Office of Technology Transfer

The goal of the International HapMap Project is to determine the common patterns of DNA sequence variation in the human genome and to make this information freely available in the public domain. An international consortium is developing a map of these patterns across the genome by determining the genotypes of one million or more sequence variants, their frequencies and the degree of association between them, in DNA samples from populations with ancestry from parts of Africa, Asia and Europe. The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance our ability to choose targets for therapeutic intervention.

BACKGROUND: Evidence indicates that hospital nursing characteristics such as staffing contribute to patient outcomes. Less attention has been given to other hospital nursing characteristics central to optimal professional practice, namely nurse education and skill mix, continuity of care, and quality of the work environment. OBJECTIVE: To assess the relative effects and importance of nurse education and skill mix, continuity of care, and quality of work environment in predicting 30-day mortality after adjusting for institutional factors and individual patients characteristics. METHOD: A cross-sectional analysis of outcome data for 18,142 patients discharged from 49 acute care hospitals in Alberta, Canada, for diagnoses of acute myocardial infarction, congestive heart failure, chronic obstructive pulmonary disease, pneumonia, or stroke between April 1, 1998, and March 31, 1999, was done. Mortality data were linked to patient demographic and comorbidity factors, institutional characteristics, and hospital nursing characteristics derived from a survey of all registered nurses working in acute care hospitals. RESULTS: Using multilevel analysis, it was determined that the log-odds for 30-day mortality varied significantly across hospitals (variance = .044, p < .001). Patient comorbidities and age explained 44.2% of the variance in 30-day mortality. After adjustment for patient comorbidities and demographic factors, and the size, teaching, and urban status of the study hospitals in a fixed-effects model, the odds ratios (95% confidence interval) of the significant hospital nursing characteristics that predict 30-day mortality were as follows: 0.81 (0.68-0.96) for higher nurse education level, 0.83 (0.73-0.96) for richer nurse skill mix, 1.26 (1.09-1.47) for higher proportion of casual or temporary positions, and 0.74 (0.60-0.91) for greater nurse-physician relationships. The institutional and hospital nursing characteristics explained an additional 36.9%. DISCUSSION: Hospital nursing characteristics are an important consideration in efforts to reduce the risk of 30-day mortality of patients.

With the advances of power electronic technology, direct-driven permanent magnet synchronous generators (PMSGs) have increasingly drawn the interest of wind turbine manufacturers. At the present time, a commercial PMSG wind turbine primarily makes use of a passive rectifier followed by an insulated gate bipolar transistor (IGBT) inverter. Although a PMSG wind turbine with two back-to-back voltage source IGBT converters is considered more efficient, it has not been widely adopted by the wind power industry. This paper investigates both the conventional and a novel vector control mechanism for a PMSG wind turbine that has two side-by-side voltage source pulsewidth modulation converters. The proposed approach is based on a direct-current vector control mechanism for control of both machine- and grid-side converters of a PMSG wind turbine. Then, an optimal control strategy is developed for integrated control of PMSG maximum power extraction, reactive power, and grid voltage support controls. A transient system simulation using SimPowerSystem is built to investigate the performance of the conventional and proposed control techniques for the PMSG wind turbine under steady and gusty wind conditions. This paper shows that when using the direct-current vector control structure, a PMSG system has excellent performance in various aspects.

Since 1992, the U.S. Food and Drug Administration (FDA) has received reports of radiation-induced injuries to the skin in patients who had undergone fluoroscopically guided interventional procedures. The reports were investigated to determine the procedure- or equipment-related factors that may have contributed to the injury. The injuries ranged in severity from erythema to moist desquamation to tissue necrosis that required skin grafting. They occurred after a variety of interventional procedures that required extended periods of fluoroscopy compared with those of typical diagnostic procedures. Medical facilities and physicians should be aware of the magnitude of radiation doses to the skin that can result from the long exposure times required by complex interventional procedures. The FDA recommends several steps for reducing these injuries, including establishing protocols for each procedure, determining radiation dose rates for specific fluoroscopy systems and operating modes, and monitoring cumulative absorbed doses to areas of the skin.

