structure of income and wealth that would have emerged in their absence.

Introduction: CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is an ongoing, prospective, multicenter study designed to evaluate the effect of maximal cholesterol-lowering on cardiovascular (CV) risk. Aggressive lipid-lowering with HMG CoA-reductase inhibitors (e.g. statins), ezetimibe, and PCSK9 inhibitors (such as evolocumab) reduce atherothrombotic events. Statins reduce cholesterol dramatically and are also felt to have pleiotropic, anti-inflammatory properties. We compared the impact of statins and ezetimibe on thrombotic biomarkers after maximal lipid lowering with PCSK9 inhibition. Methods: CHORD enrolled subjects (n=57, mean age 52 ± 15 years, 44% male, 58% diabetes) with LDL-cholesterol >100mg/dl and treated with evolocumab (140mg every 2 weeks) plus either atorvastatin (80mg/day, n=27), or ezetimibe (10mg/day, n=30) for 30-days. High-sensitivity C-reactive protein (hs-CRP) and biomarkers of thrombosis (LEGENDplex Human Thrombosis Panel) were measured at baseline and follow-up. Results: Significant LDL-C reductions were observed in both the evolocumab + atorvastatin (130 mg/dl [123 - 145] to 31 mg/dl [27 - 39], pFigure 1). Conclusion: Despite similar levels of LDL-C reduction, statins plus evolocumab cause greater reductions in biomarkers of thrombosis and inflammation than ezetimibe and evolocumab. These data suggest that statins provide benefits over and above LDL-C reduction.

Background: Dyslipidemia induces a proinflammatory endothelium and vascular dysfunction. Lipid lowering therapy (LLT) consistently reduces cardiovascular (CV) events. Clinical studies suggest that statin-based LLT has pleiotropic anti-inflammatory effects beyond cholesterol reduction. However, the impact of statins or ezetimibe on top of potent cholesterol reduction is unknown. Thus, on a background of PCSK9 inhibition (with evolocumab), we analyzed the effect of LLT with atorvastatin or ezetimibe on the endothelium using a novel direct brachial vein (BV) endothelial cell (EC) harvesting technique. Methods: CHORD (CHOlesterol lowering and Residual Risk in Diabetes) is an ongoing, prospective study designed to evaluate the effect of maximal LLT on CV risk. Subjects with LDL-C >100mg/dl were treated with evolocumab (140mg/2 weeks) and either atorvastatin (80mg/day) or ezetimibe (10mg/day) for 30 days. In a subset of participants, EC harvesting was performed by inserting a J-wire into the BV, and ECs were isolated and analyzed using next generation RNA sequencing. Results: Among 20 participants (11 atorvastatin, 9 ezetimibe) undergoing EC RNASeq, median LDL-C (130 mg/dl, IQR [110, 147]) decreased by 75% [67, 81] on background PCSK9 inhibition with no significant difference in 30-day LDL-C between atorvastatin (27 mg/dl [20, 32]) and ezetimibe (41 mg/dl [26, 53]) groups (p=0.07). Following cholesterol reduction, 850 genes were upregulated and 2468 were downregulated (p Conclusions: Robust lipid lowering with PCSK9 inhibition plus statins, as opposed to ezetimibe has anti-inflammatory effects and suggests a preferred strategy to improve the endothelium and reduce CV risk.

Background Early cancer detection could identify tumors at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. Participants and methods The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer] were divided into training and validation sets. Plasma cfDNA underwent bisulfite sequencing targeting a panel of >100 000 informative methylation regions. A classifier was developed and validated for cancer detection and tissue of origin (TOO) localization. Results Performance was consistent in training and validation sets. In validation, specificity was 99.3% [95% confidence interval (CI): 98.3% to 99.8%; 0.7% false-positive rate (FPR)]. Stage I–III sensitivity was 67.3% (CI: 60.7% to 73.3%) in a pre-specified set of 12 cancer types (anus, bladder, colon/rectum, esophagus, head and neck, liver/bile-duct, lung, lymphoma, ovary, pancreas, plasma cell neoplasm, stomach), which account for ∼63% of US cancer deaths annually, and was 43.9% (CI: 39.4% to 48.5%) in all cancer types. Detection increased with increasing stage: in the pre-specified cancer types sensitivity was 39% (CI: 27% to 52%) in stage I, 69% (CI: 56% to 80%) in stage II, 83% (CI: 75% to 90%) in stage III, and 92% (CI: 86% to 96%) in stage IV. In all cancer types sensitivity was 18% (CI: 13% to 25%) in stage I, 43% (CI: 35% to 51%) in stage II, 81% (CI: 73% to 87%) in stage III, and 93% (CI: 87% to 96%) in stage IV. TOO was predicted in 96% of samples with cancer-like signal; of those, the TOO localization was accurate in 93%. Conclusions cfDNA sequencing leveraging informative methylation patterns detected more than 50 cancer types across stages. Considering the potential value of early detection in deadly malignancies, further evaluation of this test is justified in prospective population-level studies.

