The impact of storage conditions upon gentamicin coated antimicrobial implants

A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography–mass spectrometry analysis revealed that known gentamines C1, C1a and C2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities

Notes on the integration of numerical relativity waveforms

A primary goal of numerical relativity is to provide estimates of the wave strain, $h$, from strong gravitational wave sources, to be used in detector templates. The simulations, however, typically measure waves in terms of the Weyl curvature component, $\psi_4$. Assuming Bondi gauge, transforming to the strain $h$ reduces to integration of $\psi_4$ twice in time. Integrations performed in either the time or frequency domain, however, lead to secular non-linear drifts in the resulting strain $h$. These non-linear drifts are not explained by the two unknown integration constants which can at most result in linear drifts. We identify a number of fundamental difficulties which can arise from integrating finite length, discretely sampled and noisy data streams. These issues are an artifact of post-processing data. They are independent of the characteristics of the original simulation, such as gauge or numerical method used. We suggest, however, a simple procedure for integrating numerical waveforms in the frequency domain, which is effective at strongly reducing spurious secular non-linear drifts in the resulting strain.Comment: 23 pages, 10 figures, matches final published versio

Development of a continuous process for α-thio-β-chloroacrylamide synthesis with enhanced control of a cascade transformation

A continuous process strategy has been developed for the preparation of α-thio-β chloroacrylamides, a class of highly versatile synthetic intermediates. Flow platforms to generate the α-chloroamide and α-thioamide precursors were successfully adopted, progressing from the previously employed batch chemistry, and in both instances afford a readily scalable methodology. The implementation of the key α-thio-β-chloroacrylamide casade as a continuous flow reaction on a multi-gram scale is described, while the tuneable nature of the cascade, facilitated by continuous processing, is highlighted by selective generation of established intermediates and byproducts

An axisymmetric evolution code for the Einstein equations on hyperboloidal slices

We present the first stable dynamical numerical evolutions of the Einstein equations in terms of a conformally rescaled metric on hyperboloidal hypersurfaces extending to future null infinity. Axisymmetry is imposed in order to reduce the computational cost. The formulation is based on an earlier axisymmetric evolution scheme, adapted to time slices of constant mean curvature. Ideas from a previous study by Moncrief and the author are applied in order to regularize the formally singular evolution equations at future null infinity. Long-term stable and convergent evolutions of Schwarzschild spacetime are obtained, including a gravitational perturbation. The Bondi news function is evaluated at future null infinity.Comment: 21 pages, 4 figures. Minor additions, updated to agree with journal versio

In-vivo visualisation of the anatomical structures related to the acupuncture points Dai mai and Shen mai by MRI: A single-case pilot study

BACKGROUND: The concept of acupuncture point localisation in Traditional Chinese Medicine (TCM) is based on millenary practical experience. Modern imaging methods such as PET, MRI and SPECT have been used primary for the investigation of the mechanisms of action of acupuncture. In this pilot single-case study we have evaluated the technical possibilities for in-vivo imaging of the anatomical relations of acupuncture points using state of the art MRI. METHODS: Preliminary experiments relating to the quality of acupuncture needles under the setting of MRI were done both with stainless steel and gold needles. In a second step, in-vivo imaging was carried out. A licensed acupuncture practitioner (RM) chose two points belonging to the so-called extraordinary vessels. In 2 sequential, separate procedures, he inserted himself gold acupuncture needles using a neutral technique (known as Ping Bu Ping Xie) into the Dai mai and Shen mai points, i.e. gall bladder 26 and bladder 62. Imaging was done on a Siemens Magnetom Avanto MR scanner using a head array and body coil. Mainly T1-weighted imaging sequences, as routinely used for patient exams, were used to obtain multi-slice images. RESULTS: In the preliminary experiments only acupuncture needles made of gold showed enough stability in order to be used for further imaging procedures. Using an onion and a banana as an object, further studies showed that the gold needles produced a void defect that corresponds to the tip of the inserted needle, while at the same time an artefactually increased diameter was observed. The in-vivo experiments showed that the Dai mai point was in relation to the abdominal internal oblique muscle. The Shen mai point artefact showed up close to the longus and brevis peroneal tendons at the fibular malleolus. Side effects related to heating or burning were not observed. Improved anatomical recognition was obtained using 3D-volume rendering techniques. CONCLUSION: Through an adequate choice of acupuncture material (gold needles) as well as of ideal MRI imaging sequences it has been possible to visualize the anatomical characteristics at the acupuncture points Dai mai and Shen mai in-vivo. At the selected sites the needles showed a relation to tendino-fascial and muscular structures. These anatomical structures fit well into the recently described WOMED concept of lateral tension in which these acupuncture points play a regulatory role

