Implementing Value Pricing for U.S. Roadways

This paper reviews the current status of congestion-based road pricing in the United States and examines some of the characteristics of successful and unsuccessful projects, including their marketing aspects. It is concluded that forward momentum has been established for innovative road pricing, but future progress toward more widespread use of congestionbased pricing is likely to take advantage of local opportunities which present themselves, and will proceed cautiously. Considerable emphasis will be placed on marketing strategies in order to win consumer acceptance

Edward Sullivan, correspondence with Edward D. “Sandy” Ives

Edward Sullivan, correspondence with Edward D. Sandy Ives dating between 1975 and 1977, about life in Veazie and stories he wrote about the area; photo of Lawrence (Larry) Conners, log driver and lumberman.https://digitalcommons.library.umaine.edu/mf064/1008/thumbnail.jp

Eicosapentaenoic acid and oxypurinol in the treatment of muscle wasting in a mouse model of cancer cachexia

Cancer cachexia is a wasting condition, driven by systemic inflammation and oxidative stress. This study investigated eicosapentaenoic acid (EPA) in combination with oxypurinol as a treatment in a mouse model of cancer cachexia. Mice with cancer cachexia were randomized into 4 treatment groups (EPA (0.4 g/kg/day), oxypurinol (1 mmol/L ad-lib), combination, or control), and euthanized after 29 days. Analysis of oxidative damage to DNA, mRNA analysis of pro-oxidant, antioxidant and proteolytic pathway components, along with enzyme activity of pro- and antioxidants were completed on gastrocnemius muscle. The control group displayed earlier onset of tumor compared to EPA and oxypurinol groups (P&lt;0.001). The EPA group maintained body weight for an extended duration (20 days) compared to the oxypurinol (5 days) and combination (8 days) groups (P&lt;0.05). EPA (18.2&plusmn;3.2 pg/ml) and combination (18.4&plusmn;3.7 pg/ml) groups had significantly higher 8-OH-dG levels than the control group (12.9&plusmn;1.4 pg/ml, P&le;0.05) indicating increased oxidative damage to DNA. mRNA levels of GPx1, MURF1 and MAFbx were higher following EPA treatment compared to control (P&le;0.05). Whereas oxypurinol was associated with higher GPx1, MnSOD, CAT, XDH, MURF1, MAFbx and UbB mRNA compared to control (P&le;0.05). Activity of total SOD was higher in the oxypurinol group (32.2&plusmn;1.5 U/ml) compared to control (27.0&plusmn;1.3 U/ml, P&lt;0.01), GPx activity was lower in the EPA group (8.76&plusmn;2.0 U/ml) compared to control (14.0&plusmn;1.9 U/ml, P&lt;0.05), and catalase activity was lower in the combination group (14.4&plusmn;2.8 U/ml) compared to control (20.9&plusmn;2.0 U/ml, P&lt;0.01). There was no change in XO activity. The increased rate of weight decline in mice treated with oxypurinol indicates that XO may play a protective role during the progression of cancer cachexia, and its inhibition is detrimental to outcomes. In combination with EPA, there was little significant improvement from control, indicating oxypurinol is unlikely to be a viable treatment compound in cancer cachexia.<br /

IUE archived spectra

The International Ultraviolet Explorer (IUE) Satellite has been in continuous operation since January 26, 1978. To date, approximately 65,000 spectra have been stored in an archive at Goddard Space Flight Center in Greenbelt, MD. A number of procedures have been generated to facilitate access to the data in the IUE spectral archive. This document describes the procedures which include on-line quick look of the displays, search of an observation data base for selected observations, and several methods for ordering data from the archive

The Joint Council on Thoracic Surgery Education (JCTSE) “Educate the Educators” Faculty Development Course: Analysis of the First 5 Years

