First in Elections, First in Reforms: Can New Hampshire be First in the Nation to Implement Changes to Campaign Finance?

As Americans prepare for the 2020 presidential election, one thing is for certain—the candidates will make their way into your home. While they might not physically step foot into your living room, they will appear on your television, on your laptop, and on your phone. Why? Because in the United States, campaigns are won by candidates communicating with you, the voters. It is not feasible to physically shake hands with the entire population of the country. Instead, individuals running for office have to introduce themselves to voters some other way. Television advertisements, sponsored posts on social media, and robocalls are all methods politicians use to persuade the public that they are deserving of your vote in the upcoming election. This outreach costs money. In the weeks, months, and even years before an election, candidates running for office must find a way to fund their campaigns. The race to raise money is a full-contact sport, as candidates bombard potential contributors with calls, mailings, and emails. Candidates attend house parties, high-priced dinners, and donor meetings in hopes of winning the fundraising race, separate, of course, from the actual political race to win the election. Candidates are not the only ones raising and spending money. Other groups—such as political parties, Political Action Committees, and unions—support favorable candidates by advertising and providing other outreach to show their support. And with the impact of the Citizens United decision, corporations now have a bigger seat at the table than before. The race to raise, buy, and spend on a political campaign has become just as arduous and contentious as the race for an elected position. Americans are frustrated by this constant battle. Too often, they don’t know who is funding an election or who is paying for an advertisement. Candidates are also vocal about their desire to change the system. Many have suggested modifications and some have even taken personal pledges to limit the influence of money in politics. But without true reform, the wealthier candidates—those who have “succeeded” at the fundraising race—will have the money needed to work their way into your living room, while the candidates with less campaign funds may remain unknown and unelected. How can we achieve a better balance of spending less and disclosing more, while still ensuring candidates have the ability to market themselves to the public? Part I of this Note looks at the current campaign finance system in the United States and the impact of Citizens United. Part II assesses what has been done or considered in other countries and across the United States to lessen the influence of money in politics. Part III applies these ideas on a smaller scale to New Hampshire—the home of the first-in-the-nation presidential primary and the state with the largest legislative body aside from the U.S. Congress—to suggest ways the system can be improved and transformed. Unlike a seat for elected office, the race to reform campaign finance is a bipartisan contest, and its victory can be celebrated by all Americans, regardless of political party

Mining grapevine downy mildew susceptibility genes: a resource for genomics-based breeding and tailored gene editing

Several pathogens continuously threaten viticulture worldwide. Until now, the investigation on resistance loci has been the main trend to understand the interaction between grapevine and the mildew causal agents. Dominantly inherited gene-based resistance has shown to be race-specific in some cases, to confer partial immunity, and to be potentially overcome within a few years since its introgression. Recently, on the footprint of research conducted in Arabidopsis, putative genes associated with downy mildew susceptibility have been discovered also in the grapevine genome. In this work, we deep-sequenced four putative susceptibility genes—namely VvDMR6.1, VvDMR6.2, VvDLO1, VvDLO2—in 190 genetically diverse grapevine genotypes to discover new sources of broad-spectrum and recessively inherited resistance. Identified Single Nucleotide Polymorphisms were screened in a bottleneck analysis from the genetic sequence to their impact on protein structure. Fifty-five genotypes showed at least one impacting mutation in one or more of the scouted genes. Haplotypes were inferred for each gene and two of them at the VvDMR6.2 gene were found significantly more represented in downy mildew resistant genotypes. The current results provide a resource for grapevine and plant genetics and could corroborate genomic-assisted breeding programs as well as tailored gene editing approaches for resistance to biotic stresse

Functionalized Carbon Nanotubes in the Brain: Cellular Internalization and Neuroinflammatory Responses

The potential use of functionalized carbon nanotubes (f-CNTs) for drug and gene delivery to the central nervous system (CNS) and as neural substrates makes the understanding of their in vivo interactions with the neural tissue essential. The aim of this study was to investigate the interactions between chemically functionalized multi-walled carbon nanotubes (f-MWNTs) and the neural tissue following cortical stereotactic administration. Two different f-MWNT constructs were used in these studies: shortened (by oxidation) amino-functionalized MWNT (oxMWNT-NH3+) and amino-functionalized MWNT (MWNT-NH3+). Parenchymal distribution of the stereotactically injected f-MWNTs was assessed by histological examination. Both f-MWNT were uptaken by different types of neural tissue cells (microglia, astrocytes and neurons), however different patterns of cellular internalization were observed between the nanotubes. Furthermore, immunohistochemical staining for specific markers of glial cell activation (GFAP and CD11b) was performed and secretion of inflammatory cytokines was investigated using real-time PCR (qRT-PCR). Injections of both f-MWNT constructs led to a local and transient induction of inflammatory cytokines at early time points. Oxidation of nanotubes seemed to induce significant levels of GFAP and CD11b over-expression in areas peripheral to the f-MWNT injection site. These results highlight the importance of nanotube functionalization on their interaction with brain tissue that is deemed critical for the development nanotube-based vector systems for CNS application