University research is one of the main drivers of knowledge creation, innovation, and economic development. In this essay, we examine the impacts of the COVID-19 global pandemic on Wilfrid Laurier University’s (Laurier’s) research community. We provide a firsthand account of events and actions taken to support our researchers through this challenging time. We also reflect upon the near-term future and longer-term prospects for the recovery of research at Laurier. Our university’s experience is not unique in either the Ontario or Canadian contexts. We offer this essay as both a historical accounting and a case study of the pandemic’s impact on this sector of Canadian society.

William Stanley Jevons’s “Sunspot Theory” of business cycles related the number of spots on the sun to economic activity, primarily through the weather and agriculture, but also through psychological components like optimism and uncertainty. The theory is widely discredited, but John Maynard Keynes agreed with Jevons’s underlying use of market participants’ moods to explain the transmission and magnification of the boom and bust phases of the cycle. Jevons’s use of psychology to explain business cycles originated in John Mills’s 1867 “On Credit Cycles and the Origin of Commercial Panics.” This paper establishes this connection between Mills, Jevons, and Keynes, which is not recorded in the literature that explores the origin of Keynes’s psychological “animal spirits” concept. John Mills’s “On Credit Cycles” is not well-known, so it is reviewed at length, noting points of comparison to the business cycle theories of both Keynes and the Austrian school. Another reason for the extensive treatment of Mills’s “On Credit Cycles” is that Jevons regarded it as an accurate description of the business cycle, even if he was unsatisfied with the unexplained fluctuations in “commercial moods.” If it is true that Jevons essentially founded the idea of market psychology and attitude determinants of the business cycle, then his impact on modern economic theory and policy via Keynes has been underestimated.

Objectives Previous surveys have demonstrated high rates of early childhood caries (ECC) in the Alaska Native (AN) population of western Alaska. There are many challenges to providing dental care in this road-less Yukon-Kuskokwim Delta region. The regional Tribal Health Organization implemented an electronic dental record (EDR) system in the late 1990s. We explored use of the EDR to establish an oral health surveillance system in children. Methods We contracted with EDR software developers to implement calculation of a summary count of decayed (d), missing (m) or filled (f) primary (dmft) score for each individual. We calculated the yearly average dmft scores for 2011-2019 for children aged 3 and 5 years with a comprehensive exam in a given year. We also assessed the number of children undergoing full mouth dental rehabilitation (FMDR). We used US census data population estimates for these age groups to calculate rates. Results Over the 9-year period, 2,427 3-year-old children (47 percent of all 3-year olds over this period), received a comprehensive exam; increasing from 24 percent in 2011 to 62 percent in 2019. Their average dmft score over the 9-years was 6.4 with a significant annual decline over this period. Seventy percent of AN children who turned 6 between 2015 and 2019 had received at least one FMDR. Conclusions An oral health surveillance system has been established in western Alaska using the Electronic Dental Record. High rates of ECC and FMDR were observed. This surveillance system will allow assessments of ECC prevalence and impact of dental interventions.

