Reliability and Validation of the PFIQ-7 and PFDI-20 in the Luganda Language.

INTRODUCTION AND HYPOTHESIS: Pelvic floor disorders (PFDs) impact women worldwide and are assessed using instruments such as the Pelvic Floor Distress Inventory (PFDI-20) and Pelvic Floor Impact Questionnaire (PFIQ-7). There are no known valid PFD instruments in Uganda. This study's purpose was to translate and test the reliability and validity of the PFDI-20 and PFIQ-7 in Luganda. It was predicted that these instruments would be reliable and valid to assess the presence and impact of PFD in parous Luganda-speaking women. METHODS: The translated PFDI-20 and PFIQ-7 were administered to parous Luganda-speaking women and readministered 4-8 months after. The Pelvic Organ Prolapse Quantification (POP-Q) examination determined the presence of pelvic organ prolapse (POP) and a cough-stress test (CST) measured urinary leakage. Analysis was completed using Cronbach's α co-efficient for internal consistency and Spearman's correlation coefficients and Wilcoxon rank sum tests for construct validity. RESULTS: Of the 159 participants, 93 (58.3%) had stage II POP or higher. The PFDI-20 and PFIQ-7 demonstrated minimal bother and impact on activities of daily living respectively. The Urinary Distress Inventory 6 (UDI-6) scores on the PFDI-20 showed a strong positive association with the presence of urinary incontinence. When PFD was defined by responses to symptom assessment, the translated PFDI-20 and PFIQ-7 could differentiate between individuals with and without PFD. CONCLUSIONS: The UDI-6 section of the PFDI-20 was found to be valid in Luganda. The PFIQ-7 and the entirety of the PFDI-20 were not found to be reliable or valid, likely because of the low prevalence of PFDs in the study population.

Eukaryotic Initiation Factor 5A2 localizes to actively translating ribosomes to promote cancer cell protrusions and invasive capacity.

BACKGROUND: Eukaryotic Initiation Factor 5A (eIF-5A), an essential translation factor, is post-translationally activated by the polyamine spermidine. Two human genes encode eIF-5A, being eIF5-A1 constitutively expressed whereas eIF5-A2 is frequently found overexpressed in human tumours. The contribution of both isoforms with regard to cellular proliferation and invasion in non-small cell lung cancer remains to be characterized. METHODS: We have evaluated the use of eIF-5A2 gene as prognosis marker in lung adenocarcinoma (LUAD) patients and validated in immunocompromised mice. We have used cell migration and cell proliferation assays in LUAD lines after silencing each eIF-5A isoform to monitor their contribution to both phenotypes. Cytoskeleton alterations were analysed in the same cells by rhodamine-phalloidin staining and fluorescence microscopy. Polysome profiles were used to monitor the effect of eIF-5A2 overexpression on translation. Western blotting was used to study the levels of eIF-5A2 client proteins involved in migration upon TGFB1 stimulation. Finally, we have co-localized eIF-5A2 with puromycin to visualize the subcellular pattern of actively translating ribosomes. RESULTS: We describe the differential functions of both eIF-5A isoforms, to show that eIF5-A2 properties on cell proliferation and migration are coincident with its features as a poor prognosis marker. Silencing of eIF-5A2 leads to more dramatic consequences of cellular proliferation and migration compared to eIF-5A1. Overexpression of eIF-5A2 leads to enhanced global translation. We also show that TGFß signalling enhances the expression and activity of eIF-5A2 which promotes the translation of polyproline rich proteins involved in cytoskeleton and motility features as it is the case of Fibronectin, SNAI1, Ezrin and FHOD1. With the use of puromycin labelling we have co-localized active ribosomes with eIF-5A2 not only in cytosol but also in areas of cellular protrusion. We have shown the bulk invasive capacity of cells overexpressing eIF-5A2 in mice. CONCLUSIONS: We propose the existence of a coordinated temporal and positional interaction between TFGB and eIF-5A2 pathways to promote cell migration in NSCLC. We suggest that the co-localization of actively translating ribosomes with hypusinated eIF-5A2 facilitates the translation of key proteins not only in the cytosol but also in areas of cellular protrusion. Video Abstract.

Operationalising masculinities in theories and practices of gender-transformative health interventions: a scoping review.

