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Intracortical microstimulation of the somatosensory cortex offers the potential for creating a sensory neuroprosthesis to restore tactile sensation. Whereas animal studies have suggested that both cutaneous and proprioceptive percepts can be evoked using this approach, the perceptual quality of the stimuli cannot be measured in these experiments. We show that microstimulation within the hand area of the somatosensory cortex of a person with long-term spinal cord injury evokes tactile sensations perceived as originating from locations on the hand and that cortical stimulation sites are organized according to expected somatotopic principles. Many of these percepts exhibit naturalistic characteristics (including feelings of pressure), can be evoked at low stimulation amplitudes, and remain stable for months. Further, modulating the stimulus amplitude grades the perceptual intensity of the stimuli, suggesting that intracortical microstimulation could be used to convey information about the contact location and pressure necessary to perform dexterous hand movements associated with object manipulation.

The Large Binocular Telescope Interferometer (LBTI) is a high spatial resolution instrument developed for coherent imaging and nulling interferometry using the 14.4 m baseline of the 2×8.4 m LBT. The unique telescope design, comprising of the dual apertures on a common elevation-azimuth mount, enables a broad use of observing modes. The full system is comprised of dual adaptive optics systems, a near-infrared phasing camera, a 1-5 μm camera (called LMIRCam), and an 8-13 μm camera (called NOMIC). The key program for LBTI is the Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS), a survey using nulling interferometry to constrain the typical brightness from exozodiacal dust around nearby stars. Additional observations focus on the detection and characterization of giant planets in the thermal infrared, high spatial resolution imaging of complex scenes such as Jupiter's moon, Io, planets forming in transition disks, and the structure of active Galactic Nuclei (AGN). Several instrumental upgrades are currently underway to improve and expand the capabilities of LBTI. These include: Improving the performance and limiting magnitude of the parallel adaptive optics systems; quadrupling the field of view of LMIRcam (increasing to 20"x20"); adding an integral field spectrometry mode; and implementing a new algorithm for path length correction that accounts for dispersion due to atmospheric water vapor. We present the current architecture and performance of LBTI, as well as an overview of the upgrades.

The Large Binocular Telescope Interferometer uses a near-infrared camera to measure the optical path length variations between the two AO-corrected apertures and provide high-angular resolution observations for all its science channels (1.5-13 $\mu$m). There is however a wavelength dependent component to the atmospheric turbulence, which can introduce optical path length errors when observing at a wavelength different from that of the fringe sensing camera. Water vapor in particular is highly dispersive and its effect must be taken into account for high-precision infrared interferometric observations as described previously for VLTI/MIDI or the Keck Interferometer Nuller. In this paper, we describe the new sensing approach that has been developed at the LBT to measure and monitor the optical path length fluctuations due to dry air and water vapor separately. After reviewing the current performance of the system for dry air seeing compensation, we present simultaneous H-, K-, and N-band observations that illustrate the feasibility of our feedforward approach to stabilize the path length fluctuations seen by the LBTI nuller., Comment: SPIE conference proceedings

In this paper we will briefly revisit the optical vibration measurement system (OVMS) at the Large Binocular Telescope (LBT) and how these values are used for disturbance compensation and particularly for the LBT Interferometer (LBTI) and the LBT Interferometric Camera for Near-Infrared and Visible Adaptive Interferometry for Astronomy (LINC-NIRVANA). We present the now centralized software architecture, called OVMS+, on which our approach is based and illustrate several challenges faced during the implementation phase. Finally, we will present measurement results from LBTI proving the effectiveness of the approach and the ability to compensate for a large fraction of the telescope induced vibrations.

The Large Binocular Telescope Interferometer (LBTI) is a versatile instrument designed for high-angular resolution and high-contrast infrared imaging (1.5-13 microns). In this paper, we focus on the mid-infrared (8-13 microns) nulling mode and present its theory of operation, data reduction, and on-sky performance as of the end of the commissioning phase in March 2015. With an interferometric baseline of 14.4 meters, the LBTI nuller is specifically tuned to resolve the habitable zone of nearby main-sequence stars, where warm exozodiacal dust emission peaks. Measuring the exozodi luminosity function of nearby main-sequence stars is a key milestone to prepare for future exoEarth direct imaging instruments. Thanks to recent progress in wavefront control and phase stabilization, as well as in data reduction techniques, the LBTI demonstrated in February 2015 a calibrated null accuracy of 0.05% over a three-hour long observing sequence on the bright nearby A3V star beta Leo. This is equivalent to an exozodiacal disk density of 15 to 30 zodi for a Sun-like star located at 10pc, depending on the adopted disk model. This result sets a new record for high-contrast mid-infrared interferometric imaging and opens a new window on the study of planetary systems., 17 pages, 18 figures (resubmitted to ApJ with referee's comments)

Leaks in water distribution systems waste energy and water resources, increase damage to infrastructure, and may allow contamination of potable water. This research develops an evolutionary algorithm-based approach to minimize the cost of water loss, new infrastructure, and operations that reduce background leakage. A new design approach is introduced that minimizes capital and operational costs, including energy and water loss costs. Design decisions identify a combination of infrastructure improvements, including pipe replacement and valve installment, and operation rules for tanks and pumps. Solution approaches are developed to solve both a single-objective and multiobjective problem formulation. A genetic algorithm and a nondominated sorting genetic algorithm are implemented within a high-performance computing platform to select tank sizes, pump placement and operations, placement of pressure-reducing valves, and pipe diameters for replacing pipes. The evolutionary algorithm approaches identif...

