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1.
mSphere ; 7(6): e0054522, 2022 12 21.
Article in English | MEDLINE | ID: mdl-36468887

ABSTRACT

White and brown rot fungi efficiently deconstruct lignocellulose in wood, Earth's largest pool of aboveground biotic carbon and an important natural resource. Despite its vital importance, little is known about the metabolomic signatures among fungal species and nutritional modes (rot types). In this study, we used GC-MS metabolomics in solid wood substrates (in planta) to compare brown rot fungi (Rhodonia placenta and Gloeophylum trabeum) and white rot fungi (Trametes versicolor and Pleurotus ostreatus) at two decay stages (earlier and later), finding identifiable patterns for brown rot fungi at later decay stages. These patterns occurred in highly reducing environments that were not observed in white rot fungi. Metabolomes measured among the two white rot fungi were notably different, but we found a potential biomarker compound, galactitol, that was characteristic to white rot taxa. In addition, we found that white rot fungi were more efficient at catabolizing phenolic compounds that were originally present in wood. Collectively, white rot fungi were characterized by measured sugar release relative to higher carbohydrate solubilization by brown rot fungi, a distinction in soluble sugar availability that might shape success in the face of "cheater" competitors. This need to protect excess free sugars may explain the differentially high brown rot fungal production of pyranones and furanones, likely linked to an expansion of polyketide synthase genes. IMPORTANCE Despite the ecological and economic importance of wood-degrading fungi, little is known about the array of metabolites that fungi produce during wood decomposition. This study provides an in-depth insight into the wood decomposition process by analyzing and comparing the changes of >100 compounds produced by fungi with metabolic distinct nutritional modes (white and brown rot fungi) at different decay stages. We found a unique pattern of metabolites that correlated well with brown rot (carbohydrate selective mode) in later decay. These compounds were in line with some of the physiochemical and genetic features previously seen in these fungi such as a faster sugar release, lower pH, and the expansion of polyketide-synthase genes compared to white rot fungi (lignin-degrading mode). This study provides spatiotemporally resolved mechanism insights as well as critical groundwork that will be valuable for studies in basic biology and ecology, as well as applied biomass deconstruction and bioremediation.


Subject(s)
Life History Traits , Wood/chemistry , Trametes , Carbohydrates , Sugars/analysis , Sugars/metabolism
3.
Nature ; 596(7871): 221-226, 2021 08.
Article in English | MEDLINE | ID: mdl-34381232

ABSTRACT

Research on magnetic confinement of high-temperature plasmas has the ultimate goal of harnessing nuclear fusion for the production of electricity. Although the tokamak1 is the leading toroidal magnetic-confinement concept, it is not without shortcomings and the fusion community has therefore also pursued alternative concepts such as the stellarator. Unlike axisymmetric tokamaks, stellarators possess a three-dimensional (3D) magnetic field geometry. The availability of this additional dimension opens up an extensive configuration space for computational optimization of both the field geometry itself and the current-carrying coils that produce it. Such an optimization was undertaken in designing Wendelstein 7-X (W7-X)2, a large helical-axis advanced stellarator (HELIAS), which began operation in 2015 at Greifswald, Germany. A major drawback of 3D magnetic field geometry, however, is that it introduces a strong temperature dependence into the stellarator's non-turbulent 'neoclassical' energy transport. Indeed, such energy losses will become prohibitive in high-temperature reactor plasmas unless a strong reduction of the geometrical factor associated with this transport can be achieved; such a reduction was therefore a principal goal of the design of W7-X. In spite of the modest heating power currently available, W7-X has already been able to achieve high-temperature plasma conditions during its 2017 and 2018 experimental campaigns, producing record values of the fusion triple product for such stellarator plasmas3,4. The triple product of plasma density, ion temperature and energy confinement time is used in fusion research as a figure of merit, as it must attain a certain threshold value before net-energy-producing operation of a reactor becomes possible1,5. Here we demonstrate that such record values provide evidence for reduced neoclassical energy transport in W7-X, as the plasma profiles that produced these results could not have been obtained in stellarators lacking a comparably high level of neoclassical optimization.

4.
Phys Rev Lett ; 127(26): 269902, 2021 Dec 24.
Article in English | MEDLINE | ID: mdl-35029505

ABSTRACT

Retraction of DOI: 10.1103/PhysRevLett.102.197002.

