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Abstract Background Opioids are still widely prescribed to long-term pain patients although they are no longer recommended for long-term treatments due to poor evidence for long-term efficacy, risks of serious side effects, and the possibility of inducing opioid hyperalgesia. In a Cochrane study from 2017, the authors identified an urgent need for more randomized controlled trials investigating the efficiency and effects of opioid tapering. The study aimed to assess (1) the efficiency of a structured intervention in causing stable reductions of opioid consumption in a population with long-term non-malignant pain and (2) effects on pain, pain cognitions, physical and mental health, quality of life, and functioning in response to opioid tapering. Methods The study is a randomized controlled trial. The sample size was set to a total of 140 individuals after estimation of power and dropout. Participants will be recruited from a population with long-term non-malignant pain who will be randomly allocated to (1) the start of tapering immediately or (2) the control group who return to usual care and will commence tapering of opioids 4 months later. A 12-month follow-up is included. When all follow-ups are closed, data from the Swedish drug register of the National Board of Health and Welfare will be collected and individual mean daily opioid dose in morphine equivalents will be calculated at three time points: baseline, 4 months, and 12 months after the start of the intervention. At the same time points, participants fill out the following questionnaires: Numeric Pain Rating Scale (NPRS), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), Chronic Pain Acceptance Questionnaire (CPAQ-8), Hospital Anxiety and Depression Scale (HADS), and RAND-36. At baseline and follow-up, a clinical assessment of opioid use disorder is performed. Discussion A better understanding of the efficiency and effects of opioid tapering could possibly facilitate attempts to taper opioid treatments, which might prove beneficial for both the individual and society. Trial registration ClinicalTrials.gov NCT03485430 . Retrospectively registered on 26 March 2018, first release date. “Tapering of Long-term Opioid Therapy in Chronic Pain Population. RCT with 12 Months Follow up (TOPIO).” First patient in trial 22 March 2018.

Anders Håkansson,1,2 Carolina Widinghoff1,2 1Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, Lund, Sweden; 2Malmö Addiction Center, Region Skåne, Malmö, SwedenCorrespondence: Anders Håkansson Tel +46 46 175596Email anders_c.hakansson@med.lu.seBackground: Problem gambling traditionally is markedly more common in men than in women. However, recent data in online gamblers have indicated at least a comparable risk of problem gambling in women in this sub-group. The present study aimed to compare the characteristics of male and female moderate-risk and problem gamblers in online gamblers in Sweden.Methods: In a web survey addressing online gamblers (past-year online gambling on 10 or more occasions), women and men with moderate-risk or problem gambling (n=327) were compared with respect to gambling severity, financial consequences, comorbidity, socio-demographic characteristics, and fulfilled screening items.Results: Female gender was associated with psychological distress, over-indebtedness, higher problem gambling severity and with screening items indicating financial consequences and guilt, with no gender difference for the self-reported need to seek treatment for substance use problems. In the sub-group of problem gamblers, female gender remained associated with psychological distress.Conclusion: In a setting displaying high rates of online gambling and novel findings of a higher risk of problem gambling in women than previously seen, psychological distress appears to separate female and male problem gamblers. Given the higher level of severity and financial consequence, these findings call for screening and early intervention in female at-risk gamblers.Keywords: problem gambling, gender, comorbidity, gambling disorder, behavioral addiction

This article explores external facilitation for school improvement; more specifically, it examines the practical work of external facilitators. It is based on a Swedish case in which facilitators at the Swedish National Agency for Education support low-performing schools. The article aims to develop knowledge about how external facilitators in their practical work both promote and prevent developed understanding and improvement capacity. Based on observations and documents, facilitators' endeavours and critical situations in their work to support school improvement are identified. The findings show five different endeavours to promote development of understanding and improvement capacity. However, they also show how taking ownership, simplification, and model focus, three of five identified recurring critical situations, prevent such development. The conclusion is that there are several aspects for external facilitators to balance to promote school improvement and turn around low-performing schools. When planning for external facilitation, it is important to consider how the facilitators' practical work can be adapted to the local contexts of those who are facilitated in order to promote their ownership of the processes. Without balance and adaptation, external facilitation can lead to deprofessionalisation instead of development of improvement capacity.