Hypophosphorous acid (HPA) additive could effectively reduce the Sn vacancy density of CsSnIBr 2 films and achieve highly thermal stable PSCs.

Tout passage d’un objet culturel d’un contexte dans un autre a pour conséquence une transformation de son sens, une dynamique de resémantisation, qu’on ne peut pleinement reconnaître qu’en tenant compte des vecteurs historiques du passage. On peut donc dire d’emblée que la recherche sur les transferts culturels concerne la plupart des sciences humaines même si elle s’est développée à partir d’un certain nombre de points d’ancrage précis. L’étude des transferts culturels conduit à relativiser l’importance de la comparaison et, par dessus tout, la notion de centre.

BACKGROUND: Elderly patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) have a poor prognosis, with a low complete remission (CR) rate, high induction mortality, and short remission duration. Imatinib (IM) has a favorable toxicity profile but limited antileukemic activity in advanced Ph+ALL. Imatinib in combination with intensive chemotherapy has yielded promising results as front-line therapy, but its value as monotherapy in newly diagnosed Ph+ALL is not known. METHODS: Patients with de novo Ph+ALL were randomly assigned to induction therapy with either imatinib (Ind(IM)) or multiagent, age-adapted chemotherapy (Ind(chemo)). Imatinib was subsequently coadministered with consolidation chemotherapy. RESULTS: In all, 55 patients (median age, 68 years) were enrolled. The overall CR rate was 96.3% in patients randomly assigned to Ind(IM) and 50% in patients allocated to Ind(chemo) (P = .0001). Nine patients (34.6%) were refractory and 2 patients died during Ind(chemo); none failed imatinib induction. Severe adverse events were significantly more frequent during Ind(chemo) (90% vs 39%; P = .005). The estimated overall survival (OS) of all patients was 42% +/- 8% at 24 months, with no significant difference between the 2 cohorts. Median disease-free survival was significantly longer in the 43% of patients (21 of 49 evaluable) in whom BCR-ABL transcripts became undetectable (18.3 months vs 7.2 months; P = .002). CONCLUSIONS: In elderly patients with de novo Ph+ALL, imatinib induction results in a significantly higher CR rate and lower toxicity than induction chemotherapy. With subsequent combined imatinib and chemotherapy consolidation, this initial benefit does not translate into improved survival compared with chemotherapy induction.

BACKGROUND: Historically, public-sector researchers have performed the upstream, basic research that elucidated the underlying mechanisms of disease and identified promising points of intervention, whereas corporate researchers have performed the downstream, applied research resulting in the discovery of drugs for the treatment of diseases and have carried out development activities to bring them to market. However, the boundaries between the roles of the public and private sectors have shifted substantially since the dawn of the biotechnology era, and the public sector now has a much more direct role in the applied-research phase of drug discovery. METHODS: We identified new drugs and vaccines approved by the Food and Drug Administration (FDA) that were discovered by public-sector research institutions (PSRIs) and classified them according to their therapeutic category and potential therapeutic effect. RESULTS: We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. These drugs included 93 small-molecule drugs, 36 biologic agents, 15 vaccines, 8 in vivo diagnostic materials, and 1 over-the-counter drug. More than half of these drugs have been used in the treatment or prevention of cancer or infectious diseases. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect. CONCLUSIONS: Public-sector research has had a more immediate effect on improving public health than was previously realized.

