Diffusion tensor imaging can identify amyotrophic lateral sclerosis-associated patterns of brain alterations at the group level. Recently, a neuropathological staging system for amyotrophic lateral ...sclerosis has shown that amyotrophic lateral sclerosis may disseminate in a sequential regional pattern during four disease stages. The objective of the present study was to apply a new methodological diffusion tensor imaging-based approach to automatically analyse in vivo the fibre tracts that are prone to be involved at each neuropathological stage of amyotrophic lateral sclerosis. Two data samples, consisting of 130 diffusion tensor imaging data sets acquired at 1.5 T from 78 patients with amyotrophic lateral sclerosis and 52 control subjects; and 55 diffusion-tensor imaging data sets at 3.0 T from 33 patients with amyotrophic lateral sclerosis and 22 control subjects, were analysed by a tract of interest-based fibre tracking approach to analyse five tracts that become involved during the course of amyotrophic lateral sclerosis: the corticospinal tract (stage 1); the corticorubral and the corticopontine tracts (stage 2); the corticostriatal pathway (stage 3); the proximal portion of the perforant path (stage 4); and two reference pathways. The statistical analyses of tracts of interest showed differences between patients with amyotrophic lateral sclerosis and control subjects for all tracts. The significance level of the comparisons at the group level was lower, the higher the disease stage with corresponding involved fibre tracts. Both the clinical phenotype as assessed by the amyotrophic lateral sclerosis functional rating scale-revised and disease duration correlated significantly with the resulting staging scheme. In summary, the tract of interest-based technique allowed for individual analysis of predefined tract structures, thus making it possible to image in vivo the disease stages in amyotrophic lateral sclerosis. This approach can be used not only for individual clinical work-up purposes, but enlarges the spectrum of potential non-invasive surrogate markers as a neuroimaging-based read-out for amyotrophic lateral sclerosis studies within a clinical context.
Non-O157 Shiga toxin-producing Escherichia coli (STEC) can cause severe illness, including hemolytic uremic syndrome (HUS). STEC O145 is the sixth most commonly reported non-O157 STEC in the United ...States, although outbreaks have been infrequent. In April and May 2010, we investigated a multistate outbreak of STEC O145 infection. Confirmed cases were STEC O145 infections with isolate pulsed-field gel electrophoresis patterns indistinguishable from those of the outbreak strain. Probable cases were STEC O145 infections or HUS in persons who were epidemiologically linked. Case-control studies were conducted in Michigan and Ohio; food exposures were analyzed at the restaurant, menu, and ingredient level. Environmental inspections were conducted in implicated food establishments, and food samples were collected and tested. To characterize clinical findings associated with infections, we conducted a chart review for case patients who sought medical care. We identified 27 confirmed and 4 probable cases from five states. Of these, 14 (45%) were hospitalized, 3 (10%) developed HUS, and none died. Among two case-control studies conducted, illness was significantly associated with consumption of shredded romaine lettuce in Michigan (odds ratio OR = undefined; 95% confidence interval CI = 1.6 to undefined) and Ohio (OR = 10.9; 95% CI = 3.1 to 40.5). Samples from an unopened bag of shredded romaine lettuce yielded the predominant outbreak strain. Of 15 case patients included in the chart review, 14 (93%) had diarrhea and abdominal cramps and 11 (73%) developed bloody diarrhea. This report documents the first foodborne outbreak of STEC O145 infections in the United States. Current surveillance efforts focus primarily on E. coli O157 infections; however, non-O157 STEC can cause similar disease and outbreaks, and efforts should be made to identify both O157 and non-O157 STEC infections. Providers should test all patients with bloody diarrhea for both non-O157 and O157 STEC.
Grain refinement which improves the mechanical strength of copper (Cu) results in substantial loss of its electrical conductivity. We demonstrate that synergistic effects of grain refinement and ...reinforcement of few layered graphene (Gr) can result in exceptionally high strength Cu without much degradation of electrical conductivity. For this study, the Cu-Gr composite foils are fabricated by pulsed electrodeposition from an additive-free copper sulphate bath. An aqueous suspension of few layer graphene, synthesized using a novel airless high-pressure exfoliation technique, was used as a reinforcement to copper. Electrodeposited pure Cu showed a strong columnar microcrystalline grain structure, and its grain size decreased slightly along with significant changes in the preferred growth direction upon increasing the current density and accordingly, the tensile yield strength improved moderately. Graphene reinforcement in copper resulted in significant grain refinement to ∼750 nm, increased growth-twin density and shift in crystallographic growth direction, and a remarkable tensile yield strength of ∼800 MPa which is much higher than previously reported values. The electrical conductivity of Cu-Gr composites was greater than 90% IACS and is comparable to pure copper. Detailed microstructural investigation and analysis suggest that uniformly dispersed graphene layers in conjunction with the reinforcement-induced microstructural features in electrodeposited Cu could have contributed to the observed high strength and good electrical conductivity.
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•Addition of few layer graphene significantly improves strength of copper without compromising electrical conductivity.•Graphene addition can result in grain refinement, increased growth twin density and texture change.•Ultrafine grained copper-graphene composite exhibited a maximum yield strength of ∼800 MPa.
