Opioids Delay Healing of Spinal Fusion: A Rabbit Posterolateral Lumbar Fusion Model

Background Context Opioid use is prevalent in the management of pre- and postoperative pain in patients undergoing spinal fusion. There is evidence that opioids downregulate osteoblasts in vitro, and a previous study found that morphine delays the maturation and remodeling of callus in a rat femur fracture model. However, the effect of opioids on healing of spinal fusion has not been investigated before. Isolating the effect of opioid exposure in humans would be limited by the numerous confounding factors that affect fusion healing. Therefore, we have used a well-established rabbit model to study the process of spinal fusion healing that closely mimics humans. Purpose The objective of this work was to study the effect of systemic opioids on the process of healing of spinal fusion in a rabbit posterolateral spinal fusion model. Study Design/Setting This is a preclinical animal study. Materials and Methods Twenty-four adult New Zealand white rabbits were studied in two groups after approval from the Institutional Animal Care and Use Committee (IACUC). The opioid group (n=12) received 4 weeks\u27 preoperative and 6 weeks\u27 postoperative transdermal fentanyl. Serum fentanyl levels were measured just before surgery and 4 weeks postoperatively to ensure adequate levels. The control group (n=12) received only perioperative pain control as necessary. All animals underwent a bilateral L5–L6 posterolateral spinal fusion using iliac crest autograft. Animals were euthanized at the 6-week postoperative time point, and assessment of fusion was done by manual palpation, plain radiographs, microcomputed tomography (microCT), and histology. Results Twelve animals in the control group and 11 animals in the opioid group were available for analysis at the end of 6 weeks. The fusion scores on manual palpation, radiographs, and microCT were not statistically different. Three-dimensional microCT morphometry found that the fusion mass in the opioid group had a lower bone volume (p=.09), a lower trabecular number (p=.02), and a higher trabecular separation (p=.02) compared with the control group. Histologic analysis found areas of incorporation of autograft and unincorporated graft fragments in both groups. In the control group, there was remodeling of de novo woven bone to lamellar organization with incorporation of osteocytes, formation of mature marrow, and relative paucity of hypertrophied osteoblasts lining new bone. Sections from the opioid group showed formation of de novo woven bone, and hypertrophied osteoblasts were seen lining the new bone. There were no sections showing lamellar organization and development of mature marrow elements in the opioid group. Less dense trabeculae on microCT correlated with histologic findings of relatively immature fusion mass in the opioid group. Conclusions Systemic opioids led to an inferior quality fusion mass with delay in maturation and remodeling at 6 weeks in this rabbit spinal fusion model. These preliminary results lay the foundation for further research to investigate underlying cellular mechanisms, the temporal fusion process, and the dose-duration relationship of opioids responsible for our findings

A 275–425-GHz Tunerless Waveguide Receiver Based on AlN-Barrier SIS Technology

We report on a 275–425-GHz tunerless waveguide receiver with a 3.5–8-GHz IF. As the mixing element, we employ a high-current-density Nb–AlN–Nb superconducting–insulating– superconducting (SIS) tunnel junction. Thanks to the combined use of AlN-barrier SIS technology and a broad bandwidth waveguide to thin-film microstrip transition, we are able to achieve an unprecedented 43% instantaneous bandwidth, limited by the receiver's corrugated feedhorn. The measured double-sideband (DSB) receiver noise temperature, uncorrected for optics loss, ranges from 55 K at 275 GHz, 48 K at 345 GHz, to 72 K at 425 GHz. In this frequency range, the mixer has a DSB conversion loss of 2.3 1 dB. The intrinsic mixer noise is found to vary between 17–19 K, of which 9 K is attributed to shot noise associated with leakage current below the gap. To improve reliability, the IF circuit and bias injection are entirely planar by design. The instrument was successfully installed at the Caltech Submillimeter Observatory (CSO), Mauna Kea, HI, in October 2006

Characterization of wild and captive baboon gut microbiota and their antibiotic resistomes