Anders Håkansson,1 Madison Ford1,2 1Faculty of Medicine, Department of Clinical Sciences Lund, Psychiatry, Lund University, Lund, Sweden; 2McGill Group for Suicide Studies, McGill University, Montreal, QC, CanadaCorrespondence: Anders HåkanssonLund University, Malmö Addiction Center, Södra Förstadsgatan 35, Plan 4, Malmö S-205 02, SwedenTel +46 703 135677Email anders_c.hakansson@med.lu.seBackground: More remains to be understood about attitudes towards treatment for gambling disorder and where to seek treatment. Given the low degree of treatment seeking behaviour in this condition, it may be of interest to study people’s perception about where to seek help in case of problem gambling. From a study originally aiming to address health correlates of problem gambling, the present sub-study aimed to examine the general population’s attitudes towards where to advise a person with problem gambling to seek treatment, and correlates of recommending a formal professional treatment modality.Methods: A cross-sectional general population web survey in Sweden (N=2,038, 55% women, 6% lifetime problem gamblers) was conducted. Preferred advice for gambling-related treatment seeking was defined with a question asking about where one would hypothetically advise a friend to seek help for gambling addiction. Advice for professional vs peer support help was compared with respect to individual characteristics, in problem gamblers and non-problem gamblers.Results: Fifty percent preferred to recommend peer support help for gambling, whereas among professional treatment options, the largest share preferred primary care (22%) or psychiatry/addiction psychiatry (18%), while few suggested occupational health-care (6%) or social services (3%). Opting for a professional treatment modality for problem gambling was unrelated to one’s own problem gambling, whereas those recommending professional treatment were younger and more likely to report psychological distress. In problem gamblers specifically, history of indebtedness was associated with recommending professional treatment.Conclusion: Many people may not perceive gambling disorder to require professional treatment, and may recommend peer support outside of formal treatment systems. Younger individuals, as well as those with a personal history of psychological treatment needs, may be more prone to recommending formal treatment. The findings may have implications for treatment trajectories and may facilitate overcoming perceived treatment barriers.Keywords: gambling disorder, problem gambling, treatment seeking, barriers, attitudes

Protein tandem mass spectrometry (MS/MS) often generates sequence-informative fragments from backbone bond cleavages near the termini. This lack of fragmentation in the protein interior is particularly apparent in native top-down mass spectrometry (MS). Improved sequence coverage, critical for reliable annotation of posttranslational modifications and sequence variants, may be obtained from internal fragments generated by multiple backbone cleavage events. However, internal fragment assignments can be error prone due to isomeric/isobaric fragments from different parts of a protein sequence. Also, internal fragment generation propensity depends on the chosen MS/MS activation strategy. Here, we examine internal fragment formation in electron capture dissociation (ECD) and electron transfer dissociation (ETD) following native and denaturing MS, as well as LC/MS of several proteins. Experiments were undertaken on multiple instruments, including quadrupole time-of-flight, Orbitrap, and high-field Fourier-transform ion cyclotron resonance (FT-ICR) across four laboratories. ECD was performed at both ultrahigh vacuum and at similar pressure to ETD conditions. Two complementary software packages were used for data analysis. When feasible, ETD-higher energy collision dissociation MS3 was performed to validate/refute potential internal fragment assignments, including differentiating MS3 fragmentation behavior of radical versus even-electron primary fragments. We show that, under typical operating conditions, internal fragments cannot be confidently assigned in ECD or ETD. On the other hand, such fragments, along with some b-type terminal fragments (not typically observed in ECD/ETD spectra) appear at atypical ECD operating conditions, suggesting they originate from a separate ion-electron activation process. Furthermore, atypical fragment ion types, e.g., x ions, are observed at such conditions as well as upon EThcD, presumably due to vibrational activation of radical z-type ions.

