The Genomes of Recombinant Inbred Lines: The Gory Details

Recombinant inbred lines (RILs) can serve as powerful tools for genetic mapping. Recently, members of the Complex Trait Consortium have proposed the development of a large panel of eight-way RILs in the mouse, derived from eight genetically diverse parental strains. Such a panel would be a valuable community resource. The use of such eight-way RILs will require a detailed understanding of the relationship between alleles at linked loci on an RI chromosome. We extend the work of Haldane and Waddington (1931) on twoway RILs and describe the map expansion, clustering of breakpoints, and other features of the genomes of multiple-strain RILs as a function of the level of crossover interference in meiosis. In this technical report, we present all of our results, in their gory detail. We don’t intend to include such details in the final publication, but want to present them here for those who might be interested.

Periprocedural and late consequences of overlapping Cypher sirolimus-eluting stents: pooled analysis of five clinical trials

OBJECTIVES: The purpose of this research was to determine the relative safety and efficacy of multiple (> or =2) overlapping Cypher sirolimus-eluting stents (SES) (Johnson ; Johnson, New Brunswick, New Jersey). BACKGROUND: Overlapping coronary stents are common. The periprocedural and late clinical and angiographic consequences of overlapped coronary stents are not clearly defined, particularly for drug-eluting stents. METHODS: All patients enrolled into five clinical trials of the SES were analyzed. Three of these trials were prospective randomized comparisons of the SES to the bare-metal stent (BMS), and two were prospective non-randomized trials of SES-treated patients with historical controls. All clinical and angiographic outcomes in overlap-stent-treated patients were compared by stent type and with single-stent-treated patients for the same stent device. RESULTS: In all, 575 patients with stent overlap (337 SES, 238 BMS) and 1,162 patients with single stents (697 SES, 465 BMS) were analyzed. Stent overlap was associated with a greater late lumen loss in stent and more frequent angiographic restenosis regardless of stent type. Among overlap-stent-treated patients, the SES provided similar magnitude of restenosis benefit as observed for single-stent-treated patients. Overlapped SES was not associated with an increase in myocardial infarction. CONCLUSIONS: The strategy of SES overlap, when required, is both safe and efficacious in reducing restenosis with no increase in the incidence of myocardial infarction or major adverse cardiovascular events, when compared with a bare metal coronary stent prosthesis.

Effect of segmented anodes on the performance and plume of a hall thruster

Development of alternative propellants for Hall thruster operation is an active area of research. Xenon is the current propellant of choice for Hall thrusters, but can be costly in large thrusters and for extended test periods. Condensible propellants may offer an alternative to xenon, as they will not require costly active pumping to remove from a test facility, and may be less expensive to purchase. A method has been developed which uses segmented electrodes in the discharge channel of a Hall thruster to divert discharge current to and from the main anode and thus control the anode temperature. By placing a propellant reservoir in the anode, the evaporation rate, and hence, mass flow of propellant can be controlled. Segmented electrodes for thermal control of a Hall thruster represent a unique strategy of thruster design, and thus the performance of the thruster must be measured to determine the effect the electrodes have on the thruster. Furthermore, the source of any changes in thruster performance due to the adjustment of discharge current between the shims and the main anode must be characterized. A Hall thruster was designed and constructed with segmented electrodes. It was then tested at anode voltages between 300 and 400 V and mass flows between 4 and 6 mg/s, as well as 100%, 75%, 50%, 25%, and <5% of the discharge current on the shim electrodes. The level of current on the shims was adjusted by changing the shim voltage. At each operating point, the thruster performance, plume divergence, ion energy, and multiply charged ion fraction were measured performance exhibited a small change with the level of discharge current on the shim electrodes. Thrust and specific impulse increased by as much as 6% and 7.7%, respectively, as discharge current was shifted from the main anode to the shims at constant anode voltage. Thruster efficiency did not change. Plume divergence was reduced by approximately 4 degrees of half-angle at high levels of current on the shims and at all combinations of mass flow and anode voltage. The fraction of singly charged xenon in the thruster plume varied between approximately 80% and 95% as the anode voltage and mass flow were changed, but did not show a significant change with shim current. Doubly and triply charged xenon made up the remainder of the ions detected. Ion energy exhibited a mixed behavior. The highest voltage present in the thruster largely dictated the most probable energy; either shim or anode voltage, depending on which was higher. The overall change in most probable ion energy was 20-30 eV, the majority of which took place while the shim voltage was higher than the anode voltage. The thrust, specific impulse, plume divergence, and ion energy all indicate that the thruster is capable of a higher performance output at high levels of discharge current on the shims. The lack of a change in efficiency and fraction of multiply charged ions indicate that the thruster can be operated at any level of current on the shims without detrimental effect, and thus a condensible propellant thruster can control the anode temperature without a decrease in efficiency or a change in the multiply charged ion fraction.

