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The assessment of research performance is widely seen as a vital tool in upholding the highest standards of quality, with selection and competition believed to drive progress. Academic institutions need to take critical decisions on hiring and promotion, while facing external pressure by also being subject to research assessment 1 , 2 , 3 – 4 . Here we present an outlook on research assessment for career progression with specific focus on promotion to full professorship, based on 314 policies from 190 academic institutions and 218 policies from 58 government agencies, covering 32 countries in the Global North and 89 countries in the Global South. We investigated how frequently various promotion criteria are mentioned and carried out a statistical analysis to infer commonalities and differences across policies. Although quantitative methods of assessment remain popular, in agreement with what is found in more geographically restricted studies 5 , 6 , 7 , 8 – 9 , they are not omnipresent. We find differences between the Global North and the Global South as well as between institutional and national policies, but less so between disciplines. A preference for bibliometric indicators is more marked in upper-middle-income countries. Although we see some variation, many promotion policies are based on the assumption of specific career paths that become normative rather than embracing diversity. In turn, this restricts opportunities for researchers. These results challenge current practice and have strategic implications for researchers, research managers and national governments. Analysis of policies for promotion criteria to full professor from academic institutions and government agencies worldwide reveals considerable variation in assessment practices, particularly between the Global North and South.

Pompe disease is a rare metabolic disorder, due to mutations in the gene encoding acid alpha-glucosidase (GAA), of which infantile and late-onset forms may occur. Aim of the work was to analyze clinical and laboratory data of a cohort of late-onset Pompe disease (LOPD) patients, collected during the last 15 years and to point out unusual phenotypic/genotypic features as well as enzyme replacement therapy (ERT) responses. We diagnosed 30 LOPD patients; at follow-up, they underwent motor, respiratory, cardiac and muscle MRI evaluations. Motor performances were tested by Walton Gardner-Medwin, GSGC and 6MWT tests. Respiratory function was assessed as FVC % in upright/supine position. LOPD presentations were represented by presymptomatic hyperCKemia (37 %), proximal/axial muscle weakness (53 %) and respiratory impairment (10 %). Median diagnostic delay was 8.6 years (±8.8). Atypical features were observed in 4 patients: marked distal muscle weakness and severe hearing loss at onset, as well as leukoencephalopathy and mesial temporal sclerosis during the disease course. By GAA sequence analysis, two causing mutations were detected in 22/30 patients, only one in the remaining 8 subjects. Overall, 29/30 patients harbored the common c.−32−13T>G mutation (2 were homozygous). Two new DNA variations were discovered (c.2395C>G, c.1771C>T). 14 patients received ERT for up to 60 months. Our study confirms LOPD clinical and genetic heterogeneity: atypical features may contribute to expand the clinical phenotype highlighting its multi-systemic nature. A timely diagnosis could allow early ERT start. An accurate follow-up is recommended to evaluate treatment responses.

ObjectiveA multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool.Design/methods17 Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis.ResultsIn a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW.ConclusionsLOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.

Background In order to improve assessment and outcome prediction in patients suffering from traumatic brain injury (TBI), cerebral protein levels in serum have been suggested as biomarkers of injury. However, despite much investigation, biomarkers have yet to reach broad clinical utility in TBI. This study is a 9-year follow-up and clinical experience of the two most studied proteins, neuron-specific enolase (NSE) and S100B, in a neuro-intensive care TBI population. Our aims were to investigate to what extent NSE and S100B, independently and in combination, could predict outcome, assess injury severity, and to investigate if the biomarker levels were influenced by extracranial factors. Methods All patients treated at the neuro-intensive care unit at Karolinska University Hospital, Stockholm, Sweden between 2005 and 2013 with at least three measurements of serum S100B and NSE (sampled twice daily) were retrospectively included. In total, 417 patients fulfilled the criteria. Parameters were extracted from the computerized hospital charts. Glasgow Outcome Score (GOS) was used to assess long-term functional outcome. Univariate, and multivariate, regression models toward outcome and what explained the high levels of the biomarkers were performed. Nagelkerke’s pseudo-R 2 was used to illustrate the explained variance of the different models. A sliding window assessed biomarker correlation to outcome and multitrauma over time. Results S100B was found a better predictor of outcome as compared to NSE (area under the curve (AUC) samples, the first 48 hours had Nagelkerke’s pseudo-R 2 values of 0.132 and 0.038, respectively), where the information content of S100B peaks at approximately 1 day after trauma. In contrast, although both biomarkers were independently correlated to outcome, NSE had limited additional predictive capabilities in the presence of S100B in multivariate models, due to covariance between the two biomarkers (correlation coefficient 0.673 for AUC 48 hours). Moreover, NSE was to a greater extent correlated to multitrauma the first 48 hours following injury, whereas the effect of extracerebral trauma on S100B levels appears limited to the first 12 hours. Conclusions While both biomarkers are independently correlated to long-term functional outcome, S100B is found a more accurate outcome predictor and possibly a more clinically useful biomarker than NSE for TBI patients.

