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Purpose To investigate power Doppler (PD) activity and tendon structure (between the injured and contralateral limb) in patients with unilateral patellar tendinopathy (PT) using ultrasonography (US). Secondly, the aim was to determine the intra-rater reliability of the PD activity and tendon structure. Methods This study analyzed US baseline data from 57 male participants with symptomatic unilateral PT who had been enrolled in one of two randomized clinical trials. Data were analyzed to examine if systematic differences existed between injured and contralateral limbs using Fiji ImageJ. Results The PD activity of the symptomatic tendon was larger 25.6 (Q1 = 14.9; Q3 = 41.6) mm2 than the asymptomatic 0 (Q1 = 0.0; Q3 = 0.0) mm2 (p < 0.001). There was a significantly greater tendon thickness at the proximal (2.5 mm 95% CI [2.0; 3.0]), mid (0.8 mm 95% CI [0.5; 1.1]), and distal (0.2 mm 95% CI [0.1; 0.4]) part of the tendon for the symptomatic compared to the asymptomatic tendon. Intra-rater reliability for PD activity and tendon structure ranged from moderate-to-excellent (0.74; 0.99). Conclusion These results provide mean estimates for tendon thickness of symptomatic and asymptomatic tendons, that can be used for clinicians to reliably estimate pathological tendon thickness., Purpose: To investigate power Doppler (PD) activity and tendon structure (between the injured and contralateral limb) in patients with unilateral patellar tendinopathy (PT) using ultrasonography (US). Secondly, the aim was to determine the intra-rater reliability of the PD activity and tendon structure. Methods: This study analyzed US baseline data from 57 male participants with symptomatic unilateral PT who had been enrolled in one of two randomized clinical trials. Data were analyzed to examine if systematic differences existed between injured and contralateral limbs using Fiji ImageJ. Results: The PD activity of the symptomatic tendon was larger 25.6 (Q1 = 14.9; Q3 = 41.6) mm2 than the asymptomatic 0 (Q1 = 0.0; Q3 = 0.0) mm2 (p < 0.001). There was a significantly greater tendon thickness at the proximal (2.5 mm 95% CI [2.0; 3.0]), mid (0.8 mm 95% CI [0.5; 1.1]), and distal (0.2 mm 95% CI [0.1; 0.4]) part of the tendon for the symptomatic compared to the asymptomatic tendon. Intra-rater reliability for PD activity and tendon structure ranged from moderate-to-excellent (0.74; 0.99). Conclusion: These results provide mean estimates for tendon thickness of symptomatic and asymptomatic tendons, that can be used for clinicians to reliably estimate pathological tendon thickness.

It is well known that cells can generate endogenous forces onto the extracellular matrix, but to what extent the mechanical properties of the matrix influences these endogenous cellular forces remains unclear. We therefore sought to quantify the influence of matrix rigidity on cell-matrix interactions by inducing cross-links using increasing concentrations of genipin (0.01–1 mM) or by blocking cross-link formation using beta-aminopropionitrile (BAPN) in engineered human tendon tissue constructs. The cell-matrix mechanics of the tendon constructs were evaluated as cell-generated tissue re-tensioning and stress-relaxation responses using a novel custom-made force monitor, which can apply and detect tensional forces in real-time in addition to mechanical failure testing. Genipin treatment had no influence on the biochemical profile (hydroxyproline, glycosaminoglycan and DNA content) of the constructs and cell viability was comparable between genipin-treated and control constructs, except at the highest genipin concentration. Endogenous re-tension after unloading was significantly decreased with increasing genipin concentrations compared to controls. Mechanical failure testing of tendon constructs showed increased (56%) peak stress at the highest genipin concentration but decreased (72%) with BAPN treatment when compared to controls. Tendon construct stiffness increased with high genipin concentrations (0.1 and 1 mM) and decreased by 70% in BAPN-treated constructs, relative to the controls. These data demonstrate that human tendon fibroblasts regulate their force exertion inversely proportional to increased cross-link capacity but did so independently of matrix stiffness. Overall, these findings support the notion of an interaction between cell force generation and cross-linking, and thus a role for this interplay in mechanical homeostasis of the tissue.

