Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

Low-pressure regional aureoles with steep metamorphic field gradients are critical to understanding progressive metamorphism in high-temperature metasedimentary rocks. Delicately layered pelitic and psammitic metasedimentary rocks at Mt Stafford, central Australia, record a greenschist- to granulite-facies Palaeoproterozoic regional aureole, associated with S-type granite plutons, reflecting metamorphism in the range 500–800 °C and at ∼3 kbar. The rocks experienced minimal deformation during metamorphism and partial melting. Partial melting textures evolve progressively along the steep metamorphic field gradient from the incipient stages of melting marked by cuspate grains with low dihedral angles, to melt proportions sufficient to form diatexite with schollen. Phase equilibria modelling in the NCKFMASHTO system for pelitic, semi-pelitic and high- and low-ferromagnesian psammitic samples quantitatively illustrates the dependence of partial melting on rock composition and water volume. Pelitic compositions are more fertile than psammitic compositions when the water content in the rocks is low, especially during the early stages of melting. The whole-rock ferromagnesian component additionally influences melt fertility, with ferromagnesian-rich psammite being more fertile than psammite with a lower ferromagnesian component. Subtle variations in free water content can result in obvious changes in melt volume but limited variation in melt composition. Distinct melting histories of pelitic and psammitic rocks inferred from field relationships may be partially attributed to potential differences in water volume retained to super-solidus conditions. Melt composition is more dependent on the rock composition than the variation in water content.

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, traumatic spinal cord injury, or multiple sclerosis. These syndromes are distinctly less common than peripheral neuropathic pain, and less is known regarding the underlying pathophysiology, appropriate pharmacotherapy, and long-term outcomes. The objective of this study was to determine the long-term clinical effectiveness of the management of central neuropathic pain relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified for analysis from a prospective observational cohort study of patients with chronic neuropathic pain recruited from seven Canadian tertiary pain centers. Data regarding patient characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome measure was the composite of a reduction in average pain intensity and pain interference. Secondary outcome measures included assessments of function, mood, quality of life, catastrophizing, and patient satisfaction. Results: At 12-month follow-up, 13.5% (95% confidence interval [CI], 5.6-25.8) of patients with central neuropathic pain and complete data sets (n=52) achieved a ≥30% reduction in pain, whereas 38.5% (95% CI, 25.3-53.0) achieved a reduction of at least 1 point on the Pain Interference Scale. The proportion of patients with central neuropathic pain achieving both these measures, and thus the primary outcome, was 9.6% (95% CI, 3.2-21.0). Patients with peripheral neuropathic pain and complete data sets (n=463) were more likely to achieve this primary outcome at 12 months (25.3% of patients; 95% CI, 21.4-29.5) (p=0.012). Conclusion: Patients with central neuropathic pain syndromes managed in tertiary care centers were less likely to achieve a meaningful improvement in pain and function compared with patients with peripheral neuropathic pain at 12-month follow-up.

Background: Central neuropathic pain syndromes are a result of central nervous system injury, most commonly related to stroke, spinal cord injury, or multiple sclerosis. These syndromes are much less common than peripheral etiologies, with less known regarding optimal treatment. The objective of this study was to determine the long-term clinical effectiveness of the management of central relative to peripheral neuropathic pain at tertiary pain centers. Methods: Patients diagnosed with central (n=79) and peripheral (n=710) neuropathic pain were identified from a prospective observational cohort from seven Canadian tertiary centers. Data regarding patient -characteristics, analgesic use, and patient-reported outcomes were collected at baseline and 12-month follow-up. The primary outcome was the composite of reduced average pain intensity and pain interference. Secondary outcomes included assessments of function, mood, and quality-of-life. Results: At 12-month follow-up, 13.5% (95%CI,5.6-25.8) of patients achieved ≥30% reduction in pain, whereas 38.5% (95%CI,25.3-53.0) achieved a ≥1 point reduction in pain interference; 9.6% (95%CI,3.2-21.0) of patients achieving both these measures. Patients with peripheral neuropathic pain were more likely to achieve this primary outcome at 12-months (25.3% of patients; 95%CI,21.4-29.5) (p=.012). Conclusions: Patients with central neuropathic pain were less likely to achieve a meaningful improvement in pain and function compared to patients with peripheral neuropathic pain at 12-month follow-up.

OBJECTIVES/SPECIFIC AIMS: The current treatment for amyotrophic lateral sclerosis (ALS) includes systemic delivery of neurotrophic factors (NTFs). Although this approach may seem theoretically sound, NTF efficacy within the central nervous system (CNS) is largely limited by the blood-brain barrier. Thus, a cell-based approach, which allows for targeted delivery of molecular therapies locally from the CNS, could lead to a paradigm shift in the field. METHODS/STUDY POPULATION: The Windebank and Staff group at Mayo Clinic completed a Phase I dose-escalation safety trial of autologous, adipose-derived mesenchymal stem cells (adMSCs) in an effort to move toward personalized medical treatment of ALS. The adMSCs were injected into the intrathecal space by lumbar puncture in 27 patients and the results showed an excellent safety profile across a range of doses. The team is moving forward with this idea by using gene-editing technology to develop clinical-grade, genetically modified autologous MSCs. The patient-derived adMSCs are modified at defined “safe-harbor” regions of the human genome through transcription activator-like effector nuclease (TALEN) technology. RESULTS/ANTICIPATED RESULTS: Our results show that electroporating adMSCs with plasmid DNA leads to efficient GFP or TALEN transgene expression, but yields low cell survival and a low rate of genetic modification. DISCUSSION/SIGNIFICANCE OF IMPACT: It can be concluded that: (1) TALEN technology may be used to target safe harbor loci for gene integration to produce therapeutic adMSC for ALS. (2) Primary barriers to adMSC modification are inefficient TALEN and donor template uptake, low cutting efficiency, and poor cell survival after electroporation. Future directions include optimizing the protocol to obtain 48 base pairs in the homology arms and increasing transfection efficiency.