Gender-transformative health interventions that involve men and boys are gaining global reach, adaptability to specific geographical, population and epidemiological contexts, public endorsement, and conceptual sophistication. However, the ways in which masculinities are conceptualised and operationalised in theory and practice across these interventions remains unclear. The purpose of this scoping review is to map intervention studies that conceptually grapple with masculinities and analyse: a) how the concept of masculinities is adapted and operationalised in gender-transformative interventions, with respect to intervention population and context, b) what the relationship between the concept of masculinities and its wider theoretical embedding is, and c) on which levels transformation can be observed when working with 'masculinities'.We conducted a search in APA Psych Articles, APA PsycINFO, and CINAHL via EBSCO, MedLine, PubMed, and Web of Sciences (December 2021) looking for peer-reviewed studies on gender-transformative health interventions which engaged with masculinities conceptually. There were no restrictions regarding language, publication date, or geography. Forty-two articles were included in this review. Our abductive analysis finds that 'hegemonic masculinities' is a central concept in almost all included studies. This shows how the concept is adaptable to a range of different intervention contexts. The review further identifies five theoretical approaches, that help operationalise masculinities on an analytical level: feminist framework, affect theory, critical pedagogy, theories of social change, and ecological approaches. Lastly, this review draws out six levels on which transformation can be observed in the intervention outcomes: relational level, symbolic level, material level, affective level, cognitive-behavioural level, and community-structural level. The discussion underlines that processes and practices of (gender) transformation also require engagement with theories of transformation more widely and advocates for theoretical pluralism. Lastly, implications for practice, including preventative, ecological and community-based care models, are drawn out.

Translation and cultural adaption of the emergency department-consumer assessment of healthcare providers and systems (ED CAPHS)-A questionnaire to measure patient experience in Denmark.

AIM: The aim of this study was to translate and culturally adapt The Emergency Department-Consumer Assessment of Healthcare Providers and Systems (ED CAPHS) to the Danish ED context. BACKGROUND: In Denmark, a large number of patients attend emergency departments (ED) every year. During their ED visits, examinations, tests and encounters with different healthcare professionals occur frequently. Moreover, patients receive much information. Patients' direct experiences of care can provide valuable insights into what works and what does not in health care. The emergency department-consumer assessment of healthcare providers and systems (ED CAPHS) is a valid questionnaire designed to measure patients' experiences with ED care and is intended for patients discharged home following their ED visit. METHOD: The translation process was systematically planned and executed using the principles of good practice for the translation and cultural adaptation process for patient-reported outcomes (PRO) guidelines by the ISPOR. RESULTS: The translation and cultural adaption process were successfully conducted. Three items concerning language and race were omitted as they are not distinct in Danish ED context. Furthermore, a few conceptual factors and linguistic challenges were discussed and harmonised during the reconciliation and harmonisation process respectively. The Danish survey ED CAPHS DK containing 32 items was proofread and finalised. CONCLUSION: Overall, patients reported that the survey was relevant and comprehensive, as it focused on essential factors when discharged directly home after an ED admission. ED CAPHS DK is found to be content valid and ready for use. However, a future study testing the Danish version using confirmative factor analysis and internal consistency reliability is needed to ensure construct validity and reliability.

Cross-Cultural Translation and Adaptation of the Perceived Recovery Status Scale to Brazilian Portuguese.

CONTEXT: One of the primary training variables, although often overlooked, is recovery level achieved before starting subsequent training sessions. To find a more practical measurement that is consonant with the daily training routine, the Perceived Recovery Status (PRS) scale is proposed. In this perspective, the present study aimed to translate and culturally adapt the PRS scale into Brazilian Portuguese. DESIGN: This was a clinical measurement. METHODS: The cross-cultural translation was performed according to guidelines. Linguistic validation consisted of 5 stages: forward translation, translation synthesis, back translation, analysis of inconsistencies, and cognitive debriefing. RESULTS: During forward translation, different interpretations were obtained from the 2 translators (versions V1 and V2). Supported by an expert committee, a combined version (V3) was obtained from V1 and V2. During back translation, different interpretations were obtained from the 2 translators (versions V4 and V5). Discrepancies, applicability, and cultural equivalence were documented and analyzed by the expert committee participating in the cross-cultural translation procedure. During the cognitive debriefing, a group of 5 Brazilian people from the general population were asked to participate in a cognitive debriefing to assess the comprehensibility of the translated items. CONCLUSIONS: The PRS was translated and culturally adapted to Brazilian Portuguese (PRS-Brasil).