Background Recent studies have shown that brain-machine interfaces (BMIs) offer great potential for restoring upper limb function. However, grasping objects is a complicated task and the signals extracted from the brain may not always be capable of driving these movements reliably. Vision-guided robotic assistance is one possible way to improve BMI performance. We describe a method of shared control where the user controls a prosthetic arm using a BMI and receives assistance with positioning the hand when it approaches an object. Methods Two human subjects with tetraplegia used a robotic arm to complete object transport tasks with and without shared control. The shared control system was designed to provide a balance between BMI-derived intention and computer assistance. An autonomous robotic grasping system identified and tracked objects and defined stable grasp positions for these objects. The system identified when the user intended to interact with an object based on the BMI-controlled movements of the robotic arm. Using shared control, BMI controlled movements and autonomous grasping commands were blended to ensure secure grasps. Results Both subjects were more successful on object transfer tasks when using shared control compared to BMI control alone. Movements made using shared control were more accurate, more efficient, and less difficult. One participant attempted a task with multiple objects and successfully lifted one of two closely spaced objects in 92 % of trials, demonstrating the potential for users to accurately execute their intention while using shared control. Conclusions Integration of BMI control with vision-guided robotic assistance led to improved performance on object transfer tasks. Providing assistance while maintaining generalizability will make BMI systems more attractive to potential users. Trial registration NCT01364480 and NCT01894802. Electronic supplementary material The online version of this article (doi:10.1186/s12984-016-0134-9) contains supplementary material, which is available to authorized users.

Purpose The purpose of this study was to use Web of Knowledge to determine which published arthroscopic surgery–related articles have been cited most frequently by other authors by ranking the 25 most cited articles. We furthermore wished to determine whether there is any difference between a categorical "journal-by-journal" analysis and an "all-database" analysis in arthroscopic surgery and whether such a search methodology would alter the results of previously published lists of "citation classics" in the field. We analyzed the characteristics of these articles to determine what qualities make an article important to this subspecialty of orthopaedic surgery. Methods Web of Knowledge was searched on March 7, 2011, using the term "arthroscopy" for citations to articles related to arthroscopy in 61 orthopaedic journals and using the all-database function. Each of the 61 orthopaedic journals was searched separately for arthroscopy-related articles to determine the 25 most cited articles. An all-database search for arthroscopy-related articles was carried out and compared with a journal-by-journal search. Each article was reviewed for basic information including the type of article, authorship, institution, country, publishing journal, and year published. Results The number of citations ranged from 189 to 567 in a journal-by-journal search and from 214 to 1,869 in an all-database search. The 25 most cited articles on arthroscopic surgery were published in 11 journals: 8 orthopaedic journals and 3 journals from other specialties. The most cited article in arthroscopic orthopaedic surgery was published in The New England Journal of Medicine , which was not previously identified by a journal-by-journal search. Conclusions An all-database search in Web of Knowledge gives a more in-depth methodology of determining the true citation ranking of articles. Among the top 25 most cited articles, autologous chondrocyte implantation/transplantation is currently the most cited and most popular topic in arthroscopic orthopaedic surgery and research. Clinical Relevance Analysis of the 25 most cited articles allows us to identify the most popular field of research in arthroscopic orthopaedic surgery and gives us insight into the quality and characteristics that are required for an article to become highly cited.

This paper presents a simulation–optimization-based method for identification of contamination source characteristics in a water distribution system using filtered data from threshold-based binary water quality signals. The effects of quality and quantity of the data on the accuracy of the source identification methodology are investigated. This study also addresses the issue of non-uniqueness in contaminant source identification under various data availability conditions. To establish the robustness and applicability of the methodology, numerous scenarios are investigated for a wide range of contamination incidents associated with two different networks. Results indicate that, even though use of lower resolution sensors lead to more non-unique solutions, the true source location is always included among these solutions.

Oocyte donors have high serum estradiol (E2) levels similar to the serum levels seen in the first trimester of pregnancy. We report in this article our studies comparing cell proliferation, Ki67 (MIB1), and estrogen and progesterone receptor levels (ERα, PRA, and PRB) in the breast terminal duct lobular units of oocyte donors, women in early pregnancy, and in normally cycling women. Breast tissue and blood samples were obtained from 10 oocyte donors, and 30 pregnant women at 5–18 weeks of gestation. Breast tissue samples were also obtained from 26 normally cycling women. In the oocyte donors: peak E2 (mean ~15,300 pmol/l) was reached on the day before oocyte (and tissue) donation; peak progesterone (P4; mean 36.3 nmol/l) was reached on the day of donation; Ki67 was positively associated with level of E2, and the mean Ki67 was 7.0% significantly greater than the mean 1.8% of cycling women. In the pregnant women: mean E2 rose from ~2,000 pmol/l at 5 weeks of gestation to ~27,000 pmol/l at 18 weeks; mean P4 did not change from ~40 nmol/l until around gestational week 11 when it increased to ~80 nmol/l; mean Ki67 was 15.4% and did not vary with gestational age or E2. Oocyte donors have greatly increased levels of E2 and of breast-cell proliferation, both comparable in the majority of donors to the levels seen in the first trimester of pregnancy. Whether their short durations of greatly increased E2 levels are associated with any long-term beneficial effects on the breast, as occurring in rodent models, is not known.

Peripheral nerve injury causes sensory dysfunctions that are thought to be attributable to changes in neuronal activity occurring in somatosensory cortices both contralateral and ipsilateral to the injury. Recent studies suggest that distorted functional response observed in deprived primary somatosensory cortex (S1) may be the result of an increase in inhibitory interneuron activity and is mediated by the transcallosal pathway. The goal of this study was to develop a strategy to manipulate and control the transcallosal activity to facilitate appropriate plasticity by guiding the cortical reorganization in a rat model of sensory deprivation. Since transcallosal fibers originate mainly from excitatory pyramidal neurons somata situated in laminae III and V, the excitatory neurons in rat S1 were engineered to express halorhodopsin, a light-sensitive chloride pump that triggers neuronal hyperpolarization. Results from electrophysiology, optical imaging, and functional MRI measurements are concordant with that within the deprived S1, activity in response to intact forepaw electrical stimulation was significantly increased by concurrent illumination of halorhodopsin over the healthy S1. Optogenetic manipulations effectively decreased the adverse inhibition of deprived cortex and revealed the major contribution of the transcallosal projections, showing interhemispheric neuroplasticity and thus, setting a foundation to develop improved rehabilitation strategies to restore cortical functions.