ANKLE IMPEDANCE AND ANKLE ANGLES DURING STEP TURN AND STRAIGHT WALK: IMPLICATIONS FOR THE DESIGN OF A STEERABLE ANKLE-FOOT PROSTHETIC ROBOT

During locomotion, turning is a common and recurring event which is largely neglected in the current state-of-the-art ankle-foot prostheses, forcing amputees to use different steering mechanisms for turning, compared to non-amputees. A better understanding of the complexities surrounding lower limb prostheses will lead to increased health and well-being of amputees. The aim of this research is to develop a steerable ankle-foot prosthesis that mimics the human ankle mechanical properties. Experiments were developed to estimate the mechanical impedance of the ankle and the ankles angles during straight walk and step turn. Next, this information was used in the design of a prototype, powered steerable ankle-foot prosthesis with two controllable degrees of freedom. One of the possible approaches in design of the prosthetic robots is to use the human joints’ parameters, especially their impedance. A series of experiments were conducted to estimate the stochastic mechanical impedance of the human ankle when muscles were fully relaxed and co-contracting antagonistically. A rehabilitation robot for the ankle, Anklebot, was employed to provide torque perturbations to the ankle. The experiments were performed in two different configurations, one with relaxed muscles, and one with 10% of maximum voluntary contraction (MVC). Surface electromyography (sEMG) was used to monitor muscle activation levels and these sEMG signals were displayed to subjects who attempted to maintain them constant. Time histories of ankle torques and angles in the lateral/medial (LM) directions, inversion-eversion (IE), and dorsiflexionplantarflexion (DP) were recorded. Linear time-invariant transfer functions between the measured torques and angles were estimated providing an estimate of ankle mechanical impedance. High coherence was observed over a frequency range up to 30 Hz. The main effect of muscle activation was to increase the magnitude of ankle mechanical impedance in all degrees of freedom of the ankle. Another experiment compared the three-dimensional angles of the ankle during step turn and straight walking. These angles were measured to be used for developing the control strategy of the ankle-foot prosthesis. An infrared camera system was used to track the trajectories and angles of the foot and leg. The combined phases of heel strike and loading response, mid stance, and terminal stance and pre-swing were determined and used to measure the average angles at each combined phase. The Range of motion (ROM) in IE increased during turning while ML rotation decreased and DP changed the least. During the turning step, ankle displacement in DP started with similar angles to straight walk and progressively showed less plantarflexion. In IE, the ankle showed increased inversion leaning the body toward the inside of the turn. ML rotation initiated with an increased medial rotation during the step turn relative to the straight walk transitioning to increased lateral rotation at the toe off. A prototype ankle-foot prosthesis capable of controlling both DP and IE using a cable driven mechanism was developed and assessed as part of a feasibility study. The design is capable of reproducing the angles required for straight walk and step turn; generates 712N of lifting force in plantarflexion, and shows passive stiffness comparable to a nonload bearing ankle impedance. To evaluate the performance of the ankle-foot prosthesis, a circular treadmill was developed to mimic human gait during steering. Preliminary results show that the device can appropriately simulate human gait with loading and unloading the ankle joint during the gait in circular paths.