Purpose: Whether the quality of the ethical climate in the intensive care unit (ICU) improves the identification of patients receiving excessive care and affects patient outcomes is unknown. Methods: In this prospective observational study, perceptions of excessive care (PECs) by clinicians working in 68 ICUs in Europe and the USA were collected daily during a 28-day period. The quality of the ethical climate in the ICUs was assessed via a validated questionnaire. We compared the combined endpoint (death, not at home or poor quality of life at 1 year) of patients with PECs and the time from PECs until written treatment-limitation decisions (TLDs) and death across the four climates defined via cluster analysis. Results: Of the 4747 eligible clinicians, 2992 (63%) evaluated the ethical climate in their ICU. Of the 321 and 623 patients not admitted for monitoring only in ICUs with a good (n = 12, 18%) and poor (n = 24, 35%) climate, 36 (11%) and 74 (12%), respectively were identified with PECs by at least two clinicians. Of the 35 and 71 identified patients with an available combined endpoint, 100% (95% CI 90.0–1.00) and 85.9% (75.4–92.0) (P = 0.02) attained that endpoint. The risk of death (HR 1.88, 95% CI 1.20–2.92) or receiving a written TLD (HR 2.32, CI 1.11–4.85) in patients with PECs by at least two clinicians was higher in ICUs with a good climate than in those with a poor one. The differences between ICUs with an average climate, with (n = 12, 18%) or without (n = 20, 29%) nursing involvement at the end of life, and ICUs with a poor climate were less obvious but still in favour of the former. Conclusion: Enhancing the quality of the ethical climate in the ICU may improve both the identification of patients receiving excessive care and the decision-making process at the end of life.

Tendon pathology is related to metabolic disease and mechanical overloading, but the effect of metabolic disease on tendon mechanics is unknown. This study investigated the effect of diet and apolipoprotein E deficiency (ApoE(-/-)) on mechanical properties and advanced glycation end product (AGE) cross-linking of non-weight-bearing mouse tail tendons. Twenty ApoE(-/-) male mice were used as a model for hypercholesterolemia along with 26 wild-type (WT) mice. One-half of the mice from each group was fed a normal diet (ND) and the other half was fed a high-fat diet (HFD) to induce obesity. All were killed at 40 wk, and tail tendon fascicles were mechanically tested to failure and analyzed for AGEs. Diets were also analyzed for AGEs. ApoE(-/-) mice displayed a 14% increase in plateau modulus compared with WT mice (P < 0.05), whereas HFD mice displayed a 13% decrease in plateau modulus (P < 0.05) and a 12% decrease in total modulus (P < 0.05) compared with ND mice. Tail tendons of HFD mice had significantly lower concentrations of AGEs [carboxymethyllysine (CML): 26%, P < 0.0001; methylglyoxal-derived hydroimidazolone 1 (MG-H1): 15%, P < 0.005; pentosidine: 13%, P < 0.0005]. The HFD had ∼44-fold lower content of CML (P < 0.01), ∼29-fold lower content of carboxyethyllysine (P < 0.005), and ∼16-fold lower content of MG-H1 (P < 0.05) compared with ND. ApoE(-/-) increased, whereas HFD decreased mouse tail tendon stiffness. Dietary AGE content may be a crucial determinant for accumulation of AGE cross-links in tendons and for tissue compliance. The results demonstrate how systemic metabolic factors may influence tendon health.