The modification of land and water resources for human use alters the natural hydrologic flow regime of a downstream receiving body of water. The natural flow regime is essential for sustaining biotic structure and equilibrium within the ecosystem. Best management practices mitigate the increased storm water runoff due to increased imperviousness and are typically designed and located within a watershed to match peak and minimum flows for a small set of targeted design storms. Ecosystems are, however, affected by all the characteristics of a long-term flow regime, including the magnitude, duration, frequency, and timing of flows. A more environmentally sustainable approach for watershed development is presented based on the minimization of differences in the characteristics of the flow regime between predevelopment and postdevelopment conditions. The indicator of hydrologic alteration (IHA) is a set of 33 hydrologic indices that characterize a flow regime and, coupled with the range of variability approac...

Objectives This randomized, prospective, double-blind, multicenter study compared nephrotoxicity of the nonionic iso-osmolar contrast media (CM) iodixanol versus the ionic low-osmolar CM ioxaglate in patients with chronic renal insufficiency undergoing coronary angiography. Background The properties of iodinated CM might contribute to the incidence of contrast-induced nephropathy (CIN). Methods Patients with renal impairment undergoing coronary angiography were randomly assigned to iodixanol (n = 72) or ioxaglate (n = 74). Results Baseline characteristics were well-matched between the 2 groups. The predicted risk score for CIN was similar in the iodixanol and in the ioxaglate groups (11.9 ± 4.1 vs. 11.8 ± 4.1), as was the use of N-acetylcysteine (70% vs. 73%). The primary end point of the study, median peak increase of serum creatinine from day 0 through day 3 after angiography, did not differ between the iodixanol (0.09 mg/dl; interquartile range 0.00 to 0.30 mg/dl) and the ioxaglate (0.15 mg/dl; interquartile range 0.00 to 0.40 mg/dl; p = 0.07) groups. The percentages of patients with a peak increase of serum creatinine ≥0.5 mg/dl (15.9% in iodixanol vs. 18.2% in ioxaglate), ≥1.0 mg/dl (1.4% vs. 4.5%), and ≥25% or ≥0.5 mg/dl (15.9% vs. 24.2%, respectively) also did not differ significantly between the 2 groups. Conclusions In high-risk patients undergoing coronary angiographic procedures, use of the nonionic iso-osmolar CM iodixanol does not reduce renal deterioration in patients with renal impairment, compared with the ionic low-osmolar CM ioxaglate. Given that the study was underpowered to compare nephrotoxicity of the 2 groups under the active medical protection of CIN, a larger randomized study is warranted that will enroll patients with higher risks of CIN under a strict control of hydration regimens and adjunctive medications.

We report here our studies of nuclear staining for the progesterone and estrogen receptors (PRA, PRB, ERalpha) and cell proliferation (MIB1) in the breast terminal duct lobular unit epithelium of 26 naturally cycling premenopausal women and 30 pregnant women (median 8.1 weeks gestation). Square root transformations of the PRA, PRB and ERalpha values, and a logarithmic transformation of the MIB1 values, were made to achieve more normal distributions of the values. PRA expression decreased from a mean of 17.8% of epithelial cells in cycling subjects to 6.2% in pregnant subjects (P = 0.013). MIB1 expression increased from 1.7% in cycling subjects to 16.0% in pregnant subjects (P0.001). PRB and ERalpha expression was slightly lower in pregnant subjects but the differences were not statistically significant. Sixteen of the non-pregnant subjects were nulliparous and ten were parous so that we had limited power to detect changes associated with parity. PRA was statistically significantly lower in parous women than in nulliparous women (32.2% in nulliparous women vs. 10.2%; P = 0.014). PRB (23.5 vs. 12.9%), ERalpha (14.4 vs. 8.6%) and MIB1 (2.2 vs. 1.2%) were also lower in parous women, but the differences were not statistically significant. The marked decreases in PRA in pregnancy and in parous women has also been found in the rat. A reduction in PRA expression may be a useful marker of the reduction in risk with pregnancy and may be of use in evaluating the effect of any chemoprevention regimen aimed at mimicking pregnancy. Short-term changes in PRA expression while the chemoprevention is being administered may be a more useful marker.

Summary Background Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes, but can also increase the rate of thrombotic complications including stent thrombosis. The TRITON–TIMI 38 trial has shown that prasugrel—a novel, potent thienopyridine—can reduce ischaemic events compared with standard clopidogrel therapy. We assessed the rate, outcomes, and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON–TIMI 38 study. Methods Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following randomisation in TRITON-TIMI 38, and were further subdivided by type of stent received. Patients were randomly assigned in a 1 to 1 fashion to receive a loading dose of study drug (prasugrel 60 mg or clopidogrel 300 mg) as soon as possible after randomisation, followed by daily maintenance therapy (prasugrel 10 mg or clopidogrel 75 mg). All patients were to receive aspirin therapy. Treatment was to be continued for a minimum of 6 months and a maximum of 15 months. Randomisation was not stratified by stents used or stent type. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Stent thrombosis was assessed using Academic Research Consortium definitions, and analysis was by intention to treat. TRITON-TIMI 38 is registered with ClinicalTrials.gov, number NCT00097591. Findings 12 844 patients received at least one coronary stent; 5743 received only drug-eluting stents, and 6461 received only bare-metal stents. Prasugrel compared with clopidogrel reduced the primary endpoint (9·7 vs 11·9%, HR 0·81, p=0·0001) in the stented cohort, in patients with only drug-eluting stents (9·0 vs 11·1%, HR 0·82, p=0·019), and in patients with only bare-metal stents (10·0 vs 12·2%, HR 0·80, p=0·003). Stent thrombosis was associated with death or myocardial infarction in 89% (186/210) of patients. Stent thrombosis was reduced with prasugrel overall (1·13 vs 2·35%, HR 0·48, p vs 2·31%, HR 0·36, p vs 2·41%, HR 0·52, p=0·0009). Interpretation Intensive antiplatelet therapy with prasugrel resulted in fewer ischaemic outcomes including stent thrombosis than with standard clopidogrel. These findings were statistically robust irrespective of stent type, and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents. Funding TRITON–TIMI 38 was supported by research grants from Daiichi Sankyo and Eli Lilly.