Prioritizing the management of invasive alien species (IAS) is of global importance and within Europe integral to the EU IAS regulation. To prioritize management effectively, the risks posed by IAS need to be assessed, but so too does the feasibility of their management. While the risk of IAS to the EU has been assessed, the feasibility of management has not. We assessed the feasibility of eradicating 60 new (not yet established) and 35 emerging (established with limited distribution) species that pose a threat to the EU, as identified by horizon scanning. The assessment was carried out by 34 experts in invasion management from across Europe, applying the Non-Native Risk Management scheme to defined invasion scenarios and eradication strategies for each species, assessing the feasibility of eradication using seven key risk management criteria. Management priorities were identified by combining scores for risk (derived from horizon scanning) and feasibility of eradication. The results show eradication feasibility score and risk score were not correlated, indicating that risk management criteria evaluate different information than risk assessment. In all, 17 new species were identified as particularly high priorities for eradication should they establish in the future, whereas 14 emerging species were identified as priorities for eradication now. A number of species considered highest priority for eradication were terrestrial vertebrates, a group that has been the focus of a number of eradication attempts in Europe. However, eradication priorities also included a diverse range of other taxa (plants, invertebrates and fish) suggesting there is scope to broaden the taxonomic range of attempted eradication in Europe. We demonstrate that broad scale structured assessments of management feasibility can help prioritize IAS for management. Such frameworks are needed to support evidence-based decision-making. ispartof: GLOBAL CHANGE BIOLOGY vol:26 issue:11 pages:6235-6250 ispartof: location:England status: published

Arsenic exposure has been related to numerous adverse cardiovascular outcomes. The aim of this study was to investigate the cross-sectional and prospective association between arsenic exposure with echocardiographic measures of left ventricular (LV) geometry and functioning.A total of 1337 young adult participants free of diabetes mellitus and cardiovascular disease were recruited from the SHFS (Strong Heart Family Study). The sum of inorganic and methylated arsenic concentrations in urine (ΣAs) at baseline was used as a biomarker of arsenic exposure. LV geometry and functioning were assessed using transthoracic echocardiography at baseline and follow-up.Mean follow-up was 5.6 years, and median (interquartile range) of ΣAs was 4.2 (2.8-6.9) µg/g creatinine. Increased arsenic exposure was associated with prevalent LV hypertrophy, with an odds ratio (95% CI) per a 2-fold increase in ΣAs of 1.47 (1.05-2.08) in all participants and of 1.58 (1.04-2.41) among prehypertensive or hypertensive individuals. Measures of LV geometry, including LV mass index, left atrial systolic diameter, interventricular septum, and LV posterior wall thickness, were positively and significantly related to arsenic exposure. Among measures of LV functioning, stroke volume, and ejection fraction were associated with arsenic exposure.Arsenic exposure was related to an increase in LV wall thickness and LV hypertrophy in young American Indians with a low burden of cardiovascular risk factors. The relationship was stronger in participants with prehypertension or hypertension, suggesting that potential cardiotoxic effects of arsenic might be more pronounced in individuals already undergoing cardiovascular adaptive mechanisms following elevated systemic blood pressure.

Deployment of distributed energy resources (DERs) is accelerating across the United States. These assets have the potential to provide cost-effective grid services and bulk power while supporting a low-cost energy transition to carbon-free electricity. Full integration of these resources into the bulk power system remains a barrier to unlocking the potential value of these assets. The regional wholesale energy markets, originally designed to integrate centralized, dispatchable power plants, must be reformed to adapt to the changing potential resource mix. The current day-ahead and real-time system is poorly designed for DERs. Day-ahead DER forecast errors create exposure to real-time price variations, as resources committed in the day-ahead market are required to rebalance in real-time, challenging the business model for DERs. New intraday markets with multiple discrete intermediate auctions between the day-ahead market and real-time market are needed to enable proper integration of DERs and efficient mitigation of forecast uncertainty risk. These markets must incorporate financially-binding commitments, closer-to-dispatch price signals, and adequate liquidity to ensure competition. Intermediate auctions should be built on top of existing intraday processes in each regional market, incorporating the principles of the existing market structures and leveraging the benefits of the centralized dispatch systems. Regional transmission organization (RTOs) and Independent System Operators (ISOs) should pursue and implement intermediate auctions to support fair, open, and efficient markets in the U.S.

One of the EPPO (European and Mediterranean Plant Protection Organization) data sheets on pests recommended for regulation, being an output from the expert working group that risk assessed A. philoxeroides in April 2015.