Effect of fluid resuscitation on mortality and organ function in experimental sepsis models

Introduction Several recent studies have shown that a positive fluid balance in critical illness is associated with worse outcome. We tested the effects of moderate vs. high-volume resuscitation strategies on mortality, systemic and regional blood flows, mitochondrial respiration, and organ function in two experimental sepsis models. Methods 48 pigs were randomized to continuous endotoxin infusion, fecal peritonitis, and a control group (n = 16 each), and each group further to two different basal rates of volume supply for 24 hours [moderate-volume (10 ml/kg/h, Ringer's lactate, n = 8); high-volume (15 + 5 ml/kg/h, Ringer's lactate and hydroxyethyl starch (HES), n = 8)], both supplemented by additional volume boli, as guided by urinary output, filling pressures, and responses in stroke volume. Systemic and regional hemodynamics were measured and tissue specimens taken for mitochondrial function assessment and histological analysis. Results Mortality in high-volume groups was 87% (peritonitis), 75% (endotoxemia), and 13% (controls). In moderate-volume groups mortality was 50% (peritonitis), 13% (endotoxemia) and 0% (controls). Both septic groups became hyperdynamic. While neither sepsis nor volume resuscitation strategy was associated with altered hepatic or muscle mitochondrial complex I- and II-dependent respiration, non-survivors had lower hepatic complex II-dependent respiratory control ratios (2.6 +/- 0.7, vs. 3.3 +/- 0.9 in survivors; P = 0.01). Histology revealed moderate damage in all organs, colloid plaques in lung tissue of high-volume groups, and severe kidney damage in endotoxin high-volume animals. Conclusions High-volume resuscitation including HES in experimental peritonitis and endotoxemia increased mortality despite better initial hemodynamic stability. This suggests that the strategy of early fluid management influences outcome in sepsis. The high mortality was not associated with reduced mitochondrial complex I- or II-dependent muscle and hepatic respiration.

Unprotected left main stenting in the real world: two-year outcomes of the French left main taxus registry

BACKGROUND: Cardiac surgery is the reference treatment for patients with left main (LM) disease, although percutaneous coronary intervention with drug-eluting stents is emerging as a possible alternative. The objective of this registry was to evaluate the 2-year outcome of elective percutaneous coronary intervention for unprotected LM disease with paclitaxel-eluting stents. METHODS AND RESULTS: A total of 291 patients were prospectively included from 4 centers. Acute myocardial infarction and cardiogenic shock were the only exclusion criteria. Patients were 69+/-11 years old, 29% were diabetic, and 25% had 3-vessel disease. For distal LM lesions (78%), the provisional side-branch T-stenting approach was used in 92% of cases and final kissing balloon inflation in 97%. Angiographic success was obtained in 99.7% of cases. At 2-year follow-up, the total cardiac death rate was 5.4% (1 EuroSCORE point was associated with a 15% [95% confidence interval 2.9% to 28.2%, P=0.013] higher risk of cardiac death), target-lesion revascularization was 8.7%, and incidence of Q-wave or non-Q-wave myocardial infarction was 0.9% and 3.1%, respectively. The combined end point occurred in 15.8% of cases and stroke in 0.7%. The incidence of definite and probable LM stent thrombosis was 0.7%, whereas the incidence of any stent thrombosis was 3.8%, with a higher risk in patients with side-branch stenting in the presence of LM bifurcation lesions (hazard ratio 9.6, 95% confidence interval 1.2 to 77.7, P=0.035). CONCLUSIONS: Unprotected LM stenting with paclitaxel-eluting stents, with a strategy of provisional side-branch T-stenting for distal lesions, provides excellent acute angiographic results and good mid-term clinical outcomes, with a 15.8% rate of major adverse cardiac events at 2-year follow-up.