OBJECTIVE: We aimed to explore the added value of common machine learning (ML) algorithms for prediction of outcome for moderate and severe traumatic brain injury. STUDY DESIGN AND SETTING: We performed logistic regression (LR), lasso regression, and ridge regression with key baseline predictors in the IMPACT-II database (15 studies, n = 11,022). ML algorithms included support vector machines, random forests, gradient boosting machines, and artificial neural networks and were trained using the same predictors. To assess generalizability of predictions, we performed internal, internal-external, and external validation on the recent CENTER-TBI study (patients with Glasgow Coma Scale <13, n = 1,554). Both calibration (calibration slope/intercept) and discrimination (area under the curve) was quantified. RESULTS: In the IMPACT-II database, 3,332/11,022 (30%) died and 5,233(48%) had unfavorable outcome (Glasgow Outcome Scale less than 4). In the CENTER-TBI study, 348/1,554(29%) died and 651(54%) had unfavorable outcome. Discrimination and calibration varied widely between the studies and less so between the studied algorithms. The mean area under the curve was 0.82 for mortality and 0.77 for unfavorable outcomes in the CENTER-TBI study. CONCLUSION: ML algorithms may not outperform traditional regression approaches in a low-dimensional setting for outcome prediction after moderate or severe traumatic brain injury. Similar to regression-based prediction models, ML algorithms should be rigorously validated to ensure applicability to new populations.

The doubly-fed induction generator (DFIG) wind turbine is a variable speed wind turbine widely used in the modern wind power industry. At present, commercial DFIG wind turbines primarily make use of the technology that was developed a decade ago. But, it is found in this paper that there is a limitation in the conventional vector control technique. This paper presents a direct-current vector control method in a DFIG wind turbine, based on which an integrated control strategy is developed for wind energy extraction, reactive power, and grid voltage support controls of the wind turbine. A transient simulation system using SimPowerSystem is built to validate the effectiveness of the proposed control method. The conventional control approach is compared with the proposed control technique for DFIG wind turbine control under both steady and gust wind conditions. The paper shows that under the dc vector control configuration, a DFIG system has a superior performance in various aspects.

Data visualization combines principles from psychology, usability, graphic design, and statistics to highlight important data in accessible and appealing formats. Doing so helps bridge knowledge producers with knowledge users, who are often inundated with information and increasingly pressed for time.

The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives; 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure; 3) aiding risk stratification in chronic disease patients, using a common strategy; 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing); 5) proposing a common simulation tool to assist physicians; and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).

A rapidly changing and expanding livestock and poultry production sector is causing a range of environmental problems on local, regional and global scales. Animal Manure Recycling: Treatment and Management presents an accessible overview of environmentally friendly technologies for managing animal manure more efficiently and in a sustainable manner. The book describes the physical and chemical characteristics of animal manure and microbial processes, featuring detailed examples and case studies showing how this knowledge can be used in practice. Readers are introduced to the sustainable use of animal manure for crop fertilisation and soil amelioration. Environmentally friendly technologies for reducing emissions of ammonia, odour and the greenhouse gases nitrous oxide and methane are presented, and reduction of plant nutrient losses using separation technologies is introduced. Finally and most importantly, the book describes methods to commercialise and transfer knowledge about innovations to end-users.

When the exotic Acer platanoides L. (Norway maple) and the native A. saccharum Marsh. (sugar maple) grow together in the understories of urban Quercus forests in the eastern USA, average annual height growth increments are nearly twice as large in A. platanoides as in A. saccharum, 19.26 +/- 3.22 versus 10.01 +/- 1.69 cm. We examined several ecophysiological mechanisms that might be associated with the superior invasive ability and growth of A. platanoides in two urban oak forests in Pennsylvania. Leaf longevity was 12 days greater in A. platanoides than in A. saccharum. In addition, leaf mass/leaf area ratio was greater in A. platanoides than in A. saccharum (2.67 +/- 0.03 versus 2.32 +/- 0.02 mg cm(-2)); however, leaf thickness was significantly lower in A. platanoides than in A. saccharum suggesting that A. platanoides contains more dense palisade and mesophyll cell layers than A. saccharum. Field net photosynthesis (mass basis) and photosynthetic light response curves (area basis) indicated significantly greater carbon assimilation, and nitrogen and phosphorus use efficiencies in A. platanoides than in A. saccharum. Acer platanoides also exhibited higher water use efficiency than A. saccharum (0.88 +/- 0.12 versus 0.32 +/- 0.09 mmol CO(2) mol(-1) H(2)O). Acer platanoides exhibited significantly lower osmotic potentials than A. saccharum, but a similar relative water content at zero turgor. We conclude that A. platanoides utilizes light, water and nutrients more efficiently than A. saccharum.

