Objective: To evaluate the efficacy of ultrasound guided dry needling and autologous blood injection for the treatment of patellar tendinosis. Design: Prospective cohort study. Setting: ...Hospital/clinic based. Patients: 47 knees in 44 patients (40 men, 7 women, mean age 34.5 years, age range 17 to 54 years) with refractory tendinosis underwent sonographic examination of the patellar tendon following referral with a clinical diagnosis of patellar tendinosis (mean symptom duration 12.9 months). Interventions: Ultrasound guided dry needling and injection of autologous blood into the site of patellar tendinosis was performed on two occasions four weeks apart. Main outcome measures: Pre- and post-procedure Victorian Institute of Sport Assessment scores (VISA) were collected to assess patient response to treatment. Follow up ultrasound examination was done in 21 patients (22 knees). Results: Therapeutic intervention led to a significant improvement in VISA score: mean pre-procedure score = 39.8 (range 8 to 72) v mean post procedure score = 74.3 (range 29 to 100), p<0.001; mean follow up 14.8 months (range 6 to 22 months). Patients were able to return to their sporting interests. Follow up sonographic assessment showed a reduction in overall tendon thickness and in the size of the area of tendinosis (hypoechoic/anechoic areas within the proximal patellar tendon). A reduction was identified in interstitial tears within the tendon substance. Neovascularity did not reduce significantly or even increased. Conclusions: Dry needling and autologous blood injection under ultrasound guidance shows promise as a treatment for patients with patellar tendinosis.
The use of administrative data for surgical site infection (SSI) surveillance leads to inaccurate reporting of SSI rates 1. A quality improvement (QI) initiative was conducted linking clinical ...registry and administrative databases to improve reporting and reduce the incidence of SSI 2.
At our institution, The Society of Thoracic Surgeons Congenital Heart Surgery Database (STS-CHSD) and infection surveillance database (ISD) were linked to the enterprise data warehouse containing electronic health record (EHR) billing data. A data visualization tool was created to (1) use the STS-CHSD for case ascertainment, (2) resolve discrepancies between the databases, and (3) assess impact of QI initiatives, including wound alert reports, bedside reviews, prevention bundles, and billing coder education.
Over the 24-month study period, 1,715 surgical cases were ascertained according to the STS-CHSD clinical criteria, with 23 SSIs identified through the STS-CHSD, 20 SSIs identified through the ISD, and 32 SSIs identified through the billing database. The rolling 12-month STS-CHSD SSI rate decreased from 2.73% (21 of 769 as of January 2013) to 1.11% (9 of 813 as of December 2014). Thirty reporting discrepancies were reviewed to ensure accuracy. Workflow changes facilitated communication and improved adjudication of suspected SSIs. Billing coder education increased coding accuracy and narrowed variation between the 3 SSI sources. The data visualization tool demonstrated temporal relationships between QI initiatives and SSI rate reductions.
Linkage of registry and infection control surveillance data with the EHR improves SSI surveillance. The visualization tool and workflow changes facilitated communication, SSI adjudication, and assessment of the QI initiatives. Implementation of these initiatives was associated with decreased SSI rates.
The endoplasmic reticulum (ER) is a key organelle in the eukaryotic cell and is responsible for protein folding and quality control, mediated by protein chaperones. It is also home to the ...oxidoreductase system which is required for disulphide bond formation and is the main theme of this thesis. Two of the vital proteins in the ER-localised oxidoreductase system are protein disulphide isomerase (PDI) and endoplasmic reticulum oxidoreductase 1 α (Ero1α). These proteins work alongside other specialist PDI family members such as anterior gradient 2 (AGR2). This thesis examines the role of both PDI and AGR2 in protein quality control, together with important clients such as collagen, a major component of the extracellular matrix (ECM) and a secreted product of fibroblast cells present in the skin. The role of AGR2 in oesophageal cancer was explored, with data dependant acquisition (DDA) mass spectrometry (MS) used to identify novel interacting partners of AGR2. AGR2 was found to be over expressed in certain oesophageal cell lines and key interacting partners such as MUC5AC and SQSTM1 were identified. Research was undertaken in this thesis to compare the effectiveness and application of the reducing agent dithiobutylamine (DTBA) to biological systems and how this reducing agent affects the cellular proteome and the redox state of PDI. Live cell imaging was used to see how the structure of the ER was affected by reductive stress. Data independent acquisition (DIA) MS was used to identify new molecular players in the cellular response to reductive stress, in the response to PDI inhibitors, in the response to growth factors (PDGF) and in the response to skin bioactive (e.g. niacinamide). Taken together, these analyses lay the foundations for understanding new mechanistic control points in the quality control of protein secretion and homeostasis.