Minnesota Tobacco Withdrawal Scale revision 2020, validated Czech translation.

Most smokers are addicted to tobacco or nicotine not only psychosocially but also physically, what results in withdrawal symptoms after they miss their dose. These are one of the major barriers to quitting. In the treatment of tobacco dependence, the evaluation of the degree of withdrawal symptoms helps to guide psychobehavioral intervention and, above all, the choice of the type, dose, and duration of pharmacotherapy. The Minnesota Withdrawal Symptoms Scale is one of the most widely used for this purpose, revised in 2020. We present a validated translation of this update.

Validity and reliability of the Brazilian version of the Body Image in Pregnancy Scale.

OBJECTIVES: To describe the translation and cultural adaptation, and evaluate the psychometric properties of the Body Image in Pregnancy Scale when applied to Brazilian pregnant women. BACKGROUND: Poor body image of pregnant women is associated with negative outcomes for maternal and child health. However, there is a lack of psychometric studies aiming to evaluate the body image experiences during pregnancy. METHODS: A methodological study was carried out with 187 Brazilian pregnant women. We performed translation and cross-cultural adaptation (evidence of content validity), and evaluated the psychometric properties (factorial validity through principal component analysis, discriminant validity, and estimated internal consistency) of the Brazilian version of the Body Image in Pregnancy Scale. RESULTS: The scale items presented semantic, idiomatic, cultural, and conceptual equivalences, showing evidence of content validity. Principal component analysis resulted in a 6-factor structure with 35 items which showed an adequate adjustment of the scale among Brazilian pregnant women. Adequate estimated internal consistency (Cronbach's α = .88) was found. The Brazilian version was not able to discriminate pregnant women from different gestational age. CONCLUSION: The Brazilian version of the Body Image in Pregnancy Scale showed evidence of content validity, factorial validity, and estimated internal consistency.

Translation, transcultural adaptation and validation to Brazilian Portuguese of tools for adverse drug reaction assessment in children.

BACKGROUND: Children are more vulnerable to adverse drug reactions (ADRs) due to complex changes in the body during the growth process and lack specific pharmacoepidemiologic studies. Causality and Avoidability assessment of ADRs are relevant to clinical guidelines development and pharmacovigilance. This study aimed to translate and transcultural adapt two new tools-Liverpool Causality Assessment Tool (LCAT) and the Liverpool Avoidability Assessment Tool (LAAT)-to Brazilian-Portuguese and evaluate the psychometric properties of these tools to analyse ADRs in Brazilian children. METHODS: The validation of the cross-cultural adaptation of tools was obtained by the functional (conceptual, semantic, operational, and measurement) equivalence between the original and translated versions of each instrument. The translated version of LCAT and LAAT was applied to assessing the twenty-six case reports of suspected adverse drug reactions in a Brazilian teaching paediatric hospital. The inter-rater reliability (a pharmacist and a physician) was evaluated using Cronbach's alpha. The exact agreement percentages (%EA) and extreme disagreement (%ED) were computed. Overall Kappa index was calculated with a 95% confidence interval. RESULTS: There was a need to modify some terms translated into Portuguese for semantic and conceptual equivalence. The Cronbach's alpha coefficient values obtained were 0.95 and 0.85, and the weighted Kappa (95% confidence interval) were 0.82 (0.67-0.97) and 0.68 (0.45-0.91) for LCAT and LAAT, respectively. The Brazilian-Portuguese versions of the LCAT and LAAT showed reliable and valid tools for the diagnosis and follow-up of ADRs in children. CONCLUSION: The methodological approach allowed the translation, transcultural adaptation, and validation to Brazilian-Portuguese of two easy and quick to perform tools for causality and avoidability of ADRs in children by a multidisciplinary expert specialist committee, including the authors of original tools. We believe these versions may be applied by professionals (patient safety teams) and researchers in Brazil in groups or by a single reviewer. TRIAL REGISTRATION: This study was evaluated and approved by the Research Ethics Committee (Instituto de Pediatria e Puericultura Martagão Gesteira - Federal University of Rio de Janeiro - Number: 3.264.238.