5.
Nanotechnology ; 31(29): 294003, 2020 May 01.
Article in English | MEDLINE | ID: mdl-32213675

ABSTRACT

We report a novel mechanism that allows the incorporation of Si into GaN nanowires up to and beyond the solubility limit. This mechanism is documented during the growth on vicinal (misoriented) SiC/Si hybrid substrates having the step bunches. Nanowires that are grown at these locations become heavily Si doped. Such high Si concentrations were verified by secondary-ion mass spectrometry. Photoluminescence data also point to very high carrier concentrations. Moreover, Raman spectroscopy together with quantum chemical modelling shows the build up of Si into Ga sites and indicates even the possibility of the formation of a Ga(Si)N solid solution. The microscopic mechanism responsible for heavy doping and even alloying is diffusion driven by the mechano-chemical effect, which allows for the extremely efficient injection of Si atoms into the nanowires from the step bunches at the vicinal SiC/Si substrates.

6.
Semin Musculoskelet Radiol ; 23(2): e36-e55, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30925633

ABSTRACT

Radiologists should be familiar with basic principles of fracture fixation and the normal imaging appearances of implant constructs and their complications. The surgeon's selection of external fixation, intramedullary nail fixation, open reduction and internal fixation, or some combination depends on patient factors, fracture configuration, injury to the soft tissue envelope, and surgeon experience. Complications including loss of fixation with resultant malalignment, nonunion, infection, and posttraumatic osteoarthritis present additional challenges for the surgeon as well as the radiologist. This article reviews the rationale behind fracture fixation in fractures of the lower leg, ankle, and foot. Examples of postoperative complications are also reviewed.


Subject(s)
Ankle Injuries/diagnostic imaging , Ankle Injuries/surgery , Foot Bones/diagnostic imaging , Foot Bones/injuries , Foot Bones/surgery , Fracture Fixation, Internal/methods , Fractures, Bone/diagnostic imaging , Fractures, Bone/surgery , Internal Fixators , Postoperative Complications/diagnostic imaging , Tibial Fractures/diagnostic imaging , Tibial Fractures/surgery , Fracture Fixation, Internal/instrumentation , Humans , Prosthesis Design , Prosthesis Failure , Reoperation
7.
Rev Sci Instrum ; 89(7): 073505, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30068134

ABSTRACT

We present a detailed overview and first results of the new laser blow-off system on the stellarator Wendelstein 7-X. The system allows impurity transport studies by the repetitive and controlled injection of different tracer ions into the plasma edge. A Nd:YAG laser is used to ablate a thin metal film, coated on a glass plate, with a repetition rate of up to 20 Hz. A remote-controlled adjustable optical system allows the variation of the laser spot diameter and enables the spot positioning to non-ablated areas on the target between laser pulses. During first experiments, clear spectral lines from higher ionization stages of the tracer ions have been observed in the X-ray to the extreme ultraviolet spectral range. The temporal behavior of the measured emission allows the estimate of transport properties, e.g., impurity transport times in the order of 100 ms. Although the strong injection of impurities is well detectable, the global plasma parameters are barely changed.

8.
Phys Rev Lett ; 121(3): 037004, 2018 Jul 20.
Article in English | MEDLINE | ID: mdl-30085803

ABSTRACT

Ytterbium (Yb) metal is divalent and nonmagnetic (4f^{14} configuration). Under pressure its valence increases significantly leading to the expectation that magnetic instabilities and other highly correlated electron effects may appear before a stable trivalent state is reached (4f^{13} configuration). We carried out electrical resistivity and ac magnetic susceptibility measurements to 179 GPa over the temperature range 1.4-295 K. No evidence for magnetic order is observed. However, Yb becomes a superconductor at 86 GPa with T_{c}≃1.4 K, increasing to 4.6 K at 179 GPa. X-ray absorption spectroscopy shows that Yb remains mixed valent to at least 125 GPa, pointing to an active role of f electrons in the emergence of superconductivity in this simple, elemental solid.