Several studies have reported an association between serum biomarker values and functional outcome following traumatic brain injury. We aimed to examine the incremental (added) prognostic value of serum biomarkers over demographic, clinical, and radiological characteristics and over established prognostic models, such as IMPACT and CRASH, for prediction of functional outcome. We used data from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) core study. We included patients aged 14 years or older who had blood sampling within 24 h of injury, results from a CT scan, and outcome assessment according to the Glasgow Outcome Scale-Extended (GOSE) at 6 months. Amounts in serum of six biomarkers (S100 calcium-binding protein B, neuron-specific enolase, glial fibrillary acidic protein, ubiquitin C-terminal hydrolase L1 [UCH-L1], neurofilament protein-light, and total tau) were measured. The incremental prognostic value of these biomarkers was determined separately and in combination. The primary outcome was the GOSE 6 months after injury. Incremental prognostic value, using proportional odds and a dichotomised analysis, was assessed by delta C-statistic and delta R2 between models with and without serum biomarkers, corrected for optimism with a bootstrapping procedure. Serum biomarker values and 6-month GOSE were available for 2283 of 4509 patients. Higher biomarker levels were associated with worse outcome. Adding biomarkers improved the C-statistic by 0·014 (95% CI 0·009–0·020) and R2 by 4·9% (3·6–6·5) for predicting GOSE compared with demographic, clinical, and radiological characteristics. UCH-L1 had the greatest incremental prognostic value. Adding biomarkers to established prognostic models resulted in a relative increase in R2 of 48–65% for IMPACT and 30–34% for CRASH prognostic models. Serum biomarkers have incremental prognostic value for functional outcome after traumatic brain injury. Our findings support integration of biomarkers—particularly UCH-L1—in established prognostic models. European Union's Seventh Framework Programme, Hannelore Kohl Stiftung, OneMind, Integra LifeSciences, and NeuroTrauma Sciences

Ubiquitin C-terminal hydrolase-L1 (UCH-L1) is a neuron-specific enzyme that has been identified as a potential biomarker of traumatic brain injury (TBI). The study objectives were to determine UCH-L1 exposure and kinetic metrics, determine correlations between biofluids, and assess outcome correlations in severe TBI patients. Data were analyzed from a prospective, multicenter study of severe TBI (Glasgow Coma Scale [GCS] score ≤8). Cerebrospinal fluid (CSF) and serum data from samples taken every 6 h after injury were analyzed by enzyme-linked immunosorbent assay (ELISA). UCH-L1 CSF and serum data from 59 patients were used to determine biofluid correlations. Serum samples from 86 patients and CSF from 59 patients were used to determine outcome correlations. Exposure and kinetic metrics were evaluated acutely and up to 7 days post-injury and compared to mortality at 3 months. There were significant correlations between UCH-L1 CSF and serum median concentrations (rs =0.59, p<0.001), AUC (rs =0.3, p=0.027), Tmax (rs =0.68, p<0.001), and MRT (rs =0.65, p<0.001). Outcome analysis showed significant increases in median serum AUC (2016 versus 265 ng/mL*min, p=0.006), and Cmax (2 versus 0.4 ng/mL, p=0.003), and a shorter Tmax (8 versus 19 h, p=0.04) in those who died versus those who survived, respectively. In the first 24 h after injury, there was a statistically significant acute increase in CSF and serum median Cmax(0–24h) in those who died. This study shows a significant correlation between UCH-L1 CSF and serum median concentrations and biokinetics in severe TBI patients, and relationships with clinical outcome were detected.