Comprehensive analysis of the translatome reveals the relationship between the translational and transcriptional control in high fat diet-induced liver steatosis.

Translational regulation plays a critical role in gene expression. However, there are few genome-wide studies on translational regulation in non-alcoholic fatty liver disease (NAFLD), which is a severe non-communicable epidemic worldwide. In this study, we performed RNC-mRNA (mRNAs bound to ribosome-nascent chain complex) sequencing and mRNA sequencing to probe the translation status of high-fat-diet (HFD) induced mouse fatty liver. Generally, in the HFD group compared to the control group, changes of translation ratios and changes in mRNA abundance had a negative correlation. The relative abundance of RNC-mRNAs and mRNAs were positively correlated, yet the former changed more slowly than the latter. However, the rate of change became more balanced when it came to the livers of mice that were fed the HFD plus lycopene, an antioxidant. This indicated relatively independent roles of translational modulation and transcriptional regulation. Furthermore, many genes were differentially regulated at the transcriptional or translational levels, suggesting a new screening strategy for functional genes. In conclusion, our analysis revealed the different and correlated role of translational control with transcriptional regulation in the HFD-induced mouse fatty liver relative to the control, which indicates critical roles of translational control for liver steatosis; thus, adding a new dimension towards a better understanding and improvement of treatment for NAFLD.

Pulled away: the experience of bilingual nurses as ad hoc interpreters in the emergency department.

This study aimed to understand the experiences of bilingual nurses asked to interpret in the Emergency Department (ED), and the subsequent impact on safety climate. Australian ED clinicians assess and treat high numbers of linguistically diverse patients, many with limited English proficiency. New South Wales Health policy mandates the use of accredited interpreters when collecting personal and health information, and when obtaining consent for medical procedures. Semi-structured interviews with 12 nurses (representing 12 languages) from two metropolitan EDs were audio-recorded and analysed using qualitative content analysis, guided by Glendon & Stanton's model of organisational climate and culture. Analysis revealed widespread underlying assumptions that engaging interpreters is difficult, time-consuming and costly. Bilingual ED nurses with variable language fluency were used across organisations as the first choice due to clinical urgency, task urgency, and hospital workflow pressures. While the use of nurse interpreters facilitated timely assessment for the benefit of patients, it equally led to increased nurse workload, missed or misinterpreted information and subsequent perceived clinical risk. These practices were supported and facilitated by unit level managerial and multidisciplinary team practices, physician pressure and the nurses' own values and beliefs. While some, (but not all) participants were aware of the interpreter policy, they were torn between their acknowledgement of risky translation practices and their desire to support their colleagues to provide timely, culturally-competent assessment and care. Findings suggests a 'top-down' approach to translation policy has failed to influence the local safety culture and practices and does not address a climate created by clinical urgency and workflow. Formal training and accreditation of bilingual nurses, and/or embedded interpreters for common language groups may reduce risks for non-English speaking patients.

The Qualitative Assessment of Two Translated Dutch Spirituality Scales for Children.

PURPOSE: This article describes the translation and qualitative assessment and small scale validation of two spirituality scales designed for children from English to Dutch and includes the translation and validation process and the results of the two most commonly used and best validated measurement instruments for spirituality in children: the Feeling Good, Living Life scale (FGLL) by Fisher (2004, 2009) and the Spirituality Sensitivity Scale for Children by Stoyles et al. (2012). DESIGN AND METHODS: The translation process was designed according to Beaton et al. (2000) and both the translation and the validation process followed the instructions of the Consensus-based Standards for the Selection of Health Measurement Instruments (COSMIN, 2018). The qualitative validation was done by a three-step test-interview eliciting the face validity of both questionnaires. RESULTS AND CONCLUSIONS: The results show that both instruments were reliably translated, are face valid with some minor alterations and structurally validated overall in the small-scale pilot. PRACTICE IMPLICATIONS: More attention from healthcare professionals and educators should be directed at using spiritual measuring instrument to develop the spiritual vocabulary of children. A larger study is needed to also confirm the cultural validity of the translated scales.

Brain Plasticity in Humans and Model Systems: Advances, Challenges, and Future Directions.