9.
Br J Anaesth ; 120(4): 745-760, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29576115

ABSTRACT

BACKGROUND: Exposure of the developing brain to propofol results in cognitive deficits. Recent data suggest that inhibition of neuronal apoptosis does not prevent cognitive defects, suggesting mechanisms other than neuronal apoptosis play a role in anaesthetic neurotoxicity. Proper neuronal growth during development is dependent upon growth cone morphology and axonal transport. Propofol modulates actin dynamics in developing neurones, causes RhoA-dependent depolymerisation of actin, and reduces dendritic spines and synapses. We hypothesised that RhoA inhibition prevents synaptic loss and subsequent cognitive deficits. The present study tested whether RhoA inhibition with the botulinum toxin C3 (TAT-C3) prevents propofol-induced synapse and neurite loss, and preserves cognitive function. METHODS: RhoA activation, growth cone morphology, and axonal transport were measured in neonatal rat neurones (5-7 days in vitro) exposed to propofol. Synapse counts (electron microscopy), dendritic arborisation (Golgi-Cox), and network connectivity were measured in mice (age 28 days) previously exposed to propofol at postnatal day 5-7. Memory was assessed in adult mice (age 3 months) previously exposed to propofol at postnatal day 5-7. RESULTS: Propofol increased RhoA activation, collapsed growth cones, and impaired retrograde axonal transport of quantum dot-labelled brain-derived neurotrophic factor, all of which were prevented with TAT-C3. Adult mice previously treated with propofol had decreased numbers of total hippocampal synapses and presynaptic vesicles, reduced hippocampal dendritic arborisation, and infrapyramidal mossy fibres. These mice also exhibited decreased hippocampal-dependent contextual fear memory recall. All anatomical and behavioural changes were prevented with TAT-C3 pre-treatment. CONCLUSION: Inhibition of RhoA prevents propofol-mediated hippocampal neurotoxicity and associated cognitive deficits.


Subject(s)
Axonal Transport/drug effects , Behavior, Animal/drug effects , Growth Cones/drug effects , Propofol , Synapses/drug effects , rhoA GTP-Binding Protein/antagonists & inhibitors , Animals , Botulinum Toxins , Brain/drug effects , Disease Models, Animal , Hypnotics and Sedatives , Male , Mice , Mice, Inbred C57BL , Neurons/drug effects , Neurotoxicity Syndromes , Rats , Rats, Sprague-Dawley , rhoA GTP-Binding Protein/genetics
10.
Br J Anaesth ; 119(3): 465-471, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28969308

ABSTRACT

BACKGROUND: Isoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. METHODS: Neonatal mouse pups were pretreated with either TAT-Pep5 (25 µl, 10 µM i.p.) or a scrambled control peptide (TAT-ctrl; 25 µl, 10 µM i.p.) prior to isoflurane exposure (1.4%; 4 h) or control ( n = 15-26/group). Three to 5 months after exposure, behavioural testing and endpoint assays [brain volume (stereology) and immunoblotting] were performed. RESULTS: No significant difference was observed in open field, T-maze, balance beam or wire-hanging testing. The Barnes maze revealed a significant effect of isoflurane ( P = 0.019) in errors to find the escape tunnel during the day 5 probe trial, a finding indicative of impaired short-term spatial memory. No difference was found for brain volumes or protein expression. TAT-Pep5 treatment did not reverse the effects of isoflurane on neurocognitive behaviour. CONCLUSION: A single isoflurane exposure to early post-natal mice caused a hippocampal-dependent memory deficit that was not prevented by pre-administration of TAT-Pep5, although TAT-Pep5, an inhibitor of p75NTR, has been shown to reduce isoflurane-induced apoptosis. These findings suggest that neuronal apoptosis is not requisite for the development of cognitive deficits in the adults attendant with neonatal anaesthetic exposure.


Subject(s)
Anesthetics, Inhalation/adverse effects , Cognition Disorders/chemically induced , Isoflurane/adverse effects , Receptor, Nerve Growth Factor/antagonists & inhibitors , Animals , Animals, Newborn , Disease Models, Animal , Female , Immunoblotting , Male , Maze Learning/drug effects , Mice , Mice, Inbred C57BL
11.
Rev. cient. odontol ; 3(2): 364-371, jul.-dic. 2015. ilus
Article in Spanish | LILACS, LIPECS | ID: biblio-1006815

