Entrepreneurial Experiments in Science Policy: Analizing the Human Genome Project

We re-conceptualize the role of science policy makers, envisioning and illustrating their move from being simple investors in scientific projects to entrepreneurs who create the conditions for entrepreneurial experiments and initiate them. We argue that reframing science policy around the notion of conducting entrepreneurial experiments – experiments that increase the diversity of technical, organizational and institutional arrangements in which scientific research is conducted – can provide policy makers with a wider repertoire of effective interventions. To illustrate the power of this approach, we analyze the Human Genome Project (HGP) as a set of successful, entrepreneurial experiments in organizational and institutional innovation. While not designed as such, the HGP was an experiment in funding a science project across a variety of organizational settings, including seven public and one private (Celera) research centers. We assess the major characteristics and differences between these organizational choices, using a mix of qualitative and econometric analyses to examine their impact on scientific progress. The planning and direction of the Human Genome Project show that policy makers can use the levers of entrepreneurial experimentation to transform scientific progress, much as entrepreneurs have transformed economic progress.Entrepreneurial Experiments; Science Policy; Human Genome Project

Relationship of serum prolactin with severity of drug use and treatment outcome in cocaine dependence.

RATIONALE: Alteration in serum prolactin (PRL) levels may reflect changes in central dopamine activity, which modulates the behavioral effects of cocaine. Therefore, serum PRL may have a potential role as a biological marker of drug severity and treatment outcome in cocaine dependence. OBJECTIVE: We investigated whether serum PRL levels differed between cocaine-dependent (CD) subjects and controls, and whether PRL levels were associated with severity of drug use and treatment outcome in CD subjects. METHODS: Basal PRL concentrations were assayed in 141 African-American (AA) CD patients attending an outpatient treatment program and 60 AA controls. Severity of drug use was assessed using the Addiction Severity Index (ASI). Measures of abstinence and retention during 12 weeks of treatment and at 6-month follow-up were employed as outcome variables. RESULTS: The basal PRL (ng/ml) in CD patients (9.28+/-4.13) was significantly higher than controls (7.33+/-2.94) (t=3.77, P\u3c0.01). At baseline, PRL was positively correlated with ASI-drug (r=0.38, P\u3c0.01), ASI-alcohol (r=0.19, P\u3c0.05), and ASI-psychological (r=0.25, P\u3c0.01) composite scores, and with the quantity of cocaine use (r=0.18, P\u3c0.05). However, PRL levels were not significantly associated with number of negative urine screens, days in treatment, number of sessions attended, dropout rate or changes in ASI scores during treatment and at follow-up. Also, basal PRL did not significantly contribute toward the variance in predicting any of the outcome measures. CONCLUSION: Although cocaine use seems to influence PRL levels, it does not appear that PRL is a predictor of treatment outcome in cocaine dependence

Recent Changes in Farm Structure: A Canada-U.S. Comparison

Following a series of bilateral and multilateral agreements, the past two decades have seen increased trade and investment liberalization between Canada and the United States in the agri-food sector. Changes in trade policy are one of several paths by which farm structure can change. This increased liberalization, together with the largest drop in Canadian farm numbers recorded by the Census of Agriculture in thirty years, has provided the impetus to review some aspects of farm structure. In particular, this article presents the latest Canadian and U.S. data on the number of farms by sales class, the concentration of sales and other production-related variables, and the distribution of income and receipts. We explore whether significant changes in the latter two elements of farm structure have occurred during this period of trade and investment liberalization.Crop Production/Industries, Farm Management, International Relations/Trade,

Increased prevalence of precancerous changes in relatives of gastric cancer patients: critical role of H. pylori

Background & Aims:Helicobacter pylori is believed to predispose to gastric cancer by inducing gastric atrophy and hypochlorhydria. First-degree relatives of patients with gastric cancer have an increased risk of developing gastric cancer. The aim of this study was to determine the prevalence of atrophy and hypochlorhydria and their association with H. pylori infection in first-degree relatives of patients with gastric cancer. Methods:H. pylori status, gastric secretory function, and gastric histology were studied in 100 first-degree relatives of patients with noncardia gastric cancer and compared with those of controls with no family history of this cancer. Results: Compared with healthy controls, relatives of patients with gastric cancer had a higher prevalence of hypochlorhydria (27% vs. 3%) but a similar prevalence of H. pylori infection (63% vs. 64%). Relatives of cancer patients also had a higher prevalence of atrophy (34%) than patients with nonulcer dyspepsia (5%) matched for H. pylori prevalence. Among the relatives of cancer patients, the prevalence of atrophy and hypochlorhydria was increased only in those with evidence of H. pylori infection, was greater in relatives of patients with familial cancer than in relatives of sporadic cancer index patients, and increased with age. Eradication of H. pylori infection produced resolution of the gastric inflammation in each subject and resolution of hypochlorhydria and atrophy in 50% of the subjects. Conclusions: Relatives of patients with gastric cancer have an increased prevalence of precancerous gastric abnormalities, but this increase is confined to those with H. pylori infection. Consequently, prophylactic eradication of the infection should be offered to such subjects

