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Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

Many recent higher education reforms worldwide have been legitimated by their potential impact on the performance of universities and colleges. However, we know less about the actual impact of the changes implemented. This article examines the extent to which research performance can be associated with specific organizational characteristics at the department level. The analysis is based on Norwegian university departments, where high- and low-performing departments have been selected as cases for further investigations. The policy context is the organizational reform in Norway from 2016 onwards aiming at reorganizing the higher education landscape through institutional mergers. The key findings indicate that there are few distinct departmental characteristics associated with research performance, such as elected or appointed leadership, single or multi-campus organization, or departmental size. However, the study reveals that highly productive individuals do matter and suggests that cultural dimensions and working conditions may be interesting factors to pursue in further research.

Abstract Several mental disorders emerge during childhood or adolescence and are often characterized by socioemotional difficulties, including alterations in emotion perception. Emotional facial expressions are processed in discrete functional brain modules whose connectivity patterns encode emotion categories, but the involvement of these neural circuits in psychopathology in youth is poorly understood. This study examined the associations between activation and functional connectivity patterns in emotion circuits and psychopathology during development. We used task-based fMRI data from the Philadelphia Neurodevelopmental Cohort (PNC, N = 1221, 8–23 years) and conducted generalized psycho-physiological interaction (gPPI) analyses. Measures of psychopathology were derived from an independent component analysis of questionnaire data. The results showed positive associations between identifying fearful, sad, and angry faces and depressive symptoms, and a negative relationship between sadness recognition and positive psychosis symptoms. We found a positive main effect of depressive symptoms on BOLD activation in regions overlapping with the default mode network, while individuals reporting higher levels of norm-violating behavior exhibited emotion-specific lower functional connectivity within regions of the salience network and between modules that overlapped with the salience and default mode network. Our findings illustrate the relevance of functional connectivity patterns underlying emotion processing for behavioral problems in children and adolescents.

Abstract Background Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further. Methods Here we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years. Results We found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression. Discussion In our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.

Abstract Background The aetiology of delirium is not known, but pre-existing cognitive impairment is a predisposing factor. Here we explore the associations between delirium and cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), proteins with important roles in both acute injury and chronic neurodegeneration. Methods Using a 13-plex Discovery Assay®, we quantified CSF levels of 9 MMPs and 4 TIMPs in 280 hip fracture patients (140 with delirium), 107 cognitively unimpaired individuals, and 111 patients with Alzheimer’s disease dementia. The two delirium-free control groups without acute trauma were included to unravel the effects of acute trauma (hip fracture), dementia, and delirium. Results Here we show that delirium is associated with higher levels of MMP-2, MMP-3, MMP-10, TIMP-1, and TIMP-2; a trend suggests lower levels of TIMP-4 are also associated with delirium. Most delirium patients had pre-existing dementia and low TIMP-4 is the only marker associated with delirium in adjusted analyses. MMP-2, MMP-12, and TIMP-1 levels are clearly higher in the hip fracture patients than in both control groups and several other MMP/TIMPs are impacted by acute trauma or dementia status. Conclusions Several CSF MMP/TIMPs are significantly associated with delirium in hip fracture patients, but alterations in most of these MMP/TIMPs could likely be explained by acute trauma and/or pre-fracture dementia. Low levels of TIMP-4 appear to be directly associated with delirium, and the role of this marker in delirium pathophysiology should be further explored.