The lateral vertical thoracic excision has been a useful adjunct to more traditional techniques. As more patients undergo massive weight loss, more patients will present to plastic surgeons with complaints of fullness and excess in areas of the body not addressed by more traditional techniques. The lateral vertical thoracic excision can offer a solution to a difficult problem.

The purpose of this study was to determine the effects of inspiratory muscle training (IMT) on exercise in hypoxia (H) and normoxia (N). A 4-week IMT program was implemented with 12 healthy subjects using an inspiratory muscle trainer set at either 15% (C; n=5) or 50% (IMT; n=7) maximal inspiratory mouth pressure (PImax). Two treadmill tests (85% VO2max) to exhaustion and measures of diaphragm thickness (Tdi) and function were completed before and after training in H and N. Significant increases of 8-12% and 24.5+/-3.1% in Tdi and PImax, respectively, were seen in the IMT group. Time to exhaustion remained unchanged in all conditions. Inspiratory muscle fatigue (downward arrowPImax) following exercise was reduced approximately 10% (P0.05) in IMT after both N and H. During H, IMT reduced (P0.05) VO2 by 8-12%, cardiac output by 14+/-2%, ventilation by 25+/-3%; and increased arterial oxygen saturation by 4+/-1% and lung diffusing capacity by 22+/-3%. Ratings of perceived exertion and dyspnea were also significantly reduced. These data suggest that IMT significantly improves structural and functional physiologic measures in hypoxic exercise.

This study compared late survival after primary percutaneous coronary intervention (PCI) in patients with cardiogenic shock due to right ventricular (RV) infarction versus left ventricular (LV) pump failure. Consecutive patients with ST-elevation myocardial infarction treated with primary PCI (n = 2,496) were prospectively enrolled in a registry from 1984 to 2004. Cardiogenic shock occurred before PCI in 189 patients (7.6%). Shock was attributed to predominant RV infarction when there was right coronary artery occlusion with preserved LV function and increased right atrial pressure. Patients with shock due to RV infarction (n = 30) versus LV pump failure (n = 136) had fewer previous infarctions (10% vs 29%, p = 0.03), less multivessel disease (20% vs 47%, p = 0.007), higher right atrial pressure (21 vs 16 mm, p = 0.003), and better LV ejection fraction (57% vs 32%, p

The Large Binocular Telescope Interferometer (LBTI) is a strategic instrument of the LBT designed for high-sensitivity, high-contrast, and high-resolution infrared (1.5-13 $\mu$m) imaging of nearby planetary systems. To carry out a wide range of high-spatial resolution observations, it can combine the two AO-corrected 8.4-m apertures of the LBT in various ways including direct (non-interferometric) imaging, coronagraphy (APP and AGPM), Fizeau imaging, non-redundant aperture masking, and nulling interferometry. It also has broadband, narrowband, and spectrally dispersed capabilities. In this paper, we review the performance of these modes in terms of exoplanet science capabilities and describe recent instrumental milestones such as first-light Fizeau images (with the angular resolution of an equivalent 22.8-m telescope) and deep interferometric nulling observations., Comment: 12 pages, 6 figures, Proc. SPIE

We report on the first nulling interferometric observations with the Large Binocular Telescope Interferometer (LBTI), resolving the N' band (9.81 - 12.41 um) emission around the nearby main-sequence star eta Crv (F2V, 1-2 Gyr). The measured source null depth amounts to 4.40% +/- 0.35% over a field-of-view of 140 mas in radius (~2.6\,AU at the distance of eta Corvi) and shows no significant variation over 35{\deg} of sky rotation. This relatively low null is unexpected given the total disk to star flux ratio measured by Spitzer/IRS (~23% across the N' band), suggesting that a significant fraction of the dust lies within the central nulled response of the LBTI (79 mas or 1.4 AU). Modeling of the warm disk shows that it cannot resemble a scaled version of the Solar zodiacal cloud, unless it is almost perpendicular to the outer disk imaged by Herschel. It is more likely that the inner and outer disks are coplanar and the warm dust is located at a distance of 0.5-1.0 AU, significantly closer than previously predicted by models of the IRS spectrum (~3 AU). The predicted disk sizes can be reconciled if the warm disk is not centrosymmetric, or if the dust particles are dominated by very small grains. Both possibilities hint that a recent collision has produced much of the dust. Finally, we discuss the implications for the presence of dust at the distance where the insolation is the same as Earth's (2.3 AU)., Comment: 9 pages, 6 figures, accepted for publication in ApJ

Symptoms suggesting altered pain and temperature processing have been described in dementia diseases. Using a semi-structured caregiver questionnaire and MRI voxel-based morphometry in patients with frontotemporal degeneration or Alzheimer’s disease, Fletcher et al. show that these symptoms are underpinned by atrophy in a distributed thalamo-temporo-insular network implicated in somatosensory processing., Symptoms suggesting altered processing of pain and temperature have been described in dementia diseases and may contribute importantly to clinical phenotypes, particularly in the frontotemporal lobar degeneration spectrum, but the basis for these symptoms has not been characterized in detail. Here we analysed pain and temperature symptoms using a semi-structured caregiver questionnaire recording altered behavioural responsiveness to pain or temperature for a cohort of patients with frontotemporal lobar degeneration (n = 58, 25 female, aged 52–84 years, representing the major clinical syndromes and representative pathogenic mutations in the C9orf72 and MAPT genes) and a comparison cohort of patients with amnestic Alzheimer’s disease (n = 20, eight female, aged 53–74 years). Neuroanatomical associations were assessed using blinded visual rating and voxel-based morphometry of patients’ brain magnetic resonance images. Certain syndromic signatures were identified: pain and temperature symptoms were particularly prevalent in behavioural variant frontotemporal dementia (71% of cases) and semantic dementia (65% of cases) and in association with C9orf72 mutations (6/6 cases), but also developed in Alzheimer’s disease (45% of cases) and progressive non-fluent aphasia (25% of cases). While altered temperature responsiveness was more common than altered pain responsiveness across syndromes, blunted responsiveness to pain and temperature was particularly associated with behavioural variant frontotemporal dementia (40% of symptomatic cases) and heightened responsiveness with semantic dementia (73% of symptomatic cases) and Alzheimer’s disease (78% of symptomatic cases). In the voxel-based morphometry analysis of the frontotemporal lobar degeneration cohort, pain and temperature symptoms were associated with grey matter loss in a right-lateralized network including insula (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest) and anterior temporal cortex (P < 0.001 uncorrected over whole brain) previously implicated in processing homeostatic signals. Pain and temperature symptoms accompanying C9orf72 mutations were specifically associated with posterior thalamic atrophy (P < 0.05 corrected for multiple voxel-wise comparisons within the prespecified anatomical region of interest). Together the findings suggest candidate cognitive and neuroanatomical bases for these salient but under-appreciated phenotypic features of the dementias, with wider implications for the homeostatic pathophysiology and clinical management of neurodegenerative diseases.