Crater population and resurfacing of the Martian north polar layered deposits

Present-day accumulation in the north polar layered deposits (NPLD) is thought to occur via deposition on the north polar residual cap. Understanding current mass balance in relation to current climate would provide insight into the climatic record of the NPLD. To constrain processes and rates of NPLD resurfacing, a search for craters was conducted using images from the Mars Reconnaissance Orbiter Context Camera. One hundred thirty craters have been identified on the NPLD, 95 of which are located within a region defined to represent recent accumulation. High Resolution Imaging Science Experiment images of craters in this region reveal a morphological sequence of crater degradation that provides a qualitative understanding of processes involved in crater removal. A classification system for these craters was developed based on the amount of apparent degradation and infilling and where possible depth/diameter ratios were determined. The temporal and spatial distribution of crater degradation is interpreted to be close to uniform. Through comparison of the size-frequency distribution of these craters with the expected production function, the craters are interpreted to be an equilibrium population with a crater of diameter D meters having a lifetime of ~30.75D^(1.14) years. Accumulation rates within these craters are estimated at 7.2D^(−0.14) mm/yr, which corresponds to values of ~3–4 mm/yr and are much higher than rates thought to apply to the surrounding flat terrain. The current crater population is estimated to have accumulated in the last ~20 kyr or less

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

State-Chart Autocoder

A computer program translates Unified Modeling Language (UML) representations of state charts into source code in the C, C++, and Python computing languages. ( State charts signifies graphical descriptions of states and state transitions of a spacecraft or other complex system.) The UML representations constituting the input to this program are generated by using a UML-compliant graphical design program to draw the state charts. The generated source code is consistent with the "quantum programming" approach, which is so named because it involves discrete states and state transitions that have features in common with states and state transitions in quantum mechanics. Quantum programming enables efficient implementation of state charts, suitable for real-time embedded flight software. In addition to source code, the autocoder program generates a graphical-user-interface (GUI) program that, in turn, generates a display of state transitions in response to events triggered by the user. The GUI program is wrapped around, and can be used to exercise the state-chart behavior of, the generated source code. Once the expected state-chart behavior is confirmed, the generated source code can be augmented with a software interface to the rest of the software with which the source code is required to interact

Gene targets of mouse miR-709: regulation of distinct pools

MicroRNA (miRNA) are short non-coding RNA molecules that regulate multiple cellular processes, including development, cell differentiation, proliferation and death. Nevertheless, little is known on whether miRNA control the same gene networks in different tissues. miR-709 is an abundant miRNA expressed ubiquitously. Through transcriptome analysis, we have identified targets of miR-709 in hepatocytes. miR-709 represses genes implicated in cytoskeleton organization, extracellular matrix attachment, and fatty acid metabolism. Remarkably, none of the previously identified targets in non-hepatic tissues are silenced by miR-709 in hepatocytes, even though several of these genes are abundantly expressed in liver. In addition, miR-709 is upregulated in hepatocellular carcinoma, suggesting it participates in the genetic reprogramming that takes place during cell division, when cytoskeleton remodeling requires substantial changes in gene expression. In summary, the present study shows that miR-709 does not repress the same pool of genes in separate cell types. These results underscore the need for validating gene targets in every tissue a miRNA is expressed

Buried shallow fault slip from the South Napa earthquake revealed by near-field geodesy.

Earthquake-related fault slip in the upper hundreds of meters of Earths surface has remained largely unstudied because of challenges measuring deformation in the near field of a fault rupture. We analyze centimeter-scale accuracy mobile laser scanning (MLS) data of deformed vine rows within ±300 m of the principal surface expression of the M (magnitude) 6.0 2014 South Napa earthquake. Rather than assuming surface displacement equivalence to fault slip, we invert the near-field data with a model that allows for, but does not require, the fault to be buried below the surface. The inversion maps the position on a preexisting fault plane of a slip front that terminates ~3 to 25 m below the surface coseismically and within a few hours postseismically. The lack of surface-breaching fault slip is verified by two trenches. We estimate near-surface slip ranging from ~0.5 to 1.25 m. Surface displacement can underestimate fault slip by as much as 30%. This implies that similar biases could be present in short-term geologic slip rates used in seismic hazard analyses. Along strike and downdip, we find deficits in slip: The along-strike deficit is erased after ~1 month by afterslip. We find no evidence of off-fault deformation and conclude that the downdip shallow slip deficit for this event is likely an artifact. As near-field geodetic data rapidly proliferate and will become commonplace, we suggest that analyses of near-surface fault rupture should also use more sophisticated mechanical models and subsurface geomechanical tests

Flight Demonstration Of Low Overpressure N-Wave Sonic Booms And Evanescent Waves

The recent flight demonstration of shaped sonic booms shows the potential for quiet overland supersonic flight, which could revolutionize air transport. To successfully design quiet supersonic aircraft, the upper limit of an acceptable noise level must be determined through quantitative recording and subjective human response measurements. Past efforts have concentrated on the use of sonic boom simulators to assess human response, but simulators often cannot reproduce a realistic sonic boom sound. Until now, molecular relaxation effects on low overpressure rise time had never been compared with flight data. Supersonic flight slower than the cutoff Mach number, which generates evanescent waves, also prevents loud sonic booms from impacting the ground. The loudness of these evanescent waves can be computed, but flight measurement validation is needed. A novel flight demonstration technique that generates low overpressure N-waves using conventional military aircraft is outlined, in addition to initial quantitative flight data. As part of this demonstration, evanescent waves also will be recorded