Michel Kabamba Nzaji,1 Anselme Manyong Kapit,1 Kristen B Stolka,2 Shanice Fezeu Meyou,2 Charlie K Kasendue,3 Melissa Dahlke,4 Robert T Perry,4 Reena H Doshi,4 Brooke Noel Aksnes,4 Richard R Luce,3 Stephane Hans Bateyi Mustafa,5 Crispin Kazadi Mwina-Ngoie,5 Cikomola Mwana Wa Bene Aimé,5 Pia DM MacDonald,1,6 Claire J Standley7,8 1Social, Statistical, & Environmental Sciences, RTI International, Kinshasa, Democratic Republic of the Congo; 2Social, Statistical, & Environmental Sciences, RTI International, Research Triangle Park, NC, United States America; 3Division of Global Health Protection (DGHP), U.S. Centers for Disease Control and Prevention (CDC), Kinshasa, Democratic Republic of the Congo; 4Global Immunization Division (GID), U.S. Centers for Disease Control and Prevention (CDC), Atlanta, GA, United States America; 5Expanded Programme on Immunization (EPI), Ministry of Public Health & Hygiene, Kinshasa, Democratic Republic of the Congo; 6Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, United States America; 7Center for Global Health Science and Security, Georgetown University, Washington, DC, United States America; 8Heidelberg Institute of Global Health, University of Heidelberg, Heidelberg, GermanyCorrespondence: Michel Kabamba Nzaji, RTI International, Social, Statistical, & Environmental Sciences, Kinshasa, Democratic Republic of the Congo, Tel +243978467432, Email michelnzaji@yahoo.frBackground: Low levels of COVID-19 vaccination coverage in many countries prompted the use of rapid assessments to characterize barriers to vaccination and identify corrective measures. The World Health Organization recommended the use of intra-action reviews (IARs) to identify best practices, gaps, and lessons learned to make real-time improvements to the COVID-19 vaccination response.Objective: The Democratic Republic of the Congo (DRC) implemented a national IAR in July 2021 that was poorly attended by the provincial health level, where vaccination activities are planned and implemented. To bridge this gap, we proposed sub-national IARs focused on COVID-19 vaccine program implementation at the provincial level.Methods: Using the WHO methodology, we organized a four-day provincial IAR workshop and invited national, provincial and health zone Ministry of Health (MoH) representatives and private and non-governmental organizations involved in the provincial COVID-19 vaccination response. Participants were divided into six groups based on their expertise, affiliation, and role within the health system to assess and identify lessons learned, challenges and the solutions within each of the six technical areas: (1) coordination, planning and monitoring; (2) service delivery; (3) risk communication and community engagement; (4) adverse effects following immunization (AEFI); (5) logistics; (6) and data management, monitoring and evaluation.Results: The first provincial COVID-19 IAR was conducted in Goma, North Kivu, from January 19– 22, 2022. A total of 56 participants came from provincial and health zone offices, and non-governmental organizations. Through work group discussions, they identified best practices, challenges, and lessons learned, and made recommendations to improve implementation of vaccination activities and reach coverage targets. Activities were proposed to operationalize recommendations and address challenges to improve the provincial response.Conclusion: This provincial IAR was a useful tool for reviewing progress and areas of improvement, while evaluating aspects of the COVID-19 vaccine rollout. It provided a means to share information with vaccination partners on areas of intervention, tailored to the local context.Keywords: COVID-19, intra-action review, COVID-19 vaccination, public health preparedness and response, Democratic Republic of Congo, public health emergency management

Research on the use of digital devices to conduct tasks across work and non-work domains (i.e., boundary-crossing ICT use) grows rapidly. To gain an overview of this expanding field, we conducted a systematic search in 14 databases (e.g., WoS, PsycINFO) for studies examining the outcomes of performing 1) work-related tasks during non-work time and 2) non-work tasks during work time. After screening 17,388 abstracts, 398 were read in full text, and 159 publications were included. Most studies used cross-sectional interviews or self-report survey data of employees in high-income countries. The work-family interface, individual work and health outcomes were commonly studied, while family and organizational outcomes received little attention. Moreover, research with a multilevel perspective and studies examining objective outcomes (e.g., divorce, sick leave) were scarce and the performance of non-work tasks during work time was often ignored. Despite the burgeoning literature, there is an urgent need to arrive at a common conceptualization and operationalization of boundary-crossing ICT use to be able to compare findings across studies and disciplines. We suggest a new definition and future agenda to contribute to a deeper understanding of the field.

Abstract Primary familial brain calcification (PFBC) is characterized by calcium deposition in the brain, causing progressive movement disorders, psychiatric symptoms, and cognitive decline. PFBC is a heterogeneous disorder currently linked to variants in six different genes, but most patients remain genetically undiagnosed. Here, we identify biallelic NAA60 variants in ten individuals from seven families with autosomal recessive PFBC. The NAA60 variants lead to loss-of-function with lack of protein N-terminal (Nt)-acetylation activity. We show that the phosphate importer SLC20A2 is a substrate of NAA60 in vitro. In cells, loss of NAA60 caused reduced surface levels of SLC20A2 and a reduction in extracellular phosphate uptake. This study establishes NAA60 as a causal gene for PFBC, provides a possible biochemical explanation of its disease-causing mechanisms and underscores NAA60-mediated Nt-acetylation of transmembrane proteins as a fundamental process for healthy neurobiological functioning.