The Large Binocular Telescope Interferometer is a NASA-funded nulling and imaging instrument designed to coherently combine the two 8.4-m primary mirrors of the LBT for high-sensitivity, high-contrast, and high-resolution infrared imaging (1.5-13 um). PHASECam is LBTI's near-infrared camera used to measure tip-tilt and phase variations between the two AO-corrected apertures and provide high-angular resolution observations. We report on the status of the system and describe its on-sky performance measured during the first semester of 2014. With a spatial resolution equivalent to that of a 22.8-meter telescope and the light-gathering power of single 11.8-meter mirror, the co-phased LBT can be considered to be a forerunner of the next-generation extremely large telescopes (ELT)., Comment: 8 pages, 5 figures, SPIE Conference proceedings

A genetic algorithm (GA)-based method for the least-cost design of looped pipe networks for various levels of redundancy is presented in this paper. Redundancy constraints are introduced in the optimization model by considering the number of pipes assumed to be out of service at any one time. Using this approach, trade-off relationships between cost and redundancy are developed. The GA-based approach is computationally intensive, and implementations on a custom fault-tolerant distributed computing framework, called Vitri, are used to satisfy the computational requirements. The design methodology is applied to two water distribution networks of different sizes, and a comparison of the performance of the distributed GAs for the design problems is also presented. We conclude that a GA-based approach to obtaining cost-effective, redundant solutions for the least-cost design of looped pipe networks can be effectively used on a heterogeneous network of nondedicated workstations.

The authors believe it would be useful to have surgical robots capable of some degree of autonomous action in cooperation with the human members of a surgical team. They believe that a starting point for such development would be a system for delivering and retrieving instruments during a surgical procedure.The described robot delivers instruments to the surgeon and retrieves the instruments when they are no longer being used. Voice recognition software takes in requests from the surgeon. A mechanical arm with a gripper is used to handle the instruments. Machine-vision cameras locate the instruments after the surgeon puts them down. Artificial intelligence software makes decisions about the best response to the surgeon's requests.A robot was successfully used in surgery for the first time June 16, 2005. The operation involved excision of a benign lipoma. The procedure lasted 31 min, during which time the robot performed 16 instrument deliveries and 13 instrument returns with no significant errors. The average time between verbal request and delivery of an instrument was 12.4 s.The described robot is capable of delivering instruments to a surgeon at command and can retrieve them independently using machine vision. This robot, termed a "surgical instrument server," represents a new class of information-processing machines that will relieve the operating room team of repetitive tasks and allow the members to focus more attention on the patient.

ObjectivesThe purpose of this study was to evaluate the impact of door-to-balloon time with primary percutaneous coronary intervention (PCI) on late cardiac mortality.BackgroundThe impact of door-to-balloon time on outcomes is controversial, and the impact on late mortality has not been studied.MethodsConsecutive patients (n = 2,322) treated with primary PCI from 1984 to 2003 were prospectively identified and followed up for a median of 83 months.ResultsProlonged door-to-balloon times (0 to 1.4 h vs. 1.5 to 1.9 h vs. 2.0 to 2.9 h vs. ≥3.0 h) were associated with higher in-hospital mortality (4.9% vs. 6.1% vs. 8.0% vs. 12.2%, p < 0.0001) and late mortality (12.6% vs. 16.4% vs. 20.4% vs. 27.1% at 7 years, p < 0.0001) and were an independent predictor of late mortality by Cox regression (p = 0.0004). Prolonged door-to-balloon times (≥2 h vs. 3 h) (21.1% vs. 18.5%; HR, 0.95; 95% CI, 0.62 to 1.45; p = 0.80).ConclusionsDelays in door-to-balloon time impact late survival in high-risk but not low-risk patients and in patients presenting early but not late after the onset of symptoms. These findings have implications for the triage of patients for primary PCI.

SERI Surgical Scaffold is a long-term bioresorbable silk-derived biological scaffold developed to provide soft-tissue support and repair.SURE-001 (ClinicalTrials.gov identification no. NCT01256502) is a prospective, single-arm study in the United States of patients undergoing two-stage, implant-based breast reconstruction using SERI.A total of 139 patients were enrolled and will be followed for 2 years; in this article, the authors report interim data on 71 patients followed for 1 year. Investigator satisfaction scores (mean ± SD) at 6 and 12 months were 9.2 ± 0.98 and 9.4 ± 0.91, respectively (10 = very satisfied). SERI was rated easy/very easy to use in 98 percent or more of cases across five categories in stage I surgery. Patient satisfaction with the treated breast(s) (mean ± SD) was higher at 6 (4.3 ± 0.87; 5 = very satisfied) and 12 months (4.5 ± 0.82) compared with screening (3.6 ± 1.09; p0.0001). Key complication rates (per breast) were tissue necrosis (6.7 percent), seroma (5.7 percent), hematoma (4.8 percent), implant loss (3.8 percent), capsular contracture (1.9 percent), and breast infection (1.0 percent). None were attributed to SERI by the investigators. In 13 patients (14 breasts) who underwent unplanned radiation therapy, one complication was reported.In this interim report, high levels of investigator and patient satisfaction, and ease of use of SERI were reported. Prospectively collected complication rates were similar to those reported in primarily retrospective studies of two-stage, implant-based breast reconstructions using other implantable soft-tissue support materials such as acellular dermal matrices.Therapeutic, IV.