Plasticity, and in particular, neurogenesis, is a promising target to treat and prevent a wide variety of diseases (e.g., epilepsy, stroke, dementia). There are different types of plasticity, which vary with age, brain region, and species. These observations stress the importance of defining plasticity along temporal and spatial dimensions. We review recent studies focused on brain plasticity across the lifespan and in different species. One main theme to emerge from this work is that plasticity declines with age but that we have yet to map these different forms of plasticity across species. As part of this effort, we discuss our recent progress aimed to identify corresponding ages across species, and how this information can be used to map temporal variation in plasticity from model systems to humans.

Balanced Activation of Striatal Output Pathways by Faster Off-Rate PDE10A Inhibitors Elicits Not Only Antipsychotic-Like Effects But Also Procognitive Effects in Rodents.

BACKGROUND: Faster off-rate competitive enzyme inhibitors are generally more sensitive than slower off-rate ones to binding inhibition by enzyme substrates. We previously reported that the cyclic adenosine monophosphate concentration in dopamine D1 receptor-expressing medium spiny neurons (D1-MSNs) may be higher than that in D2-MSNs. Consequently, compared with slower off-rate phosphodiesterase 10A inhibitors, faster off-rate ones comparably activated D2-MSNs but partially activated D1-MSNs. We further investigated the pharmacological profiles of phosphodiesterase 10A inhibitors with different off-rates. METHODS: Phosphodiesterase 10A inhibitors with slower (T-609) and faster (T-773) off-rates were used. D1- and D2-MSN activation was assessed by substance P and enkephalin mRNA induction, respectively, in rodents. Antipsychotic-like effects were evaluated by MK-801- and methamphetamine-induced hyperactivity and prepulse inhibition in rodents. Cognition was assessed by novel object recognition task and radial arm maze in rats. Prefrontal cortex activation was evaluated by c-Fos immunohistochemistry in rats. Gene translations in D1- and D2-MSNs were evaluated by translating ribosome affinity purification and RNA sequencing in mice. RESULTS: Compared with T-609, T-773 comparably activated D2-MSNs but partially activated D1-MSNs. Haloperidol (a D2 antagonist) and T-773, but not T-609, produced antipsychotic-like effects in all paradigms. T-773, but not T-609 or haloperidol, activated the prefrontal cortex and improved cognition. Overall gene translation patterns in D2-MSNs by all drugs and those in D1-MSNs by T-773 and T-609 were qualitatively similar. CONCLUSIONS: Differential pharmacological profiles among those drugs could be attributable to activation balance of D1- and D2-MSNs. The "balanced activation" of MSNs by faster off-rate phosphodiesterase 10A inhibitors may be favorable to treat schizophrenia.

Cross-cultural adaptation and validation for the Brazilian population of the instrument Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF).

OBJECTIVE: This study aims to produce and validate the version of the instrument Amyotrophic Lateral Sclerosis-Specific Quality of Life-Short Form (ALSSQOL-SF) into Portuguese, adapted to the Brazilian cultural context. METHODOLOGY: It is a cross-cultural adaptation and validation study, carried out in two Brazilian Public Universities, in the period from March, 2017, to November, 2018, according to the six steps guidelines of cultural and linguistic adaptation proposed by Beaton et al. (Spine 25(24):3186-3191, 2000). The World Health Organization Quality of Life (WHOQOL-BREF) and the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) were used for perform the validation. In order to analyze the correlations between the ALSSQOL-SF, WHOQOL-BREF, and ALSFRS-R scores, Spearman's correlation coefficients were calculated. The project was approved by the Research Ethics Committee of the two participating institutions. RESULT: All steps of the transcultural adaptation process were performed without intercurrence. The pilot test had the participation of 30 individuals, and the "Questionário Breve Específico de Qualidade de Vida para Pacientes com ELA (QVELA-20/Br)" tool was developed. During the validation phase, 100 patients were included, most of them were male (58%) with a median age of 59 years. The created version of the questionnaire are positively and strongly correlated with the WHOQOL-BREF and positively and weakly correlated with ALSFRS-R, as expected. CONCLUSION: The study produced and validated a version of the instrument ALSSQOL-SF into Portuguese that is adapted to the Brazilian cultural context.

Incorporation of nonstandard amino acids into proteins: principles and applications.