ACuteTox is a project within the 6th European Framework Programme which had as one of its goals to develop, optimise and prevalidate a non-animal testing strategy for predicting human acute oral toxicity. In its last 6months, a challenging exercise was conducted to assess the predictive capacity of the developed testing strategies and final identification of the most promising ones. Thirty-two chemicals were tested blind in the battery of in vitro and in silico methods selected during the first phase of the project. This paper describes the classification approaches studied: single step procedures and two step tiered testing strategies. In summary, four in vitro testing strategies were proposed as best performing in terms of predictive capacity with respect to the European acute oral toxicity classification. In addition, a heuristic testing strategy is suggested that combines the prediction results gained from the neutral red uptake assay performed in 3T3 cells, with information on neurotoxicity alerts identified by the primary rat brain aggregates test method. Octanol-water partition coefficients and in silico prediction of intestinal absorption and blood-brain barrier passage are also considered. This approach allows to reduce the number of chemicals wrongly predicted as not classified (LD(50)>2000mg/kg b.w.).

Swedish recycling centres are manned facilities for waste collection. There is no special category in the official injury statistics for employees at recycling centres, which precludes a straightforward analysis of reported occupational injuries. This study aimed at identifying the frequency of reported accidents and diseases and the type of events that contribute to such injuries at recycling centres, based on official injury statistics. The employees were identified as being affected by more than three to five times as many accidents compared with the total workforce in Sweden. The reported accidents had occurred during a wide range of situations, but most frequently during manual handling of waste. Reported work-related diseases were mostly associated with musculoskeletal disorders, mainly due to heavy lifting. A more detailed classification of sanitation professions and workplaces in the official injury statistics would facilitate future studies of injuries in a specific professional category, e.g. employees at recycling centres. Suggestions for prevention are given. Statement of Relevance: The present article describes all reported work accidents and diseases among employees at recycling centres from 1992 to February 2005. It also highlights the problem of identifying new working groups in the official statistics and gives advice for a detailed classification to facilitate such future studies of injuries., QC 20110516

Recycling is a new and developing industry, which has only been researched to a limited extent. This article describes the development and use of instruments for data collection within a multidisciplinary research programme "Recycling centres in Sweden - working conditions, environmental and system performance". The overall purpose of the programme was to form a basis for improving the function of recycling centres with respect to these three perspectives and the disciplines of: ergonomics, safety, external environment, and production systems. A total of 10 instruments were developed for collecting data from employees, managers and visitors at recycling centres. including one instrument for observing visitors. Validation tests were performed in several steps. This, along with the quality of the collected data, and experience from the data collection, showed that the instruments and methodology used were valid and suitable for their purpose., QC 20100525

The trimeric membrane protein microsomal glutathione transferase 1 (MGST1) possesses glutathione transferase and peroxidase activity. Previous data indicated one active site/trimer whereas structural data suggests three GSH-binding sites. Here we have determined ligand interactions of MGST1 by several techniques. Nanoelectrospray mass spectrometry of native MGST1 revealed binding of three GSH molecules/trimer and equilibrium dialysis showed three product molecules/trimer (K(d) = 320 +/- 50 mu M). All three product molecules Could be competed out with GSH. Reinvestigation of GSH-binding showed one high affinity site per trimer, consistent with earlier data. Using single turnover stopped flow kinetic measurements, Kd could be determined for a low affinity GSH-binding site (2.5 +/- 0.5 mu M). Thus we can reconcile previous observations and show here that MGST1 contains three active sites with different affinities for GSH and that only the high affinity site is catalytically competent., QC 20120214