ABSTRACT

La displasia fibrosa es una lesión congénita, lentamente progresiva que puede provocar graves alteraciones morfológicas y funcionales, y estar sujeta a complicaciones de tipo infeccioso. En este reporte de caso se presenta a un paciente masculino de 8 años de edad diagnosticado con una displasia fibrosa madura luego de un hallazgo incidental durante un examen de rutina, el paciente durante el curso de los últimos cinco años ha presentado osteomielitis a repetición en el sitio de biopsia y de exfoliación dentaría, el cuadro clínico se ha tratado mediante curetajes y aseos quirúrgicos y con la indicación antibiótica de clindamicina sin resultados positivos. Se concluye que el manejo de las displasias fibrosas maduras puede ser difícil una vez que se ha instalado un proceso infeccioso crónico sin poder dar de alta al paciente, manteniéndolo permanentemente en control. (AU)


Fibrous dysplasia is a slowly progressive congenital lesion that can cause serious morphological and functional alterations , and complications of infectious type . This case report presents a 8 years old male patient diagnosed with a mature fibrous dysplasia after an incidental finding during a routine examination, the patient during the course of the last five years has been presented recurrent osteomyelitis episodes in the biopsy site and temporal tooth during exfoliation, it has been treated by surgical curettage and clindamycin with no positive results. We conclude that the management of mature fibrous dysplasia can be difficult once a chronic infectious process has been installed without being able to discharge the patient, constantly keeping it in control.(AU)


Subject(s)
Humans , Male , Child , Osteomyelitis/complications , Clindamycin/therapeutic use , Fibrous Dysplasia of Bone/diagnosis , Fibrous Dysplasia of Bone/therapy
12.
Sci Total Environ ; 536: 130-141, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26204049

ABSTRACT

Analysis of soil C and O horizon samples in a recent regional geochemical survey of Nord-Trøndelag, central Norway (752 sample sites covering 25,000 km2), identified a strong enrichment of several potentially toxic elements (PTEs) in the O horizon. Of 53 elements analysed in both materials, Cd concentrations are, on average, 17 times higher in the O horizon than in the C horizon and other PTEs such as Ag (11-fold), Hg (10-fold), Sb (8-fold), Pb (4-fold) and Sn (2-fold) are all strongly enriched relative to the C horizon. Geochemical maps of the survey area do not reflect an impact from local or distant anthropogenic contamination sources in the data for O horizon soil samples. The higher concentrations of PTEs in the O horizon are the result of the interaction of the underlying geology, the vegetation zone and type, and climatic effects. Based on the general accordance with existing data from earlier surveys in other parts of northern Europe, the presence of a location-independent, superordinate natural trend towards enrichment of these elements in the O horizon relative to the C horizon soil is indicated. The results imply that the O and C horizons of soils are different geochemical entities and that their respective compositions are controlled by different processes. Local mineral soil analyses (or published data for the chemical composition of the average continental crust) cannot be used to provide a geochemical background for surface soil. At the regional scale used here surface soil chemistry is still dominated by natural sources and processes.


Subject(s)
Environmental Monitoring , Forests , Hazardous Substances/analysis , Soil Pollutants/analysis , Norway , Soil/chemistry
13.
Exp Clin Endocrinol Diabetes ; 123(7): 398-404, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26011174

ABSTRACT

In this study we investigated changes of serum leptin in 74 newborn lambs and associations with environmental temperature (from - 8°C to + 25°C), body temperature, and concentrations of plasma lipids, 3-beta-hydroxybutyric acid and blood glucose. A leptin radioimmunoassay was established, using an antiserum (rabbit) produced against a partial sequence of ovine leptin (31-44). Before measurement, serum samples were denatured. The sensitivity of the assay was 0.4 µg l(-1) and intra- and interassay coefficients of variation were 5.1% and 2.5%, respectively. Blood samples were collected immediately after birth up to 24 h postnatally (pn). Median leptin concentrations at birth and 24 h pn were 20.9 and 52.7 µg l(-1), respectively. Because of non-normal distribution, leptin concentrations were converted to log(leptin) before further statistical processing. The change in log(leptin) during the first 24 h was highly significant (p<0.0001). Correlation analysis showed significant associations between serum leptin and the following variables: environmental temperature 24 h pn (r=0.34, p<0.005), log(plasma triglycerides) 24 h pn (r=0.50, p<0.001), log(plasma 3-beta-hydroxybutyric acid) 24 h pn (r=-0.50, p<0.001), blood glucose 6 h pn (r=0.43, p<0.001) and plasma cholesterol 12 h pn (r=0.38, p=0.001). We conclude that this radioimmunoassay is suited to measure total serum ovine leptin and that total leptin is already regulated in the very early postnatal phase. Leptin is increased at higher environmental temperatures, consistent with leptin's suppressive effect on energy expenditure and appetite. Furthermore, leptin levels are associated with plasma concentrations of lipids and lipid metabolites.