Anders Håkansson, Virginia Jesionowska Department of Clinical Sciences Lund, Psychiatry, Faculty of Medicine, Lund University, Lund, Sweden Aim: The present study aimed to study the associations between substance use patterns and types of crimes in prisoners with substance use problems, and specifically whether substance use patterns were different in violent offenders.Methods: Interview data of prisoners with substance use problems (N=4,202, mean age 33.5 years, SD 9.8), derived from the Addiction Severity Index, were run against criminal register data on main types of crimes in the verdict.Results: In binary analyses, compared to those with acquisitive and drug crimes, violent offenders had lower prevalence of illicit drugs and homelessness, but higher prevalence of binge drinking, and higher prevalence of sedative use than clients sentenced with drug crimes. Clients with violent crime had lower prevalence of injecting drug use, compared to all other crimes. In logistic regression, binge drinking and sedatives were positively associated with violent crime (as opposed to non-violent crime), whereas heroin, amphetamine, cocaine, and injecting drug use were negatively associated with violent crime. Among violent offenders only, sedatives tended to be associated with fatal violence (p=0.06), whereas amphetamine, homelessness, age, and (marginally significant, p=0.05) heroin were negatively associated with fatal violence, as opposed to non-fatal violence.Conclusion: Treatment and risk assessment in violent perpetrators with substance use may need to address sedatives and alcohol specifically. Limitations of the study are due to self-reported and cross-sectional data and because a large majority of the prison sample studied here are men. Keywords: Addiction Severity Index, prison, criminal justice, violence, substance use disorder, alcohol, sedatives

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value

Most small land-terminating glaciers in Svalbard have experienced large recession since the Little Ice Age (LIA) and today are thin, cold, and largely inactive. This likely contrasts to their LIA conditions, but the observational record from that time is sparse. We investigate the evolution of five small glaciers in central Nordenskiöld Land, Svalbard, from the LIA to 2019. Photogrammetric reconstructions and ground penetrating radar are used to reconstruct their geometric changes since 1936, and historical observation, photographs, and geomorphological mapping extend this history to before the 1900s. Our results show that from 1936 to 2019, the study glaciers on average lost 49.6% of their area and 77.4% ± 7.7% of their volume, with the greatest volume loss at Scott Turnerbreen of 91% ± 5%. Four out of these five glaciers strongly indicate a history of surge-like advances near the end of the LIA within one or two decades, and the rate of subsequent mass loss seems connected to their previous dynamics. This apparent switch to high activity during a period of rapid climatic change, could have implications for our understanding of past and future glacier evolution; climate change and highly dynamic glacier responses may be more connected than previously thought.

Abstract Vestibular evoked myogenic potentials (VEMPs) are a tool to assess otolith function and a component of sensor specific vestibular diagnostics. The aim of the present study was to measure VEMP trough bone conducted (BC) stimulation using the B250 prototype and to report amplitudes, latencies and threshold levels for patients before resection of a sporadic unilateral vestibular schwannoma (VS) in order to assess function regarding to the reported nerve of origin. Twenty-seven participants (9 male/18 female) with a mean age of 55.9 years (SD: 10.8) were included for the analysis. In the side contralateral to the tumor, in 24 (89%) of the patients cVEMP could be measured, while oVEMP were recordable in 20 patients (74%). For patients with inferior vestibular nerve of origin (n = 11), cVEMP amplitudes of the affected side were significantly lower as compared to the non-affected side, while the force threshold level was increased. No statistically significant differences were observed for neither, oVEMP amplitudes nor threshold levels in the group with superior vestibular nerve of origin (n = 7). Across groups, p13 latency was significantly increased in the affected ear while all other VEMP latencies were not different between the ears. The B250 transducer was applicable to all participants of the clinical cohort. The sample size, however, was too low for a reliable statistical analysis and only allowed for exploratory analysis.