Adolescence may be regarded as a critical phase of tissue plasticity in young growing athletes, as the adaptation process of muscle‐tendon unit is affected by both environmental mechanical stimuli ...and maturation. The present study investigated potential imbalances of knee extensor muscle strength and patellar tendon properties in adolescent compared with middle‐aged athletes featuring long‐term musculotendinous adaptations. Nineteen adolescent elite volleyball athletes (A), 15.9 ± 0.6 years and 18 middle‐aged competitively active former elite volleyball athletes (MA), 46.9 ± 0.6 years participated in magnetic resonance imaging and ultrasound‐dynamometry sessions to determine quadriceps femoris muscle strength, vastus lateralis morphology and patellar tendon mechanical and morphological properties. There was no significant age effect on the physiological cross‐sectional area of the vastus lateralis and maximum knee extension moment (P > 0.05) during voluntary isometric contractions. However, the patellar tendon cross‐sectional area was significantly smaller (A: 107.4 ± 27.5 mm2; MA: 121.7 ± 39.8 mm2) and the tendon stress during the maximal contractions was significantly higher in adolescent compared with the middle‐aged athletes (A: 50.0 ± 10.1 MPa; MA: 40.0 ± 9.5 MPa). These findings provide evidence of an imbalanced development of muscle strength and tendon mechanical and morphological properties in adolescent athletes, which may have implications for the risk of tendon overuse injuries.
Functional imaging by thoracic electrical impedance tomography (EIT) is a non-invasive approach to continuously assess central stroke volume variation (SVV) for guiding fluid therapy. The early ...available data were from healthy lungs without injury-related changes in thoracic impedance as a potentially influencing factor. The aim of this study was to evaluate SVV measured by EIT (SVVEIT) against SVV from pulse contour analysis (SVVPC) in an experimental animal model of acute lung injury at different lung volumes.
We conducted a randomized controlled trial in 30 anaesthetized domestic pigs. SVVEIT was calculated automatically analysing heart–lung interactions in a set of pixels representing the aorta. Each initial analysis was performed automatically and unsupervised using predefined frequency domain algorithms that had not previously been used in the study population. After baseline measurements in normal lung conditions, lung injury was induced either by repeated broncho-alveolar lavage (n=15) or by intravenous administration of oleic acid (n=15) and SVVEIT was remeasured.
The protocol was completed in 28 animals. A total of 123 pairs of SVV measurements were acquired. Correlation coefficients (r) between SVVEIT and SVVPC were 0.77 in healthy lungs, 0.84 after broncho-alveolar lavage, and 0.48 after lung injury from oleic acid.
EIT provides automated calculation of a dynamic preload index of fluid responsiveness (SVVEIT) that is non-invasively derived from a central haemodynamic signal. However, alterations in thoracic impedance induced by lung injury influence this method.
Myeloid-derived suppressor cells (MDSCs) are an immature innate cell population that expands in pathological conditions such as cancer and suppresses T cells via production of immunosuppressive ...factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs) to cross-present tumor antigens to CD8+ T cells, a process that requires a specific subtype of dendritic cells (DCs) called conventional DC1 (cDC1) which are often dysfunctional in cancer. One way to activate cDC1 is ligation of CD40 which is abundantly expressed by myeloid cells and its agonism leads to myeloid cell activation. Thus, targeting MDSCs while simultaneously expanding cross-presenting DCs represents a promising strategy that, when combined with agonistic CD40, may result in long-lasting protective immunity. In this study, we investigated the effect of PKC agonists PEP005 and prostratin on MDSC expansion, differentiation, and recruitment to the tumor microenvironment. Our findings demonstrate that PKC agonists decreased MDSC expansion from hematopoietic progenitors and induced M-MDSC differentiation to an APC-like phenotype that expresses cDC1-related markers via activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Simultaneously, PKC agonists favored cDC1 expansion at the expense of cDC2 and plasmacytoid DCs (pDC). Functionally, PKC agonists blunted MDSC suppressive activity and enhanced MDSC cross-priming capacity both in vitro and in vivo. Finally, combination of PKC agonism with agonistic CD40 mAb resulted in a marked reduction in tumor growth with a significant increase in intratumoral activated CD8+ T cells and tissue-resident memory CD8+ T cells in a syngeneic breast cancer mouse model. In sum, this work proposes a novel promising strategy to simultaneously target MDSCs and promote APC function that may have highly impactful clinical relevance in cancer patients.
Overview figure: PKC agonism decreases MDSC and increases cDC1 expansion from the bone marrow, induces M-MDSC differentiation to CD103+ DC-like cells that can cross-prime CD8+ T cells, and synergizes with agonistic CD40 mAb therapy to increase intratumoral activated CD8+ T cells, thus resulting in blunting of tumor growth. Display omitted
•PKC agonism suppresses murine breast cancer tumor growth in vivo.•PKC agonism impairs MDSC expansion, trafficking, and suppressive capacity and favors cDC1 expansion.•PKC agonism induces M-MDSC differentiation to cross-presenting DC-like cells via activation of the p38 MAPK pathway.•Combination of PKC agonism and agonistic CD40 synergistically promotes activation of intratumoral CD8+ T cells and tissue-resident memory CD8+ T cells (Trm) in vivo.
