Effects of electronic correlation on X-Ray absorption and dichroic spectra at L2,3_{2,3} edge

We present a new theoretical approach to describe X-Ray absorption and Magnetic Circular Dichroism spectra in the presence of e-e correlation. Our approach provides an unified picture to include correlations in both charged and neutral excitations, namely in direct / inversion photoemission where electrons are removed/added, and photo absorption where electrons are promoted from core levels to empty states. We apply this approach to the prototypical case of L$_{2,3}$ edge of 3$d$ transition metals and we show that the inclusion of many body effects in the core level excitations is essential to reproduce, together with satellite structures in core level photoemission, the observed asymmetric line shapes in X-ray absorption and dichroic spectra.Comment: 3 figures, 5 pages, submitted to Phys. Rev.

Long-term cognitive and behavioral therapies, combined with augmentative communication, are related to uncinate fasciculus integrity in autism

Recent evidence points to white-matter abnormalities as a key factor in autism physiopathology. Using Diffusion Tensor Imaging, we studied white-matter structural properties in a convenience sample of twenty-two subjects with low-functioning autism exposed to long-term augmentative and alternative communication, combined with sessions of cognitive and behavioral therapy. Uncinate fasciculus structural properties correlated significantly with therapy length and early onset, as well as to clinical outcome, independently from IQ, age or symptoms severity at therapy onset. Moreover, adherence to therapy was linked with better clinical outcome and uncinate fasciculus structural integrity. The results point to the capability of a long-term rehabilitation of subjects with low-functioning autism to produce white-matter structural modifications, which could thus play a role in the rehabilitative outcome

Technology Review of Nondestructive Methods for Examination of Water Intrusion Areas on Hanford’s Double-Shell Waste Tanks

Under a contract with CH2M Hill Hanford Group, Inc., PNNL has performed a review of the NDE technology and methods for examination of the concrete dome structure of Hanford’s double-shell tanks. The objective was to provide a matrix of methodologies that could be evaluated based on applicability, ease of deployment, and results that could provide information that could be used in the ongoing structural analysis of the tank dome. PNNL performed a technology evaluation with the objective of providing a critical literature review for all applicable technologies based on constraints provided by CH2M HILL. These constraints were not mandatory, but were desired. These constraints included performing the evaluation without removing any soil from the top of the tank, or if necessary, requesting that the hole diameter needed to gain access to evaluate the top of the tank structure to be no greater than approximately 12-in. in diameter. PNNL did not address the details of statistical sampling requirements as they depend on an unspecified risk tolerance. PNNL considered these during the technology evaluation and have reported the results in the remainder of this document. Many of the basic approaches to concrete inspection that were reviewed in previous efforts are still in use. These include electromagnetic, acoustic, radiographic, etc. The primary improvements in these tools have focused on providing quantitative image reconstruction, thus providing inspectors and analysts with three-dimensional data sets that allow for operator visualization of relevant abnormalities and analytical integration into structural performance models. Available instruments, such as radar used for bridge deck inspections, rely on post-processing algorithms and do not provide real-time visualization. Commercially available equipment only provides qualitative indications of relative concrete damage. It cannot be used as direct input for structural analysis to assess fitness for use and if necessary to de-rate critical components. There are currently no tools that automatically convert the NDE data to formats compatible with structural analysis programs. While radiographic techniques still provide significant advantages in spatial resolution, non-ionizing techniques are still preferred. Radar imagining in the 1–5 GHz has become the most useful. Unfortunately the algorithms and underlying assumptions used in these reconstructions are proprietary, and it is not possible to assess the quality and limitations of the analytical methods used to generate the derived structural data. The hypothesis that water intrusion may contribute to potential rebar corrosion of the tank domes provided the primary guidance in reviewing and evaluating available NDE technologies. Of primary concern is the need to employ technologies that provide the best opportunity for visualizing the rebar and providing quantitative data that can be integrated into structural analysis efforts to better understand and quantify the structural capacity of the domes. The conclusion is that an imaging system capable of locating and quantifying the distribution and conditions of the cement, aggregate, and rebar will provide the most valuable baseline upon which to build a case for the integrity of the structure. If successful, such a system would fulfill the need to incorporate valuable data into current structural load capacity analysis

Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

Total Synthesis of Asparenydiol by Two Sonogashira Cross-Coupling Reactions Promoted by Supported Pd and Cu Catalysts

Asparenydiol, which is an important natural compound with potential pharmacological activities, was synthesized through two Sonogashira cross-coupling reactions catalyzed by supported Pd and Cu catalysts and by a Mitsunobu etherification. The optimization of the Sonogashira couplings allowed the use of catalysts supported on different matrices with good results in terms of catalytic efficiency and yields

Bone-Anchored Hearing Aids Fitted According to NAL and DSL Procedures in Adults with Mixed Hearing Loss

