Auswahl der wissenschaftlichen Literatur zum Thema „DUPLICATE BLOCKS REMOVAL“

Background: Chronic mid back and upper back pain caused by thoracic facet joints has been reported in 34% to 48% of patients based on responses to controlled diagnostic blocks. Systematic reviews have established moderate evidence for controlled comparative local anesthetic blocks of thoracic facet joints in the diagnosis of mid back and upper back pain, moderate evidence for therapeutic thoracic medial branch blocks, and limited evidence for radiofrequency neurotomy of thoracic medial branches. Study Design: Systematic review of therapeutic thoracic facet joint interventions. Objective: To determine the clinical utility of therapeutic thoracic facet joint interventions in the therapeutic management of chronic upper back and mid back pain. Methods: The available literature for the utility of facet joint interventions in the therapeutic management of thoracic facet joint pain was reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, and limited (or poor) based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to March 2012, and manual searches of the bibliographies of known primary and review articles. Outcome Measures: The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. Results: For this systematic review, 13 studies were identified. Of these, 7 studies were excluded, and a total of 4 studies (after removal of duplicate publication) met inclusion criteria for methodological quality assessment with one randomized trial and 3 non-randomized studies. The evidence is fair for therapeutic thoracic facet joint nerve blocks, limited for thoracic radiofrequency neurotomy, and not available for thoracic intraarticular injections. Limitations: The limitation of this systematic review includes a paucity of literature. The only positive studies were of medial branch blocks performed by the same group of authors. Conclusion: The evidence for therapeutic facet joint interventions is fair for medial branch blocks, whereas it is not available for intraarticular injections, and limited for radiofrequency neurotomy due to lack of literature. Key words: Chronic thoracic pain, mid back or upper back pain, thoracic facet or zygapophysial joint pain, facet joint nerve blocks, medial branch blocks, therapeutic thoracic medial branch blocks, thoracic radiofrequency neurotomy, thoracic intraarticular facet joint injections