Context. For many years, there seemed to be significant differences between the continuum intensity distributions derived from observations and simulations of the solar photosphere. Aims. In order to ...settle the discussion on these apparent discrepancies, we present a detailed comparison between simulations and seeing-free observations that takes into account the crucial influence of instrumental image degradation. Methods. We use a set of images of quiet Sun granulation taken in the blue, green and red continuum bands of the Broadband Filter Imager of the Solar Optical Telescope (SOT) onboard Hinode. The images are deconvolved with point spread functions (PSF) that account for non-ideal contributions due to instrumental stray-light and imperfections. In addition, synthetic intensity images are degraded with the corresponding PSFs. The results are compared with respect to spatial power spectra, intensity histograms, and the centre-to-limb variation of the intensity contrast. Results. The intensity distribution of SOT granulation images is broadest for the blue continuum at disc-centre and narrows towards the limb and for longer wavelengths. The distributions are relatively symmetric close to the limb but exhibit a growing asymmetry towards disc-centre. The intensity contrast, which is connected to the width of the distribution, is found to be (12.8 ± 0.5)%, (8.3 ± 0.4)%, and (6.2 ± 0.2)% at disc-centre for blue, green, and red continuum, respectively. Removing the influence of the PSF unveils much broader intensity distributions with a secondary component that is otherwise only visible as an asymmetry between the darker and brighter than average part of the distribution. The contrast values increase to (26.7 ± 1.3)%, (19.4 ± 1.4)%, and (16.6 ± 0.7)% for blue, green, and red continuum, respectively. The power spectral density of the images exhibits a pronounced peak at spatial scales characteristic for the granulation pattern and a steep decrease towards smaller scales. The observational findings like the absolute values and centre-to-limb variation of the intensity contrast, intensity histograms, and power spectral density are well matched with corresponding synthetic observables from three-dimensional radiation (magneto-)hydrodynamic simulations. Conclusions. We conclude that the intensity contrast of the solar continuum intensity is higher than usually derived from ground-based observations and is well reproduced by modern radiation (magneto-)hydrodynamic models. Properly accounting for image degradation effects is of crucial importance for comparisons between observations and numerical models.
Aim
To evaluate the effectiveness of direct pulp capping under general practice conditions. It was hypothesized that direct pulp capping is an effective procedure in the majority of cases and ...prevents the need for root canal treatment or extraction.
Methodology
Claims data were collected from the digital database of a major German national health insurance company. Only patients who had been insurance members for the entire 3 year period 2010 to 2012 were eligible. Kaplan–Meier survival analyses were conducted for all teeth with direct pulp capping. Success was defined as not undergoing root canal treatment. Survival was defined as not undergoing extraction. Differences between survival functions were tested with the log rank test.
Results
A total of 148 312 teeth were included. The overall success rate was 71.6% at 3 years. The overall survival rate was 95.9% at 3 years. The success rates for single‐rooted teeth (71.8%) and multirooted teeth (71.5%) were similar although significantly different (P < 0.001). Best 3‐year success rates were found at low (79.7%; <18 years.) and very high age (81.8%; >85 years.).
Conclusions
After direct pulp capping, more than two‐thirds of the affected teeth did not undergo root canal treatment within 3 years. Although this study has the typical limits of a claims data analysis, it can be concluded that direct pulp capping is an effective intervention to avoid root canal treatment and extraction in a general practice setting.
The ability to effectively increase the base of support is crucial to prevent from falling due to stability disturbances and has been commonly assessed using the forward-directed lean-and-release ...test. With this multicentre study we examined whether the assessment of stability recovery performance using two different forward lean-and-release test protocols is reliable in adults over a wide age range. Ninety-seven healthy adults (age from 21 to 80 years) were randomly assigned to one out of two lean angle protocols: gradual increase to maximal forward-lean angle (maximal lean angle; n = 43; seven participants were excluded due to marker artefacts) or predefined lean angle (single lean angle; n = 26; 21 participants needed to be excluded due to multiple stepping after release or marker artefacts). Both protocols were repeated after 0.5 h and 48 h to investigate intra- and inter-session reliability. Stability recovery performance was examined using the margin of stability at release (MoSRL) and touchdown (MoSTD) and increase in base of support (BoSTD). Intraclass correlation coefficients (confidence intervals at 95%) for the maximal lean angle and for the single lean angle were respectively 0.93 (0.89–0.96) and 0.94 (0.89–0.97) in MoSRL, 0.85 (0.77–0.91) and 0.67 (0.48–0.82) in MoSTD and 0.88 (0.81–0.93) and 0.80 (0.66–0.90) in BoSTD, with equivalence being revealed for each parameter between all three measurements (p < 0.01). We concluded that the assessment of stability recovery performance parameters in adults over a wide age range with the means of the forward lean-and-release test is reliable, independent of the used lean angle protocol.
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