“Forward-Thinking” in U.S. Biobanking

Aims: Do biobanks enact policies and plans that allow them to anticipate and respond to potential challenges? If a biobank has one such policy or plan, is it likely to have more? Using survey data from 456 U.S. biobanks, we assess four possible indicators of such “forward-thinking.

The chromatin remodelers ISWI and ACF1 directly repress Wingless transcriptional targets

AbstractThe highly conserved Wingless/Wnt signaling pathway controls many developmental processes by regulating the expression of target genes, most often through members of the TCF family of DNA-binding proteins. In the absence of signaling, many of these targets are silenced, by mechanisms involving TCFs that are not fully understood. Here we report that the chromatin remodeling proteins ISWI and ACF1 are required for basal repression of WG target genes in Drosophila. This regulation is not due to global repression by ISWI and ACF1 and is distinct from their previously reported role in chromatin assembly. While ISWI is localized to the same regions of Wingless target gene chromatin as TCF, we find that ACF1 binds much more broadly to target loci. This broad distribution of ACF1 is dependent on ISWI. ISWI and ACF1 are required for TCF binding to chromatin, while a TCF-independent role of ISWI-ACF1 in repression of Wingless targets is also observed. Finally, we show that Wingless signaling reduces ACF1 binding to WG targets, and ISWI and ACF1 regulate repression by antagonizing histone H4 acetylation. Our results argue that WG signaling activates target gene expression partly by overcoming the chromatin barrier maintained by ISWI and ACF1

Biobanks containing clinical specimens: Defining characteristics, policies, and practices

Biobanks – collections of human biological specimens stored for future research use – are crucial for biomedical advancement. One of the most common ways that biobanks acquire specimens is to obtain residual or “leftover” samples originally collected for clinical care from hospitals, clinical laboratories and pathology departments. Little is known about the characteristics of biobanks that store specimens from clinical sources, or their policies and practices.In this paper, we present data from the subset of 261 biobanks in our 2012 national survey that stores specimens from clinical sources, focusing on a number of ethical issues that have been raised in the literature.Most biobanks are part of larger organizations, mainly academic medical centers, and most report standardized systems for managing acquisition, storage, and release to researchers. Yet, there is considerable diversity in policies and practices regarding informed consent, return of research results, ownership of specimens and technology developed, utilization, and disposition of remaining specimens after researchers have acquired, them. We document tremendous heterogeneity in the composition of these collections, the number and type of specimens stored, and number of requests for specimens per year.Responding to this variation presents significant challenges for those who manage the collections, demanding careful consideration and planning to maintain high quality practices in acquisition, storage, and release of specimens all the while striving to protect the rights of subjects

Biobanks in the United States: How to Identify an Undefined and Rapidly Evolving Population

As part of a larger organizational study, we sought to survey biobanks in the United States. However, we encountered two problems with this population. First, no common definition of biobanks exists. Second, no census is available of these facilities from which to sample in order to implement a survey. In light of these problems, we employed a multifaceted approach using electronic searches of PubMed, RePORTER, and Google. In addition, we systematically searched for biobanks housed within universities that have NIH-designated Clinical and Translational Science Awards (CTSA). We expanded this part of the search by looking for biobanks among all members of the American Association of Medical Colleges (AAMC). Finally, we added banks to our database found previously by other researchers and banks found via correspondence with our colleagues. Our search strategy produced a database of 624 biobanks for which we were able to confirm contact information in order to conduct our online survey. Another 140 biobanks were identified but did not respond to our requests to confirm their existence or contact information. In order to maximize both the uniqueness of banks found and the greatest return on effort for each search, we suggest targeting resources that are already organized. In our work, these included the CTSA, AAMC, and part of the Google searches. We contend that our search provides a model for analysis of new fields of research and/or rapidly evolving industries. Furthermore, our approach demonstrates that with the appropriate tools it is possible to develop a systematic and comprehensive database to investigate undefined populations

