High quality evidence shows decompressive craniectomy (DC) following traumatic brain injury (TBI) may improve survival but increase the number of severely disabled survivors. Contemporary... Show moreHigh quality evidence shows decompressive craniectomy (DC) following traumatic brain injury (TBI) may improve survival but increase the number of severely disabled survivors. Contemporary international practice is unknown. We sought to describe international use of DC, and the alignment with evidence and clinical practice guidelines, by analyzing the harmonized Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) and Australia-Europe NeuroTrauma Effectiveness Research in Traumatic Brain Injury (OzENTER-TBI) core study datasets, which include patients admitted to intensive care units (ICUs) in Europe, the United Kingdom, and Australia between 2015 and 2017. Outcomes of interest were treatment with DC relative to clinical trial evidence and the Brain Trauma Foundation guidelines. Of 2336 people admitted to ICUs following TBI, DC was performed in 320 (13.7%): in 64/1422 (4.5%) patients with diffuse TBI and 195/640 (30.5%) patients with traumatic mass lesions. Secondary DC (for treatment of intracranial hypertension) was used infrequently in patients who met enrollment criteria of the two randomized clinical trials informing the guidelines-specifically, in 11/124 (8.9%) of those matching Decompressive Craniectomy in Diffuse Traumatic Brain Injury trial (DECRA) enrollment, and in 30/224 (13.4%) of those matching Randomised Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of Intracranial Pressure (RESCUEicp). Of patients who underwent DC, 258/320 (80.6%) were ineligible for either trial: 149/320 (46.6%) underwent primary DC, 62/320 (19.4%) were outside the trials' age criteria, and 126/320 (39.4%) did not develop intracranial hypertension refractory to non-operative therapies prior to DC. Secondary DC was used infrequently in patients in whom it had been shown to increase survival with severe disability, indicating alignment between contemporaneous evidence and practice. However, most patients who underwent DC were ineligible for the key trials; whether they benefited from DC remains unknown. Show less
Steinbuechel, N. von; Rauen, K.; Krenz, U.; Wu, Y.J.; Covic, A.; Plass, A.M.; ... ; Linguistic Validation Grp CENTER 2021
Assessing outcomes in multinational studies on traumatic brain injury (TBI) poses major challenges and requires relevant instruments in languages other than English. Of the 19 outcome instruments... Show moreAssessing outcomes in multinational studies on traumatic brain injury (TBI) poses major challenges and requires relevant instruments in languages other than English. Of the 19 outcome instruments selected for use in the observational Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) study, 17 measures lacked translations in at least one target language. To fill this gap, we aimed to develop well-translated linguistically and psychometrically validated instruments. We performed translations and linguistic validations of patient-reported measures (PROMs), clinician-reported (ClinRO), and performance-based (PerfO) outcome instruments, using forward and backward translations, reconciliations, cognitive debriefings with up to 10 participants, iterative revisions, and international harmonization with input from over 150 international collaborators. In total, 237 translations and 211 linguistic validations were carried out in up to 20 languages. Translations were evaluated at the linguistic and cultural level by coding changes when the original versions are compared with subsequent translation steps, using the output of cognitive debriefings, and using comprehension rates. The average comprehension rate per instrument varied from 88% to 98%, indicating a good quality of the translations. These outcome instruments provide a solid basis for future TBI research and clinical practice and allow the aggregation and analysis of data across different countries and languages. Show less
Programmed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading... Show moreProgrammed ribosomal frameshifting (PRF) is a mechanism used by arteriviruses like porcine reproductive and respiratory syndrome virus (PRRSV) to generate multiple proteins from overlapping reading frames within its RNA genome. PRRSV employs -1 PRF directed by RNA secondary and tertiary structures within its viral genome (canonical PRF), as well as a noncanonical -1 and -2 PRF that are stimulated by the interactions of PRRSV nonstructural protein 1 beta (nsp1 beta) and host protein poly(C)-binding protein (PCBP) 1 or 2 with the viral genome. Together, nsp1 beta and one of the PCBPs act as transactivators that bind a C-rich motif near the shift site to stimulate -1 and -2 PRF, thereby enabling the ribosome to generate two frameshift products that are implicated in viral immune evasion. How nsp1 beta and PCBP associate with the viral RNA genome remains unclear. Here, we describe the purification of the nsp1 beta:PCBP2:viral RNA complex on a scale sufficient for structural analysis using small-angle X-ray scattering and stochiometric analysis by analytical ultracentrifugation. The proteins associate with the RNA C-rich motif as a 1:1:1 complex. The monomeric form of nsp1 beta within the complex differs from previously reported homodimer identified by X-ray crystallography. Functional analysis of the complex via mutational analysis combined with RNA-binding assays and cell-based frameshifting reporter assays reveal a number of key residues within nsp1 beta and PCBP2 that are involved in complex formation and function. Our results suggest that nsp1 beta and PCBP2 both interact directly with viral RNA during formation of the complex to coordinate this unusual PRF mechanism. Show less