Subject(s)
3-Hydroxybutyric Acid/blood , Blood Glucose , Body Temperature/physiology , Cholesterol/blood , Leptin/blood , Temperature , Triglycerides/blood , Animals , Animals, Newborn/blood , Female , Male , Radioimmunoassay , Sheep
14.
Orthod Craniofac Res ; 18 Suppl 1: 18-28, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25865530

ABSTRACT

OBJECTIVES: To investigate the 3D morphological variations in 169 temporomandibular ioint (TMJ) condyles, using novel imaging statistical modeling approaches. SETTING AND SAMPLE POPULATION: The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Cone beam CT scans were acquired from 69 subjects with long-term TMJ osteoarthritis (OA, mean age 39.1±15.7 years), 15 subjects at initial consult diagnosis of OA (mean age 44.9±14.8 years), and seven healthy controls (mean age 43±12.4 years). MATERIALS AND METHODS: 3D surface models of the condyles were constructed, and homologous correspondent points on each model were established. The statistical framework included Direction-Projection-Permutation (DiProPerm) for testing statistical significance of the differences between healthy controls and the OA groups determined by clinical and radiographic diagnoses. RESULTS: Condylar morphology in OA and healthy subjects varied widely with categorization from mild to severe bone degeneration or overgrowth. DiProPerm statistics supported a significant difference between the healthy control group and the initial diagnosis of OA group (t=6.6, empirical p-value=0.006) and between healthy and long-term diagnosis of OA group (t=7.2, empirical p-value=0). Compared with healthy controls, the average condyle in OA subjects was significantly smaller in all dimensions, except its anterior surface, even in subjects with initial diagnosis of OA. CONCLUSION: This new statistical modeling of condylar morphology allows the development of more targeted classifications of this condition than previously possible.


Subject(s)
Cone-Beam Computed Tomography/statistics & numerical data , Image Processing, Computer-Assisted/statistics & numerical data , Imaging, Three-Dimensional/statistics & numerical data , Osteoarthritis/diagnostic imaging , Temporomandibular Joint Disorders/diagnostic imaging , Adult , Anatomic Landmarks/diagnostic imaging , Ankylosis/diagnostic imaging , Bone Resorption/diagnostic imaging , Computer Simulation/statistics & numerical data , Humans , Mandibular Condyle/diagnostic imaging , Middle Aged , Models, Anatomic , Principal Component Analysis , Temporomandibular Joint/diagnostic imaging , Young Adult
15.
Mucosal Immunol ; 8(6): 1388-99, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25669147

ABSTRACT

Urinary tract infections (UTIs) are frequent, commonly recurrent, and costly. Deficiency in a key autophagy protein, ATG16L1, protects mice from infection with the predominant bacterial cause of UTIs, Uropathogenic E. coli (UPEC). Here, we report that loss of ATG16L1 in macrophages accounts for this protective phenotype. Compared with wild-type macrophages, macrophages deficient in ATG16L1 exhibit increased uptake of UPEC and enhanced secretion of interleukin-1ß (IL-1ß). The increased IL-1ß production is dependent upon activation of the NLRP3 inflammasome and caspase-1. IL-1ß secretion was also enhanced during UPEC infection of ATG16L1-deficient mice in vivo, and inhibition of IL-1ß signaling abrogates the ATG16L1-dependent protection from UTIs. Our results argue that ATG16L1 normally suppresses a host-protective IL-1ß response to UPEC by macrophages.