Long-term clinical outcomes after exposure to non-ionic iso-osmolar contrast medium (IOCM) or ionic low-osmolar CM (LOCM) in patients with chronic kidney disease (CKD) undergoing coronary angiography are unclear.The ICON trial was a prospective, double-blinded, multicentre study that randomly assigned 146 patients with CKD undergoing coronary angiography with or without percutaneous coronary intervention to the non-ionic IOCM Iodixanol or the ionic LOCM Ioxaglate. We report the 1-year clinical outcomes.After randomization, baseline and procedural characteristics were well-matched between the two groups. At 1 year, three deaths (4.1%) occurred in the ioxaglate and nine deaths in the iodixanol group (13.6%, P = 0.07). The cardiac death rate at 1 year was 2.7% in the ioxaglate group and 9.1% in the iodixanol group (P = 0.07). There were no significant differences in the rates of myocardial infarction (1.4% vs. 1.5%; P = 1.00) and repeated revascularization (6.8% vs. 9.1%; P = 0.75).The use of ionic LOCM ioxaglate was associated with a numerically lower mortality at 1 year as compared to iodixanol in patients who underwent cardiac catheterization. Future studies evaluating long-term safety following exposure to different types of CM are warranted.

Auditory spatial processing is vulnerable in dementia. Golden et al. show that patients with typical Alzheimer’s disease or posterior cortical atrophy are impaired relative to controls in detecting the movement and location of sounds. The deficits have anatomical correlates in right parietal cortex, with implications for studies of network degeneration., The location and motion of sounds in space are important cues for encoding the auditory world. Spatial processing is a core component of auditory scene analysis, a cognitively demanding function that is vulnerable in Alzheimer’s disease. Here we designed a novel neuropsychological battery based on a virtual space paradigm to assess auditory spatial processing in patient cohorts with clinically typical Alzheimer’s disease (n = 20) and its major variant syndrome, posterior cortical atrophy (n = 12) in relation to healthy older controls (n = 26). We assessed three dimensions of auditory spatial function: externalized versus non-externalized sound discrimination, moving versus stationary sound discrimination and stationary auditory spatial position discrimination, together with non-spatial auditory and visual spatial control tasks. Neuroanatomical correlates of auditory spatial processing were assessed using voxel-based morphometry. Relative to healthy older controls, both patient groups exhibited impairments in detection of auditory motion, and stationary sound position discrimination. The posterior cortical atrophy group showed greater impairment for auditory motion processing and the processing of a non-spatial control complex auditory property (timbre) than the typical Alzheimer’s disease group. Voxel-based morphometry in the patient cohort revealed grey matter correlates of auditory motion detection and spatial position discrimination in right inferior parietal cortex and precuneus, respectively. These findings delineate auditory spatial processing deficits in typical and posterior Alzheimer’s disease phenotypes that are related to posterior cortical regions involved in both syndromic variants and modulated by the syndromic profile of brain degeneration. Auditory spatial deficits contribute to impaired spatial awareness in Alzheimer’s disease and may constitute a novel perceptual model for probing brain network disintegration across the Alzheimer’s disease syndromic spectrum.

Background: Preclinical studies have demonstrated that macroporous silk fibroin protein scaffolds are capable of promoting physiologically durable supportive tissue, which favors application of these engineered tissues for clinical implantation. The safety and effectiveness of a long-lasting, transitory, 510(k)-cleared purified silk fibroin biologic scaffold (SBS) are investigated for soft-tissue support and repair of the abdominal wall. Methods: We conducted a multicenter retrospective review of all consecutive patients who underwent abdominal wall soft-tissue reinforcement with an SBS device between 2011 and 2013. Indications, comorbid conditions, surgical technique, complications, and outcomes were evaluated. Results: We reviewed the records of 172 consecutive patients who received an SBS for soft-tissue support. Of those, 77 patients underwent abdominal wall fascial repair, with a mean follow-up of 18.4 ± 7.5 months. Procedures using an SBS included reinforcement of an abdominal-based flap donor site (31.2%), ventral hernia repair (53.2%), and abdominoplasty (15.6%). The overall complication rate was 6.5%, consisting of 2 wound dehiscences, 1 with device exposure, 1 seroma, 1 infection with explantation, and a perioperative bulge requiring reoperation. There were no reports of hernia. Conclusions: Postoperative complication rates after 18 months were low, and most surgical complications were managed nonoperatively on an outpatient basis without mesh removal. To our knowledge, this is the only series to report on a long-lasting, transitory SBS for abdominal wall repair and reinforcement. Procedure-specific outcome studies are warranted to delineate optimal patient selection and define potential device characteristic advantages.