Community Engagement in US Biobanking: Multiplicity of Meaning and Method

Efforts to improve individual and population health increasingly rely on large scale collections of human biological specimens and associated data. Such collections or “biobanks” are hailed as valuable resources for facilitating translational biomedical research. However, biobanks also raise important ethical considerations, such as whether, how and why biobanks might engage with those who contributed specimens. This paper examines perceptions and practices of community engagement (CE) among individuals who operate six diverse biobanks in the U.S

The UN in the lab

We consider two alternatives to inaction for governments combating terrorism, which we term Defense and Prevention. Defense consists of investing in resources that reduce the impact of an attack, and generates a negative externality to other governments, making their countries a more attractive objective for terrorists. In contrast, Prevention, which consists of investing in resources that reduce the ability of the terrorist organization to mount an attack, creates a positive externality by reducing the overall threat of terrorism for all. This interaction is captured using a simple 3×3 “Nested Prisoner’s Dilemma” game, with a single Nash equilibrium where both countries choose Defense. Due to the structure of this interaction, countries can benefit from coordination of policy choices, and international institutions (such as the UN) can be utilized to facilitate coordination by implementing agreements to share the burden of Prevention. We introduce an institution that implements a burden-sharing policy for Prevention, and investigate experimentally whether subjects coordinate on a cooperative strategy more frequently under different levels of cost sharing. In all treatments, burden sharing leaves the Prisoner’s Dilemma structure and Nash equilibrium of the game unchanged. We compare three levels of burden sharing to a baseline in a between-subjects design, and find that burden sharing generates a non-linear effect on the choice of the efficient Prevention strategy and overall performance. Only an institution supporting a high level of mandatory burden sharing generates a significant improvement in the use of the Prevention strategy

Effect of losartan on performance and physiological responses to exercise at high altitude (5035 m)

Objective: Altitude-related and exercise-related elevations in blood pressure (BP) increase the likelihood of developing pulmonary hypertension and high-altitude illness during high-altitude sojourn. This study examined the antihypertensive effect and potential exercise benefit of the angiotensin II receptor antagonist losartan when taken at altitude. Methods: Twenty participants, paired for age and ACE genotype status, completed a double-blinded, randomised study, where participants took either losartan (100 mg/day) or placebo for 21 days prior to arrival at 5035 m (Whymper Hut, Mt Chimborazo, Ecuador). Participants completed a maximal exercise test on a supine cycle ergometer at sea level (4 weeks prior) and within 48 hours of arrival to 5035 m (10-day ascent). Power output, beat-to-beat BP, oxygen saturation (SpO2) and heart rate (HR) were recorded during exercise, with resting BP collected from daily medicals during ascent. Before and immediately following exercise at 5035 m, extravascular lung water prevalence was assessed with ultrasound (quantified via B-line count). Results: At altitude, peak power was reduced relative to sea level (p<0.01) in both groups (losartan vs placebo: down 100±29 vs 91±28 W, p=0.55), while SpO2 (70±6 vs 70±5%, p=0.96) and HR (146±21 vs 149±24 bpm, p=0.78) were similar between groups at peak power, as was the increase in systolic BP from rest to peak power (up 80±37 vs 69±33 mm Hg, p=0.56). Exercise increased B-line count (p<0.05), but not differently between groups (up 5±5 vs 8±10, p=0.44). Conclusion: Losartan had no observable effect on resting or exercising BP, exercise-induced symptomology of pulmonary hypertension or performance at 5035 m

Predicting the Performance of Highway Embankment Slopes

Resilience of transportation infrastructure, such as highway embankments, is critical to avoiding commuter delays and costly repairs. The majority of highway embankments in Louisiana and Texas are in marginal condition because the high-plasticity clays that are used during construction will moisten with time to significantly lower strengths. The ring shear tests demonstrate that the Gamez and Stark [1] empirical correlations are applicable to Texas and Louisiana soils. The soil water retention curves at each site were fitted to the Van Genuchten model [2]. For example, the air entry values vary from 0.013 to 0.053 kPa-1 in Louisiana and from 0.008 to 0.01 kPa-1 in Texas. The implications of this wide range of air entry values is that the matric suction pressure required to saturate and desaturate controls the pore-water pressure build-up during a rainfall event