The longwave infrared (LWIR) range, which spans from 6 µm to 14 µm, is appealing for sensing due to strong molecular fingerprints in this range. However, the limited availability of low-loss materials that can provide higher-index waveguiding and lower-index cladding in the LWIR range presents challenges for integrated photonics. In this work, we introduce a low-loss germanium-on-zinc selenide (GOZ) platform that could serve as a versatile platform for nanophotonics in the LWIR. By bonding high-quality thin-film germanium (Ge) to a zinc selenide (ZnSe) substrate, we demonstrate transparency from 2 µm to 14 µm and optical losses of just 1 cm−1 at 7.8 µm. Our results demonstrate that hybrid photonic platforms could be invaluable for overcoming the losses of epitaxially grown materials and could enable a wide range of future quantum and nonlinear photonics.

The representation of three-dimensional integrated photonic structures in two-dimensional designs has been investigated through finite element analysis using COMSOL Multiphysics. The accuracy of the effective index method for various waveguide designs is studied. An alternative to the effective index method, here named the inverse effective index method, is derived in this paper. The results indicate that the commonly used effective index method has a deviation in propagation constant up to 17%, where the error is largest for low-confinement factor waveguides. The inverse effective index method vastly reduces this error to $< $0.01% for low confinement-factor geometries. This enables an accurate simulation in two-dimensions while retaining the waveguiding properties of the third dimension. As with the effective index method, the inverse effective index method does not require proprietary software.

This is a scoping review of literature on positive employment outcomes for people with disabilities (PWD) and stakeholders in the organization. The aim is to investigate the connection between workplace practices and positive employment outcomes contributing to sustainable employment. Methodologically, the scoping process commenced with four electronic databases and resulted in a total of 42 articles. We identified seven categories of workplace practices that contributed to positive employment outcomes: accommodation, cultural practices, human resource management (HRM) practices, leadership, participation, support, and training. We identified five categories of positive employment outcomes: employment experiences of PWD, employment outcomes of PWD, employment outcomes of stakeholders in the organizations, work performance, and organizational outcomes. The article discusses the findings in relation to studies on employment of PWD which often focus on discrimination and barriers faced by PWD. The scoping process revealed a research gap where the majority of articles described positive employment experiences of PWD, while only a few articles described positive employment experiences of stakeholders in the organization. We propose that future research focus on workplace practices that can advance our theoretical and empirical understanding of what contributes to sustainable employment of PWD.

Teorien om bakkebyråkratiet fremstår nærmest som en standardreferanse for forskere som studerer førstelinjen på arbeidsinkluderingsfeltet. I artikkelen drøfter jeg hvorvidt teorien egner seg til å analysere nye og mer grenseoverskridende roller som har vokst frem som respons på en mer samarbeidsorientert og arbeidsgiverrettet inkluderingspolitikk. Én slik rolle er såkalte næringslivskonsulenter, som jobber som bindeledd mellom tiltaksbedrifter og arbeidsgivere. Teoriens styrke er at den får frem dynamikken mellom dilemmaene på bakkeplan og den overordnede politikken. Teoriens begrensning knyttes til at arbeidsinkludering i stor grad foregår utenfor Nav-kontoret, og at det derfor gir begrenset verdi å forstå de nye rollene innenfor en avgrenset byråkratisk kontekst. I artikkelen foreslår jeg å i større grad benytte nyutviklede bakkebyråkratiperspektiver samt perspektiver på boundary spanning (brobygging) for å få frem aktørskap, kreativitet og nye initiativer og løsninger som forekommer på arbeidsinkluderingsfeltet.

Many studies on research productivity and performance suggest that men consistently outperform women. However, women and men are spread unevenly throughout the academy both horizontally (e.g., by scientific field) and vertically (e.g., by academic position), suggesting that aggregate numbers (comparing all men with all women) may reflect the different publication practices in different corners of the academy rather than gender per se. We use Norwegian bibliometric data to examine how the "what" (which publication practices are measured) and the "who" (how the population sample is disaggregated) matter in assessing apparent gender differences among academics in Norway. We investigate four clusters of indicators related to publication volume, publication type, authorship, and impact or quality (12 indicators in total) and explore how disaggregating the population by scientific field, institutional affiliation, academic position, and age changes the gender gaps that appear at the aggregate level. For most (but not all) indicators, we find that gender differences disappear or are strongly reduced after disaggregation. This suggests a composition effect, whereby apparent gender differences in productivity can to a considerable degree be ascribed to the composition of the group examined and the different publication practices common to specific groups. We argue that aggregate figures can exaggerate some gender disparities while obscuring others. Our study illustrates the situated nature of research productivity and the importance of comparing men and women within similar academic positions or scientific fields--of comparing apples with apples--when using bibliometric indicators to identify gender disparities in research productivity.