Antibiotic exposure results in acute and persistent shifts in the composition and function of microbial communities associated with vertebrate hosts. However, little is known about the state of these communities in the era before the widespread introduction of antibiotics into clinical and agricultural practice. We characterized the fecal microbiota and antibiotic resistomes of wild and captive baboon populations to understand the effect of human exposure and to understand how the primate microbiota may have been altered during the antibiotic era. We used culture-independent and bioinformatics methods to identify functional resistance genes in the guts of wild and captive baboons and show that exposure to humans is associated with changes in microbiota composition and resistome expansion compared to wild baboon groups. Our results suggest that captivity and lifestyle changes associated with human contact can lead to marked changes in the ecology of primate gut communities.Environmental microbes have harbored the capacity for antibiotic production for millions of years, spanning the evolution of humans and other vertebrates. However, the industrial-scale use of antibiotics in clinical and agricultural practice over the past century has led to a substantial increase in exposure of these agents to human and environmental microbiota. This perturbation is predicted to alter the ecology of microbial communities and to promote the evolution and transfer of antibiotic resistance (AR) genes. We studied wild and captive baboon populations to understand the effects of exposure to humans and human activities (e.g., antibiotic therapy) on the composition of the primate fecal microbiota and the antibiotic-resistant genes that it collectively harbors (the “resistome”). Using a culture-independent metagenomic approach, we identified functional antibiotic resistance genes in the gut microbiota of wild and captive baboon groups and saw marked variation in microbiota architecture and resistomes across habitats and lifeways. Our results support the view that antibiotic resistance is an ancient feature of gut microbial communities and that sharing habitats with humans may have important effects on the structure and function of the primate microbiota

Science Objectives and Early Results of the DEEP2 Redshift Survey

The DEIMOS spectrograph has now been installed on the Keck-II telescope and commissioning is nearly complete. The DEEP2 Redshift Survey, which will take approximately 120 nights at the Keck Observatory over a three year period and has been designed to utilize the power of DEIMOS, began in the summer of 2002. The multiplexing power and high efficiency of DEIMOS enables us to target 1000 faint galaxies per clear night. Our goal is to gather high-quality spectra of \~60,000 galaxies with z>0.75 in order to study the properties and large scale clustering of galaxies at z ~ 1. The survey will be executed at high spectral resolution, $R=\lambda/\Delta \lambda \approx 5000$, allowing us to work between the bright OH sky emission lines and to infer linewidths for many of the target galaxies (for several thousand objects, we will obtain rotation curves as well). The linewidth data will facilitate the execution of the classical redshift-volume cosmological test, which can provide a precision measurement of the equation of state of the Universe. This talk reviews the project, summarizes our science goals and presents some early DEIMOS data.Comment: 12 pages, 5 figures, talk presented at SPIE conference, Aug. 200

The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers.

Encapsulation of drugs within nanocarriers that selectively target malignant cells promises to mitigate side effects of conventional chemotherapy and to enable delivery of the unique drug combinations needed for personalized medicine. To realize this potential, however, targeted nanocarriers must simultaneously overcome multiple challenges, including specificity, stability and a high capacity for disparate cargos. Here we report porous nanoparticle-supported lipid bilayers (protocells) that synergistically combine properties of liposomes and nanoporous particles. Protocells modified with a targeting peptide that binds to human hepatocellular carcinoma exhibit a 10,000-fold greater affinity for human hepatocellular carcinoma than for hepatocytes, endothelial cells or immune cells. Furthermore, protocells can be loaded with combinations of therapeutic (drugs, small interfering RNA and toxins) and diagnostic (quantum dots) agents and modified to promote endosomal escape and nuclear accumulation of selected cargos. The enormous capacity of the high-surface-area nanoporous core combined with the enhanced targeting efficacy enabled by the fluid supported lipid bilayer enable a single protocell loaded with a drug cocktail to kill a drug-resistant human hepatocellular carcinoma cell, representing a 10(6)-fold improvement over comparable liposomes

Seroprevalence of Zika virus in wild African green monkeys and baboons

ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available

Modeling metallic island coalescence stress via adhesive contact between surfaces

Tensile stress generation associated with island coalescence is almost universally observed in thin films that grow via the Volmer-Weber mode. The commonly accepted mechanism for the origin of this tensile stress is a process driven by the reduction in surface energy at the expense of the strain energy associated with the deformation of coalescing islands during grain boundary formation. In the present work, we have performed molecular statics calculations using an embedded atom interatomic potential to obtain a functional form of the interfacial energy vs distance between two closely spaced free surfaces. The sum of interfacial energy plus strain energy provides a measure of the total system energy as a function of island separation. Depending on the initial separation between islands, we find that in cases where coalescence is thermodynamically favored, gap closure can occur either spontaneously or be kinetically limited due to an energetic barrier. Atomistic simulations of island coalescence using conjugate gradient energy minimization calculations agree well with the predicted stress as a function of island size from our model of spontaneous coalescence. Molecular dynamics simulations of island coalescence demonstrate that only modest barriers to coalescence can be overcome at room temperature. A comparison with thermally activated coalescence results at room temperature reveals that existing coalescence models significantly overestimate the magnitude of the stress resulting from island coalescence.Comment: 20 pages, 8 figures, 2 tables, submitted to PR