Background Increased activity of matrix metalloproteinase-9 (MMP-9) has been well documented in many diseases associated with inflammation, such as chronic wounds, bullous pemphigoid, liver failure, and tumor metastases. The mechanism for the proteolytic activation of pro–MMP-9 in human tissue still remains unknown. Methods We investigated this mechanism through reconstitution of an inflammatory condition in normal human skin, and epidermal and dermal cells derived from skin. Normal human skin was cultured with exogenous cytokines associated with inflammation and tissue repair. MMP-9 induction and activation were measured, and potential mechanisms were probed by inhibitors. Results Pathophysiologic concentrations of interleukin (IL)-1α rapidly induced pro–MMP-9 synthesis by human skin. In contrast, IL-1–induced activation of pro–MMP-9 was a slow process, which required 3 days. Tumor growth factor-β induced pro–MMP-9 but failed to promote activation of the precursor. When the skin was stimulated with the combination of tumor growth factor-β and IL-1α, substantial induction and activation of pro–MMP-9 occurred. This IL-1 induced activation of pro–MMP-9 was observed in intact skin but not in isolated dermal fibroblasts or keratinocytes. IL-1–induced activation of pro–MMP-9 was inhibited by chymostatin, a chymotrypsinlike proteinase inhibitor. Furthermore, IL-1α decreased tissue inhibitor of metalloproteinase 1 without changing MMP-9 activator activity. Conclusions The proteolytic activation of pro–MMP-9 in skin inflammatory diseases likely occurs via a pathway including IL-1α. The activation is mediated by downregulation of tissue inhibitor of MMP-1 and involves an as yet unidentified chymotrypsinlike proteinase.

OBJECTIVES This study was a randomized, patient- and evaluator-blinded, placebo-controlled trial in patients treated using percutaneous myocardial laser revascularization. BACKGROUND Previous studies using similar therapies have been confounded by placebo bias. METHODS A total of 298 patients with severe angina were randomly assigned to receive low-dose or high-dose myocardial laser channels or no laser channels, blinded as a sham procedure. The primary end point was the change in exercise duration from baseline examination to six months. RESULTS The incidence of 30-day death, stroke, myocardial infarction, coronary revascularization, or left ventricular perforation occurred in two patients in the placebo, eight patients in the low-dose, and four patients in the high-dose groups (p = 0.12); 30-day myocardial infarction incidence was higher in patients receiving either low-dose or high-dose laser (nine patients) compared with placebo (no patients, p = 0.03). At six months, there were no differences in the change in exercise duration between those receiving a sham (28.0 s, n = 100), low-dose laser (33.2 s, n = 98), or high-dose laser (28.0 s, n = 98, p = 0.94) procedure. There were also no differences in the proportion of patients improving to better than Canadian Cardiovascular Society class III angina symptoms at six months. The follow-up visual summed stress single-photon-emission computed tomography scores were not significantly different from baseline in any group and were no different between groups. The modest improvement in angina symptoms assessed by the Seattle Angina Questionnaire also was not statistically different among the arms. CONCLUSIONS Treatment with percutaneous myocardial laser revascularization provides no benefit beyond that of a similar sham procedure in patients blinded to their treatment status.

Background After open bariatric surgery, many patients develop incisional hernia. Patients who were once morbidly obese provide a unique challenge to hernia repair, given the larger nature of their fascial defects and the concomitant problem of extreme amounts of abdominal wall laxity. We reviewed a technique for surgical repair of incisional hernias combined with panniculectomy. Methods A retrospective review of 50 consecutive patients status post–open bariatric surgery who underwent incisional hernia repair with overlay mesh and combined panniculectomy between 2000 and 2003. Results Hernia repair and panniculectomy were performed 18 months after open bariatric surgery. The patients had an average weight loss of 58.6 kg. Mean follow-up after hernia repair and panniculectomy was 18 months. Patients underwent prefascial hernia repair with plication of the fascial edges followed by midline anchoring of overlay mesh. The averave amount of excess tissue excised via panniculectomy was 3001 g. The average hospital stay was 4 days. Minor wound problems (eg, suture abscess, seroma) occurred in 20 patients. Seromas were treated with serial aspiration in the office. There were no intra-abdominal complications or recurrences of the incisional hernias. Conclusion Closed hernia repair with prefascial plication and overlay mesh is a safe, effective alternative to traditional incisional hernia repair. It provides adequate hernia repair without recurrence and eliminates intra-abdominal complications. It is our belief that combining the hernia repair and panniculectomy minimizes the risk of hernia recurrence through alleviation of stress on the repair by removing excess abdominal wall tissue.

Primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) due to saphenous vein graft (SVG) occlusion has been associated with poor procedural results and poor short-term outcomes, but long-term graft patency and patient survival have not been evaluated. Consecutive patients (n = 2,240) with STEMI treated with primary PCI from 1984 to 2003 were followed for 6.6 years (median). Follow-up angiography was obtained in 80% of hospital survivors following primary PCI for SVG occlusion at 2.3 years (median). Patients with primary PCI for SVG occlusion (n = 57) vs. native artery occlusion had more prior MI, advanced Killip class, and three-vessel coronary disease and lower acute ejection fraction (EF). Patients with SVG occlusion had lower rates of TIMI 3 flow post-PCI (80.7% vs. 93.6%; P = 0.0001), higher in-hospital mortality (21.1% vs. 8.0%; P = 0.0004), and lower follow-up EF (49.3% vs. 54.7%; P = 0.055). Culprit SVGs were patent in 64% of patients at 1 year and 56% at 5 years. Late survival was strikingly worse in patients with primary PCI for SVG occlusion vs. native vessel occlusion (49% vs. 76% at 10 years), and SVG occlusion was the second strongest predictor of late cardiac mortality by multivariate analysis (HR = 2.11; 95% CI = 1.38-3.23; P = 0.0006). Patients with STEMI due to SVG occlusion treated with primary PCI have poor acute procedural results, frequent late reocclusion, and very high late mortality. The introduction of new adjunctive therapies (distal protection, thrombectomy, and drug-eluting stents) may improve short-term outcomes, but improved long-term outcomes may require new and more durable revascularization strategies.

Summary Effective pain management remains an elusive goal within the profession of nursing. While considerable improvement has occurred, patients continue to experience inappropriate levels of pain. To date, research has focused on objective factors that influence pain management. Few studies have examined attitudinal factors that may influence nurses' decision-making. This quasi-experiment was based on preliminary data showing that nurses' preconceived notions regarding certain patient groups influenced their management of pain. An intervention was tested for its' effect on nurses' preconceived notions regarding specific patient groups. A significant difference in a positive direction was found. Nurses were more willing to spend time and energy managing pain across all patient groups following the intervention.