Subject(s)
Carrier Proteins/immunology , Escherichia coli Infections/immunology , Interleukin-1beta/immunology , Macrophages/immunology , Urinary Tract Infections/immunology , Animals , Autophagy-Related Proteins , Blotting, Western , Carrier Proteins/genetics , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Female , Flow Cytometry , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Polymerase Chain Reaction , Uropathogenic Escherichia coli/immunology
16.
Osteoarthritis Cartilage ; 22(10): 1657-67, 2014 Oct.
Article in English | MEDLINE | ID: mdl-25278075

ABSTRACT

OBJECTIVE: To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA). DESIGN: Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology. RESULTS: Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFßb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls. CONCLUSIONS: Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFß1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.


Subject(s)
Inflammation Mediators/metabolism , Osteoarthritis/diagnostic imaging , Synovial Fluid/metabolism , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint/diagnostic imaging , Adult , Biomarkers/metabolism , Bone Resorption/diagnostic imaging , Bone Resorption/etiology , Case-Control Studies , Cone-Beam Computed Tomography , Female , Humans , Imaging, Three-Dimensional , Middle Aged , Osteoarthritis/complications , Temporomandibular Joint Disorders/complications , Young Adult
17.
Ann Oncol ; 25(12): 2363-2372, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25223482

ABSTRACT

BACKGROUND: The GeparQuinto study showed that adding bevacizumab to 24 weeks of anthracycline-taxane-based neoadjuvant chemotherapy increases pathological complete response (pCR) rates overall and specifically in patients with triple-negative breast cancer (TNBC). No difference in pCR rate was observed for adding everolimus to paclitaxel in nonearly responding patients. Here, we present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1948) with HER2-negative tumors of a median tumor size of 4 cm were randomly assigned to neoadjuvant treatment with epirubicin/cyclophosphamide followed by docetaxel (EC-T) with or without eight infusions of bevacizumab every 3 weeks before surgery. Patients without clinical response to EC ± Bevacizumab were randomized to 12 weekly cycles paclitaxel with or without everolimus 5 mg/day. To detect a hazard ratio (HR) of 0.75 (α = 0.05, ß = 0.8) 379 events had to be observed in the bevacizumab arms. RESULTS: With a median follow-up of 3.8 years, 3-year DFS was 80.8% and 3-year OS was 89.7%. Outcome was not different for patients receiving bevacizumab (HR 1.03; P = 0.784 for DFS and HR 0.974; P = 0.842 for OS) compared with patients receiving chemotherapy alone. Patients with TNBC similarly showed no improvement in DFS (HR = 0.99; P = 0.941) and OS (HR = 1.02; P = 0.891) when treated with bevacizumab. No other predefined subgroup (HR+/HER2-; locally advanced (cT4 or cN3) or not; cT1-3 or cT4; pCR or not) showed a significant benefit. No difference in DFS (HR 0.997; P = 0.987) and OS (HR 1.11; P = 0.658) was observed for nonearly responding patients receiving paclitaxel with or without everolimus overall as well as in subgroups. CONCLUSIONS: Long-term results, in opposite to the results of pCR, do not support the neoadjuvant use of bevacizumab in addition to an anthracycline-taxane-based chemotherapy or everolimus in addition to paclitaxel for nonearly responding patients. CLINICAL TRIAL NUMBER: NCT 00567554, www.clinicaltrials.gov.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Breast Neoplasms/drug therapy , Sirolimus/analogs & derivatives , Adult , Angiogenesis Inhibitors/administration & dosage , Antibodies, Monoclonal, Humanized/administration & dosage , Bevacizumab , Breast Neoplasms/metabolism , Chemotherapy, Adjuvant , Drug Therapy, Combination , Everolimus , Female , Humans , Middle Aged , Receptor, ErbB-2/metabolism , Sirolimus/administration & dosage , Sirolimus/therapeutic use , Survival Analysis
18.
Dentomaxillofac Radiol ; 43(1): 20130273, 2014.
Article in English | MEDLINE | ID: mdl-24170802