The cellular ribosome shows a naturally evolved strong preference for the synthesis of proteins with standard amino acids. An in-depth understanding of the translation process enables scientists to go beyond this natural limitation and engineer translating systems capable of synthesizing proteins with artificially designed and synthesized non-standard amino acids (nsAA) featuring more bulky sidechains. The sidechains can be functional groups, with chosen biophysical or chemical activities, that enable the direct application of these proteins. Alternatively, the sidechains can be designed to contain highly reactive groups: enabling the ready formation of conjugates via a covalent bond between the sidechain and other chemicals or biomolecules. This co-translational incorporation of nsAAs into proteins allows for a vast number of possible applications. In this paper, we first systematically summarized the advances in the engineering of the translation system. Subsequently, we reviewed the extensive applications of these nsAA-containing proteins (after chemical modification) by discussing representative reports on how they can be utilized for different purposes. Finally, we discussed the direction of further studies which could be undertaken to improve the current technology utilized in incorporating nsAAs in order to use them to their full potential and improve accessibility across disciplines.

A fuzzy evaluation and selection of construction and demolition waste utilization modes in Xi'an, China.

The inadequate reuse and recycle of construction and demolition waste (C&DW) has been identified as a major issue, as it implies the depletion of natural aggregates, massive occupation of landfill and inefficiency of construction industry. However, a holistic view involving economic, technical and comprehensive dimensions has rarely been adopted for C&DW utilization evaluation against both qualitative and quantitative criteria. In this study, we propose a framework in a heterogeneous group decision-making environment to solve the C&DW utilization mode selection problem by integrating the Choquet integral and the elimination and choice translating reality (ELECTRE) method with two data forms, that is, interval-valued hesitant fuzzy numbers and real numbers. Firstly, an evaluation index system is constructed to assess multiple representative C&DW utilization modes in Xi'an, China. Secondly, a novel method is proposed to apply the Choquet integral for aggregation of evaluation values and fuzzy ELECTRE for outranking of C&DW utilization modes after the heterogenous evaluation data are unified into interval numbers. Thirdly, to illustrate the application of the proposed framework, this paper evaluates four typical C&DW utilization modes based on a case study in Xi'an, China, and the result shows that the most preferable mode is A3 (off-site crushing, roadbed backfilling). Finally, a comparative analysis is conducted to verify the effectiveness of this framework. This study presents useful findings to C&DW practitioners and can help avoid intuitive selection among available C&DW utilization modes.

Astrocyte-specific transcriptome analysis using the ALDH1L1 bacTRAP mouse reveals novel biomarkers of astrogliosis in response to neurotoxicity.

Neurotoxicology is hampered by the inability to predict regional and cellular targets of toxicant-induced damage. Evaluating astrogliosis overcomes this problem because reactive astrocytes highlight the location of toxicant-induced damage. While enhanced expression of glial fibrillary acidic protein is a hallmark of astrogliosis, few other biomarkers have been identified. However, bacterial artificial chromosome - translating ribosome affinity purification (bacTRAP) technology allows for characterization of the actively translating transcriptome of a particular cell type; use of this technology in aldehyde dehydrogenase 1 family member L1 (ALDH1L1) bacTRAP mice can identify genes selectively expressed in astrocytes. The aim of this study was to characterize additional biomarkers of neurotoxicity-induced astrogliosis using ALDH1L1 bacTRAP mice. The known dopaminergic neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 12.5 mg/kg s.c.) was used to induce astrogliosis. Striatal tissue was obtained 12, 24, and 48 h following exposure for the isolation of actively translating RNA. Subsequently, MPTP-induced changes in this RNA pool were analyzed by microarray and 184 statistically significant, differentially expressed genes were identified. The dataset was interrogated by gene ontology, pathway, and co-expression network analyses, which identified novel genes, as well as those with known immune and inflammatory functions. Using these analyses, we were directed to several genes associated with reactive astrocytes. Of these, TIMP1 and miR-147 were identified as candidate biomarkers because of their robust increased expression following both MPTP and trimethyl tin exposures. Thus, we have demonstrated that bacTRAP can be used to identify new biomarkers of astrogliosis and aid in the characterization of astrocyte phenotypes induced by toxicant exposures. OPEN SCIENCE BADGES: This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: 10.1111/jnc.14518.