Policy Contexts of Social Work in Britain: the wider implications of 'New' Labour and the 'New Legal Regime'

Several commentators have expressed disappointment with New Labour's apparent adherence to the policy frameworks of the previous Conservative administrations. The employment orientation of its welfare programmes, the contradictory nature of the social exclusion initiatives, and the continuing obsession with public sector marketisation, inspections, audits, standards and so on, have all come under critical scrutiny (c.f., Blyth 2001; Jordan 2001; Orme 2001). This paper suggests that in order to understand the socio-economic and political contexts affecting social work we need to examine the relationship between New Labour's modernisation project and its insertion within an architecture of global governance. In particular, membership of the European Union (EU), International Monetary Fund (IMF) and World Trade Organisation (WTO) set the parameters for domestic policy in important ways. Whilst much has been written about the economic dimensions of 'globalisation' in relation to social work rather less has been noted about the ways in which domestic policy agenda are driven by multilateral governance objectives. This policy dimension is important in trying to respond to various changes affecting social work as a professional activity. What is possible, what is encouraged, how things might be done, is tightly bounded by the policy frameworks governing practice and affected by those governing the lives of service users. It is unhelpful to see policy formulation in purely national terms as the UK is inserted into a network governance structure, a regulatory framework where decisions are made by many countries and organisations and agencies. Together, they are producing a 'new legal regime', characterised by a marked neo-liberal policy agenda. This paper aims to demonstrate the relationship of New Labour's modernisation programme to these new forms of legality by examining two main policy areas and the welfare implications they are enmeshed in. The first is privatisation, and the second is social policy in the European Union. Examining these areas allows a demonstration of how much of the New Labour programme can be understood as a local implementation of a transnational strategy, how parts of that strategy produce much of the social exclusion it purports to address, and how social welfare, and particularly social work, are noticeable by their absence within policy discourses of the strategy. The paper details how the privatisation programme is considered to be a crucial vehicle for the further development of a transnational political-economy, where capital accumulation has been redefined as 'welfare'. In this development, frameworks, codes and standards are central, and the final section of the paper examines how the modernisation strategy of the European Union depends upon social policy marked by an employment orientation and risk rationality, aimed at reconfiguring citizen identities.The strategy is governed through an 'open mode of coordination', in which codes, standards, benchmarks and so on play an important role. The paper considers the modernisation strategy and new legality within which it is embedded as dependent upon social policy as a technology of liberal governance, one demonstrating a new rationality in comparison to that governing post-Second World War welfare, and which aims to reconfigure institutional infrastructure and citizen identity.

Rollout of CampusContent

CampusContent (CC) is a DFG-funded competence center for eLearning with its own portal. It links content and people who support sharing and reuse of high quality learning materials and codified pedagogical know-how, such as learning objectives, pedagogical scenarios, recommended learning activities, and learning paths. The heart of the portal is a distributed repository whose contents are linked to various other CampusContent portals. Integrated into each portal are user-friendly tools for designing reusable learning content, exercises, and templates for learning units and courses. Specialized authoring tools permit the configuration, adaption, and automatic generation of interactive Flash animations using Adobe's Flexbuilder technology. More coarse-grained content components such as complete learning units and entire courses, in which contents and materials taken from the repository are embedded, can be created with XML-based authoring tools. Open service interface allow the deep or shallow integration of the portal provider's preferred authoring and learning tools. The portal is built on top of the Enterprise Content Management System Alfresco, which comes with social networking functionality that has been adapted to accommmodate collaboration, sharing and reuse within trusted communities of practice.