Small, 1st and 2nd-order, headwater streams and ponds play essential roles in providing natural flood control, trapping sediments and contaminants, retaining nutrients, and maintaining biological diversity, which extend into downstream reaches, lakes and estuaries. However, the large geographic extent and high connectivity of these small water bodies with the surrounding terrestrial ecosystem makes them particularly vulnerable to growing land-use pressures and environmental change. The greatest pressure on the physical processes in these waters has been their extension and modification for agricultural and forestry drainage, resulting in highly modified discharge and temperature regimes that have implications for flood and drought control further downstream. The extensive length of the small stream network exposes rivers to a wide range of inputs, including nutrients, pesticides, heavy metals, sediment and emerging contaminants. Small water bodies have also been affected by invasions of non-native species, which along with the physical and chemical pressures, have affected most groups of organisms with consequent implications for the wider biodiversity within the catchment. Reducing the impacts and restoring the natural ecosystem function of these water bodies requires a three-tiered approach based on: restoration of channel hydromorphological dynamics; restoration and management of the riparian zone; and management of activities in the wider catchment that have both point-source and diffuse impacts. Such activities are expensive and so emphasis must be placed on integrated programmes that provide multiple benefits. Practical options need to be promoted through legislative regulation, financial incentives, markets for resource services and voluntary codes and actions., Graphical abstract Unlabelled Image, Highlights • Small Water Bodies (SWB) provide a suite of vital ecosystem services. • Hydromorphology of SWBs makes them highly vulnerable to anthropogenic pressures. • Land-use and environmental changes are disrupting the ecosystem functions of SWBs. • 3-tier restoration is needed: channel, riparian and wider catchment management. • Success will require government prioritization, expert advice, and stakeholder buy-in.

Horizon scanning for high-risk invasive non-native species (INNS) is crucial in preparing andimplementing measures to prevent introductions, as well as to focus efforts in the control of species already present. We initiated a trans-national horizon-scanning exercise focused on four countries in western Europe: Great Britain, France, Belgium and The Netherlands, which share similar environmental and socio-economic characteristics. We followed a structured four-step approach combining existing knowledge about INNS, with a collaborative identification of priorities for research and management: (1) systematic review of potential INNS of concern, (2)discrimination of INNS into an Alert and Black List depending on their absence or presence in the study area respectively, (3) risk analysis of the Alert List, and (4) expert ranking of species in the Black List. Amongst species not yet present in the four countries (i.e. Alert List), assessors reliably pointed to the Emerald ash-borer (Agrilus planipennis) and Sosnowski’s hogweed (Heracleum sosnowskyi) as those INNS with the highest risk of invasion and impact. The Japanese knotweed (Fallopia japonica), Himalayan balsam (Impatiens glandulifera), zebra mussel (Dreissena polymorpha) and killer shrimp (Dikerogammarus villosus) were consistently highlightedas some of the most problematic INNS alreadypresent in the study area (i.e. Black List). Theadvantages of our combined approach include that itis inclusive of all-taxa, prioritizes both established andemerging biological threats across trans-nationalscales, and considers not only the ecological impact,but also potential direct economic consequences aswell as the manageability of invasive species.

Background: The effect of a whole-food plant-based vegan diet vs an AHA-recommended diet on inflammatory, lipid, and glucometabolic profiles remains uncertain. Methods: This prospective blinded end-point trial randomized 100 patients with invasive angiographically-defined coronary artery disease (CAD) to 8 weeks of a vegan or AHA diet. Participants were provided weekly groceries for their assigned diet strategy, sample 2-week menus, tools to measure portion size, and on-going consultation with the study dietitian. Dietary adherence was measured by two weekly 24-hour dietary recalls and plasma and urine trimethylamine- N -oxide levels. Participants also completed a 4-day food record during the week prior to the baseline, 4-, and 8-week study visits. The primary endpoint was serum hsCRP concentration. A linear mixed effect model was used to model the log-transformed endpoints (to correct for skewness), evaluate the change in endpoint over time within treatment group, and test the interaction between time and treatment. The primary analysis was also covariate-adjusted. Results: Baseline characteristics are shown in Table 1. Two subjects withdrew from the vegan group after randomization, but dietary adherence remained higher in the vegan vs AHA group at the 4-week (96% vs 84%, p=0.09) and 8-week (94% vs 70%, p=0.003) visits. Endpoints are shown in Table 2. Conclusion: A vegan diet significantly reduced systemic inflammation, as evidenced by hsCRP, in patients with CAD on guideline-directed medical therapy, while an AHA diet did not. This is the first rigorous study to comprehensively assess multiple indices of cardiovascular risk between a vegan and AHA diet.

