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Google Scholar (GS), a commonly used web-based academic search engine, catalogues between 2 and 100 million records of both academic and grey literature (articles not formally published by commercial academic publishers). Google Scholar collates results from across the internet and is free to use. As a result it has received considerable attention as a method for searching for literature, particularly in searches for grey literature, as required by systematic reviews. The reliance on GS as a standalone resource has been greatly debated, however, and its efficacy in grey literature searching has not yet been investigated. Using systematic review case studies from environmental science, we investigated the utility of GS in systematic reviews and in searches for grey literature. Our findings show that GS results contain moderate amounts of grey literature, with the majority found on average at page 80. We also found that, when searched for specifically, the majority of literature identified using Web of Science was also found using GS. However, our findings showed moderate/poor overlap in results when similar search strings were used in Web of Science and GS (10-67%), and that GS missed some important literature in five of six case studies. Furthermore, a general GS search failed to find any grey literature from a case study that involved manual searching of organisations' websites. If used in systematic reviews for grey literature, we recommend that searches of article titles focus on the first 200 to 300 results. We conclude that whilst Google Scholar can find much grey literature and specific, known studies, it should not be used alone for systematic review searches. Rather, it forms a powerful addition to other traditional search methods. In addition, we advocate the use of tools to transparently document and catalogue GS search results to maintain high levels of transparency and the ability to be updated, critical to systematic reviews.

Aliya ® Pulsed Electric Field (PEF) technology is an emerging strategy in the field of cancer treatment, offering a novel approach to ablation therapy that does not rely on thermal mechanisms. By employing a multi-stage experimental setup, including potato tuber, porcine liver, and murine breast cancer models, we explored the dose-response relationship on ablation and immune modulation by varying the pulse packets delivered from 20 to 100. The biologic response observed with 60 packets represented a minimum effective dose yielding reproducible ablation parameters, immune response, and efficacy which could be augmented with immune checkpoint blockade. This pre-clinical analysis provides a first step toward understanding the therapeutic index for PEF technology beyond ablation, a consideration that will require robust clinical validation in well-designed prospective studies.

Chemo-immunotherapy uses combined systemic therapies for resectable and unresectable tumors. This approach is gaining clinical momentum, but survival increases leave considerable room for improvement. A novel form of Pulsed Electric Field (PEF) ablation combines focal tissue destruction with immune activation in preclinical settings. The PEFs induce lethal cell damage without requiring thermal processes, leaving cellular proteins intact. This affords PEF a favorable safety profile, improved antigenicity, and significant immunostimulatory damage-associated molecular pattern release compared to other focal therapies. Preclinical investigations demonstrate a combinatorial benefit of PEF with immunostimulation. This study evaluates whether this proprietary PEF therapy induces an immunostimulatory effect sufficient to augment systemic neoadjuvant chemotherapy and immunotherapy to reverse metastatic disease in an immune-cold murine tumor model. To determine whether PEF improves a neoadjuvant chemo-immunotherapy standard-of-care, partial PEF ablation was delivered to orthotopically inoculated 4T1 metastatic tumors in addition to combinations of cisplatin chemotherapy and/or αPD-1 immunotherapy, followed by resection. In addition, to determine whether PEF combined with chemo-immunotherapy improves local and metastatic response in unresectable populations, partial PEF ablation was added to chemo-immunotherapy in mice that did not receive resection. Blood cytokines and flow cytometry evaluated immune response. Partial PEF ablation generates an immunostimulatory tumor microenvironment, increases systemic immune cell populations, slows tumor growth, and prolongs survival relative to neoadjuvant systemic therapies-alone. These data suggest the addition of this proprietary PEF locoregional therapy may synergize with systemic standard-of-care paradigms to improve outcomes with potential or demonstrated metastatic disease in both resectable and unresectable patient cohorts.