Mining downy mildew susceptibility genes: a diversity study in grapevine

Several pathogens continuously threaten viticulture worldwide. Until now, the investigation on resistance loci has been the main trend to understand the interaction between grapevine and mildew causal agents. Dominantly inherited gene-based resistance has shown to be race-specific in some cases, to confer partial immunity and to be potentially overcome within a few years since its introgression. Recently, on the footprint of research conducted on Arabidopsis, the putative hortologues of genes associated with downy mildew susceptibility in this species, have been discovered also in the grapevine genome. In this work, we deep-resequenced four putative susceptibility genes in 190 highly genetically diverse grapevine genotypes to discover new sources of broad-spectrum recessively inherited resistance. The scouted genes are VvDMR6-1, VvDMR6-2, VvDLO1, VvDLO2 and predicted to be involved in susceptibility to downy mildew. From all identified mutations, 56% were Single Nucleotide Polymorphisms (SNPs) in heterozygosity, while the remaining 44% were homozygous. Regarding the identified mutations with putative impact on gene function, we observed ~4% genotypes mutated in VvDMR6-1 and ~8% mutated in VvDMR6-2, only a handful of genotypes that were mutated in both genes. ~2% and ~7% genotypes showed mutations in VvDLO1 and VvDLO2 respectively, and again a few genotypes resulted mutated in both genes. In particular, 80% of impacting mutations were heterozygous while 20% were homozygous. The current results will inform grapevine genetics and corroborate genomic-assisted breeding programs for resistance to biotic stresses

Capturing Students\u27 International Experiences: eScholarship@UMMS and International Medical Education

Type of engagement and location: eScholarship@UMMS (http://escholarship.umassmed.edu/intmeded/) is an electronic repository sponsored by the Lamar Soutter Library. The Library is collaborating with the Office of Medical Education’s International Medical Education initiative under the direction of Dr. Michael Godkin. Purpose/objective: The purpose of the collaboration is to provide an archive to preserve and promote clinical and language experiences of UMMS students serving in developing countries. Description: The Library is building a database of student trips that includes descriptions of sites and clinical experiences, photos, personal reflections, maps, and advice for future students. Library staff worked with Dr. Godkin to convert paper records into an electronic format and added metadata to enhance searching. Reports are organized by country and year, and are full-text searchable. Conclusion: eScholarship@UMMS offers an efficient and convenient means of promoting student interest in international medical education. More than 50 student trip reports from almost 20 countries have been entered into the database. In just four months the site has already had an impact and generated increased student interest. By archiving these trip reports, eScholarship@UMMS ensures that the information will be available for future UMMS students. Implications: eScholarship@UMMS supports the primary goals of the International Medical Education program: to develop linguistic, cultural and physical diagnosis skills and enable the students to better serve a rapidly expanding immigrant and refugee population in Massachusetts and the United States. Presented at the UMass Global Health Symposium, Shrewsbury, MA, on May 3-4, 2007

GSTP1 DNA Methylation and Expression Status Is Indicative of 5-aza-2′-Deoxycytidine Efficacy in Human Prostate Cancer Cells