Robust tools are needed to prioritise the management of invasive non-native species (INNS). Risk assessment is commonly used to prioritise INNS, but fails to take into account the feasibility of management. Risk management provides a structured evaluation of management options, but has received little attention to date. We present a risk management scheme to assess the feasibility of eradicating INNS that can be used, in conjunction with existing risk assessment schemes, to support prioritisation. The Non-Native Risk Management scheme (NNRM) can be applied to any predefined area and any taxa. It uses semi-quantitative response and confidence scores to assess seven key criteria: Effectiveness, Practicality, Cost, Impact, Acceptability, Window of opportunity and Likelihood of re-invasion. Scores are elicited using expert judgement, supported by available evidence, and consensus-building methods. We applied the NNRM to forty-one INNS that threaten Great Britain (GB). Thirty-three experts provided scores, with overall feasibility of eradication assessed as ‘very high’ (8 species), ‘high’ (6), ‘medium’ (8), ‘low’ (10) and ‘very low’ (9). The feasibility of eradicating terrestrial species was higher than aquatic species. Lotic freshwater and marine species scored particularly low. Combining risk management and existing risk assessment scores identified six established species as priorities for eradication. A further six species that are not yet established were identified as priorities for eradication on arrival as part of contingency planning. The NNRM is one of the first INNS risk management schemes that can be used with existing risk assessments to prioritise INNS eradication in any area.

Introduction: Patients with coronary artery disease (CAD) who make healthy lifestyle changes can greatly impact their disease trajectories. However, the clinical profile of patients more likely to participate in programs aimed at improving lifestyle choices remains uncertain. The objective of this analysis was to examine the baseline clinical profile of patients with CAD motivated to enroll in an eight-week diet study versus those who chose not to enroll. Methods: The study population included patients with angiographically-defined CAD (≥50% lesion in an artery ≥2 mm caliber or prior percutaneous coronary intervention) who provided informed consent to participate in a single-center, prospective, blinded end-point, randomized trial assessing the impact of a vegan versus AHA-recommended diet on inflammatory and glucometabolic profiles. Data collection was obtained by direct interview and exam of patients who chose to enroll in and complete the trial. Electronic medical records were reviewed for patients who provided informed consent but subsequently declined to participate in the study prior to any study intervention, including randomization. Normally distributed and skewed continuous variables were examined by enrollment status with independent samples t-test and Mann-Whitney U test, respectively. Categorical variables were examined by enrollment status by Fisher’s exact test or Chi-square test. Results: Of the 90 patients consented, 60 chose to enroll into the study while 30 chose not to enroll. Compared to those who chose to participate in the study, those who chose not to participate were less likely to be of white race (70% (21/30) vs. 85% (51/60), p=0.002). Other demographic variables including age, sex, ethnicity or BMI did not differ by enrollment. Regarding medical history, patients who chose not to participate were more likely to have diagnoses associated with cardiovascular risk, including hypertension (86.7% (26/30) vs. 56.7% (34/60), p=0.005), hyperlipidemia (96.7% (29/30) vs. 71.7% (43/60), p=0.005), and diabetes mellitus (43.3% (13/30) vs. 21.7% (13/60), p=0.048). Analyses of laboratory parameters revealed that patients who did not participate in the study also had poorer risk factor control, including higher hemoglobin A1c (6.0% (IQR 5.7-7.8%) vs. 5.8% (IQR 5.5-6.3%), p=0.043) as well as lower HDL cholesterol levels (42 g/dL (IQR 34-47) vs. 45 g/dL (IQR 37-55), p=0.046). Conclusion: Among this sample of patients with angiographically-defined CAD, those who chose not to participate in an eight week dietary intervention to lower disease risk were more likely to be of a minority race with a higher proportion of poorly controlled cardiovascular risk factors at baseline. This analysis emphasizes the need for health care teams to consider different strategies of encouraging these high-risk patients to enroll in programs aimed at healthy lifestyle changes.