There are prominent sex/gender differences in the prevalence, expression, and life span course of mental health and neurodiverse conditions. However, the underlying sex- and gender-related mechanisms and their interactions are still not fully understood. This lack of knowledge has harmful consequences for those with mental health problems. Therefore, we set up a cocreation session in a 1-week workshop with a multidisciplinary team of 25 researchers, clinicians, and policy makers to identify the main barriers in sex and gender research in the neuroscience of mental health. Based on this work, here we provide recommendations for methodologies, translational research, and stakeholder involvement. These include guidelines for recording, reporting, analysis beyond binary groups, and open science. Improved understanding of sex- and gender-related mechanisms in neuroscience may benefit public health because this is an important step toward precision medicine and may function as an archetype for studying diversity.

Abstract The forest cover of Northern Europe has been steadily expanding during the last 120 years. More terrestrial vegetation and carbon fixation leads to more export to surface waters. This may cause freshwater browning, as more degraded plant‐litter ends up as chromophoric (colored) dissolved organic matter. Although most freshwater ultimately drains to coastal waters, the link between freshwater browning and coastal water darkening is poorly understood. Here, we explore this relationship through a combination of centennial records of forest cover and coastal water clarity, contemporary optical measurements in lakes and coastal waters, as well as an ocean drift model. We suggest a link between forest cover in Northern Europe and coastal water clarity in the Baltic, Kattegat, and Skagerrak Sea and show how brown‐colored freshwater from Northern European catchments can dictate coastal water clarity across thousands of kilometers, from the Baltic lakes to the Barents Sea.

Abstract Protein N-terminal (Nt) acetylation is one of the most abundant modifications in eukaryotes, covering ~50-80 % of the proteome, depending on species. Cells with defective Nt-acetylation display a wide array of phenotypes such as impaired growth, mating defects and increased stress sensitivity. However, the pleiotropic nature of these effects has hampered our understanding of the functional impact of protein Nt-acetylation. The main enzyme responsible for Nt-acetylation throughout the eukaryotic kingdom is the N-terminal acetyltransferase NatA. Here we employ a multi-dimensional proteomics approach to analyze Saccharomyces cerevisiae lacking NatA activity, which causes global proteome remodeling. Pulsed-SILAC experiments reveals that NatA-deficient strains consistently increase degradation of ribosomal proteins compared to wild type. Explaining this phenomenon, thermal proteome profiling uncovers decreased thermostability of ribosomes in NatA-knockouts. Our data are in agreement with a role for Nt-acetylation in promoting stability for parts of the proteome by enhancing the avidity of protein-protein interactions and folding.

Introduction: Ethiopia introduced a second dose of measles-containing vaccine (MCV2) in 2019 to provide further protection against measles and further progress toward elimination. However, the sub-optimal coverage of both MCV1 and MCV2 suggest challenges with vaccine uptake. In this qualitative study, we explored barriers to the uptake of MCV2 among caregivers, community leaders, and healthcare workers (HCWs). Method: A qualitative study was conducted between mid-April and mid-May 2021. We selected ten woredas (districts) in the Oromia Region, Ethiopia, stratified by settlement type (urban/rural), MCV1 coverage (high ≥ 80%; low < 80%), and history of measles outbreaks between June 2019 and June 2020. Experiences surrounding barriers to MCV2 uptake were discussed via focus group discussions (FGDs) and in-depth interviews (IDIs) with caregivers of children 12–23 and 24–36 months and key informant interviews (KIIs) with HCWs who administer vaccines and with community leaders. Participants were recruited via snowball sampling. Recorded data were transcribed, translated to English, and analyzed using ATLAS.ti v.09. Results: Forty FGDs and 60 IDIs with caregivers, 60 IDIs with HCWs, and 30 KIIs with community leaders were conducted. Barriers among caregivers included lack of knowledge and awareness about MCV2 and the vaccination schedule, competing priorities, long wait times at health facilities, vaccine unavailability, negative interactions with HCWs, and transportation challenges. At the community level, trusted leaders felt they lacked adequate knowledge about MCV2 to address caretakers’ questions and community misconceptions. HCWs felt additional training on MCV2 would prepare them to better respond to caretakers’ concerns. Health system barriers identified included the lack of human, material, and financial resources to deliver vaccines and provide immunization outreach services, which caretakers reported as their preferred way of accessing immunization. Conclusions: Barriers to MCV2 uptake occur at multiple levels of immunization service delivery. Strategies to address these barriers include tools to help caretakers track appointments, enhanced community engagement, HCW training to improve provider–client interactions and MCV2 knowledge, and efforts to manage HCW workload.