ABSTRACT

OBJECTIVES: To investigate the reliability of regional three-dimensional registration and superimposition methods for assessment of temporomandibular joint condylar morphology across subjects and longitudinally. METHODS: The sample consisted of cone beam CT scans of 36 patients. The across-subject comparisons included 12 controls, mean age 41.3 ± 12.0 years, and 12 patients with temporomandibular joint osteoarthritis, mean age 41.3 ± 14.7 years. The individual longitudinal assessments included 12 patients with temporomandibular joint osteoarthritis, mean age 37.8 ± 16.7 years, followed up at pre-operative jaw surgery, immediately after and one-year post-operative. Surface models of all condyles were constructed from the cone beam CT scans. Two previously calibrated observers independently performed all registration methods. A landmark-based approach was used for the registration of across-subject condylar models, and temporomandibular joint osteoarthritis vs control group differences were computed with shape analysis. A voxel-based approach was used for registration of longitudinal scans calculated x, y, z degrees of freedom for translation and rotation. Two-way random intraclass correlation coefficients tested the interobserver reliability. RESULTS: Statistically significant differences between the control group and the osteoarthritis group were consistently located on the lateral and medial poles for both observers. The interobserver differences were ≤0.2 mm. For individual longitudinal comparisons, the mean interobserver differences were ≤0.6 mm in translation errors and 1.2° in rotation errors, with excellent reliability (intraclass correlation coefficient >0.75). CONCLUSIONS: Condylar registration for across-subjects and longitudinal assessments is reliable and can be used to quantify subtle bony differences in the three-dimensional condylar morphology.


Subject(s)
Cone-Beam Computed Tomography/methods , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Mandibular Condyle/diagnostic imaging , Temporomandibular Joint/diagnostic imaging , Adult , Anatomic Landmarks/diagnostic imaging , Computer Graphics , Computer Simulation , Cone-Beam Computed Tomography/statistics & numerical data , Follow-Up Studies , Humans , Image Processing, Computer-Assisted/statistics & numerical data , Longitudinal Studies , Mandibular Condyle/surgery , Models, Anatomic , Observer Variation , Osteoarthritis/diagnostic imaging , Osteoarthritis/surgery , Reproducibility of Results , Software , Temporomandibular Joint/surgery , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint Disorders/surgery
19.
Vet Rec ; 171(4): 97, 2012 Jul 28.
Article in English | MEDLINE | ID: mdl-22678620

ABSTRACT

Shampoo therapy is frequently used on pruritic dogs. However, there are few double-blinded, placebo-controlled studies of this form of therapy. This randomised, double-blinded, placebo-controlled study evaluated the efficacy of a commercial medicated shampoo (DermaTopic; Almapharm) containing chlorhexidine, lactoferrin, piroctone olamine, chitosan and essential fatty acids in 27 dogs with mild to moderate allergic pruritus without secondary skin infections. All dogs received shampoo therapy with either DermaTopic or a shampoo vehicle as placebo twice weekly for four weeks. The extent of pruritus was evaluated before the study and then on a daily basis by the owners using a visual analogue scale. Before beginning the treatment and after four weeks, the skin lesions were evaluated by an experienced clinician with a validated lesion score (Canine Atopic Dermatitis Extent and Severity Index - CADESI). The pruritus was reduced significantly by both DermaTopic and placebo. However, there was no significant difference between both groups. There was no statistically significant difference in the CADESI scores pre- and post-treatment in either group or between the two types of treatment. This study provides further evidence of the benefit of shampoo therapy for pruritic dogs.


Subject(s)
Dermatologic Agents/administration & dosage , Dog Diseases/therapy , Hair Preparations/therapeutic use , Pruritus/veterinary , Administration, Cutaneous , Animals , Dermatitis, Atopic/therapy , Dermatitis, Atopic/veterinary , Dogs , Double-Blind Method , Female , Food Hypersensitivity/therapy , Food Hypersensitivity/veterinary , Hypersensitivity, Immediate/therapy , Hypersensitivity, Immediate/veterinary , Male , Pruritus/therapy , Severity of Illness Index , Treatment Outcome
20.
Phys Rev Lett ; 104(5): 057004, 2010 Feb 05.
Article in English | MEDLINE | ID: mdl-20366788

ABSTRACT

In those cases where charge-stripe order has been observed in cuprates, the crystal structure is such that the average rotational symmetry of the CuO2 planes is reduced from fourfold to twofold. As a result, one could argue that the reduced lattice symmetry is essential to the existence of stripe order. We use pressure to restore the average fourfold symmetry in a single crystal of La1.875Ba0.125CuO4, and show by x-ray diffraction that charge-stripe order still occurs. Thus, electronically driven stripe order can spontaneously break the lattice symmetry.

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