BACKGROUND: Since 2010, the Joint Council on Thoracic Surgery Education, Inc (JCTSE) has sponsored an annual "Educate the Educators" (EtE) course. The goal is to provide United States academic cardiothoracic surgeons (CTS) the fundamentals of teaching skills, educational curriculum development, and using education for academic advancement. This report describes the course development and evaluation along with attendee's self-assessment of skills through the first 5 years of the program. METHODS: The content of this 2½-day course was based on needs assessment surveys of CTS and residents attending annual meetings in 2009. From 2010 to 2014, EtE was offered to all CTS at training programs approved by the Accreditation Council for Graduate Medical Education. Course content was evaluated by using end-of-course evaluation forms. A 5-point Likert scale (1 = poor, 5 = excellent) was used to obtain composite assessment mean scores for the 5 years on course variables, session presentations, and self-assessments. RESULTS: With 963 known academic CTS in the United States, 156 (16.3%) have attended, representing 70 of 72 training programs (97%), and 1 international surgeon attended. There were also 7 program coordinators. Ratings of core course contents ranged from 4.4 to 4.8, accompanied with highly complementary comments. Through self-assessment, skills and knowledge in all content areas statistically improved significantly. The effect of the course was evaluated with a follow-up survey in which responders rated the program 4.3 on the usefulness of the information for their career and 3.9 for educational productivity. CONCLUSIONS: The EtE program offers an excellent opportunity for academic CTS to enhance their teaching skills, develop educational activities, and prepare for academic promotion. With its unique networking and mentorship environment, the EtE program is an important resource in the evolution of cardiothoracic surgical training in the United States

IR Background Anisotropies in Spitzer GOODS images and constraints on first galaxies

We describe the angular power spectrum of unresolved 3.6 micron IR light in Spitzer GOODS fields. The amplitude of the anisotropy spectrum decreases with decreasing flux threshold to which resolved sources are removed from images. When all pixels brighter than a Vega magnitude of 24.6 are removed, the amplitude of the power spectrum at arcminute angular scales can be described with an extra component of z>8 sources with a IRB contribution around 0.4 nW m^-2 sr-1. The shape of the power spectrum, however, is more consistent with that expected for unresolved, faint galaxies at lower redshifts with Vega magnitudes fainter than 23 with a total 3.6 micron intensity between 0.1 to 0.8 nW m^-2 sr^-1. We confirm this assumption by showing that large-scale power decreases rapidly when the unresolved clustering spectrum is measured from a processed HDF-N IRAC image where locations of faint ACS sources with no IR counterparts were also masked. Based on resolved counts and unresolved fluctuations, we find that, at most, about 7.0 nW m^-2 sr^-1 can be ascribed to galaxies.Comment: 4 pages, 3 figures; for additional information see astro-ph/0609451 ; data products are available at http://www.cooray.org/spitzer.htm

Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.

PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses

Docosahexaenoic acid lowers cardiac mitochondrial enzyme activity by replacing linoleic acid in the phospholipidome

Cardiac mitochondrial phospholipid acyl chains regulate respiratory enzymatic activity. In several diseases, the rodent cardiac phospholipidome is extensively rearranged; however, whether specific acyl chains impair respiratory enzyme function is unknown. One unique remodeling event in the myocardium of obese and diabetic rodents is an increase in docosahexaenoic acid (DHA) levels. Here, we first confirmed that cardiac DHA levels are elevated in diabetic humans relative to controls. We then used dietary supplementation of a Western diet with DHA as a tool to promote cardiac acyl chain remodeling and to study its influence on respiratory enzyme function. DHA extensively remodeled the acyl chains of cardiolipin (CL), mono-lyso CL, phosphatidylcholine, and phosphatidylethanolamine. Moreover, DHA lowered enzyme activities of respiratory complexes I, IV, V, and I+III. Mechanistically, the reduction in enzymatic activities were not driven by a dramatic reduction in the abundance of supercomplexes. Instead, replacement of tetralinoleoyl-CL with tetradocosahexaenoyl-CL in biomimetic membranes prevented formation of phospholipid domains that regulate enzyme activity. Tetradocosahexaenoyl-CL inhibited domain organization due to favorable Gibbs free energy of phospholipid mixing. Furthermore, in vitro substitution of tetralinoleoyl-CL with tetradocosahexaenoyl-CL blocked complex-IV binding. Finally, reintroduction of linoleic acid, via fusion of phospholipid vesicles to mitochondria isolated from DHA-fed mice, rescued the major losses in the mitochondrial phospholipidome and complexes I, IV, and V activities. Altogether, our results show that replacing linoleic acid with DHA lowers select cardiac enzyme activities by potentially targeting domain organization and phospholipid-protein binding, which has implications for the ongoing debate about polyunsaturated fatty acids and cardiac health