The XMM Cluster Survey: The Stellar Mass Assembly of Fossil Galaxies

This paper presents both the result of a search for fossil systems (FSs) within the XMM Cluster Survey and the Sloan Digital Sky Survey and the results of a study of the stellar mass assembly and stellar populations of their fossil galaxies. In total, 17 groups and clusters are identified at z < 0.25 with large magnitude gaps between the first and fourth brightest galaxies. All the information necessary to classify these systems as fossils is provided. For both groups and clusters, the total and fractional luminosity of the brightest galaxy is positively correlated with the magnitude gap. The brightest galaxies in FSs (called fossil galaxies) have stellar populations and star formation histories which are similar to normal brightest cluster galaxies (BCGs). However, at fixed group/cluster mass, the stellar masses of the fossil galaxies are larger compared to normal BCGs, a fact that holds true over a wide range of group/cluster masses. Moreover, the fossil galaxies are found to contain a significant fraction of the total optical luminosity of the group/cluster within 0.5R200, as much as 85%, compared to the non-fossils, which can have as little as 10%. Our results suggest that FSs formed early and in the highest density regions of the universe and that fossil galaxies represent the end products of galaxy mergers in groups and clusters. The online FS catalog can be found at http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.html.Comment: 30 pages, 50 figures. ApJ published version, online FS catalog added: http://www.astro.ljmu.ac.uk/~xcs/Harrison2012/XCSFSCat.htm

Combined multidimensional single-cell protein and RNA profiling dissects the cellular and functional heterogeneity of thymic epithelial cells

The network of thymic stromal cells provides essential niches with unique molecular cues controlling T cell development and selection. Recent single-cell RNA sequencing studies have uncovered previously unappreciated transcriptional heterogeneity among thymic epithelial cells (TEC). However, there are only very few cell markers that allow a comparable phenotypic identification of TEC. Here, using massively parallel flow cytometry and machine learning, we deconvoluted known TEC phenotypes into novel subpopulations. Using CITEseq, these phenotypes were related to corresponding TEC subtypes defined by the cells' RNA profiles. This approach allowed the phenotypic identification of perinatal cTEC and their physical localisation within the cortical stromal scaffold. In addition, we demonstrate the dynamic change in the frequency of perinatal cTEC in response to developing thymocytes and reveal their exceptional efficiency in positive selection. Collectively, our study identifies markers that allow for an unprecedented dissection of the thymus stromal complexity, as well as physical isolation of TEC populations and assignment of specific functions to individual TEC subtypes.ISSN:2041-172

The effect of acupuncture duration on analgesia and peripheral sensory thresholds