In low-lying coastal regions, flooding arises from oceanographic (storm surges plus tides and/or waves), fluvial (increased river discharge), and/or pluvial (direct surface run-off) sources. The adverse consequences of a flood can be disproportionately large when these different sources occur concurrently or in close succession, a phenomenon that is known as “compound flooding”. In this paper, we assess the potential for compound flooding arising from the joint occurrence of high storm surge and high river discharge around the coast of the UK. We hypothesise that there will be spatial variation in compound flood frequency, with some coastal regions experiencing a greater dependency between the two flooding sources than others. We map the dependence between high skew surges and high river discharge, considering 326 river stations linked to 33 tide gauge sites. We find that the joint occurrence of high skew surges and high river discharge occurs more frequently during the study period (15–50 years) at sites on the south-western and western coasts of the UK (between three and six joint events per decade) compared to sites along the eastern coast (between zero and one joint events per decade). Second, we investigate the meteorological conditions that drive compound and non-compound events across the UK. We show, for the first time, that spatial variability in the dependence and number of joint occurrences of high skew surges and high river discharge is driven by meteorological differences in storm characteristics. On the western coast of the UK, the storms that generate high skew surges and high river discharge are typically similar in characteristics and track across the UK on comparable pathways. In contrast, on the eastern coast, the storms that typically generate high skew surges are mostly distinct from the types of storms that tend to generate high river discharge. Third, we briefly examine how the phase and strength of dependence between high skew surge and high river discharge is influenced by the characteristics (i.e. flashiness, size, and elevation gradient) of the corresponding river catchments. We find that high skew surges tend to occur more frequently with high river discharge at catchments with a lower base flow index, smaller catchment area, and steeper elevation gradient. In catchments with a high base flow index, large catchment area, and shallow elevation gradient, the peak river flow tends to occur several days after the high skew surge. The previous lack of consideration of compound flooding means that flood risk has likely been underestimated around UK coasts, particularly along the south-western and western coasts. It is crucial that this be addressed in future assessments of flood risk and flood management approaches.

Irreversible electroporation (IRE) is a therapeutic technology for the ablation of soft tissues using electrodes to deliver intense but short electric pulses across a cell membrane, creating nanopores that lead to cell death. This phenomenon only affects the cell membrane, leaving the extracellular matrix and sensitive structures intact, making it a promising technique for the treatment many types of tumors. In this paper, we present the first in vivo study to achieve tumor regression using a translatable, clinically relevant single needle electrode for treatment administration. Numerical models of the electric field distribution for the protocol used suggest that a 1000 V/cm field threshold is sufficient to treat a tumor, and that the electric field distribution will slightly decrease if the same protocol were used on a tumor deep seated within a human breast. Tumor regression was observed in 5 out of 7 MDA-MB231 human mammary tumors orthotopically implanted in female Nu/Nu mice, with continued growth in controls.

There is general agreement in the burgeoning literature on the subject that translation plays a key role in minority languages, fulfilling a variety of functions, including bolstering the literary canon. This leads to a prevalent assumption that this veritable entails a dependence on translation that renders minority languages ‘weak’. Following a theoretical review of the literature and a brief presentation of the languages, this paper discusses the results of a study based on a broad-based, original dataset representative of the wide range of literature currently available in Breton and Welsh. The paper concludes that a portrayal of minority language literary systems as ‘weak’ is overly simplistic and fails to address and attempt to explain the factors underpinning the complex and often contradictory dynamics played by translation both within and between such languages. Hi ha un acord general en els estudis, que van proliferant, que expliquen el paper clau de la traducció en les llengües minoritàries: hi compleix una varietat de funcions, incloent-hi reforçar el cànon literari. Això fa assumir predominantment que aquest fet comporta realment una dependència de la traducció que fa que les llengües minoritàries siguin «febles». Després de revisar teòricament aquests estudis i de presentar breument les llengües, en aquest article es discuteixen els resultats d’un estudi basat en un conjunt de dades original i ampli que representa un bon ventall de literatura actualment disponible en bretó i gal·lès. L’article arriba a la conclusió que representar els sistemes literaris de llengües minoritàries com a «febles» és massa simplista i no aborda ni intenta explicar els factors que sustenten la dinàmica complexa i sovint contradictòria de la traducció tant dins com entre aquestes llengües.