BACKGROUND: Bone-anchored hearing aids represent a valid alternative for patients with conductive/mixed hearing loss who cannot use hearing aids. To date, these devices have given good audiological results, thanks to various fitting prescription programs (i.e., National Acoustic Laboratories and Desired Sensation Level). The aim of this study is to compare 2 types of fitting algorithms (National Acoustic Laboratories and Desired Sensation Level) implemented for bone-anchored hearing devices. METHODS: We retrospectively enrolled 10 patients followed at our operative unit, suffering from bilateral symmetrical mixed hearing loss and who underwent bone-anchored hearing aid implantation. All patients experienced each prescriptive procedure, National Acoustic Laboratories and Desired Sensation Level, for 7 months (on average), and they were subjected to audiological tests and questionnaires to evaluate the best program. RESULTS: National Acoustic Laboratories and Desired Sensation Level prescriptions yielded similar results. Desired Sensation Level allowed less amplification of the low frequencies than the National Acoustic Laboratories prescription, and these differences were the only statistically significant. Desired Sensation Level allowed better disyllabic word and sentence recognition scores only in quiet and not in noisy conditions. The subjective questionnaires showed similar results. At the end of the trial sessions, more patients (60%) definitively chose the Desired Sensation Level program for their device. These patients were those with a worse hearing threshold. CONCLUSION: The 2 prescriptive programs allowed similar results although patients with a worse threshold seem to prefer the DSL program. This is the first evaluation of the 2 prescriptive programs, National Acoustic Laboratories versus Desired Sensation Level, for bone conduction devices available in the literature. Further studies are needed to confirm this initial finding

Defining responders to therapies by a statistical modeling approach applied to randomized clinical trial data

Background: Personalized medicine is the tailoring of treatment to the individual characteristics of patients. Once a treatment has been tested in a clinical trial and its effect overall quantified, it would be of great value to be able to use the baseline patients' characteristics to identify patients with larger/lower benefits from treatment, for a more personalized approach to therapy. Methods: We show here a previously published statistical method, aimed at identifying patients' profiles associated to larger treatment benefits applied to three identical randomized clinical trials in multiple sclerosis, testing laquinimod vs placebo (ALLEGRO, BRAVO, and CONCERTO). We identified on the ALLEGRO patients' specific linear combinations of baseline variables, predicting heterogeneous response to treatment on disability progression. We choose the best score on the BRAVO, based on its ability to identify responders to treatment in this dataset. We finally got an external validation on the CONCERTO, testing on this new dataset the performance of the score in defining responders and non-responders. Results: The best response score defined on the ALLEGRO and the BRAVO was a linear combination of age, sex, previous relapses, brain volume, and MRI lesion activity. Splitting patients into responders and non-responders according to the score distribution, in the ALLEGRO, the hazard ratio (HR) for disability progression of laquinimod vs placebo was 0.38 for responders, HR = 1.31 for non-responders (interaction p = 0.0007). In the BRAVO, we had similar results: HR = 0.40 for responders and HR = 1.24 for non-responders (interaction p = 0.006). These findings were successfully replicated in the CONCERTO study, with HR = 0.44 for responders and HR=1.08 for non-responders (interaction p = 0.033). Conclusions: This study demonstrates the possibility to refine and personalize the treatment effect estimated in randomized studies by using the baseline demographic and clinical characteristics of the included patients. The method can be applied to any randomized trial in any medical condition to create a treatment-specific score associated to different levels of response to the treatment tested in the trial. This is an easy and affordable method toward therapy personalization, indicating patient profiles related to a larger benefit from a specific drug, which may have implications for taking clinical decisions in everyday clinical practice

Socio-demographic aspects and therapeutic pathways in patients with rheumatoid arthritis in Italy

The research carried out by Censis Foundation, in collaboration with SIR (Italian Society of Rheumatology) and ANMAR (National Association of Rheumatic patients), with the sponsorship of Roche S.p.A., involved more than 600 patients, diagnosed with arthritis by a rheumatologist according to ACR criteria. The patients were recruited through a representative sample of 300 general practitioners. A number of different research and survey tools were used to collect data, helping to identify several of the problems that affect Italian patients: a survey form to be filled by the GPs, in order to verify the diagnosis and the comorbidity level; a questionnaire for the self-assessment of the disease activity, Rheumatoid Arthritis Disease Activity Index (RADAI), and a sociological questionnaire set up for the analysis of the main aspects of the patients' path. Among the most serious criticalities found, the difficulties and the time needed for the patients to get a clear AR diagnosis, the problems in interacting with health structures, and the differences in accessing pharmaceutical therapies (only a slight majority of patients use DMARDs drugs, a small amount takes biological drugs, while a large number of patients is treated exclusively with symptomatic drugs) stand out. The differences in patients' condition appear then to be exaggerated, regarding the chances to get an early diagnosis, the access path to specialised centres, and in receiving the most appropriate treatments. Moreover, these differences appear to be strongly dependent on both the social characteristics of the patients and the supply arrangement in their area