<p>Abstract</p> <p>Background</p> <p>Acupuncture provides a means of peripheral stimulation for pain relief. However, the detailed neuronal mechanisms by which acupuncture relieves pain are still poorly understood and information regarding optimal treatment settings is still inadequate. Previous studies with a short burst of unilateral electroacupuncture (EA) in the Tendinomuscular Meridians (TMM) treatment model for pain demonstrated a transient dermatomally correlated bilateral analgesic effect with corresponding peripheral modality-specific sensory threshold alterations. However, the impact of EA duration on the analgesic effect in this particular treatment model is unknown. To obtain mechanistically and clinically important information regarding EA analgesia, this current prospective cross-over study assesses the effects of EA duration on analgesia and thermal sensory thresholds in the TMM treatment model.</p> <p>Methods</p> <p>Baseline peripheral sensory thresholds were measured at pre-marked testing sites along the medial aspects (liver and spleen meridians) of bilateral lower extremities. A 5-second hot pain stimulation was delivered to the testing sites and the corresponding pain Visual Analog Scale (VAS) scores were recorded. Three different EA (5Hz) stimulation durations (5, 15 and 30 minutes) were randomly tested at least one week apart. At the last 10 seconds of each EA session, 5 seconds of subject specific HP stimulation was delivered to the testing sites. The corresponding pain and EA VAS scores of de qi sensation (tingling) during and after the EA were recorded. The measurements were repeated immediately, 30 and 60 minutes after the EA stimulation. A four-factor repeat measures ANOVA was used to assess the effect of stimulation duration, time, location (thigh vs. calf) and side (ipsilateral vs. contralateral) of EA on sensory thresholds and HP VAS scores.</p> <p>Results</p> <p>A significant (P < 0.01) main effect of time and location with warm, cold and hot pain thresholds at the four testing sites without any significant difference in duration effect was observed. Similar time and location effects were observed with HP VAS with the longer durations (15 and 30 minutes) of stimulation showed a slower onset, but a more sustainable bilateral analgesic benefit than the short stimulation duration (5 minutes). The 15-minute stimulation resulted in an earlier onset of analgesic effect than the 30-minute stimulation paradigm.</p> <p>Conclusion</p> <p>Longer durations of EA stimulation provide a more sustainable analgesic benefit to hot noxious stimulation than a shorter duration of stimulation. The increase of cold threshold with sustained warm threshold temperature elevation as observed in the longer durations of EA suggests that as the duration of EA lengthened, there is a gradual shifting from an initial predominantly spinally mediated analgesic effect to a supraspinally mediated modulatory mechanism of thermal pain. The 15-minute stimulation appeared to be the optimal setting for treating acute pain in the lower extremities.</p

Magnetic field exposure and long-term survival among children with leukaemia

We examined the association between magnetic field (MF) exposure and survival among children with acute lymphoblastic leukaemia (ALL) treated at 51 Pediatric Oncology Group centres between 1996 and 2001. Of 1672 potentially eligible children under treatment, 482 (29%) participated and personal 24-h MF measurements were obtained from 412 participants. A total of 386 children with ALL and 361 with B-precursor ALL were included in the analysis of event-free survival (time from diagnosis to first treatment failure, relapse, secondary malignancy, or death) and overall survival. After adjustment for risk group and socioeconomic status, the event-free survival hazard ratio (HR) for children with measurements ⩾0.3 μT was 1.9 (95% confidence interval (CI) 0.8, 4.9), compared to <0.1 μT. For survival, elevated HRs were found for children exposed to ⩾0.3 μT (multivariate HR=4.5, 95% CI 1.5–13.8) but based on only four deaths among 19 children. While risk was increased among children with exposures above 0.3 μT, the small numbers limited inferences for this finding

Efficacy of acupuncture for chronic low back pain: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Chronic back pain is a major public health problem and the primary reason patients seek acupuncture treatment. Therefore, an objective assessment of acupuncture efficacy is critical for making informed decisions about its appropriate role for patients with this common condition. This study addresses methodological shortcomings that have plagued previous studies evaluating acupuncture for chronic low back pain.</p> <p>Methods and Design</p> <p>A total of 640 participants (160 in each of four arms) between the ages of 18 and 70 years of age who have low back pain lasting at least 3 months will be recruited from integrated health care delivery systems in Seattle and Oakland. They will be randomized to one of two forms of Traditional Chinese Medical (TCM) acupuncture needling (individualized or standardized), a "control" group (simulated acupuncture), or to continued usual medical care. Ten treatments will be provided over 7 weeks. Study participants and the "Diagnostician" acupuncturists who evaluate participants and propose individualized treatments will be masked to the acupuncture treatment actually assigned each participant. The "Therapist" acupuncturists providing the treatments will not be masked but will have limited verbal interaction with participants. The primary outcomes, standard measures of dysfunction and bothersomeness of low back pain, will be assessed at baseline, and after 8, 26, and 52 weeks by telephone interviewers masked to treatment assignment. General health status, satisfaction with back care, days of back-related disability, and use and costs of healthcare services for back pain will also be measured. The primary analysis comparing outcomes by randomized treatment assignment will be analysis of covariance adjusted for baseline value. For both primary outcome measures, this trial will have 99% power to detect the presence of a minimal clinically significant difference among all four treatment groups and over 80% power for most pairwise comparisons. Secondary analyses will compare the proportions of participants in each group that improve by a clinically meaningful amount.</p> <p>Conclusion</p> <p>Results of this trial will help clarify the value of acupuncture needling as a treatment for chronic low back pain.</p> <p>Trial registration</p> <p>Clinical Trials.gov NCT00065585.</p