Modulating the thermo-responsive behaviour of poly(sulfobetaine methacrylates) whereby small structural changes cause big effects but show little logic.

BACKGROUND: The credibility of modern science is grounded on the perception of the objectivity of its scientists, but that credibility can be undermined by financial conflicts of interest. The US Public Health Service and the National Science Foundation issued regulations effective October 1, 1995, regarding the disclosure of financial interests in the submission of grant proposals. Several scientific journals have also established pertinent policies for authors and editors. The objectives of this study were: (1) to select a set of published articles and observe the degree to which a sample of authors hold a financial interest in areas related to their research that are reportable under current standards, and (2) to examine the hypothesis that significant numbers of authors of articles in life science and biomedical journals have verifiable financial interests that might be important for journal editors and readers to know. This paper measures the frequency of selected financial interests held among lead authors of certain types of scientific publications and assesses disclosure practices of authors and journals. METHOD: These objectives were applied to a pilot study of Massachusetts academic scientists who were cited as first or last author in at least one article published in 1992 in 14 leading journals of cell or molecular biology and medicine. We created a database of every original article published in 1992 by 14 leading life science and biomedical journals, supplemented by data sets consisting of (1) Massachusetts biotechnology firms, including their officers and scientific advisory boards, and (2) scientists listed as inventors on patents or patent applications registered with the World Intellectual Property Organization. RESULTS: We examined 1,105 university authors (first and last cited) from Massachusetts institutions whose 789 articles, published in 1992, appeared in 14 scientific and medical journals. Authors are said to 'possess a financial interest' if they are listed as inventors in a patent or patent application closely related to their published work; serve on a scientific advisory board of a biotechnology company; or are officers, directors, or major shareholders (beneficial owner of 10% or more of stock issued) in a firm that has commercial interests related to their research. Applying the criteria to the reference population of journals and Massachusetts academic authors, we measured the following frequencies for lead authors: 0.20 for serving on a scientific advisory board; 0.07 for being an officer, director, or major shareholder in a biotechnology firm, and 0.22 for being listed as an inventor in a related patent or patent application. The joint frequency of articles in the journals reviewed with a lead author that meets one of the three conditions is 0.34. CONCLUSIONS: One of every three articles in our sample has at least one Massachusetts-based author with a financial interest, and 15% of the authors in our sample have a financial interest relevant to one of their publications. For the year 1992, the rate of published voluntary disclosures of financial interest (as defined in our study) is virtually zero, but relatively few scientific and biomedical journals at that time required any such disclosure to journal editors and reviewers. Further research is needed to determine the effectiveness of mandatory disclosure requirements by some journals.