Background Irreversible electroporation (IRE) is a new minimally invasive technique to kill undesirable tissue in a non-thermal manner. In order to maximize the benefits from an IRE procedure, the pulse parameters and electrode configuration must be optimized to achieve complete coverage of the targeted tissue while preventing thermal damage due to excessive Joule heating. Methods We developed numerical simulations of typical protocols based on a previously published computed tomographic (CT) guided in vivo procedure. These models were adapted to assess the effects of temperature, electroporation, pulse duration, and repetition rate on the volumes of tissue undergoing IRE alone or in superposition with thermal damage. Results Nine different combinations of voltage and pulse frequency were investigated, five of which resulted in IRE alone while four produced IRE in superposition with thermal damage. Conclusions The parametric study evaluated the influence of pulse frequency and applied voltage on treatment volumes, and refined a proposed method to delineate IRE from thermal damage. We confirm that determining an IRE treatment protocol requires incorporating all the physical effects of electroporation, and that these effects may have significant implications in treatment planning and outcome assessment. The goal of the manuscript is to provide the reader with the numerical methods to assess multiple-pulse electroporation treatment protocols in order to isolate IRE from thermal damage and capitalize on the benefits of a non-thermal mode of tissue ablation.

Irreversible electroporation (IRE) is a non-thermal focal ablation technique that uses a series of brief but intense electric pulses delivered into a targeted region of tissue, killing the cells by irrecoverably disrupting cellular membrane integrity. This study investigates if there is an improved local anti-tumor response in immunocompetent (IC) BALB/c versus immunodeficient (ID) nude mice, including the potential for a systemic protective effect against rechallenge. Subcutaneous murine renal carcinoma tumors were treated with an IRE pulsing protocol that used 60% of the predicted voltage required to invoke complete regressions in the ID mice. Tumors were followed for 34 days following treatment for 11 treated mice from each strain, and 7 controls from each strain. Mouse survival based on tumor burden and the progression-free disease period was substantially longer in the treated IC mice relative to the treated ID mice and sham controls for both strains. Treated IC mice were rechallenged with the same cell line 18 days after treatment, where growth of the second tumors was shown to be significantly reduced or prevented entirely. There was robust CD3+ cell infiltration in some treated BALB/C mice, with immunocytes focused at the transition between viable and dead tumor. There was no difference in the low immunocyte presence for untreated tumors, nude mice, and matrigel-only injections in both strains. These findings suggest IRE therapy may have greater therapeutic efficacy in immunocompetent patients than what has been suggested by immunodeficient models, and that IRE may invoke a systemic response beyond the targeted ablation region.

Pulsed electric field (PEF) technologies treat many types of tissue. Many systems mandate synchronization to the cardiac cycle to avoid the induction of cardiac arrhythmias. Significant differences between PEF systems make the assessment of cardiac safety from one technology to another challenging. A growing body of evidence suggests that shorter duration biphasic pulses obviate the need for cardiac synchronization, even when delivered in a monopolar fashion. This study theoretically evaluates the risk profile of different PEF parameters. It then tests a monopolar, biphasic, microsecond-scale PEF technology for arrhythmogenic potential. PEF applications of increasing likelihood to induce an arrhythmia were delivered. The energy was delivered throughout the cardiac cycle, including both single and multiple packets, and then with concentrated delivery on the t-wave. There were no sustained changes to the electrocardiogram waveform or to the cardiac rhythm, despite delivering energy during the most vulnerable phase of the cardiac cycle, and delivery of multiple packets of PEF energy across the cardiac cycle. Only isolated premature-atrial contractions (PAC) were observed. This study provides evidence that certain varieties of biphasic, monopolar PEF delivery do not require synchronized energy delivery to prevent harmful arrhythmias.

Patients living with chronic bronchitis (CB) suffer from physical limitations and poor quality of life. In general, treatment options that directly address the mucus hypersecretion component of CB are quite limited. Chronic airway inflammation and the associated hypersecretion and cough that are pathognomonic for CB generally result from long-term exposure to airway irritants such as tobacco use and other environmental insults. This, in turn, results in an increase in the quantity and change in composition of the airway mucosa as a consequence of altered goblet cells, club cells, and submucosal glands. Pulsed electric fields (PEFs) provide a method for eradicating the cellular constituents of tissue with limited impact on the stromal proteins. Preclinical evidence in porcine airways demonstrated that particular PEF waveforms allowed for salutary remodeling of the epithelial and submucosal airway tissue layers and appeared to foster rapid regeneration and recovery of the tissue. Therefore, a therapeutic opportunity might exist whereby the application of a specific form of PEF may result in a reduction of the cellular secretory constituents of the airway while also reducing airway mucosal inflammation. This review discusses the use of such PEF to address the underlying disease processes in CB including challenges around device design, dosing, and appropriate delivery methods. Further, we outline considerations for the transition to human airways along with a brief examination of the initial work treating CB patients, suggesting that the therapy is well tolerated with limited adverse events.