"Fascinating Voids: Alexander von Humboldt and the Myth of Chimborazo"

When Alexander von Humboldt reached the village of Calpi in the Andes on 22 June 1802, he was greeted with reverence and enthusiasm. Triumphal arches adorned with cotton, cloth, and silver decorated his path. The natives performed a dance in festive dress. A singer praised the explorer's expedition, which had departed three years earlier from the Spanish port of La Coruña. Like Odysseus on the isle of the Phaeacians, the traveler listened to a local rhapsodist singing about his heroic deeds. Before his adventure ended, it had already spun a popular myth. This episode, which Humboldt recorded in his diary, occurred at a significant moment. One day later, the “Second Discoverer of America” rose to even greater fame on an excursion marking in more ways than one the climax of his enterprise. Humboldt set out to climb Chimborazo (6,310 m/20,702 ft.), the mountain then thought to be the highest in the world. He was accompanied by the French botanist Aimé Bonpland (1773–1858) and the Creole nobleman and future activist Carlos Montúfar (1780–1816), as well as native guides and assistants. They climbed to heights never reached before, setting a new record and catapulting Humboldt to fame on both continents.

Linked Services for Enabling Interoperability in the Sensing Enterprise

In future, the so called “sensing enterprise”, as part of the Future Internet, will play a crucial role in the success or the failure of an enterprise. We present our vision of an enterprise interacting with the physical world based on a retail scenario. One of the main challenges is the interoperability not only between the enterprise IT systems themselves, but also between these systems and the sensing devices. We will argue that semantically enriched service descriptions, the so called linked services will ease interoperability between two or more enterprises IT systems, and between enterprise systems and the physical environment.

Privacy Calculus on Social Networking Sites: Explorative Evidence from Germany and USA

Worldwide social networks, like Facebook, face fierce competition from local platforms when expanding globally. To remain attractive social network providers need to encourage user self-disclosure. Yet, little research exists on how cultural differences impact selfdisclosure on these platforms. Addressing this gap, this study explores the differences in perceptions of disclosure-relevant determinants between German and US users. Survey of Facebook members indicates that German users expect more damage and attribute higher probability to privacy-related violations. On the other hand, even though American users show higher level of privacy concern, they extract more benefits from their social networking activities, have more trust in the service provider and legal assurances as well as perceive more control. These factors may explain a higher level of self-disclosure indicated by American users. Our results provide relevant insights for the social network providers who can adjust their expansion strategy with regard to cultural differences.

Vertical integration and information sharing — an empirical investigation in the German apparel industry

Despite the astounding success of the fast fashion retailers, the management practices leading to these results have not been subject to extensive research so far. Given this background, we analyze the impact of information sharing and vertical integration on the performance of 51 German apparel companies. We find that the positive impact of vertical integration is mediated by information sharing, i.e. that the ability to improve the information flow is a key success factor of vertically integrated apparel supply chains. Thus, the success of an expansion strategy based on vertical integration critically depends on effective ways to share logistical information.

Cost-effectiveness of universal prophylaxis in pregnancy with prior group B streptococci colonization.

OBJECTIVE: To estimate the costs and outcomes of rescreening for group B streptococci (GBS) compared to universal treatment of term women with history of GBS colonization in a previous pregnancy. STUDY DESIGN: A decision analysis model was used to compare costs and outcomes. Total cost included the costs of screening, intrapartum antibiotic prophylaxis (IAP), treatment for maternal anaphylaxis and death, evaluation of well infants whose mothers received IAP, and total costs for treatment of term neonatal early onset GBS sepsis. RESULTS: When compared to screening and treating, universal treatment results in more women treated per GBS case prevented (155 versus 67) and prevents more cases of early onset GBS (1732 versus 1700) and neonatal deaths (52 versus 51) at a lower cost per case prevented ($8,805 versus $12,710). CONCLUSION: Universal treatment of term pregnancies with a history of previous GBS colonization is more cost-effective than the strategy of screening and treating based on positive culture results.