Background Combinations of different targeted therapies, including Bruton tyrosine kinase (BTK) inhibitors and anti-CD20 monoclonal antibodies (mAbs) could improve treatment for CLL. Unexpectedly, the combination of ibrutinib (IBR) with rituximab did not show additional clinical benefit. However, IBR inhibits many off-target molecules that may limit therapeutic mAb clinical effectiveness and a more selective BTK inhibitor, such as acalabrutinib (ACALA), could be more effective in combination with mAb therapy. Initial data from the ELEVATE TN trial support this possibility. IBR off-target effects on antibody-dependent cellular phagocytosis (ADCP), the major mechanism of therapeutic mAb activity could explain this difference. Additionally, IBR induces a higher and longer duration increase in circulating lymphocytes than ACALA. IBR off-target effects on efferocytosis, another phagocytic process involved in apoptotic cell removal, might explain this difference. Methods Using state-of-the-art direct kinetic measurements of phagocytosis by time-lapse video, (Chu et al. J Cell Sci 2020;133:jcs237883) we investigated the effects of IBR and ACALA on phagocytosis (ADCP or efferocytosis) by human monocyte-derived macrophages (hMDM) in vitro. Live cell time-lapse video of 10 μg/ml rituximab (Genentech) mediated ADCP of CLL cells by CellTracker Deep Red (CTDR, Thermofisher) labeled hMDM (20:1 CLL:hMDM cell ratio) either untreated or treated with IBR or ACALA (3-fold serial dilutions from 100 to 0.41 μM) was imaged in a stage-top environmental chamber (37°C and 5% CO2) mounted onto a Nikon Ti-Eclipse inverted microscope with an ELWD 20x/0.45NA S Plan Fluor Ph1 objective and an Andor Zyla 5.5 sCMOS camera. Images were captured sequentially every 4 min over 2.8 h. For each experiment (n = 18), duplicate or triplicate wells for each drug concentration were imaged. For efferocytosis, live cell time-lapse video imaging of phagocytosis of pHrodo iFL Red STP ester (pHrodo Red, Thermo Fisher Scientific) labeled apoptotic CLL cells by CTDR-labeled hMDM (20:1 CLL:hMDM cell ratio) either untreated or treated with IBR or ACALA (2-fold serial dilutions from 10 to 1.25 μM) was collected every 4 min over 2.8 h. For each experiment (n = 7), duplicate or triplicate wells for each drug concentration was imaged and analyzed. Finally, for efferocytosis, the intensity of pHrodo Red dye, a pH-sensitive dye that increases in intensity with acidic pH, as found in the endolysosomes, was measured in the pHrodo Red color channel and analyzed. Results IBR significantly inhibited ADCP at all measured drug concentrations (0.41 μM, p < 0.05; 1.2 μM, p < 0.01; 3.7 - 100 μM, p < 0.001). The mean peak free drug concentration (Cmax) achieved clinically by standard doses for IBR is ~0.5 μM. ACALA only significantly inhibited ADCP at the highest concentration (100 μM, p < 0.001). The Cmax achieved clinically by standard doses for ACALA is ~1.2 μM. ACALA did not inhibit efferocytosis or subsequent transition to endolysosomal compartment at all tested concentrations (p > 0.05). IBR did not inhibit efferocytosis (p > 0.05) and only inhibited transition to endolysosomal compartment at highest concentration tested (10 μM, p < 0.01) Conclusion Our study shows that BTK inhibition does not block ADCP and a more selective BTK inhibitor may prove effective in combination with therapeutic anti-CD20 mAbs. IBR off-target inhibition specifically blocks ADCP and not efferocytosis. Thus, IBR off-target inhibition of ADCP should be via proximal signaling by antibody Fc receptors and not subsequent downstream phagocytic mechanisms in common with efferocytosis. These results also imply the lack of BTK and IBR off-target molecules involvement in efferocytosis. Finally, the increased lymphocytosis seen with IBR compared to ACALA treatment in CLL cannot be explained by IBR off-target effects on efferocytosis. These findings provide a critical understanding of macrophage phagocytosis reduction by BTK inhibitor selectivity that will have important consequences for the development of combination targeted therapies with mAbs. Disclosures Chu: Acerta Pharma/AstraZeneca: Research Funding; Pfizer: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months; TG Therapeutics: Research Funding. Izumi:AstraZeneca: Current equity holder in publicly-traded company; Acerta Pharma: Current equity holder in private company, Ended employment in the past 24 months, Patents & Royalties: Acalabrutinib patents (no royalties). Munugalavadla:Gilead Sciences: Current equity holder in publicly-traded company; AstraZeneca: Current equity holder in publicly-traded company; Acerta Pharma: Current Employment. Barr:Gilead: Consultancy; Morphosys: Consultancy; TG therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy, Research Funding; Janssen: Consultancy; Merck: Consultancy; Genentech: Consultancy; Abbvie/Pharmacyclics: Consultancy, Research Funding; Verastem: Consultancy. VanDerMeid:Acerta Pharma / AstraZeneca: Research Funding. Elliott:Acerta Pharma / AstraZeneca: Research Funding. Zent:Mentrik Biotech: Research Funding; TG Therapeutics, Inc: Research Funding; Acerta / Astra Zeneca: Research Funding.

Background: Global policy to guide action on musculoskeletal (MSK) health is in a nascent phase. Lagging behind other noncommunicable diseases there is currently little global policy to assist governments to develop national approaches to MSK health. Considering the importance of comparison and learning for global policy development, we aimed to perform a comparative analysis of national MSK policies to identify areas of innovation and draw common themes and principles that could guide MSK health policy. Methods: Multi-modal search strategy incorporating a systematic online search targeted at the 30 most populated nations ; a call to networked experts; a specified question in a related eDelphi questionnaire; and snowballing methods.. Extracted data were organised using an a priori framework adapted from the WHO Building Blocks and further inductive coding. Subsequently, texts were open coded and thematically analysed to derive specific sub-themes and principles underlying texts within each theme, serving as abstracted, transferrable concepts for future global policy. Results: The search yielded 165 documents with 41 retained after removal of duplicates and exclusions. Only three documents were comprehensive national strategies addressing MSK health. The most common conditions addressed in the documents were pain (noncancer), low back pain, occupational health, inflammatory conditions, and osteoarthritis. Across eight categories, we derived 47 sub-themes with transferable principles that could guide global policy for: service delivery; workforce; medicines and technologies; financing; data and information systems; leadership and governance; citizens, consumers and communities; and research and innovation. Conclusion: There are few examples of national strategic policy to address MSK health; however, many countries are moving towards this by documenting the burden of disease and developing policies for MSK services. This review found a breadth of principles that can add to this existing work and may be adopted to develop comprehensive system-wide MSK health approaches at national and global levels.

M.TECH
Pseudorandom binary sequences find their application in diverse fields but security and cryptography is probably the best known field of their application. One-Time Pad (OTP) is a simple, fast and the most secure encryption algorithm. It provides the perfect secrecy. The encryptiondecryption process of the OTP is based on exclusive-or function computed on the plaintext/ciphertext and the key bits. The requirements for the OTP key are that: it must be a cryptographically strong truly random or pseudorandom binary sequence; must be as long as plaintext size; and must not be reused. The difference between a truly random and a pseudorandom sequence is that the truly random sequence is generated with the help of nondeterministic physical phenomenon but the pseudorandom sequence is generated from some deterministic mechanism and a seed value. In case of pseudorandom binary sequences, given the same seed the pseudorandom number generator will always output the same sequence of numbers or bits. The fundamental difficulty with a truly random sequence is its generation and distribution. Therefore pseudorandom sequences are a popular choice for the practical implementation of the OTP scheme. Many researchers have devoted their time and effort to the family of shift register based pseudorandom sequence generators. But they could not gain a key sequence having very large period equal to the plaintext length. They also tried the complex versions of shift registers but it is yet not very useful and secure

It is widely recognised that multiple autonomous agents operating together as part of a team, or swarm, could be used to assist in a variety of situations including search and rescue missions, warehouse operations and a number of military scenarios. From a sociotechnical perspective, these scenarios depict situations in which non-human and human agents are likely to work together in order to achieve a common goal. Unmanned Aerial Vehicles (UAVs) are often viewed as a convenient and cost effective way to gather information that is not easily accessible from any other means. However, we are beginning to see increasing efforts to scale up the autonomy of single-UAV systems to create aerial swarms. It is thought that aerial swarms may be used to assist in various situations including search and rescue missions, warehouse operations and military scenarios. Compared to a single robot, a swarm can provide a more efficient means to cover large areas and are scalable (i.e., can easily add or remove individual robots without significantly impacting the performance of the remaining group). Despite this, there has been some concern that Human Factors research into human-swarm partnerships is lacking. Thus, in order to understand the current ‘state of the art’, a systematic literature review was conducted to explore what Human Factors research is being conducted within the area of human-swarm partnerships and explore what design guidance exists to support the development of efficient and effective relationships. The initial search returned 143 articles. Duplicates were first removed and then the screening process involved filtering articles by titles then by abstract and then finally, full text. This approach led to 55 articles being retained. Inductive coding was used to identify themes within the text. This provided greater insight into the current focus of research with the context of human-swarm partnerships. A total of 5 themes were identified: interaction strategies, user interface design, management, operator monitoring and trust. However, the review also found that when it comes to design guidance, very little is available. One potential avenue for future research centre on the concepts of Meaningful Human Control and Effective Human Control. These concepts have been recognised as providing the foundation in which the design of human-swarm partnerships may be developed. This is because human agents are still likely to play a pivotal role in overall mission success and as such should retain full decisional awareness and possess a comprehensive understanding of the context of action in order for control to be meaningful. This implicates four of the research themes identified as part of this review: interaction strategies, user interface design, management and trust. Operator Monitoring, the final theme identified as part of this review, is indirectly linked to MHC and EHC because it acts as the mechanism in which operator engagement can be augmented. Arguably then, the building blocks to achieve MHC and EHC are beginning to take shape. However, more research is needed to bring this altogether in the quest for efficient and effective relationships between human agents and robot counterparts.