This paper reports the results of a 2-year study of water quality in the River Enborne, a rural river in lowland England. Concentrations of nitrogen and phosphorus species and other chemical determinands were monitored both at high-frequency (hourly), using automated in situ instrumentation, and by manual weekly sampling and laboratory analysis. The catchment land use is largely agricultural, with a population density of 123 persons km−2. The river water is largely derived from calcareous groundwater, and there are high nitrogen and phosphorus concentrations. Agricultural fertiliser is the dominant source of annual loads of both nitrogen and phosphorus. However, the data show that sewage effluent discharges have a disproportionate effect on the river nitrogen and phosphorus dynamics. At least 38% of the catchment population use septic tank systems, but the effects are hard to quantify as only 6% are officially registered, and the characteristics of the others are unknown. Only 4% of the phosphorus input and 9% of the nitrogen input is exported from the catchment by the river, highlighting the importance of catchment process understanding in predicting nutrient concentrations. High-frequency monitoring will be a key to developing this vital process understanding.

AquaPro project of the Bioeconomy Science Center (BioSC); NIWA core Biosecurity programme; the Netherlands Organisation for Scientific Research (Earth and Life Sciences - Research Program: Biodiversity works) [841.11.011]; Vrije Universiteit Brussel [BAS42] A. Hussner was partially funded within the AquaPro project of the Bioeconomy Science Center (BioSC), J. Clayton and D. Hofstra received funding from the NIWA core Biosecurity programme, B. Grutters was supported by the Netherlands Organisation for Scientific Research (Earth and Life Sciences - Research Program: Biodiversity works, grant 841.11.011) and Iris Stiers received financial support from the Vrije Universiteit Brussel (BAS42).; International audience; Introduced invasive alien aquatic plants (IAAPs) threaten ecosystems due to their excessive growth and have both ecological and economic impacts. To minimize these impacts, effective management of IAAPs is required according to national or international laws and regulations (e.g. the new EU regulation 1143/2014). Prevention of the introduction of IAAPs is considered the most cost effective management option. If/when prevention fails, early detection and rapid response increases the likelihood of eradication of the IAAPs and can minimize on-going management costs. For effective weed control (eradication and/or reduction), a variety of management techniques may be used. The goal or outcome of management interventions may vary depending on the site (i.e. a single waterbody, or a region with multiple waterbodies) and the feasibility of achieving the goal with the tools or methods available. Broadly defined management goals fall into three different categories of, containment, reduction or nuisance control and eradication. Management of IAAP utilises a range of control methods, either alone or in combination, to achieve a successful outcome. Here we review the biological, chemical and mechanical control methods for IAAPs, with a focus on the temperate and subtropical regions of the world and provide a management diagram illustrating the relationships between the state of the ecosystem, the management goals, outcomes and tools. (C) 2016 Elsevier B.V. All rights reserved.

When a forensic DNA sample cannot be associated directly with a previously genotyped reference sample by standard short tandem repeat profiling, the investigation required for identifying perpetrators, victims, or missing persons can be both costly and time consuming. Here, we describe the outcome of a collaborative study using the Identitas Version 1 (v1) Forensic Chip, the first commercially available all-in-one tool dedicated to the concept of developing intelligence leads based on DNA. The chip allows parallel interrogation of 201,173 genome-wide autosomal, X-chromosomal, Y-chromosomal, and mitochondrial single nucleotide polymorphisms for inference of biogeographic ancestry, appearance, relatedness, and sex. The first assessment of the chip’s performance was carried out on 3,196 blinded DNA samples of varying quantities and qualities, covering a wide range of biogeographic origin and eye/hair coloration as well as variation in relatedness and sex. Overall, 95 % of the samples (N = 3,034) passed quality checks with an overall genotype call rate >90 % on variable numbers of available recorded trait information. Predictions of sex, direct match, and first to third degree relatedness were highly accurate. Chip-based predictions of biparental continental ancestry were on average ~94 % correct (further support provided by separately inferred patrilineal and matrilineal ancestry). Predictions of eye color were 85 % correct for brown and 70 % correct for blue eyes, and predictions of hair color were 72 % for brown, 63 % for blond, 58 % for black, and 48 % for red hair. From the 5 % of samples (N = 162) with