Abstract Introduction Alzheimer’s disease (AD) can be characterised in vivo by biomarkers reflecting amyloid-β (Aβ) and tau pathology. However, there is a need for biomarkers reflecting additional pathological pathways. Matrix metalloproteinases (MMPs) have recently been highlighted as candidate biomarkers for sex-specific mechanisms and progression in AD. Methods In this cross-sectional study, we investigated nine MMPs and four tissue inhibitors of metalloproteinases (TIMPs) in the cerebrospinal fluid of 256 memory clinic patients with mild cognitive impairment or dementia due to AD and 100 cognitively unimpaired age-matched controls. We studied group differences in MMP/TIMP levels and examined the associations with established markers of Aβ and tau pathology as well as disease progression. Further, we studied sex-specific interactions. Results MMP-10 and TIMP-2 levels differed significantly between the memory clinic patients and the cognitively unimpaired controls. Furthermore, MMP- and TIMP-levels were generally strongly associated with tau biomarkers, whereas only MMP-3 and TIMP-4 were associated with Aβ biomarkers; these associations were sex-specific. In terms of progression, we found a trend towards higher MMP-10 at baseline predicting more cognitive and functional decline over time exclusively in women. Conclusion Our results support the use of MMPs/TIMPs as markers of sex differences and progression in AD. Our findings show sex-specific effects of MMP-3 and TIMP-4 on amyloid pathology. Further, this study highlights that the sex-specific effects of MMP-10 on cognitive and functional decline should be studied further if MMP-10 is to be used as a prognostic biomarker for AD.

The aim of this study is to analyze the evolution of international research collaboration from 1980 to 2021. The study examines the main global patterns as well as those specific to individual countries, country groups, and different areas of research.

As the importance of 'excellence' increases in higher education, so too does the importance of indicators to measure research productivity. We examine how such indicators might disproportionately benefit men by analysing extent to which the separate components of the Norwegian Publication Indicator (NPI), a bibliometric model used to distribute performance-based funding to research institutions, might amplify existing gender gaps in productivity. Drawing from Norwegian bibliometric data for 43,500 individuals, we find that each element of the indicator (weighting based on publication type, publication channel, and international collaboration, as well as fractionalization of co-authorship) has a small, but cumulative effect resulting in women on average receiving 10 per cent fewer publication points than men per publication. In other words, we see a gender gap that is not only caused by a difference in the level of production but is also amplified by the value ascribed to each publication.

Many studies on research productivity and performance suggest that men consistently outperform women. However, women and men are spread unevenly throughout the academy both horizontally (e.g., by scientific field) and vertically (e.g., by academic position), suggesting that aggregate numbers (comparing all men with all women) may reflect the different publication practices in different corners of the academy rather than gender per se. We use Norwegian bibliometric data to examine how the 'what' (which publication practices are measured) and the 'who' (how the population sample is disaggregated) matter in assessing apparent gender differences among academics in Norway. We investigate four clusters of indicators related to publication volume, publication type, authorship, and impact or quality (12 indicators in total) and explore how disaggregating the population by scientific field, institutional affiliation, academic position, and age changes the gender gaps that appear at the aggregate level. For most (but not all) indicators, we find that gender differences disappear or are strongly reduced after disaggregation. This suggests a composition effect, whereby apparent gender differences in productivity can to a considerable degree be ascribed to the composition of the group examined and the different publication practices common to specific groups. We argue that aggregate figures can exaggerate some gender disparities while obscuring others. Our study illustrates the situated nature of research productivity and the importance of comparing men and women within similar academic positions or scientific fields-of comparing apples with apples-when using bibliometric indicators to identify gender disparities in research productivity., Author(s): Lynn P. Nygaard [sup.1] , Dag W. Aksnes [sup.2] , Fredrik Niclas Piro [sup.2] Author Affiliations: (1) grid.425244.1, 0000 0001 1088 4063, Peace Research Institute Oslo (PRIO), , Oslo, [...]

The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE’s 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC’s work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions.