Alien Registration- Keegan, Thomas R. (Reed Plantation, Aroostook County)

https://digitalmaine.com/alien_docs/32767/thumbnail.jp

Towards a “Sample-In, Answer-Out” Point-of-Care Platform for Nucleic Acid Extraction and Amplification: Using an HPV E6/E7 mRNA Model System

The paper presents the development of a “proof-of-principle” hands-free and self-contained diagnostic platform for detection of human papillomavirus (HPV) E6/E7 mRNA in clinical specimens. The automated platform performs chip-based sample preconcentration, nucleic acid extraction, amplification, and real-time fluorescent detection with minimal user interfacing. It consists of two modular prototypes, one for sample preparation and one for amplification and detection; however, a common interface is available to facilitate later integration into one single module. Nucleic acid extracts (n = 28) from cervical cytology specimens extracted on the sample preparation chip were tested using the PreTect HPV-Proofer and achieved an overall detection rate for HPV across all dilutions of 50%–85.7%. A subset of 6 clinical samples extracted on the sample preparation chip module was chosen for complete validation on the NASBA chip module. For 4 of the samples, a 100% amplification for HPV 16 or 33 was obtained at the 1 : 10 dilution for microfluidic channels that filled correctly. The modules of a “sample-in, answer-out” diagnostic platform have been demonstrated from clinical sample input through sample preparation, amplification and final detection

Lateral flow test engineering and lessons learned from COVID-19

The acceptability and feasibility of large-scale testing with lateral flow tests (LFTs) for clinical and public health purposes has been demonstrated during the COVID-19 pandemic. LFTs can detect analytes in a variety of samples, providing a rapid read-out, which allows self-testing and decentralized diagnosis. In this Review, we examine the changing LFT landscape with a focus on lessons learned from COVID-19. We discuss the implications of LFTs for decentralized testing of infectious diseases, including diseases of epidemic potential, the ‘silent pandemic’ of antimicrobial resistance, and other acute and chronic infections. Bioengineering approaches will play a key part in increasing the sensitivity and specificity of LFTs, improving sample preparation, incorporating nucleic acid amplification and detection, and enabling multiplexing, digital connection and green manufacturing, with the aim of creating the next generation of high-accuracy, easy-to-use, affordable and digitally connected LFTs. We conclude with recommendations, including the building of a global network of LFT research and development hubs to facilitate and strengthen future diagnostic resilience

Distance Education as socio-material assemblage: Place, distribution and aggregation

This paper outlines some of the material assemblages that are formed in international distance education (DE) in Africa. It offers a first exploratory study of materialities in DE and how they potentially distribute and aggregate to form a network to provide education. Through the use of interviews, students lived experiences are explored to unpack the multiplicity of networks needed to overcome the de‐aggregated and distributed institution. The multiplicity of networks that form in DE brings challenges that question how spaces become connected and disconnected and how different materialities shape DE. The materialities in DE produce forces and effects, such as translocal and transmobilites that are more than just the human actor, but extrude materials, networks, and connectives that transform continuously. The interconnectivities of the university and home or institution and students are brought together through enabling technology, but infrastructure does not always have the ability for the facilitation of aggregation

CCP4 Cloud for structure determination and project management in macromolecular crystallography

Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at the cost of increasing data volumes. This is due to the deployment of modern high-speed, high-resolution detectors, the increased complexity and variety of crystallographic software, the use of extensive databases and high-performance computing. This limits what can be accomplished with personal, offline, computing equipment in terms of both productivity and maintainability. There is also an issue of long-term data maintenance and availability of structure-solution projects as the links between experimental observations and the final results deposited in the PDB. In this article, CCP4 Cloud, a new front-end of the CCP4 software suite, is presented which mitigates these effects by providing an online, cloud-based environment for crystallographic computation. CCP4 Cloud was developed for the efficient delivery of computing power, database services and seamless integration with web resources. It provides a rich graphical user interface that allows project sharing and long-term storage for structure-solution projects, and can be linked to data-producing facilities. The system is distributed with the CCP4 software suite version 7.1 and higher, and an online publicly available instance of CCP4 Cloud is provided by CCP4.The following funding is acknowledged: Biotechnology and Biological Sciences Research Council (grant No. BB/L007037/1; grant No. BB/S007040/1; grant No. BB/S007083/1; grant No. BB/S005099/1; grant No. BB/S007105/1; award No. BBF020384/1); Medical Research Council (grant No.MC_UP_A025_1012; grant No. MC_U105184325); Ro¨ntgenA˚ ngstro¨m Cluster (grant No. 349-2013-597); Nederlandse Wetenschappelijke Organisatie (grant No. TKI 16219)

Optimum imaging strategies for advanced prostate cancer: ASCO guideline

PURPOSE Provide evidence- and expert-based recommendations for optimal use of imaging in advanced prostate cancer. Due to increases in research and utilization of novel imaging for advanced prostate cancer, this guideline is intended to outline techniques available and provide recommendations on appropriate use of imaging for specified patient subgroups. METHODS An Expert Panel was convened with members from ASCO and the Society of Abdominal Radiology, American College of Radiology, Society of Nuclear Medicine and Molecular Imaging, American Urological Association, American Society for Radiation Oncology, and Society of Urologic Oncology to conduct a systematic review of the literature and develop an evidence-based guideline on the optimal use of imaging for advanced prostate cancer. Representative index cases of various prostate cancer disease states are presented, including suspected high-risk disease, newly diagnosed treatment-naïve metastatic disease, suspected recurrent disease after local treatment, and progressive disease while undergoing systemic treatment. A systematic review of the literature from 2013 to August 2018 identified fully published English-language systematic reviews with or without meta-analyses, reports of rigorously conducted phase III randomized controlled trials that compared $ 2 imaging modalities, and noncomparative studies that reported on the efficacy of a single imaging modality. RESULTS A total of 35 studies met inclusion criteria and form the evidence base, including 17 systematic reviews with or without meta-analysis and 18 primary research articles. RECOMMENDATIONS One or more of these imaging modalities should be used for patients with advanced prostate cancer: conventional imaging (defined as computed tomography [CT], bone scan, and/or prostate magnetic resonance imaging [MRI]) and/or next-generation imaging (NGI), positron emission tomography [PET], PET/CT, PET/MRI, or whole-body MRI) according to the clinical scenario

Results of NOPHO ALL2008 treatment for patients aged 1-45 years with acute lymphoblastic leukemia

Adults with acute lymphoblastic leukemia (ALL) do worse than children. From 7/2008 to 12/2014, Nordic and Baltic centers treated 1509 consecutive patients aged 1-45 years with Philadelphia chromosome-negative ALL according to the NOPHO ALL2008 without cranial irradiation. Overall, 1022 patients were of age 1-9 years (A), 266 were 10-17 years (B) and 221 were 18-45 years (C). Sixteen patients (three adults) died during induction. All others achieved remission after induction or 1-3 intensive blocks. Subsequently, 45 patients (12 adults) died, 122 patients relapsed (32 adults) with a median time to relapse of 1.6 years and 13 (no adult) developed a second malignancy. Median follow-up time was 4.6 years. Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, PPeer reviewe

phenix.mr_rosetta: molecular replacement and model rebuilding with Phenix and Rosetta.

The combination of algorithms from the structure-modeling field with those of crystallographic structure determination can broaden the range of templates that are useful for structure determination by the method of molecular replacement. Automated tools in phenix.mr_rosetta simplify the application of these combined approaches by integrating Phenix crystallographic algorithms and Rosetta structure-modeling algorithms and by systematically generating and evaluating models with a combination of these methods. The phenix.mr_rosetta algorithms can be used to automatically determine challenging structures. The approaches used in phenix.mr_rosetta are described along with examples that show roles that structure-modeling can play in molecular replacement

Exploring adults’ experiences of sedentary behaviour and participation in nonworkplace interventions designed to reduce sedentary behaviour: a thematic synthesis of qualitative studies

Background: Sedentary behaviour is any waking behaviour characterised by an energy expenditure of ≤1.5 metabolic equivalent of task while in a sitting or reclining posture. Prolonged bouts of sedentary behaviour have been associated with negative health outcomes in all age groups. We examined qualitative research investigating perceptions and experiences of sedentary behaviour and of participation in non-workplace interventions designed to reduce sedentary behaviour in adult populations. Method: A systematic search of seven databases (MEDLINE, AMED, Cochrane, PsychINFO, SPORTDiscus, CINAHL and Web of Science) was conducted in September 2017. Studies were assessed for methodological quality and a thematic synthesis was conducted. Prospero database ID: CRD42017083436. Results: Thirty individual studies capturing the experiences of 918 individuals were included. Eleven studies examined experiences and/or perceptions of sedentary behaviour in older adults (typically ≥60 years); ten studies focused on sedentary behaviour in people experiencing a clinical condition, four explored influences on sedentary behaviour in adults living in socio-economically disadvantaged communities, two examined university students’ experiences of sedentary behaviour, two on those of working-age adults, and one focused on cultural influences on sedentary behaviour. Three analytical themes were identified: 1) the impact of different life stages on sedentary behaviour 2) lifestyle factors influencing sedentary behaviour and 3) barriers and facilitators to changing sedentary behaviour. Conclusions: Sedentary behaviour is multifaceted and influenced by a complex interaction between individual, environmental and socio-cultural factors. Micro and macro pressures are experienced at different life stages and in the context of illness; these shape individuals’ beliefs and behaviour related to sedentariness. Knowledge of sedentary behaviour and the associated health consequences appears limited in adult populations, therefore there is a need for provision of accessible information about ways in which sedentary behaviour reduction can be integrated in people’s daily lives. Interventions targeting a reduction in sedentary behaviour need to consider the multiple influences on sedentariness when designing and implementing interventions

eXtraembryonic ENdoderm (XEN) Stem Cells Produce Factors that Activate Heart Formation

Initial specification of cardiomyocytes in the mouse results from interactions between the extraembryonic anterior visceral endoderm (AVE) and the nascent mesoderm. However the mechanism by which AVE activates cardiogenesis is not well understood, and the identity of specific cardiogenic factors in the endoderm remains elusive. Most mammalian studies of the cardiogenic potential of the endoderm have relied on the use of cell lines that are similar to the heart-inducing AVE. These include the embryonal-carcinoma-derived cell lines, END2 and PYS2. The recent development of protocols to isolate eXtraembryonic ENdoderm (XEN) stem cells, representing the extraembryonic endoderm lineage, from blastocyst stage mouse embryos offers new tools for the genetic dissection of cardiogenesis.Here, we demonstrate that XEN cell-conditioned media (CM) enhances cardiogenesis during Embryoid Body (EB) differentiation of mouse embryonic stem (ES) cells in a manner comparable to PYS2-CM and END2-CM. Addition of CM from each of these three cell lines enhanced the percentage of EBs that formed beating areas, but ultimately, only XEN-CM and PYS2-CM increased the total number of cardiomyocytes that formed. Furthermore, our observations revealed that both contact-independent and contact-dependent factors are required to mediate the full cardiogenic potential of the endoderm. Finally, we used gene array comparison to identify factors in these cell lines that could mediate their cardiogenic potential.These studies represent the first step in the use of XEN cells as a molecular genetic tool to study cardiomyocyte differentiation. Not only are XEN cells functionally similar to the heart-inducing AVE, but also can be used for the genetic dissection of the cardiogenic potential of AVE, since they can be isolated from both wild type and mutant blastocysts. These studies further demonstrate the importance of both contact-dependent and contact-independent factors in cardiogenesis and identify potential heart-inducing proteins in the endoderm