In the contemporary digitalised knowledge society, work-integrated professional development is an important and continuous activity. Continuous professional development should preferably be a hybrid format, where academia collaborates with industry and the surrounding society in a multi-directed exchange of ideas. Continuous professional development is today conducted in a blend of workplace activities, and in technology enhanced online environments. A complex blend for professionals that at the same time are working full-time with their ordinary jobs. The need for a support model to navigate in these new digital learning spaces is obvious, where the support model also should include collaboration and a community of practice. A community where the members communicate regularly to improve their skills and knowledge in their common professional domain. The aim of this paper is to describe and analyse the development of a support model that involves these aspects. Findings confirm the necessity of the four steps in the earlier model, at the same time as they indicate the need for a fifth step facilitating the creation of Communities and Landscapes of Practice. The use of the model may support higher education institutions in creating beneficial conditions for hybrid work-integrated continuous professional development for industry.

This study delves into the intricate dynamics of controversial issues in environmental education, challenging conventional notions. It explores the relationship between "controversy" and the field of environmental education, elucidating its multifaceted dimensions in and ambitions of teaching practice. In dialogue with previous research and based on our empirical study, we contend that controversy's existence transcends the mere content of education and extends to its perceived fundamental core and normative underpinnings. We argue that controversy, including controversial sustainability issues (CSIs), is not confined to educational content alone but encompasses the purposes of education. We propose that controversy in educational encounters cannot be neatly categorized as a fixed, predictable social product and is not solely dependent on student interaction. This challenges earlier research positions that linked controversy to the presence of debate or dissensus in a subject area. Our study challenges the traditional understanding of controversy, highlighting its partial spontaneity and unpredictability in teaching. This contrasts previous positions that emphasized the epistemic dimension of controversy. Instead, our findings suggest that controversy plays an active role in the process of self-formation or subjectification in relation to any content.

Gendered bias in peer-review and other forms of assessments is a well-studied area. But how do researchers actually execute their positions of power in recruitment processes? In Sweden, recruitment for academic tenure and the reviewers' reports are public and thus open for scrutiny. This study uses both bibliographic coupling and close reading of three cases of reviewers' reports to map cognitive closeness, distance and particularities as intrinsic aspects of peer review. All these concepts point towards the fact that reviewers are researchers as well. Their own research interests are both what makes their expert assessment possible as well as an aggravation, which calls for 'situated knowledges': a reflection of why and how they make the particular recruitment decisions they do. The cases are read against the backdrop of the emerging neoliberalisation of Swedish academia. At the breaking point between traditional academic ideals and neoliberal accounts of concepts like 'research quality', different forms of masculinities are struggling for hegemony, while the system's lack of transparency creates disadvantage for women academics.

The aim of this qualitative study was to explore desired ways to deliver comprehensive sexuality education (CSE) and topics, among secondary school students in a low-resource setting in Western Kenya. One school (n = 440) has received 8-9-h CSE intervention, while the other school (n = 496) served as a control. After one-year follow-up the students were asked (one open-ended question) to suggest desired topics of CSE, with a response rate of 93% (n = 867). The following topics were suggested by the students: abortion, contraception, sexual rights, abstinence and STI/HIV, and preferred CSE delivery means were school-based teaching, online resources and social media, community-based elements or trusted individuals. The students who had not received the intervention were more in favor of an abstinence-only approach and demonstrated more negative attitudes toward abortion.

In the ongoing shift to a knowledge society, the idea of a technology-enabled lifelong learning has frequently been discussed. The shift also requires a transformation of higher education with new forms for teaching and learning deployment. This ongoing transformation was formulated in a research question that has guided this study: 1) Which key themes of lifelong learning emerge from higher education literature? This study was carried out as a scoping literature review to map literature in the field. Findings from a thematic analysis pointed out seven main themes or perspectives: The Policy perspective, The Value perspective, The Employability perspective, The Reform perspective, The Collaborative perspective, The Student perspective and The Workplace learning and Professional development perspectives. Five publications of the 26 selected publications from the literature search will be further used and analysed as part of a Delphi study. This Delphi study will involve a group of leading researchers in the field of lifelong learning as an expert panel to further explore and expand the key themes of lifelong learning in higher education and digital trends in higher education reforms.

