Petawatt laser system and targeting performance

We recently demonstrated the production of 1.25 PW of peak power in the Nova/Petawatt Laser Facility, generating > 600 J in < 450 fs. Results of the first focused irradiance tests, at 500 J and deployment of a novel targeting system will be presented

Ultrahigh spatial-frequency, high-contrast periodic structures produced by interference lithography

We have developed a process to produce high-aspect ratio, high- frequency periodic profiles recorded in a photoresist layer by interference lithography. We are able to independently control the period, duty cycle, and sidewall angle of the profiles. High-contrast diazonapthoquinone-based photoresist and single mode operation of the exposure laser are critical. The high-aspect ratio profiles are necessary for many applications such as transfer etch masks for etching oxides and field emitter array patterning. 5 refs., 5 figs

Rhenium and yttrium ions as antimicrobial agents against multidrug resistant Klebsiella pneumoniae and Acinetobacter baumannii biofilms

© 2019 The Authors. Letters in Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology. Antimicrobial resistance presents major global concerns to patient health. In this study, metal ions of molybdenum, rhenium, yttrium and thallium were tested against bacteria in planktonic and biofilm form using one strain of Klebsiella pneumoniae and Acinetobacter baumannii. The antimicrobial efficacy of the metal ions was evaluated against the planktonic bacterial strains using minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations, whilst the efficacy of the metal ions against biofilms was tested using a crystal violet biofilm assay. Live Dead staining was used to visualize the antimicrobial activity elicited by the metal ions on the bacterial cell. The results showed that higher concentrations of the metals were required to inhibit the growth of biofilms (72·9 mg l −1 to 416·7 mg l −1 ), in comparison to their planktonic counterparts. MICs of the metal ions (<46·9 mg l −1 ) (planktonic cells) did not affect biofilm formation. Overall, rhenium and yttrium were effective antimicrobial agents. Molybdenum demonstrated the greatest level of biotoxicity. When taking into account these results and the known toxicity of thallium, it is possible that rhenium or yttrium ions could be developed as effective biocidal formulations in order to prevent transmission in healthcare environments. Significance and Impact of the Study: The metal ions, molybdenum, rhenium, thallium and yttrium were tested against both Klebsiella pneumoniae and Acinetobacter baumannii in planktonic and biofilm forms. This research demonstrated that all the metal ions may be effective antimicrobial agents. However, molybdenum induced high levels of cytotoxicity, whilst, there was no significant difference in the toxicity of the other metal ions tested. When considering the results for the antimicrobial efficacy and biotoxicity of the metal ions, in conjunction with the known toxicity of thallium in certain chemical compositions, it was concluded that overall rhenium or yttrium ions may be effective antimicrobial agents, one potential application may be utilizing these metal ions in hospital surface cleaning formulations

Defining the Critical Hurdles in Cancer Immunotherapy

ABSTRACT: Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators, others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet be overcome to improve outcomes of patients with cancer

Precision manufacturing using advanced optical interference lithography. Final report

Goal was to develop interference lithography (IL) as a reliable process for patterning large-area, deep-submicron scale field emission arrays for field emission display (FED) applications. We have developed a system based on IL which can easily produce an array of 0.2-0.5 micron emitters over large area (up to 400 sq. in. to date) with better than 5% height and spacing uniformity. Process development as a result of this LDRD project represents a significant advance over the current state of the art for FED manufacturing and is applicable to all types of FEDs, independent of the emitter material. Ability of IL to pattern such structures simultaneously and uniformly on a large format has application to other technology areas, such as dynamic random access memory (DRAM) production and magnetic media recording

A safe technique for insertion of heel wires for hindfoot external fixation frames: an anatomical study