Cyber Insurance and the Ransomware Challenge

The cyber insurance industry has been heavily criticised for providing coverage for ransom payments. A frequent accusation, which has become close to perceived wisdom in policymaking and cyber security discussions on ransomware, is that cyber insurance has incentivised victims to pay a ransom following a cyber incident, rather than seek alternative remediation options. Over a 12-month research project, researchers from RUSI, the University of Kent, De Montfort University and Oxford Brookes University conducted a series of expert interviews and workshops to explore the relationship between cyber insurance and ransomware in depth. This paper argues that there is, in fact, no compelling evidence that victims with cyber insurance are much more likely to pay ransoms than those without. Ransomware remains one of the most persistent cyber threats facing the UK. Despite a range of government, law enforcement and even military cyber unit initiatives, ransomware remains lucrative for criminals. During this research, we identified three main drivers that ensure its continued success: A profitable business model that continues to find innovative ways to extort victims. Challenges around securing organisations of all sizes. The low costs and risks for cybercriminals involved in the ransomware ecosystem, both in terms of the barriers to entry and the prospect of punishment. Despite this perfect storm of factors, the cyber insurance industry has been singled out for criticism with the claim that it is funding organised cybercrime by covering ransom payments. In reality, cyber insurance’s influence on victim decision-making is considerably more nuanced than the public debate has captured so far. While there is evidence that cyber insurance policies exfiltrated during attacks are used as leverage in negotiations and to set higher ransom demands, the conclusion that ransomware operators are deliberately targeting organisations with insurance has been overstated. However, the insurance industry could do much more to instil discipline in both insureds and the ransomware response ecosystem in relation to ransom payments to reduce cybercriminals’ profits. Insurers’ role as convenors of incident response services gives them considerable power to reward firms that drive best practices and only guide victims towards payment as a last resort. But the lack of clearly defined negotiation protocols and the challenges around learning from incidents make it difficult to develop a sense of collective responsibility and shared best practices around ransomware response. This has not been helped by the UK government’s black-and-white position on ransom payments, which has created a vacuum of assurance and advice on best practices for ransom negotiations and payments. This paper does not advocate for an outright ban on ransom payments or for stopping insurers from providing coverage for them. Instead, it makes the case for interventions that would improve market-wide ransom discipline so that fewer victims pay ransoms, or pay lower demands. Ultimately, this involves creating more pathways for victims that do not result in ransom payments. Beyond ransom payments, cyber insurance has a growing role in raising cyber security standards, which could make it more difficult to successfully compromise victims and increase costs for ransomware operators. Successive years of losses from ransomware have led to more stringent security requirements and risk selection by underwriters. Although the overall effect of this on the frequency and severity of ransomware attacks remains to be seen, by linking improvements in security practices to coverage, cyber insurance is currently one of the few market-based levers for incentivising organisations to implement security controls and resilience measures. However, continued challenges around collecting and assessing reliable cyber risk and forensic claims data continue to place limits on the market’s effectiveness as a mechanism for reducing ransomware risk. This, along with cyber insurance’s low market penetration, makes clear that cyber insurance should not be treated as a substitute for the legislation and regulation required to improve minimum cyber security standards and resilience. Insurers are also commercial entities that primarily exist to help organisations transfer risk, rather than to improve national security and societal cyber resilience. The cyber insurance industry could be a valuable partner for the UK government through increased ransomware attack and payment reporting, sharing aggregated claims data, and distributing National Cyber Security Centre (NCSC) guidance and intelligence to organisations. However, the government has not made a compelling enough case to insurers and insureds about the benefits of doing so. Instead, it has relied on appealing to their general sense of altruism. While insurers will benefit if governments are able to generate more accurate and actionable data on ransomware, albeit indirectly, this needs to be sold to the industry in a more convincing way. Some principles and recommendations for both the insurance industry and the UK government are listed below. These are not designed to solve all the challenges of the cyber insurance market, nor do they present wide-ranging solutions to the ransomware challenge. Instead, they focus on where