This paper introduces new insights into the hydrochemical functioning of lowland river systems using field-based spectrophotometric and electrode technologies. The streamwater concentrations of nitrogen species and phosphorus fractions were measured at hourly intervals on a continuous basis at two contrasting sites on tributaries of the River Thames – one draining a rural catchment, the River Enborne, and one draining a more urban system, The Cut. The measurements complement those from an existing network of multi-parameter water quality sondes maintained across the Thames catchment and weekly monitoring based on grab samples. The results of the sub-daily monitoring show that streamwater phosphorus concentrations display highly complex dynamics under storm conditions dependent on the antecedent catchment wetness, and that diurnal phosphorus and nitrogen cycles occur under low flow conditions. The diurnal patterns highlight the dominance of sewage inputs in controlling the streamwater phosphorus and nitrogen concentrations at low flows, even at a distance of 7 km from the nearest sewage treatment works in the rural River Enborne. The time of sample collection is important when judging water quality against ecological thresholds or standards. An exhaustion of the supply of phosphorus from diffuse and multiple septic tank sources during storm events was evident and load estimation was not improved by sub-daily monitoring beyond that achieved by daily sampling because of the eventual reduction in the phosphorus mass entering the stream during events. The results highlight the utility of sub-daily water quality measurements and the discussion considers the practicalities and challenges of in situ, sub-daily monitoring.

The project FORESIGHT stated objectives begin with the development of metrics applicable to the activity of forensic science laboratories. These metrics enable a laboratory to assess how they fit within the forensic science industry and offer a glance at the levels of performance that they might be able to achieve. FORESIGHT's mission goes on to state the intent for laboratories to use those measurements to “preserve what works, and change what does not” (Houck et al. 2009, p. 85). This paper addresses the strategic implications of those additional aspects of the FORESIGHT mandate with a view of the strategic planning process for a forensic science laboratory. The keys to the development of an ongoing strategic planning and execution process are outlined, and then the actions of one laboratory, Ontario's Centre of Forensic Sciences, are examined to demonstrate the move from metrics to action. While there cannot yet be made a claim of “best practices,” this Canadian example offers some guidance to...

Hip fracture is an unfortunate and common health problem in the elderly that is associated with a 1-year mortality of 10% to 35%. Further, only 50% of these patients regain their pre-fracture level of mobility and functional status. Hospital-based clinicians are increasingly asked to comanage these patients. The purpose of this article is to summarize evidence-based clinical management practices that are relevant to hospitalist clinicians who manage hip fracture patients, and to highlight the current evidence for implementing a formal hospitalist and orthopedic comanagement care model.

CCGA [NCT02889978] is the largest study of cfDNA-based early cancer detection; the first CCGA learnings from multiple cfDNA assays are reported here. This prospective, multi-center, observational study has enrolled 10,012 of 15,000 demographically-balanced participants at 141 sites. Blood was collected from participants with newly diagnosed therapy-naive cancer (C, case) and participants without a diagnosis of cancer (noncancer [NC], control) as defined at enrollment. This preplanned substudy included 878 cases, 580 controls, and 169 assay controls (n=1627) across 20 tumor types and all clinical stages. All samples were analyzed by: 1) Paired cfDNA and white blood cell (WBC)-targeted sequencing (60,000X, 507 gene panel); a joint caller removed WBC-derived somatic variants and residual technical noise; 2) Paired cfDNA and WBC whole-genome sequencing (WGS; 35X); a novel machine learning algorithm generated cancer-related signal scores; joint analysis identified shared events; and 3) cfDNA whole-genome bisulfite sequencing (WGBS; 34X); normalized scores were generated using abnormally methylated fragments. In the targeted assay, non-tumor WBC-matched cfDNA somatic variants (SNVs/indels) accounted for 76% of all variants in NC and 65% in C. Consistent with somatic mosaicism (i.e., clonal hematopoiesis), WBC-matched variants increased with age; several were non-canonical loss-of-function mutations not previously reported. After WBC variant removal, canonical driver somatic variants were highly specific to C (e.g., in EGFR and PIK3CA, 0 NC had variants vs 11 and 30, respectively, of C). Similarly, of 8 NC with somatic copy number alterations (SCNAs) detected with WGS, 4 were derived from WBCs. WGBS data revealed informative hyper- and hypo-fragment level CpGs (1:2 ratio); a subset was used to calculate methylation scores. A consistent “cancer-like” signal was observed in 99% specificity for invasive cancer, and support the promise of cfDNA assay for early cancer detection. Additional data will be presented on detected plasma:tissue variant concordance and on multi-assay modeling. Citation Format: Alexander A. Aravanis, Geoffrey R. Oxnard, Tara Maddala, Earl Hubbell, Oliver Venn, Arash Jamshidi, Ling Shen, Hamed Amini, John A. Beausang, Craig Betts, Daniel Civello, Konstantin Davydov, Saniya Fazullina, Darya Filippova, Sante Gnerre, Samuel Gross, Chenlu Hou, Roger Jiang, Byoungsok Jung, Kathryn Kurtzman, Collin Melton, Shivani Nautiyal, Jonathan Newman, Joshua Newman, Cosmos Nicolaou, Richard Rava, Onur Sakarya, Ravi Vijaya Satya, Seyedmehdi Shojaee, Kristan Steffen, Anton Valouev, Hui Xu, Jeanne Yue, Nan Zhang, Jose Baselga, Rosanna Lapham, Daron G. Davis, David Smith, Donald Richards, Michael V. Seiden, Charles Swanton, Timothy J. Yeatman, Robert Tibshirani, Christina Curtis, Sylvia K. Plevritis, Richard Williams, Eric Klein, Anne-Renee Hartman, Minetta C. Liu. Development of plasma cell-free DNA (cfDNA) assays for early cancer detection: first insights from the Circulating Cell-Free Genome Atlas Study (CCGA) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-343.