Purpose Immuno-MALDI (iMALDI) combines immuno-enrichment of biomarkers with MALDI-MS for fast, precise, and specific quantitation, making it a valuable tool for developing clinical assays. iMALDI... Show morePurpose Immuno-MALDI (iMALDI) combines immuno-enrichment of biomarkers with MALDI-MS for fast, precise, and specific quantitation, making it a valuable tool for developing clinical assays. iMALDI assays are optimized for the PI3-kinase signaling pathway members phosphatase and tensin homolog (PTEN) and PI3-kinase catalytic subunit alpha (p110 alpha), with regard to sensitivity, robustness, and throughput. A standardized template for developing future iMALDI assays, including automation protocols to streamline assay development and translation, is provided. Experimental Design Conditions for tryptic digestion and immuno-enrichment (beads, bead:antibody ratios, incubation times, direct vs. indirect immuno-enrichment) are rigorously tested. Different strategies for calibration and data readout are compared. Results Digestion using 1:2 protein:trypsin (wt:wt) for 1 h yielded high and consistent peptide recoveries. Direct immuno-enrichment (antibody-bead coupling prior to antigen-enrichment) yielded 30% higher peptide recovery with a 1 h shorter incubation time than indirect enrichment. Immuno-enrichment incubation overnight yielded 1.5-fold higher sensitivities than 1 h incubation. Quantitation of the endogenous target proteins is not affected by the complexity of the calibration matrix, further simplifying the workflow. Conclusions and Clinical Relevance This optimized and automated workflow will facilitate the clinical translation of high-throughput sensitive iMALDI assays for quantifying cell-signaling proteins in individual tumor samples, thereby improving patient stratification for targeted treatment. Show less
As a result of increasing globalisation the public sphere has expanded over the recent decades. Consequently Qur'an translations exhibit a highly pluralised concept of religious authority,... Show moreAs a result of increasing globalisation the public sphere has expanded over the recent decades. Consequently Qur'an translations exhibit a highly pluralised concept of religious authority, demonstrating an eclectic use of sources as authors respond simultaneously to local and global discourses. This paper shows how the commentary in a popularising Swahili tafsir by the preacher Said Moosa al-Kindy on two particular Qur'an verses, Q. 2:185 and Q. 2:189, cannot be understood as the outcome of theological and linguistic considerations only, but rather as a multi-epistemic, socially embedded product. Q. 2:185 and Q. 2:189 are often used to endorse particular viewpoints in East African moon sighting debates. This discourse revolves about the question of whether to accept a crescent sighting report from anywhere in the world to determine the beginning of the lunar month or to wait for a visible moon from a more restricted locality. This paper situates al-Kindy's translation within the wider field of Swahili Qur'an commentaries, and compares his treatment of these verses to that in two scholarly products from outside the established genre of tafsir. One is the polemical discourse on this subject by an Ibadi intellectual writing in Swahili and the second is the lunar calendar and website produced by a Tanzanian book trader. In all three of these works Qur'anic authority is paramount, but if we want to understand the diverse mediations of the Qur'anic message in a specific milieu we should not only look at the influence of exegetical traditions but also focus on social actors and their very personal, localised experiences. Show less
This article examines three Swahili books with the same title Fimbo ya Musa ('The Rod of Moses'), published between 1970 and 2010, each of which critically investigates Qur'an translations and... Show moreThis article examines three Swahili books with the same title Fimbo ya Musa ('The Rod of Moses'), published between 1970 and 2010, each of which critically investigates Qur'an translations and vernacular religious texts in Swahili. The first Fimbo was written by the Kenyan Ahmad Ahmad Badawy and criticises one of the earliest Swahili Qur'an translations, by Abdullah Saleh al-Farsy. In the second, Nurudin Hussein Shadhuly, head of the Shadhuly/Yashrutiyya ?ufi branch in Tanzania examines and condemns the translation efforts by Saidi Musa, a student of al-Farsy. The final Fimbo is a treatise by the Ibai scholar Juma al-Mazrui from Oman and digitally distributed in 2010 which deals with the doctrine of God's visibility in the hereafter and is an answer to the Salafiyya Tanzanian Kassim Mafuta's 2008 work on this topic. The example of these three polemics over the last four decades shows the shifting concerns in the reaction to the translated Qur'an in Swahili. The act of translation from Arabic to the vernacular is no longer attacked, but rather the theological implications of a deficient translation are at the heart of the more recent discussions. While authoritative knowledge is still associated with a high command of Arabic, affiliation to a particular school of law or intellectual genealogy is not. Religious learning is no longer primarily transmitted through well-established links of personal authorities, but can increasingly be derived from private study and reading. As a direct result of this opening up of a wide field of knowledge for a non-Arabic reading audience, the potential numbers of discussants increases: each new Swahili Qur'an translation reveals more of the enigmatic character of the Qur'an and fuels new debates. Show less
Fang, Y.; Treffers, E.E.; Li, Y.H.; Tas, A.; Sun, Z.; Meer, Y. van der; ... ; Firth, A.E. 2012