Aims: Anatomical atlases document classical safe corridors for the placement of transosseous fine wires through the calcaneum during circular frame external fixation. During this process, the posterior tibial neurovascular bundle (PTNVB) is placed at risk, though this has not been previously quantified. We describe a cadaveric study to investigate a safe technique for posterolateral to anteromedial fine wire insertion through the body of the calcaneum. Materials and Methods: A total of 20 embalmed cadaveric lower limbs were divided into two groups. Wires were inserted using two possible insertion points and at varying angles. In Group A, wires were inserted one-third along a line between the point of the heel and the tip of the lateral malleolus while in Group B, wires were inserted halfway along this line. Standard dissection techniques identified the structures at risk and the distance of wires from neurovascular structures was measured. The results from 19 limbs were subject to analysis. Results: In Group A, no wires pierced the PTNVB. Wires were inserted a median 22.3 mm (range 4.7 to 39.6) from the PTNVB; two wires (4%) passed within 5 mm. In Group B, 24 (46%) wires passed within 5 mm of the PTNVB, with 11 wires piercing it. The median distance of wires from the PTNVB was 5.5 mm (range 0 to 30). A Mann–Whitney U test showed that this was significantly closer than in Group A (Hodges–Lehmann shift, 14.06 mm; 95% confidence interval (CI) 10.52 to 16.88; p &lt; 0.0001). In Group B, with an increased angle of insertion there was greater risk to the PTNVB (rs = -0.80; p &lt; 0.01). Conclusion: Insertion of wires using an entry point one-third along a line from the point of the heel to the tip of the lateral malleolus (Group A) appears to be the safer technique. An insertion angle of up to 30° to the coronal plane can be used without significant risk to the PTNVB. Insertion of wires halfway along a line from the point of the heel to the tip of the lateral malleolus (Group B) carried a significantly higher risk of injury to neurovascular structures and, if necessary, an angle of insertion parallel to the coronal plane should be used

The long-acting beta2-agonist salmeterol xinafoate: effects on airway inflammation in asthma

Salmeterol xinafoate is an inhaled long-acting beta2-adrenoceptor agonist recently introduced for the treatment of asthma. Both in vitro and animal studies suggest that it may have anti-inflammatory activities of benefit in this disease. To assess this directly, the effects of 6 weeks' treatment with salmeterol on indices of clinical activity, airway dysfunction and inflammation in subjects with stable atopic asthma were investigated. In a double blind study, asthmatic patients were randomized to 6 weeks' treatment with either salmeterol 50 microg twice daily (n=14) or placebo (n=12). They underwent bronchoscopy with bronchoalveolar lavage (BAL) and bronchial biopsy immediately before starting treatment and again after 6 weeks. Treatment with salmeterol improved clinical indices of asthma activity, but there were no changes in BAL differential cell counts or mediator levels, and no change in T-cell numbers or activation status. In the biopsy specimens there were no changes in numbers of inflammatory cells, sub-basement membrane collagen deposition or mast cell degranulation. Regular treatment with salmeterol improves clinical indices of asthma but has no effect on the underlying inflammatory process. These findings strengthen guideline recommendations that long-acting beta2-agonists should not be prescribed as sole antiasthma medication

Non-compliance and professional power

The non-compliance of patients with prescribed treatments is considered as a barrier to effective health care. Non-compliance has implications for the health of patients, effective use of resources and assessments of the clinical efficacy of treatments. Research into non-compliance has increased over the last 30 years. This seems to indicate that it is seen as an important area of concern for all health care professionals. Definitions of non-compliance are problematic, as are methods of assessment of its nature and frequency. Many factors which may account for non-compliance have been proposed, as well as methods to improve compliance. Research into these factors however, mainly based on a positivist epistemology, has failed to provide any conclusive answers to the problem. Sound clinical reasons are suggested as the basis for the increase in interest in non-compliance. It is contended, however, that it is not only these reasons that account for the identification of non-compliance as a problem. Non-compliant behaviour is seen as problematic, because it contravenes professional beliefs, norms and expectations regarding the ‘proper’ roles of patients and professionals. These have formed the basis of an ideology that views patients as passive recipients of health care. It has led to an inherent tendency to ‘blame’ the patient and view non-compliance as irrational and deviant. The professional view of non-compliance as irrational, is exemplified in the case of individuals with mental illness, where there are inherent assumptions that non-compliance can be seen primarily as a symptom of illness. This denies the legitimacy of patient choice, and has led to attempts to control compliance via suggested legislative measures. Serious moral and ethical problems arise from such measures, and can be seen as the ultimate legitimization of an ideology of non-compliance. The maintenance of professional power and control is suggested as central to the debates surrounding non-compliance. The ideological assumptions underpinning the concept of non-compliance need questioning, and a re-conceptualization of the roles of patients and professionals is required. This must involve a view of patients as active participators in their own health care. Research based on an interpretative epistemology, aimed at understanding individual action, rather than control, would seem a more appropriate model to pursue