Part of urn:nbn:se:su:diva-8131

Clostridium botulinum is a taxonomic designation for many diverse anaerobic spore-forming rod-shaped bacteria which have the common property of producing botulinum neurotoxins (BoNTs). The BoNTs are exoneurotoxins that can cause severe paralysis and death in humans and other animal species. A collection of 174 C. botulinum strains was examined by amplified fragment length polymorphism (AFLP) analysis and by sequencing of the 16S rRNA gene and BoNT genes to examine genetic diversity within this species. This collection contained representatives of each of the seven different serotypes of botulinum neurotoxins (BoNT A-G). Analysis of the 16S rRNA sequences confirmed earlier identification of at least four distinct genomic backgrounds (Groups I-IV), each of which has independently acquired one or more BoNT genes through horizontal gene transfer. AFLP analysis provided higher resolution and could be used to further subdivide the four groups into sub-groups. Sequencing of the BoNT genes from multiple strains of serotypes A, B and E confirmed significant sequence variation within each serotype. Four distinct lineages within each of the BoNT A and B serotypes and five distinct lineages of serotype E strains were identified. The nucleotide sequences of the seven toxin genes of the serotypes were compared and showed varying degrees of inter-relatedness and recombination, as had been previously noted for the NTNH gene, which is linked to the BoNT gene. These analyses contribute to the understanding of the evolution and phylogeny within this species and assist in the development of improved diagnostics and therapeutics for treatment of botulism., Published in Journal of Bacteriology, v189 n3 p818-832, Feb 2007. Sponsored in part by Department of Homeland Security and Department of Energy. The original document contains color images.

Purpose: Due to the highly conformal distributions that can be obtained with intensity modulated radiation therapy (IMRT), any discrepancy between the intended and delivered distributions would likely affect the clinical outcome. Consequently, there is a need for a measure that would quantify those differences in terms of a change in the expected clinical outcome. Material and Methods: To evaluate such a measure, the case of a cervix cancer was used where the bladder and rectum, are proximal and partially overlapping with the internal target volume. A solid phantom simulating the pelvic anatomy was fabricated and a treatment plan was developed to deliver the prescribed dose to the phantom. The phantom was then irradiated with films positioned in several transverse planes. The racetrack microtron at 50MV was used in the treatment planning and delivery processes. The dose distribution delivered was analyzed based on the film measurements and compared against the treatment plan. The differences in the measurements were evaluated using both physical and biological criteria. Results: For the computerized treatment plan, the maximum value of P+ was 84.1%, for a mean dose to the ITV of = 93.3Gy, associated relative standard deviation D/ = 16.8% and biologically effective uniform dose, ITV of 89.2 Gy. The delivered dose distribution from all the beams produced a P+ value of 77.0% for ITV = 93.2Gy, D/ = 19.0% and ITV of 83.5 Gy. Discussion and Conclusions: Whereas the physical comparison of dose distributions can assess the geometric accuracy of delivery, it does not reflect the clinical impact of any measured dose discrepancies. With highly conformal IMRT, the accuracy of the patient setup and treatment delivery, are critical for the success of the treatment. A method is proposed to evaluate the precision of the delivered plan based on changes in complication and control rates as they relate to uncertainties in dose delivery.

Part of urn:nbn:se:su:diva-8131

The INTEGRAL X-ray monitor, JEM-X, (together with the two gamma ray instruments, SPI and IBIS) provides simultaneous imaging with arcminute angular resolution in the 3-35 keV band. The good angular resolution and low energy response of JEM-X plays an important role in the detection and identification of gamma ray sources as well as in the analysis and scientific interpretation of the combined X-ray and gamma ray data. JEM-X is a coded aperture X-ray telescope consisting of two identical detectors. Each detector has a sensitive area of 500 cm(2), and views the sky through its own coded aperture mask. The coded masks are located 3.4 m above the detector windows. The detector field of view is constrained by X-ray collimators (6.6degrees FOV, FWHM).

The JEM-X monitor provides X-ray spectra and imaging with arcminute angular resolution in the 3 to 35 keV band. The good angular resolution and the low energy response of JEM-X plays an important role in the identification of gamma ray sources and in the analysis and scientific interpretation of the combined X-ray and gamma ray data. JEM-X is a coded aperture instrument consisting of two identical, coaligned telescopes. Each of the detectors has a sensitive area of 500 cm(2), and views the sky through its own coded aperture mask. The two coded masks are inverted with respect to each other and provides an angular resolution of 3' across an effective field of view of about 10degrees diameter.

We summarize the inflight performance of JEM-X, the X-ray monitor on the INTEGRAL mission during the initial ten months of operations. The JEM-X instruments have now been tuned to stable operational conditions. The performance is found to be close to the pre-launch expectations. The ground calibrations and the inflight calibration data permit to determine the instruments characteristics to fully support the scientific data analysis.