The assessment of research performance is widely seen as a vital tool in upholding the highest standards of quality, with selection and competition believed to drive progress. Academic institutions need to take critical decisions on hiring and promotion, while facing external pressure by also being subject to research assessment 1–4 . Here we present an outlook on research assessment for career progression with specific focus on promotion to full professorship, based on 314 policies from 190 academic institutions and 218 policies from 58 government agencies, covering 32 countries in the Global North and 89 countries in the Global South. We investigated how frequently various promotion criteria are mentioned and carried out a statistical analysis to infer commonalities and differences across policies. Although quantitative methods of assessment remain popular, in agreement with what is found in more geographically restricted studies 5–9 , they are not omnipresent. We find differences between the Global North and the Global South as well as between institutional and national policies, but less so between disciplines. A preference for bibliometric indicators is more marked in upper-middle-income countries. Although we see some variation, many promotion policies are based on the assumption of specific career paths that become normative rather than embracing diversity. In turn, this restricts opportunities for researchers. These results challenge current practice and have strategic implications for researchers, research managers and national governments.

Background Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. Methods We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. Results We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. Conclusions Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.

Statement of purposeViolence adversely impacts individuals’ mental health and contributes to the development of neuropsychiatric disorders. This study aims to assess the psychological state of the Syrian refugee population exposed to war-related violence and analyze their association with neuropsychiatric morbidity.Methods/ApproachIn 2017, a refugee cohort in Lebanon completed the Harvard Trauma Questionnaire (HTQ), Post- Migration Living Difficulties Checklist (PMLDC), Posttraumatic Stress Disorder Checklist for DSM-5 (PCL-5), and the Depression and Anxiety Scale-21 Items (DAS-21). We performed multivariable logistic regressions to examine potential factors associated with long-term neuropsychiatric disorders.ResultsOf the 220 refugees, 191 were eligible to participate, of whom 92.15% were exposed to at least one war-related violence. As for the neuropsychiatric morbidity, 64% met the cut-off point for PTSD diagnosis, while 62.8% and 64.4% suffered from moderate to extremely severe depression and anxiety, respectively. We identified war-related violence as the strongest predictor of PTSD (adjusted [OR] 1.16, 95% CI 1.07 – 1.26; p = 0.001) and of severe and extremely severe depression (OR 1.21, 95% CI 1.05 – 1.39; p < 0.01). Only higher anxiety levels were associated with post-migration living difficulties (OR 1.03, 95% CI 1.01 – 1.05; p < 0.0001). While lower educational attainment was a significant risk factor for all three neuropsychiatric disorders, being a male was a significant protective factor for both depression (OR 0.19, 95% CI 0.04 – 0.96; p < 0.05) and anxiety (OR 0.35, 95% CI 0.15 – 0.85; p < 0.05).ConclusionsWar-related violence constitutes a major risk factor for multiple neuropsychiatric disorders. Identified prognostic factors include post-migration living difficulties, educational attainment, and gender.SignificanceThis study highlights the adverse impact of violence on individuals. Generated evidence should be adopted to develop and implement tailored psychological programs targeting refugees and displaced individuals.

We performed comparative proteomic analyses of blood of patients with RLS and healthy individuals aiming to identify potential biomarker and therapeutic target candidate for RLS. Blood serum samples from 12 patients with a clinical diagnosis of RLS (8 females and 4 males, with a mean age of 68.52 years) and 10 healthy controls (5 females and 5 males, with a mean age of 67.61 years) underwent proteomic profiling by liquid chromatography coupled with tandem mass spectrometry. Pathway analysis incorporating protein-protein interaction networks was carried out to identify pathological processes linked to the differentially expressed proteins. We quantified 272 proteins in patients with RLS and healthy controls, of which 243 were shared. Five proteins - apolipoprotein C-II, leucine-rich alpha-2-glycoprotein 1, FLJ92374, extracellular matrix protein 1, and FLJ93143 - were substantially increased in RLS patients, whereas nine proteins - vitamin D-binding protein, FLJ78071, alpha-1-antitrypsin, CD5 antigen-like, haptoglobin, fibrinogen alpha chain, complement factor H-related protein 1, platelet factor 4, and plasma protease C1 inhibitor - were decreased. Bioinformatics analyses revealed that these proteins were linked to 1) inflammatory and immune response, and complement activation, 2) brain-related development, cell aging, and memory disorders, 3) pregnancy and associated complications, 4) myocardial infarction, and 5) reactive oxygen species generation and subsequent diabetes mellitus. Our findings shed light on the multifactorial nature of RLS and identified a set of circulating proteins that may have clinical importance as biomarkers and therapeutic targets.