DNA methylation plays an important role in carcinogenesis and the reversibility of this epigenetic modification makes it a potential therapeutic target. To date, DNA methyltransferase inhibitors (DNMTi) have not demonstrated clinical efficacy in prostate cancer, with one of the major obstacles being the inability to monitor drug activity during the trial. Given the high frequency and specificity of GSTP1 DNA methylation in prostate cancer, we investigated whether GSTP1 is a useful marker of DNMTi treatment efficacy. LNCaP prostate cancer cells were treated with 5-aza-2′-deoxycytidine (5-aza-CdR) either with a single high dose (5–20 µM), every alternate day (0.1–10 µM) or daily (0.005–2.5 µM). A daily treatment regimen with 5-aza-CdR was optimal, with significant suppression of cell proliferation achieved with doses of 0.05 µM or greater (p<0.0001) and induction of cell death from 0.5 µM (p<0.0001). In contrast, treatment with a single high dose of 20 µM 5-aza-CdR inhibited cell proliferation but was not able to induce cell death. Demethylation of GSTP1 was observed with doses of 5-aza-CdR that induced significant suppression of cell proliferation (≥0.05 µM). Re-expression of the GSTP1 protein was observed only at doses of 5-aza-CdR (≥0.5 µM) associated with induction of cell death. Treatment of LNCaP cells with a more stable DNMTi, Zebularine required at least a 100-fold higher dose (≥50 µM) to inhibit proliferation and was less potent in inducing cell death, which corresponded to a lack of GSTP1 protein re-expression. We have shown that GSTP1 DNA methylation and protein expression status is correlated with DNMTi treatment response in prostate cancer cells. Since GSTP1 is methylated in nearly all prostate cancers, our results warrant its testing as a marker of epigenetic therapy response in future clinical trials. We conclude that the DNA methylation and protein expression status of GSTP1 are good indicators of DNMTi efficacy

Implantation of atrial flow regulator devices in patients with congenital heart disease and children with severe pulmonary hypertension or cardiomyopathy—an international multicenter case series

Fontan circulation; Atrial flow regulator device; Congenital heart diseaseCirculació de Fontan; Dispositiu regulador de flux auricular; Malaltia cardíaca congènitaCirculación de Fontan; Dispositivo regulador de flujo auricular; Enfermedad cardíaca congénitaBackground: The Occlutech Atrial Flow Regulator (AFR) is a self-expandable double-disc nitinol device with a central fenestration. Its use has been approved in the adult population with heart failure and described for pulmonary hypertension (PH). Only case reports and small series have been published about its use in the paediatric population and for congenital heart disease (CHD). Objectives: The authors sought to investigate the feasibility, safety, and short-term follow-up of AFR implantation in patients with CHD or children with PH or cardiomyopathy. Methods: This is a multicenter retrospective study involving 10 centers worldwide. Patients of any age with CHD or patients aged < 18 years with PH or cardiomyopathy needing AFR implantation were included. Results: A total of 40 patients underwent AFR implantation. The median age of the population at the time of the procedure was 58.5 months (IQR: 31.5–142.5) and the median weight was 17 kg (IQR: 10–46). A total of 26 (65.0%) patients had CHD, nine (22.5%) children, a cardiomyopathy, and five (12.5%), a structurally normal heart. The implantation success rate was 100%. There were two early and one late device thrombosis. Two patients (5.0%) with dilated cardiomyopathy on extracorporeal membrane oxygenator (ECMO) died during the hospital stay. At a median follow-up of 330 days (IQR: 125–593), 37 (92.5%) patients were alive. At follow-up, 20 patients improved their New York Heart Association (NYHA) class, 12 patients did not change their NYHA class, and one patient with idiopathic PH worsened. Conclusions: AFR implantation in patients with CHD and children with severe PH or cardiomyopathy is promising and seems to have beneficial effects at short-term follow-up.EP, is funded by the European Commission through the Horizon 2020 Marie Ska, odowska-Curie Actions programme under Grant number 956394 within the PremAtuRe nEwborn motor and cogNitive impairmenTs: Early diagnosis (PARENT) project. This work was supported also by the Italian Ministry of Health with Current Research funds

The Development of Competencies in Interprofessional Health Care for Use in Health Science Educational Programs

Background: The Health Education Technology Research Unit (HETRU) at the University of Ontario Institute of Technology (UOIT) has developed an interprofessional framework for use as a learning map to create computer-based simulations that can automatically assess interprofessional competencies of undergraduate health sciences students.Methods: Our interprofessional competency framework was developed through an iterative process of competency mapping. Each iteration involved: 1) a literature review of interprofessional competencies, 2) the mapping of these competencies within a meaningful taxonomy, and 3) the review of the mapping by an expert panel of educators and clinicians.Findings and Conclusions: After three iterations, the research team developed a competency taxonomy that mapped interprofessional competencies from our literature reviews into six competency domains and three cross-cutting themes for each domain. The competency matrix was then used as a learning map to define learning resources related to interprofessional education and learning activities associated with such resources to help students develop competencies in interprofessional healthcare planning and delivery. Interactive, computer-based clinical simulations were then developed to portray opportunities in which the learning resources and activities could be explored and to provide more realistic exposure to complexities in healthcare planning and delivery