the cyber insurance industry can have the most impact on key ransomware drivers. This reflects the fact that disrupting the ransomware economy involves applying pressure from different angles in a whole-of-society approach. The recommendations also start from the position that the UK government’s light-touch approach is unsustainable and requires more intervention in private markets that are involved in ransomware prevention and response. While they are specifically aimed at UK policymakers, regulators and insurers, they may be applicable to other national contexts. Recommendations Recommendation 1: To increase oversight of ransomware response, insurers should use policy language to require that insureds and incident response firms provide written evidence of negotiation strategies and outcomes. Recommendation 2: To develop and drive ransomware response best practices across the market, insurers should select specialist ransomware response firms for panels that meet a set of pre-defined minimum requirements. These should include: A proven track record of both regularly achieving outcomes that do not result in ransom payments, and of operational relationships with law enforcement and cyber security agencies. Conducting sanctions risk assessments. Compliance with anti-money laundering laws and FATF (Financial Action Task Force) standards. Ensuring payment firms that make payments on behalf of UK victims are registered with relevant financial authorities in the UK. Recommendation 3: The UK government should commission a study to improve its understanding of specialist ransomware response firms. This should aim to identify common best practices and key market players, and create a framework for benchmarking the quality of their services and products. These findings can be distributed to trusted partners in the insurance industry. To drive best practices in ransomware response and create more oversight of the incident response ecosystem, the NCSC, National Crime Agency (NCA) and international partners should also explore the feasibility and potential implications of creating a dedicated assurance scheme for firms that provide specialist ransomware services such as decryption, recovery, negotiations and payments. Recommendation 4: To increase reporting of ransom payments, the UK government and international partners should explore creating a dedicated licensing regime for firms that facilitate cryptocurrency payments on behalf of ransomware victims. In the short-term, the UK government should follow the example set by the US government and also ensure that ransomware response firms that facilitate payments are registered as money service businesses in the UK and therefore subject to national financial crime reporting requirements. Recommendation 5: To reach a market-wide consensus on what constitutes a reasonable last resort before a ransom payment is made, insurers should agree on a set of minimum conditions and obligations in ransomware coverage to ensure alternatives are explored first. These should include sanctions due diligence, a requirement to notify law enforcement and written evidence that all options have been exhausted. Recommendation 6: To increase ransomware reporting and ensure victims are able to access any relevant law enforcement and NCSC support, insurers should specify that any ransomware coverage must contain a requirement for policyholders to notify Action Fraud (the UK’s national centre for reporting fraud and cybercrime) and the NCSC before a ransom is paid. If there is no progress on this recommendation without intervention, then regulators should intervene to compel insurers to include this obligation in coverage. However, this recommendation also depends on the implementation of long-promised but delayed reforms to Action Fraud. These should include creating a dedicated category for reporting ransomware. Law enforcement and the NCSC must also provide assurances to insurers that they have the capabilities to support victims during incidents and that reporting leads to actual outcomes against ransomware actors, such as cryptocurrency seizures, arrests or offensive cyber operations. Recommendation 7: The NCSC and a UK insurer should trial integrating the NCSC’s Early Warning service into their ongoing assessments of policyholders. This would enable the insurer to distribute intelligence from Early Warning at scale and notify policyholders of potential ransomware attacks. The NCSC should also explore whether Early Warning will need to be expanded and adapted to meet the requirements of insurers and policyholders. Recommendation 8: To deepen operational collaboration with the insurance industry, the NCSC should seek to recruit secondees from the cyber insurance industry into the Industry 100 cyber security secondment scheme. This should include identifying specific tasks and roles for underwriters, claims managers and incident response professionals working for UK insurers. Recommendation 9: To increase reporting of ransom payments, the Home Office and NCA should ensure that existing financial crime reporting mechanisms – specifically, suspicious activity reports (SARs) – are fit for reporting ransom payments or money laundering linked to ransomware. Concurrently, the UK government should also identify ways to encourage cyber insurers to report ransom payments as SARs or through more informal channels