ABSTRACT Several diseases of the nervous system are characterized by neurodegeneration and death in childhood. Conventional medicine is ineffective, but fetal or neonatal gene therapy may provide an alternative route to treatment. We evaluated the ability of single‐stranded and self‐complementary adeno‐associated virus pseudotype 2/9 (AAV2/9) to transduce the nervous system and target gene expression to specific neural cell types following intravenous injection into fetal and neonatal mice, using control uninjected age‐matched mice. Fetal and neonatal administration produced global delivery to the central (brain, spinal cord, and all layers of the retina) and peripheral (myenteric plexus and innervating nerves) nervous system but with different expression profiles within the brain; fetal and neonatal administration resulted in expression in neurons and protoplasmic astrocytes, respectively. Neither single‐stranded nor self‐complementary AAV2/9 triggered a microglia‐mediated immune response following either administration. In summary, intravenous AAV2/9 targets gene expression to specific neural cell types dependent on developmental stage. This represents a powerful tool for studying nervous system development and disease. Furthermore, it may provide a therapeutic strategy for treatment of early lethal genetic diseases, such as Gaucher disease, and for disabling neuropathies, such as preterm brain injury.—Rahim, A. A., Wong, A. M. S., Hoefer, K., Buckley, S. M. K., Mattar, C. N., Cheng, S. H., Chan, J. K. Y., Cooper, J. D., Waddington, S. N. Intravenous administration of AAV2/9 to the fetal and neonatal mouse leads to differential targeting of central nervous system cell types and extensive transduction of the nervous system. FASEB J. 25, 3505–3518 (2011). www.fasebj.org

Abstract Topography may mitigate drought effects on vegetation along a hillslope gradient through redistribution of soil moisture. We examined the interaction of topography, climate, soil moisture, and transpiration in a low‐elevation, mixed‐hardwood forest in the southern Appalachian Mountains. The effects of meteorological variation (wet and dry years) and topographic position (upslope and cove) were tested on daily soil moisture amplitude and recession and plot and species‐specific transpiration. Trees in the cove plot were 17% taller and had 45% greater sapwood area than those in the upslope plot. Lower rates of soil moisture recession following rainfall events were observed at the cove plot compared to the upper plot. Greater daily soil moisture amplitude and plot transpiration, even in dry years, suggest that lower slope positions may have been buffered against moderate drought. We also observed similar transpiration inQuercusspp.,Caryaspp., andLiriodendron tulipiferain the cove plot between dry and wet years. Plot transpiration was reduced by 51% in the dry year in the upslope plot only, and transpiration by individual species in the plot reflected this pattern, suggesting water stress in dry years may be exacerbated by topography. With drought predicted to increase for these systems, the different drought responses of species, in addition to topographic effects, may lead to complex shifts in species composition.

The purpose of this paper is to assess the extent of gene identity and differentiation at 33 dinucleotide repeat loci (377 total alleles) within and among three European and three Native American populations. In order to do this, we show that a maximum-likelihood method proposed for phylogenetic trees (Cavalli-Sforza and Piazza 1975) can be used to estimate gene identity (Nei 1987) with respect to any hierarchical structure. This method allows gene differentiation to be evaluated with respect to any internal node of a hierarchy. It also allows a generalization of F- and G-statistics to situations with unequal expected levels of differentiation. Our principal finding is that levels of genetic differentiation are unique to specific populations and levels of nesting. The populations of European origin show very little internal differentiation; moreover, their continental average is close to the total population defined by the aggregate of Europeans and Native Americans. By contrast, the Native American populations show moderate levels of internal differentiation, and a great distance between their continental average and the total. The results of analyses of subsets of loci that were selected to have high gene diversities in either Europeans or Native Americans closely parallel those from the total set of loci. This suggests that the principal results are unlikely to be caused by a European ascertainment bias in locus selection. In summary, our findings demonstrate that partitions of gene diversity into within- and between-populations components are heavily biased by the populations analyzed and the models fitted. Optimistically, however, more information is available to analyze population history and evolution by quantifying, as we have done, the uniqueness of patterns of differentiation.

Based on requirements for a next-generation rocket test facility, elements of a prototype intelligent rocket test facility (IRTF) have been implemented. The preliminary results provide the basis for future advanced development and validation using rocket test stand facilities at Stennis Space Center (SSC). Key components include distributed smart sensor elements integrated using a knowledge-driven environment. One of the specific goals is to imbue sensors with the intelligence needed to perform self-diagnosis of health and to participate in a hierarchy of health determination at sensor, process, and system levels. We have identified issues important to further development of health-enabled networks, which should be of interest to others working with smart sensors and intelligent health management systems.