In the frame of the European metrological research project MetroERM, a compact portable aerosol sampling and measurement device was developed at Jožef Stefan Institute. The system incorporates a ...CeBr3 scintillation detector positioned centrally within a concertinaed filter assembly and an improved high flow rate air pump. It provides continuous on-line low level airborne radioactive particulate monitoring for field station use via 3G network communications. The calibration of the device was performed at National Physical Laboratory (NPL) with filters, spiked with a certified mixed nuclide solution. Additionally first tests were performed in an environment with an elevated radon concentration.
•A compact portable aerosol sampling device was developed at Jožef Stefan Institute.•The system incorporates a CeBr3 scintillation detector positioned centrally within a filter assembly and high flow rate air pump.•The calibration of the device with filters, contaminated with CRM was performed at National Physical Laboratory.•First tests were performed in the environment with elevated radon concentrations.
Spectroscopic X-ray imaging is an emerging technology with applications in the fields of medical imaging, security, science and industrial analysis. The wide bandgap semiconductor cadmium zinc ...telluride (CdZnTe) is the leading sensor material for this technology. Refinements in the growth process have delivered consistent improvements in both yield and quality of single crystal CdZnTe. The fabrication of metal contacts required for electronic readout is now considered to be the limiting factor for small pixel CdZnTe detector performance. This includes preparation of the CdZnTe surface, deposition of the metal contacts and pixellation. The current work is concerned with understanding and improving the detector fabrication process. A range of complementary characterisation techniques have been used to analyse the metal-semiconductor interface formed by electroless and sputter deposition of gold contacts onto CdZnTe. The characterisation included focused ion beam (FIB) cross section imaging, chemical analysis with X-ray photoelectron spectroscopy (XPS) and electronic analysis with current-voltage (IV) measurements. The electroless deposition was found to produce a complicated interface consisting of a surface gold layer on top of a mixed interface of gold, tellurium oxide and cadmium chloride. The effective barrier height of this contact was measured to be 0.78 ± 0.04 eV under positive bias and 0.83 ± 0.02 eV under negative bias. The interface of sputter deposited gold contacts was simple in comparison, with a sharp interface between the gold and CdZnTe and a barrier height of 0.64 ± 0.02 eV under positive bias and 0.78 ± 0.02 eV under negative bias. An optimised detector fabrication process has been developed. This process involves forming gold contacts on mechanically polished-only CdZnTe by electroless deposition. Pixellation is achieved with a positive photoresist prior to gold deposition. A small pixel (250 μm pitch) CdZnTe detector fabricated in this manner and bonded to the HEXITEC ASIC has produced a single pixel FWHM energy resolution at 59.54 keV of 560 eV, with a modal FWHM resolution of 1.5 keV across the full 74 × 74 pixel array.
The Context Camera (CTX) on the Mars Reconnaissance Orbiter (MRO) is a Facility Instrument (i.e., government‐furnished equipment operated by a science team not responsible for design and fabrication) ...designed, built, and operated by Malin Space Science Systems and the MRO Mars Color Imager team (MARCI). CTX will (1) provide context images for data acquired by other MRO instruments, (2) observe features of interest to NASA's Mars Exploration Program (e.g., candidate landing sites), and (3) conduct a scientific investigation, led by the MARCI team, of geologic, geomorphic, and meteorological processes on Mars. CTX consists of a digital electronics assembly; a 350 mm f/3.25 Schmidt‐type telescope of catadioptric optical design with a 5.7° field of view, providing a ∼30‐km‐wide swath from ∼290 km altitude; and a 5000‐element CCD with a band pass of 500–700 nm and 7 μm pixels, giving ∼6 m/pixel spatial resolution from MRO's nearly circular, nearly polar mapping orbit. Raw data are transferred to the MRO spacecraft flight computer for processing (e.g., data compression) before transmission to Earth. The ground data system and operations are based on 9 years of Mars Global Surveyor Mars Orbiter Camera on‐orbit experience. CTX has been allocated 12% of the total MRO data return, or about ≥3 terabits for the nominal mission. This data volume would cover ∼9% of Mars at 6 m/pixel, but overlapping images (for stereo, mosaics, and observation of changes and meteorological events) will reduce this area. CTX acquired its first (instrument checkout) images of Mars on 24 March 2006.