Deterministic lateral displacement arrays have shown great promise for size-based particle analysis and purification in medicine and biology. Here, we demonstrate that the use of an array of triangular rather than circular posts significantly enhances the performance of these devices by reducing clogging, lowering hydrostatic pressure requirements, and increasing the range of displacement characteristics. Experimental data and theoretical models are presented to create a compelling argument that future designs of deterministic lateral displacement arrays should employ triangular posts. The effect of practical considerations, such as vertex rounding, post size, and shape, is also discussed.

The possible effects of changing climate on a southern and a north-eastern English river (the Thames and the Yorkshire Ouse, respectively) were examined in relation to water and ecological quality throughout the food web. The CLASSIC hydrological model, driven by output from the Hadley Centre climate model (HadCM3), based on IPCC low and high CO2 emission scenarios for 2080 were used as the basis for the analysis. Compared to current conditions, the CLASSIC model predicted lower flows for both rivers, in all seasons except winter. Such an outcome would lead to longer residence times (by up to a month in the Thames), with nutrient, organic and biological contaminant concentrations elevated by 70–100% pro-rata, assuming sewage treatment effectiveness remains unchanged. Greater opportunities for phytoplankton growth will arise, and this may be significant in the Thames. Warmer winters and milder springs will favour riverine birds and increase the recruitment of many coarse fish species. However, warm, slow-flowing, shallower water would increase the incidence of fish diseases. These changing conditions would make southern UK rivers in general a less favourable habitat for some species of fish, such as the Atlantic salmon (Salmo salar). Accidental or deliberate, introductions of alien macrophytes and fish may change the range of species in the rivers. In some areas, it is possible that a concurrence of different pressures may give rise to the temporary loss of ecosystem services, such as providing acceptable quality water for humans and industry. An increasing demand for water in southern England due to an expanding population, a possibly reduced flow due to climate change, together with the Water Framework Directive obligation to maintain water quality, will put extreme pressure on river ecosystems, such as the Thames.

Excessive sediment pressure on aquatic habitats is of global concern. A unique dataset, comprising instantaneous measurements of deposited fine sediment in 230 agricultural streams across England and Wales, was analysed in relation to 20 potential explanatory catchment and channel variables. The most effective explanatory variable for the amount of deposited sediment was found to be stream power, calculated for bankfull flow and used to index the capacity of the stream to transport sediment. Both stream power and velocity category were highly significant (p<

This study examines the relative success rates of DNA recovery from firearm locations normally handled during the process of loading and discharging the firearm, ejected cartridge cases, and unspent cartridges to aid in the association of the firearm, ammunition, or cartridge case to a potential perpetrator by means of DNA evidence. Four firearms were selected for study: a revolver, a pistol, a break-action shotgun and a pump-action shotgun. Thirty-seven percent (37%, 47/126) of the experimental samples from the exterior locations of the four firearms tested yielded DNA quantities suitable for further processing (≥ 240 pg), with an average yield of 1.1 ng of DNA per sample. DNA recovery was most successful from the grip of all four firearms (80% of trials) and the slide serrations of the pistol (87.5% of trials). An association between the shooter and the DNA profile obtained was established in 30% of the samples. The DNA profiles obtained were either of single source or mixtures from which the sh...