The development of algorithms for agile science and autonomous exploration has been pursued in contexts ranging from spacecraft to planetary rovers to unmanned aerial vehicles to autonomous underwater vehicles. In situations where time, mission resources and communications are limited and the future state of the operating environment is unknown, the capability of a vehicle to dynamically respond to changing circumstances without human guidance can substantially improve science return. Such capabilities are difficult to achieve in practice, however, because they require intelligent reasoning to utilize limited resources in an inherently uncertain environment. Here we discuss the development, characterization and field performance of two algorithms for autonomously collecting water samples on VALKYRIE (Very deep Autonomous Laser-powered Kilowatt-class Yo-yoing Robotic Ice Explorer), a glacier-penetrating cryobot deployed to the Matanuska Glacier, Alaska (Mission Control location: 61°42′09.3″N 147°37′23.2″W). We show performance on par with human performance across a wide range of mission morphologies using simulated mission data, and demonstrate the effectiveness of the algorithms at autonomously collecting samples with high relative cell concentration during field operation. The development of such algorithms will help enable autonomous science operations in environments where constant real-time human supervision is impractical, such as penetration of ice sheets on Earth and high-priority planetary science targets like Europa.

Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of ≤3 months’ duration. Limited data are available on the long-term outcomes of this chronic disease. The objective of this study was to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 60 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials guidelines including the Brief Pain Inventory. Results: At 12-month follow-up, 37.2% (95% confidence interval [CI], 23.0-53.3) of 43 patients with complete data achieved pain reduction of ≥30%, 51.2% (95% CI, 35.5-66.7) achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, Brief Pain Inventory) and 30.2% (95% CI, 17.2-46.1) had achieved both these measures. Symptom management included at least two medication classes in 55.3% and three medication classes in 25.5% (opioids, antidepressants, anticonvulsants). Conclusions: Almost one-third of patients being managed for PDN in a tertiary care setting achieve meaningful improvements in pain and function in the long term. Polypharmacy including analgesic antidepressants and anticonvulsants were the mainstays of effective symptom management.

Background: Painful diabetic neuropathy (PDN) is a frequent complication of diabetes mellitus. Current treatment recommendations are based on short-term trials, generally of duration ≤3 months. Limited data are available on the long-term outcomes of this chronic disease. This study aims to determine the long-term clinical effectiveness of the management of chronic PDN at tertiary pain centres. Methods: From a prospective observational cohort study of patients with chronic neuropathic non-cancer pain recruited from seven Canadian tertiary pain centres, 43 patients diagnosed with PDN were identified for analysis. Data were collected according to Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) guidelines including Brief Pain Inventory (BPI). Results: At 12-month follow-up, 37.2% of 43 patients achieved pain reduction of ≥30%, 51.2% achieved functional improvement with a reduction of ≥1 on the Pain Interference Scale (0-10, BPI), and 30.2% (95% CI: 17.2% to 46.1%) had achieved both these measures. Symptom management included at least 2 medication classes in 55.3%, and 3 medications classes (opioids, antidepressants, anticonvulsants) in 25.5%. Conclusions: A sizable minority of patients being managed for PDN in a tertiary care setting achieve meaningful improvement. Polypharmacy, including analgesic antidepressants, anticonvulsants and opioids, is often necessary to attain symptom management.

Space applications have evolved to play a significant role in disaster relief by providing services including remote sensing imagery for mitigation and disaster damage assessments; satellite communication to provide access to medical services; positioning, navigation, and timing services; and data sharing. Common issues identified in past disaster response and relief efforts include lack of communication, delayed ordering of actions (eg, evacuations), and low levels of preparedness by authorities during and after disasters. We briefly summarize the Space for Health (S4H) Team Project, which was prepared during the Space Studies Program 2014 within the International Space University. The S4H Project aimed to improve the way space assets and experiences are used in support of public health during disaster relief efforts. We recommend an integrated solution based on nano-satellites or a balloon communication system, mobile self-contained relief units, portable medical scanning devices, and micro-unmanned vehicles that could revolutionize disaster relief and disrupt different markets. The recommended new system of coordination and communication using space assets to support public health during disaster relief efforts is feasible. Nevertheless, further actions should be taken by governments and organizations in collaboration with the private sector to design, test, and implement this system. (Disaster Med Public Health Preparedness. 2015;9:319-328)

The redshifted 21cm line of neutral hydrogen (Hi), potentially observable at low radio frequencies (~50–200 MHz), should be a powerful probe of the physical conditions of the inter-galactic medium during Cosmic Dawn and the Epoch of Reionisation (EoR). The sky-averaged Hi signal is expected to be extremely weak (~100 mK) in comparison to the foreground of up to 104 K at the lowest frequencies of interest. The detection of such a weak signal requires an extremely stable, well characterised system and a good understanding of the foregrounds. Development of a nearly perfectly (~mK accuracy) calibrated total power radiometer system is essential for this type of experiment. We present the BIGHORNS (Broadband Instrument for Global HydrOgen ReioNisation Signal) experiment which was designed and built to detect the sky-averaged Hi signal from the EoR at low radio frequencies. The BIGHORNS system is a mobile total power radiometer, which can be deployed in any remote location in order to collect radio frequency interference (RFI) free data. The system was deployed in remote, radio quiet locations in Western Australia and low RFI sky data have been collected. We present a description of the system, its characteristics, details of data analysis, and calibration. We have identified multiple challenges to achieving the required measurement precision, which triggered two major improvements for the future system.

Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use.