Developing a risk-based composite neurologic outcome for a trial of hydroxyurea in young children with sickle cell disease.

BACKGROUND: Studies of interventions to prevent the many neurological complications of sickle cell disease must take into account multiple outcomes of variable severity, with limited sample size. The goals of the studies presented were to use investigator preferences across outcomes to determine an attitude-based weighting of relevant clinical outcomes and to establish a valid composite outcome for a clinical trial. METHODS: In Study 1, investigators were surveyed about their practice regarding hydroxyurea therapy and opinions about outcomes for the "Hydroxyurea to Prevent the Central Nervous System Complications of Sickle Cell Disease Trial" (HU Prevent), and their minimally acceptable relative risk reduction for the two outcome components, motor and neurocognitive deficits. In Study 2, HU Prevent investigators provided overall weights for these two components. In Study 3, they provided more granular rankings, ratings, and maximum number acceptable to harm. A weighted composite outcome, the Stroke Consequences Risk Score, was constructed that incorporates the major neurologic complications of sickle cell disease. The Stroke Consequences Risk Score represents the 3-year risk of suffering the adverse consequences of stroke. In Study 4, the results of the Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP2) and Silent Infarct Transfusion Trials were reanalyzed in light of the composite outcome. RESULTS: In total, 22 to 27 investigators participated per study. In Study 1, across three samplings between 2009 and 2015, the average minimally acceptable relative risk reduction ranged from 0.36 to 0.50, at or below the target effect size of 0.50. In 2015, 21 (91%) reported that a placebo-controlled trial is reasonable; 23 (100%), that it is ethical; and 22 (96%), that they would change their practice, if the results of the trial were positive. In Studies 2 and 3, the weight elicited for a cognitive decline (of 10 IQ points) from the overall assessment was 0.67 (and for motor deficit, the complementary 0.33); from ranking, 0.6; from rating, 0.58; and from maximal number acceptable to harm, 0.5. Using data from two major clinical trials, Study 4 demonstrated the same conclusions as the original trials using the Stroke Consequences Risk Score, with smaller p-values for both reanalyses. An assessment of acceptability was performed as well. CONCLUSION: This set of studies provides the rationale, justification, and validation for the use of a weighted composite outcome and confirms the need for the phase III HU Prevent study. Surveys of investigators in multi-center studies can provide the basis of clinically meaningful outcomes that foster the translation of study results into practice while increasing the efficiency of a study.

The Expanding Toolkit of Translating Ribosome Affinity Purification.

Translating ribosome affinity purification is a method initially developed for profiling mRNA from genetically defined cell types in complex tissues. It has been applied both to identify target molecules in cell types that are important for controlling a variety of behaviors in the brain, and to understand the molecular consequences on those cells due to experimental manipulations, ranging from drugs of abuse to disease-causing mutations. Since its inception, a variety of methodological advances are opening new avenues of investigation. These advances include a variety of new methods for targeting cells for translating ribosome affinity purification by features such as their projections or activity, additional tags and mouse reagents increasing the flexibility of the system, and new modifications of the method specifically focused on studying the regulation of translation. The latter includes methods to assess cell type-specific regulation of translation in specific subcellular compartments. Here, I provide a summary of these recent advances and resources, highlighting both new experimental opportunities and areas for future technical development.

Correspondence regarding 'Assefa Y, et al., BMC Health Services Research. 2011; 11 (1):81 and 2014; 14(1):45': The Positive-Deviance approach for translating evidence into practice to improve patient retention in HIV care.

The purpose of this correspondence is to describe how the positive-deviance approach can be used to translate evidence into practice, based on successive studies conducted in Ethiopia. In earlier studies, it was identified that retention in antiretroviral treatment care was variable across health facilities; and, seeking compliance across facilities, a framework was developed based on the practices of those positive-deviant health facilities, where performance was noted to be markedly better. It was found that the positive deviance approach was effective in facilitating the transfer of innovative practices (using different mechanisms) from positive-deviant health facilities to negative-deviant health facilities. As a result, the variability in retention in care across health facilities narrowed over time, increasing from 83 to 96% in 2007/8 to 95-97% in 2013/14. In conclusion, the positive-deviance approach is a valuable tool to translate evidence into practice, spread good practices, and help achieving universal health coverage.