Sequence of arrival determines plant-mediated interactions between herbivores

Induced changes in plant quality can mediate indirect interactions between herbivores. Although the sequence of attack by different herbivores has been shown to influence plant responses, little is known about how this affects the herbivores themselves. We therefore investigated how induction by the leaf herbivore Spodoptera frugiperda influences resistance of teosinte (Zea mays mexicana) and cultivated maize (Zea mays mays) against root-feeding larvae of Diabrotica virgifera virgifera. The importance of the sequence of arrival was tested in the field and laboratory. Spodoptera frugiperda infestation had a significant negative effect on colonization by D. virgifera larvae in the field and weight gain in the laboratory, but only when S. frugiperda arrived on the plant before the root herbivore. When S. frugiperda arrived after the root herbivore had established, no negative effects on larval performance were detected. Yet, adult emergence of D. virgifera was reduced even when the root feeder had established first, indicating that the negative effects were not entirely absent in this treatment. The defoliation of the plants was not a decisive factor for the negative effects on root herbivore development, as both minor and major leaf damage resulted in an increase in root resistance and the extent of biomass removal was not correlated with root-herbivore growth. We propose that leaf-herbivore-induced increases in feeding-deterrent and/or toxic secondary metabolites may account for the sequence-specific reduction in root-herbivore performance. Synthesis. Our results demonstrate that the sequence of arrival can be an important determinant of plant-mediated interactions between insect herbivores in both wild and cultivated plants. Arriving early on a plant may be an important strategy of insects to avoid competition with other herbivores. To fully understand plant-mediated interactions between insect herbivores, the sequence of arrival should be taken into account. © 2011 The Authors. Journal of Ecology © 2011 British Ecological Society.

Intraoperative monopolar mapping during 5-ALA-guided resections of glioblastomas adjacent to motor eloquent areas: evaluation of resection rates and neurological outcome.

OBJECT Resection of glioblastoma adjacent to motor cortex or subcortical motor pathways carries a high risk of both incomplete resection and postoperative motor deficits. Although the strategy of maximum safe resection is widely accepted, the rates of complete resection of enhancing tumor (CRET) and the exact causes for motor deficits (mechanical vs vascular) are not always known. The authors report the results of their concept of combining monopolar mapping and 5-aminolevulinic acid (5-ALA)-guided surgery in patients with glioblastoma adjacent to eloquent tissue. METHODS The authors prospectively studied 72 consecutive patients who underwent 5-ALA-guided surgery for a glioblastoma adjacent to the corticospinal tract (CST; < 10 mm) with continuous dynamic monopolar motor mapping (short-train interstimulus interval 4.0 msec, pulse duration 500 μsec) coupled to an acoustic motor evoked potential (MEP) alarm. The extent of resection was determined based on early (< 48 hours) postoperative MRI findings. Motor function was assessed 1 day after surgery, at discharge, and at 3 months. RESULTS Five patients were excluded because of nonadherence to protocol; thus, 67 patients were evaluated. The lowest motor threshold reached during individual surgery was as follows (motor threshold, number of patients): > 20 mA, n = 8; 11-20 mA, n = 13; 6-10 mA, n = 10; 4-5 mA, n = 13; and 1-3 mA, n = 23. Motor deterioration at postsurgical Day 1 and at discharge occurred in 30% (n = 20) and 10% (n = 7) of patients, respectively. At 3 months, 3 patients (4%) had a persisting postoperative motor deficit, 2 caused by vascular injury and 1 by mechanical injury. The rates of intra- and postoperative seizures were 1% and 0%, respectively. Complete resection of enhancing tumor was achieved in 73% of patients (49/67) despite proximity to the CST. CONCLUSIONS A rather high rate of CRET can be achieved in glioblastomas in motor eloquent areas via a combination of 5-ALA for tumor identification and intraoperative mapping for distinguishing between presumed and actual motor eloquent tissues. Continuous dynamic mapping was found to be a very ergonomic technique that localizes the motor tissue early and reliably.