This paper describes an integrated solid waste management (ISWM) model to assist in identifying alternative SWM strategies that meet cost, energy, and environmental emissions objectives. An SWM system consisting of over 40 unit processes for collection, transfer, separation, treatment (e.g., combustion, composting), and disposal of waste as well as remanufacturing facilities for processing recycled material is defined. Waste is categorized into 48 items and their generation rates are defined for three types of sectors: single-family dwelling, multifamily dwelling, and commercial. The mass flow of each item through all possible combinations of unit processes is represented in a linear programming model using a unique modeling approach. Cost, energy consumption, and environmental emissions associated with waste processing at each unit process are computed in a set of specially implemented unit process models. A life-cycle approach is used to compute energy consumption and emissions of CO, fossil- and biomas...

The luminescent complex [Pt(terpy)OH]BF 4 undergoes photoinduced electron transfer reactions with phenyl amine electron donors and nitrophenyl electron acceptors. Stern–Volmer analysis of the quenching of metal-to-ligand charge transfer phosphorescence ( 3 MLCT) was used to calculate bimolecular rate constants for electron transfer. Rate constants vary from 10 8 to >10 10 M −1 s −1 , depending on the thermodynamic driving force of the electron transfer reaction, with rate constants indicating that [Pt(terpy)OH]BF 4 * is a powerful photo-oxidant. Aromatic triplet energy acceptors can also quench the 3 MLCT emission.

Recognition of nonverbal sounds in semantic dementia and other syndromes of anterior temporal lobe degeneration may determine clinical symptoms and help to define phenotypic profiles. However, nonverbal auditory semantic function has not been widely studied in these syndromes. Here we investigated semantic processing in two key nonverbal auditory domains – environmental sounds and melodies – in patients with semantic dementia (SD group; n = 9) and in patients with anterior temporal lobe atrophy presenting with behavioural decline (TL group; n = 7, including four cases with MAPT mutations) in relation to healthy older controls (n = 20). We assessed auditory semantic performance in each domain using novel, uniform within-modality neuropsychological procedures that determined sound identification based on semantic classification of sound pairs. Both the SD and TL groups showed comparable overall impairments of environmental sound and melody identification; individual patients generally showed superior identification of environmental sounds than melodies, however relative sparing of melody over environmental sound identification also occurred in both groups. Our findings suggest that nonverbal auditory semantic impairment is a common feature of neurodegenerative syndromes with anterior temporal lobe atrophy. However, the profile of auditory domain involvement varies substantially between individuals., Highlights • Nonverbal auditory processing is an understudied area of semantic memory. • We assessed novel auditory semantic tasks in patients with temporal lobe atrophy. • Environmental sound and music processing were comparably impaired across the cohort. • Individual patients may show relative sparing of melody processing. • Nonverbal auditory deficits integrally accompany temporal lobe degeneration.

The current study examined motor timing in frontotemporal dementia (FTD), which manifests as progressive deterioration in social, behavioural and cognitive functions. Twenty-patients fulfilling consensus clinical criteria for behavioural variant FTD (bvFTD), 11 patients fulfilling consensus clinical criteria for semantic-variant primary progressive aphasia (svPPA), four patients fulfilling criteria for nonfluent/agrammatic primary progressive aphasia (naPPA), eight patients fulfilling criteria for Alzheimer׳s disease (AD), and 31 controls were assessed on both an externally- and self-paced finger-tapping task requiring maintenance of a regular, 1500 ms beat over 50 taps. Grey and white matter correlates of deficits in motor timing were examined using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI). bvFTD patients exhibited significant deficits in aspects of both externally- and self-paced tapping. Increased mean inter-response interval (faster than target tap time) in the self-paced task was associated with reduced grey matter volume in the cerebellum bilaterally, right middle temporal gyrus, and with increased axial diffusivity in the right superior longitudinal fasciculus, regions and tracts which have been suggested to be involved in a subcortical–cortical network of structures underlying timing abilities. This suggests that such structures can be affected in bvFTD, and that impaired motor timing may underlie some characteristics of the bvFTD phenotype., Highlights • We examine motor timing in behavioural variant FTD. • Patients with behavioural variant FTD showed impaired motor timing. • Patients tended to tap faster than target and speed up during the task. • Faster tapping was associated with reduced grey matter in the cerebellum. • Impaired timing might underlie some other behavioural features of FTD.

The Large Binocular Telescope Interferometer (LBTI) is a strategically important instrument for exploiting the use of the LBT as a 22.7 m telescope. The LBTI has two science cameras (covering the 1.5-5 μm and 8-13 μm atmospheric windows), and a number of observing modes that allow it to carry out a wide range of high-spatial resolution observations. Some simple modes, such as AO imaging, are in routine use. We report here on testing and commissioning of the system for its more ambitious goals as a nulling interferometer and coherent imager. The LBTI will carry out key surveys to Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) and an LBTI Exozodi-Exoplanet Common Hunt (LEECH). The current nulling and coherent imaging performance is described.

article i nfo Recognition of nonverbal sounds in semantic dementia and other syndromes of anterior temporal lobe degener- ation may determine clinical symptoms and help to define phenotypic profiles. However, nonverbal auditory semantic function has not been widely studied in these syndromes. Here we investigated semantic processing in two key nonverbal auditory domains - environmental sounds and melodies - in patients with semantic dementia (SD group; n = 9) and in patients with anterior temporal lobe atrophy presenting with behavioural decline (TL group; n = 7, including four cases with MAPT mutations) in relation to healthy older controls (n = 20). We assessed auditory semantic performance in each domain using novel, uniform within-modality neuropsychological procedures that determined sound identification based on semantic classification of sound pairs. Both the SD and TL groups showed comparable overall impairments of environmental sound and melody identification; individual patients generally showed superior identification of environmental sounds than melodies, however relative sparing of melody over environmental sound identification also occurred in both groups. Our findings suggest that nonverbal auditory semantic impairment is a common feature of neurodegen- erative syndromes with anterior temporal lobe atrophy. However, the profile of auditory domain involvement varies substantially between individuals. © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration.