Interpreting Attoclock Measurements of Tunnelling Times

Resolving in time the dynamics of light absorption by atoms and molecules, and the electronic rearrangement this induces, is among the most challenging goals of attosecond spectroscopy. The attoclock is an elegant approach to this problem, which encodes ionization times in the strong-field regime. However, the accurate reconstruction of these times from experimental data presents a formidable theoretical challenge. Here, we solve this problem by combining analytical theory with ab-initio numerical simulations. We apply our theory to numerical attoclock experiments on the hydrogen atom to extract ionization time delays and analyse their nature. Strong field ionization is often viewed as optical tunnelling through the barrier created by the field and the core potential. We show that, in the hydrogen atom, optical tunnelling is instantaneous. By calibrating the attoclock using the hydrogen atom, our method opens the way to identify possible delays associated with multielectron dynamics during strong-field ionization.Comment: 33 pages, 10 figures, 3 appendixe

Effect of mixture proportions on the drying shrinkage and permeation properties of high strength concrete containing class F fly ash

Sustainability of concrete can be improved by using large volume of fly ash as a replacement of cement and by ensuring improved durability of concrete. Durability of concrete containing large volume of class F fly ash is dependent on the design of mixture proportions. This paper presents an experimental study on the effect of mixture proportions on the drying shrinkage and permeation properties of high strength concrete containing large volume local class F fly ash. Concrete mixtures were designed with and without adjustments in the water to binder ratio (w/b) and the total binder content to take into account the incorporation of fly ash up to 40% of total binder. Concretes, in which the mixture proportions were adjusted for fly ash inclusion achieved equivalent strength of the control concrete and showed enhanced properties of drying shrinkage, sorptivity, water permeability and chloride penetration as compared to the control concrete. The improvement of durability properties was less significant when no adjustments were made to the w/b ratio and total binder content. The results show the necessity of the adjustments in mixture proportions of concrete to achieve improved durability properties when using class F fly ash as a cement replacement

Psychopathology predicts the outcome of medial branch blocks with corticosteroid for chronic axial low back or cervical pain: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine.</p> <p>Methods</p> <p>This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: <it>Low</it>, <it>Moderate</it>, or <it>High </it>levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis.</p> <p>Results</p> <p>Eighty six (86) subjects completed the study. The <it>Low </it>psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the <it>High </it>psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the <it>Low </it>group had at least 30% improvement in pain versus 10% in the <it>High </it>group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome.</p> <p>Conclusion</p> <p>Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation.</p

Optimising corticosteroid injection for lateral epicondylalgia with the addition of physiotherapy: A protocol for a randomised control trial with placebo comparison

<p>Abstract</p> <p>Background</p> <p>Corticosteroid injection and physiotherapy are two commonly prescribed interventions for management of lateral epicondylalgia. Corticosteroid injections are the most clinically efficacious in the short term but are associated with high recurrence rates and delayed recovery, while physiotherapy is similar to injections at 6 weeks but with significantly lower recurrence rates. Whilst practitioners frequently recommend combining physiotherapy and injection to overcome harmful effects and improve outcomes, study of the benefits of this combination of treatments is lacking. Clinicians are also faced with the paradox that the powerful anti-inflammatory corticosteroid injections work well, albeit in the short term, for a non-inflammatory condition like lateral epicondylalgia. Surprisingly, these injections have not been rigorously tested against placebo injections. This study primarily addresses both of these issues.</p> <p>Methods</p> <p>A randomised placebo-controlled clinical trial with a 2 × 2 factorial design will evaluate the clinical efficacy, cost-effectiveness and recurrence rates of adding physiotherapy to an injection. In addition, the clinical efficacy and adverse effects of corticosteroid injection beyond that of a placebo saline injection will be studied. 132 participants with a diagnosis of lateral epicondylalgia will be randomly assigned by concealed allocation to one of four treatment groups – corticosteroid injection, saline injection, corticosteroid injection with physiotherapy or saline injection with physiotherapy. Physiotherapy will comprise 8 sessions of elbow manipulation and exercise over an 8 week period. Blinded follow-up assessments will be conducted at baseline, 4, 8, 12, 26 and 52 weeks after randomisation. The primary outcome will be a participant rating of global improvement, from which measures of success and recurrence will be derived. Analyses will be conducted on an intention-to-treat basis using linear mixed and logistic regression models. Healthcare costs will be collected from a societal perspective, and along with willingness-to-pay and quality of life data will facilitate cost-effectiveness and cost-benefit analyses.</p> <p>Conclusion</p> <p>This trial will utilise high quality trial methodologies in accordance with CONSORT guidelines. Findings from this study will assist in the development of evidence based practice recommendations and potentially the optimisation of resource allocation for rehabilitating lateral epicondylalgia.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Register ACTRN12609000051246</p

Effectiveness of individualized physiotherapy on pain and functioning compared to a standard exercise protocol in patients presenting with clinical signs of subacromial impingement syndrome. A randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Shoulder impingement syndrome is a common musculoskeletal complaint leading to significant reduction of health and disability. Physiotherapy is often the first choice of treatment although its effectiveness is still under debate. Systematic reviews in this field highlight the need for more high quality trials to investigate the effectiveness of physiotherapy interventions in patients with subacromial impingement syndrome.</p> <p>Methods/Design</p> <p>This randomized controlled trial will investigate the effectiveness of individualized physiotherapy in patients presenting with clinical signs and symptoms of subacromial impingement, involving 90 participants aged 18-75. Participants are recruited from outpatient physiotherapy clinics, general practitioners, and orthopaedic surgeons in Germany. Eligible participants will be randomly allocated to either individualized physiotherapy or to a standard exercise protocol using central randomization.</p> <p>The control group will perform the standard exercise protocol aiming to restore muscular deficits in strength, mobility, and coordination of the rotator cuff and the shoulder girdle muscles to unload the subacromial space during active movements. Participants of the intervention group will perform the standard exercise protocol as a home program, and will additionally be treated with individualized physiotherapy based on clinical examination results, and guided by a decision tree. After the intervention phase both groups will continue their home program for another 7 weeks.</p> <p>Outcome will be measured at 5 weeks and at 3 and 12 months after inclusion using the shoulder pain and disability index and patients' global impression of change, the generic patient-specific scale, the average weekly pain score, and patient satisfaction with treatment. Additionally, the fear avoidance beliefs questionnaire, the pain catastrophizing scale, and patients' expectancies of treatment effect are assessed. Participants' adherence to the protocol, use of additional treatments for the shoulder, direct and indirect costs, and sick leave due to shoulder complaints will be recorded in a shoulder log-book.</p> <p>Discussion</p> <p>To our knowledge this is the first trial comparing individualized physiotherapy based on a defined decision making process to a standardized exercise protocol. Using high-quality methodologies, this trial will add evidence to the limited body of knowledge about the effect of physiotherapy in patients with SIS.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN86900354</p

Transposon activation mutagenesis as a screening tool for identifying resistance to cancer therapeutics

Background: The development of resistance to chemotherapies represents a significant barrier to successful cancer treatment. Resistance mechanisms are complex, can involve diverse and often unexpected cellular processes, and can vary with both the underlying genetic lesion and the origin or type of tumor. For these reasons developing experimental strategies that could be used to understand, identify and predict mechanisms of resistance in different malignant cells would be a major advance. Methods: Here we describe a gain-of-function forward genetic approach for identifying mechanisms of resistance. This approach uses a modified piggyBac transposon to generate libraries of mutagenized cells, each containing transposon insertions that randomly activate nearby gene expression. Genes of interest are identified using next-gen high-throughput sequencing and barcode multiplexing is used to reduce experimental cost. Results: Using this approach we successfully identify genes involved in paclitaxel resistance in a variety of cancer cell lines, including the multidrug transporter ABCB1, a previously identified major paclitaxel resistance gene. Analysis of co-occurring transposons integration sites in single cell clone allows for the identification of genes that might act cooperatively to produce drug resistance a level of information not accessible using RNAi or ORF expression screening approaches. Conclusion: We have developed a powerful pipeline to systematically discover drug resistance in mammalian cells in vitro. This cost-effective approach can be readily applied to different cell lines, to identify canonical or context specific resistance mechanisms. Its ability to probe complex genetic context and non-coding genomic elements as well as cooperative resistance events makes it a good complement to RNAi or ORF expression based screens