The DEEP2 Galaxy Redshift Survey: Spectral classification of galaxies at z~1

We present a Principal Component Analysis (PCA)-based spectral classification, eta, for the first 5600 galaxies observed in the DEEP2 Redshift Survey. This parameter provides a very pronounced separation between absorption and emission dominated galaxy spectra - corresponding to passively evolving and actively star-forming galaxies in the survey respectively. In addition it is shown that despite the high resolution of the observed spectra, this parameter alone can be used to quite accurately reconstruct any given galaxy spectrum, suggesting there are not many `degrees of freedom' in the observed spectra of this galaxy population. It is argued that this form of classification, eta, will be particularly valuable in making future comparisons between high and low-redshift galaxy surveys for which very large spectroscopic samples are now readily available, particularly when used in conjunction with high-resolution spectral synthesis models which will be made public in the near future. We also discuss the relative advantages of this approach to distant galaxy classification compared to other methods such as colors and morphologies. Finally, we compare the classification derived here with that adopted for the 2dF Galaxy Redshift Survey and in so doing show that the two systems are very similar. This will be particularly useful in subsequent analyses when making comparisons between results from each of these surveys to study evolution in the galaxy populations and large-scale structure.Comment: 10 pages, 9 figures, Accepted for publication in Ap

The 'Antiretrovirals, Sexual Transmission Risk and Attitudes' (ASTRA) study. Design, methods and participant characteristics.

Life expectancy for people diagnosed with HIV has improved dramatically however the number of new infections in the UK remains high. Understanding patterns of sexual behaviour among people living with diagnosed HIV, and the factors associated with having condom-less sex, is important for informing HIV prevention strategies and clinical care. In addition, in view of the current interest in a policy of early antiretroviral treatment (ART) for all people diagnosed with HIV in the UK, it is of particular importance to assess whether ART use is associated with increased levels of condom-less sex. In this context the ASTRA study was designed to investigate current sexual activity, and attitudes to HIV transmission risk, in a large unselected sample of HIV-infected patients under care in the UK. The study also gathered background information on demographic, socio-economic, lifestyle and disease-related characteristics, and physical and psychological symptoms, in order to identify other key factors impacting on HIV patients and the behaviours which underpin transmission. In this paper we describe the study rationale, design, methods, response rate and the demographic characteristics of the participants. People diagnosed with HIV infection attending 8 UK HIV out-patient clinics in 2011-2012 were invited to participate in the study. Those who agreed to participate completed a confidential, self-administered pen-and-paper questionnaire, and their latest CD4 count and viral load test results were recorded. During the study period, 5112 eligible patients were invited to take part in the study and 3258 completed questionnaires were obtained, representing a response rate of 64% of eligible patients. The study includes 2248 men who have sex with men (MSM), 373 heterosexual men and 637 women. Future results from ASTRA will be a key resource for understanding HIV transmission within the UK, targeting prevention efforts, and informing clinical care of individuals living with HIV

The DEEP2 Galaxy Redshift Survey: The Voronoi-Delaunay Method Catalog of Galaxy Groups

We present a public catalog of galaxy groups constructed from the spectroscopic sample of galaxies in the fourth data release from the Deep Extragalactic Evolutionary Probe 2 (DEEP2) Galaxy Redshift Survey, including the Extended Groth Strip (EGS). The catalog contains 1165 groups with two or more members in the EGS over the redshift range 0 0.6 in the rest of DEEP2. Twenty-five percent of EGS galaxies and fourteen percent of high-z DEEP2 galaxies are assigned to galaxy groups. The groups were detected using the Voronoi-Delaunay method (VDM) after it has been optimized on mock DEEP2 catalogs following similar methods to those employed in Gerke et al. In the optimization effort, we have taken particular care to ensure that the mock catalogs resemble the data as closely as possible, and we have fine-tuned our methods separately on mocks constructed for the EGS and the rest of DEEP2. We have also probed the effect of the assumed cosmology on our inferred group-finding efficiency by performing our optimization on three different mock catalogs with different background cosmologies, finding large differences in the group-finding success we can achieve for these different mocks. Using the mock catalog whose background cosmology is most consistent with current data, we estimate that the DEEP2 group catalog is 72% complete and 61% pure (74% and 67% for the EGS) and that the group finder correctly classifies 70% of galaxies that truly belong to groups, with an additional 46% of interloper galaxies contaminating the catalog (66% and 43% for the EGS). We also confirm that the VDM catalog reconstructs the abundance of galaxy groups with velocity dispersions above ~300 km s^(–1) to an accuracy better than the sample variance, and this successful reconstruction is not strongly dependent on cosmology. This makes the DEEP2 group catalog a promising probe of the growth of cosmic structure that can potentially be used for cosmological tests