We find and study a variety of the spectral-temporal behavior during the decay phase of the light curve of long and bright pulse structures in gamma-ray bursts (GRBs). Even though only a small fraction of observed bursts exhibit such pulses, these are of interest to study since they reflect individual emission episodes during the burst. We have previously found that for about half of these decays, the instantaneous photon flux is consistent with a power law in time, where the photon flux proportional to 1/time. This decay behavior is a consequence of the validity of both a power-law correlation between the hardness and the intensity and an exponential correlation between the hardness and the time-integrated intensity, the fluence. Here we study a complete sample of 25 pulses (having a peak flux in 1 s time resolution of more than 5 photons s(-1) cm(-2) and a signal-to-noise ratio of 30 in at least eight time bins) and, specifically, search for other types of decay behaviors. First, we find that a power law gives a better description of the pulse decays than a stretched exponential, the most commonly assumed pulse shape so far. Then we find that about half of the decays behave approximately as 1/time, and the other half approximately as 1/(time)(3). For a few of the 1/(time)3 decays, the two correlations, the hardness-intensity correlation and the hardness-fluence correlation, are constrained and found to be consistent with the light-curve decay behavior. For these cases, the hardness-intensity correlation is still a power law, while the hardness-fluence correlation is described by a generalized function. We study and describe these behaviors analytically and examine actual burst data from the complete catalog of the Burst and Transient Source Experiment on the Compton Gamma Ray Observatory. Finally, we briefly discuss our results in a physical context., QC 20100525

For the first time, the consequences of combining two well-established empirical relations that describe different aspects of the spectral evolution of observed gamma-ray burst (GRB) pulses are explored. These empirical relations are (1) the hardness-intensity correlation and (2) the hardness-photon fluence correlation. From these we find a self-consistent, quantitative, and compact description for the temporal evolution of pulse decay phases within a GRB light curve. In particular, we show that in the case in which the two empirical relations are both valid, the instantaneous photon flux (intensity) must behave as 1/(1 + t/tau), where tau is a time constant that can be expressed in terms of the parameters of the two empirical relations. The time evolution is fully defined by two initial constants and two parameters. We study a complete sample of 83 bright GRB pulses observed by the Compton Gamma-Ray Observatory and identify a major subgroup of GRB pulses (similar to 45%) which satisfy the spectral-temporal behavior described above. In particular, the decay phase follows a reciprocal law in time. It is unclear what physics causes such a decay phase., QC 20100525

The Bacillus anthracis Sterne plasmid pXO1 was sequenced by random, "shotgun" cloning. A circular sequence of 181,654 bp was generated. One hundred forty-three open reading frames (ORFs) were predicted using GeneMark and GeneMark.hmm, comprising only 61% (110,817 bp) of the pXO1 DNA sequence. The overall guanine-plus-cytosine content of the plasmid is 32.5%. The most recognizable feature of the plasmid is a "pathogenicity island," defined by a 44.8-kb region that is bordered by inverted IS1627 elements at each end. This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs. Nearly 70% of the ORFs on pXO1 do not have significant similarity to sequences available in open databases. Absent from the pXO1 sequence are homologs to genes that are typically required to drive theta replication and to maintain stability of large plasmids in Bacillus spp. Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species. Among the remaining ORFs, there are three sequences that may encode enzymes responsible for the synthesis of a polysaccharide capsule usually associated with serotype-specific virulent streptococci.

A broad band X-, gamma-ray spectral study of the Seyfert 2 galaxy NGC 7172 is presented. We use our ASCA observations from May 1995 and combine these with the CGRO OSSE data from March 1995. The only Seyfert 2 galaxy previously to have been modelled over, Addresses: Ryde Felix, STOCKHOLM OBSERV, S-13336 SALTSJOBADEN, SWEDEN. ASTRON OBSERV, S-75120 UPPSALA, SWEDEN.