We describe, for the first time the use of hydrogel-forming microneedle (MN) arrays for minimally-invasive extraction and quantification of drug substances and glucose from skin in vitro and in vivo. ...MN prepared from aqueous blends of hydrolysed poly(methyl-vinylether-co-maleic anhydride) (11.1% w/w) and poly(ethyleneglycol) 10,000 daltons (5.6% w/w) and crosslinked by esterification swelled upon skin insertion by uptake of fluid. Post-removal, theophylline and caffeine were extracted from MN and determined using HPLC, with glucose quantified using a proprietary kit. In vitro studies using excised neonatal porcine skin bathed on the underside by physiologically-relevant analyte concentrations showed rapid (5 min) analyte uptake. For example, mean concentrations of 0.16 μg/mL and 0.85 μg/mL, respectively, were detected for the lowest (5 μg/mL) and highest (35 μg/mL) Franz cell concentrations of theophylline after 5 min insertion. A mean concentration of 0.10 μg/mL was obtained by extraction of MN inserted for 5 min into skin bathed with 5 μg/mL caffeine, while the mean concentration obtained by extraction of MN inserted into skin bathed with 15 μg/mL caffeine was 0.33 μg/mL. The mean detected glucose concentration after 5 min insertion into skin bathed with 4 mmol/L was 19.46 nmol/L. The highest theophylline concentration detected following extraction from a hydrogel-forming MN inserted for 1 h into the skin of a rat dosed orally with 10 mg/kg was of 0.363 μg/mL, whilst a maximum concentration of 0.063 μg/mL was detected following extraction from a MN inserted for 1 h into the skin of a rat dosed with 5 mg/kg theophylline. In human volunteers, the highest mean concentration of caffeine detected using MN was 91.31 μg/mL over the period from 1 to 2 h post-consumption of 100 mg Proplus® tablets. The highest mean blood glucose level was 7.89 nmol/L detected 1 h following ingestion of 75 g of glucose, while the highest mean glucose concentration extracted from MN was 4.29 nmol/L, detected after 3 hours skin insertion in human volunteers. Whilst not directly correlated, concentrations extracted from MN were clearly indicative of trends in blood in both rats and human volunteers. This work strongly illustrates the potential of hydrogel-forming MN in minimally-invasive patient monitoring and diagnosis. Further studies are now ongoing to reduce clinical insertion times and develop mathematical algorithms enabling determination of blood levels directly from MN measurements.
Electron cryotomography is currently the only method capable of visualizing cells in three dimensions at nanometer resolutions. While modern instruments produce massive amounts of tomography data ...containing extremely rich structural information, data processing is very labor intensive and the results are often limited by the skills of the personnel rather than the data. We present an integrated workflow that covers the entire tomography data processing pipeline, from automated tilt series alignment to subnanometer resolution subtomogram averaging. Resolution enhancement is made possible through the use of per-particle per-tilt contrast transfer function correction and alignment. The workflow greatly reduces human bias, increases throughput and more closely approaches data-limited resolution for subtomogram averaging in both purified macromolecules and cells.
Multidrug efflux pumps actively expel a wide range of toxic substrates from the cell and play a major role in intrinsic and acquired drug resistance. In Gram-negative bacteria, these pumps form ...tripartite assemblies that span the cell envelope. However, the in situ structure and assembly mechanism of multidrug efflux pumps remain unknown. Here we report the in situ structure of the Escherichia coli AcrAB-TolC multidrug efflux pump obtained by electron cryo-tomography and subtomogram averaging. The fully assembled efflux pump is observed in a closed state under conditions of antibiotic challenge and in an open state in the presence of AcrB inhibitor. We also observe intermediate AcrAB complexes without TolC and discover that AcrA contacts the peptidoglycan layer of the periplasm. Our data point to a sequential assembly process in living bacteria, beginning with formation of the AcrAB subcomplex and suggest domains to target with efflux pump inhibitors.
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