This article examines multilingual language use in two groups of children, one group at a state school, and one at a private IB school. The IB school has earlier been assumed to reflect an 'elite' multilingualism. Three research questions are posed: to what extent is the children's language use multilingual, what are their typological profiles, and are there any differences between the two groups in the language use patterns. The agency of the speaker is captured by self-reporting questionnaires. We use a method of circles in which the participant fills in the names and domains of the languages in use. The answers are registered according to three main dimensions: family, social interaction and media use. The study is exploratory and descriptive, and the results demonstrate that a large majority of the children at both schools used more than one language. The study is innovative in combining a sociolinguistic approach with language typology. Our results shed light on children's dynamic and flexible language use, using languages from all of the world's language families. We found similarities in the multilingualism of the two groups, and there was little to indicate that the IB pupils could be characterised as having an 'elite' multilingualism.

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Factors affecting the swelling of cellulosic fibers are considered in this review. Emphasis is placed on aqueous systems and papermaking fibers, but the review also considers cellulose solvent systems, nanocellulose research, and the behavior of cellulosic hydrogels. The topic of swelling of cellulosic fibers ranges from effects of humid air, continuing through water immersion, and extends to hydrogels and the dissolution of cellulose, as well as some of its derivatives. The degree of swelling of cellulose fibers can be understood as involving a balance between forces of expansion (especially osmotic pressure) vs. various restraining forces, some of which involve the detailed structure of layers within the fibril structure of the fibers. The review also considers hornification and its effects related to swelling. The expansive forces are highly dependent on ionizable groups, pH, and the ionic strength of solution. The restraining forces depend on the nature of lignin, cellulose, and their detailed structural arrangements.

PurposeA polygenic risk score (PRS) consisting of 313 common genetic variants (PRS313) is associated with risk of breast cancer and contralateral breast cancer. This study aimed to evaluate the association of the PRS313 with clinicopathologic characteristics of, and survival following, breast cancer.MethodsWomen with invasive breast cancer were included, 98,397 of European ancestry and 12,920 of Asian ancestry, from the Breast Cancer Association Consortium (BCAC), and 683 women from the European MINDACT trial. Associations between PRS313 and clinicopathologic characteristics, including the 70-gene signature for MINDACT, were evaluated using logistic regression analyses. Associations of PRS313 (continuous, per standard deviation) with overall survival (OS) and breast cancer-specific survival (BCSS) were evaluated with Cox regression, adjusted for clinicopathologic characteristics and treatment.ResultsThe PRS313 was associated with more favorable tumor characteristics. In BCAC, increasing PRS313 was associated with lower grade, hormone receptor-positive status, and smaller tumor size. In MINDACT, PRS313 was associated with a low risk 70-gene signature. In European women from BCAC, higher PRS313 was associated with better OS and BCSS: hazard ratio (HR) 0.96 (95% CI, 0.94 to 0.97) and 0.96 (95% CI, 0.94 to 0.98), but the association disappeared after adjustment for clinicopathologic characteristics (and treatment): OS HR, 1.01 (95% CI, 0.98 to 1.05) and BCSS HR, 1.02 (95% CI, 0.98 to 1.07). The results in MINDACT and Asian women from BCAC were consistent.ConclusionAn increased PRS313 is associated with favorable tumor characteristics, but is not independently associated with prognosis. Thus, PRS313 has no role in the clinical management of primary breast cancer at the time of diagnosis. Nevertheless, breast cancer mortality rates will be higher for women with higher PRS313 as increasing PRS313 is associated with an increased risk of disease. This information is crucial for modeling effective stratified screening programs.