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BackgroundAcute kidney injury (AKI) is a common and severe complication in patients treated at an Intensive Care Unit (ICU). The pathogenesis of AKI has been reported to involve hypoperfusion, diminished oxygenation, systemic inflammation, and damage by increased intracellular iron concentration. Hepcidin, a regulator of iron metabolism, has been shown to be associated with sepsis and septic shock, conditions that can result in AKI. Heparin binding protein (HBP) has been reported to be associated with sepsis and AKI. The aim of the present study was to compare serum hepcidin and heparin binding protein (HBP) levels in relation to AKI in patients admitted to the ICU.MethodsOne hundred and forty patients with community acquired illness admitted to the ICU within 24 hours after first arrival to the hospital were included in the study. Eighty five of these patients were diagnosed with sepsis and 55 with other severe non-septic conditions. Logistic and linear regression models were created to evaluate possible correlations between circulating hepcidin and heparin-binding protein (HBP), stage 2-3 AKI, peak serum creatinine levels, and the need for renal replacement therapy (RRT).ResultsDuring the 7-day study period, 52% of the 85 sepsis and 33% of the 55 non-sepsis patients had been diagnosed with AKI stage 2-3 already at inclusion. The need for RRT was 20% and 15%, respectively, in the groups. Hepcidin levels at admission were significantly higher in the sepsis group compared to the non-sepsis group but these levels did not significantly correlate to the development of stage 2-3 AKI in the sepsis group (p = 0.189) nor in the non-sepsis group (p = 0.910). No significant correlation between hepcidin and peak creatinine levels, nor with the need for RRT was observed. Stage 2-3 AKI correlated, as expected, significantly with HBP levels at admission in both groups (Odds Ratio 1.008 (CI 1.003-1.014, p = 0.005), the need for RRT, as well as with peak creatinine in septic patients.ConclusionInitial serum hepcidin, and HBP levels in patients admitted to the ICU are biomarkers for septic shock but in contrast to HBP, hepcidin does not portend progression of disease into AKI or a later need for RRT. Since hepcidin is a key regulator of iron metabolism our present data do not support a decisive role of initial iron levels in the progression of septic shock into AKI.

Political trust is a well-used construct and serves both as an explanation and an outcome in the social sciences. Considering the importance of the construct, relatively little attention has been allocated to its measurement. While the exist-ing literature on the measurement of political trust focuses on either developing and validating new scales, or scaling and equivalence assessment of the more gen-eral measures, this article contributes by analysing the contents of the widely used survey items of political trust. Put differently, what is in a typical political trust measure? The analysis uses relevant observational data from Sweden (n = 1760) with repeated questions over six public agencies, where the typically used trust measurement is regressed on theoretically motivated psychological antecedents of trust using a hierarchical heteroskedastic ordered probit model. Results imply that the typical trust measurement contains traces of perceived competence and less so perceived motivation. The results also suggest that political actors do carry meaning beyond the trust construct, influencing both the location and scale of the response distribution.

För- och nackdelar med anonymisering av examinationer har diskuterats i decennier. Det är inte svårt att förstå varför ämnet har varit brännande och att det varit så under lång tid. Frågan har i hög grad varit studentdriven, både i Sverige och internationellt, och har sin grund i oro för bias vid bedömning och betygsättning. I Sverige infördes anonymisering av examinationer vid många lärosäten för 10–15 år sedan. Åtgärden föregicks dock sällan av diskussioner om eventuella pedagogiska konsekvenser. Senare års studier av effekterna av anonymisering, tillsammans med kunskaper om hur examination och bedömning påverkar studenters lärande, visar emellertid att en sådan diskussion bör föras. Forskningen har inte kunnat finna tydliga belägg för att anonymisering har positiva konsekvenser i form av minskad bias vid betygsättning. Det finns dessutom risk att centrala kvaliteter som framåtsyftande återkoppling, bedömning av progression, utvecklandet av lärandeorienterade examinationsformer samt en relationsrik högre utbildning motverkas av en examinationskultur som styrs av anonymiseringskrav. I diskussionen som följer argumenterar jag för en viss försiktighet vad gäller tillämpandet av anonymisering samt efterlyser en nyanserad diskussion där studenters lärande står i fokus. ENGLISH ABSTRACT Pedagogical dilemmas when anonymizing examination and assessment Advantages and disadvantages of anonymisation of assessment procedures have been discussed for decades. It is not difficult to understand why the issue has been on the agenda for such a long time. To a large extent, both in Sweden and internationally, it is the students who request anonymisation in examination procedures, and their demands stem from a concern about bias in assessment and grading. In Sweden, anonymized assessment was introduced at many higher education institutions about a decade ago. The implementation, however, was rarely preceded by discussions about potential pedagogical consequences. Research of later years on effects of anonymisation, as well as knowledge about the effects of assessment on student learning, call for a discussion. Researchers have not been able to find evidence of positive consequences of anonymisation in terms of reduced bias in grading. Instead, there is a risk that central qualities in assessment procedures are undermined by an assessment culture steered by requirements on anonymisation. For example, qualities such as feed forward, assessment of progression, the development of learning-oriented assessment forms and a relationship rich higher education are at risk. In this article, I advocate a certain degree of caution when it comes to the implementation of anonymized assessment methods, and call for a nuanced discussion, focusing assessment as a tool for student learning.

The upscaling of novel carbon dioxide removal, such as bioenergy carbon capture and storage (BECCS), to gigatonne scales is an urgent priority if global warming is to be limited to well below 2 °C. But political, economic, social, technological, environmental and regulatory uncertainty permeates BECCS projects and deters investors. To address this, we explore options to improve the robustness of BECCS deployment strategies in the face of multi-dimensional uncertainties. We apply Dynamic Adaptive Planning (DAP) through expert interviews and Robust Decision Making (RDM) through exploratory modelling, two decision making under deep uncertainty methods, to the case of Stockholm Exergi, an early mover aiming to deploy BECCS at a combined heat and power plant in the capital of Sweden. The main contributions of the research are to 1) illustrate how a quantification of robustness against uncertainty can support an investment decision to deploy BECCS 2) comprehensively cover uncertain vulnerabilities and opportunities of deploying BECCS, and 3) identify critical scenarios and adaptations to manage these uncertainties. The main conclusions are: investing in BECCS is relatively robust if assessing performance across many scenarios and if comparing the worst-cases of either investing, or not doing so. Not investing could miss out on up to € 3.8 billion in terms of net present value. The critical uncertainties of BECCS can be managed by strengthening biomass sustainability strategies and by gaining support for negative emission trading regulation on carbon markets, e.g., voluntary or Paris Agreement Article 6. Even in vulnerable scenarios of average electricity prices above 82 €/MWh, if trading regulation is implemented before 2030 and if negative emission prices exceed 151 €/CO2, investing in BECCS performs better than not doing so in 96% of cases. We suggest that facility-level parameters and cost-reductions are of little importance for BECCS investments and upscaling. It is regulatory certainty of operating revenues, e.g., through negative emission markets, that needs to be provided by policymakers.

Abstract Background Using a longitudinal design, aim of this study was to investigate the relation between mental adjustment to cancer and anxiety, depression, health-related quality of life (HRQL) and survival in patients treated for laryngeal cancer. Methods 95 patients with Tis-T4 laryngeal cancer were assessed at one and 12 months after start of treatment, respectively, using the Mini-Mental Adjustment to Cancer Scale (Mini-MAC), the European Organisation for Research and Treatment of Cancer (EORTC) Study Group on Quality of Life core questionnaire (EORTC QLQ-C30) supplemented with the Head and Neck cancer module (QLQ-H&N35) and the Hospital Anxiety and Depression (HAD) Scale. For survival analyses patients were followed up for a median time of 4.22 years from inclusion. Results The most commonly used adjustment response at both occasions was Fighting Spirit. The use of adjustment responses was relatively stable over time. Correlation analyses showed that patients using Helpless-Hopeless and Anxious Preoccupation responses reported more anxiety and depression, as well as decreased HRQL. Tumour site and stage showed no effect on adjustment response. Survival analysis indicated that use of a Helpless-Hopeless response was related to poorer survival (HR 1.17, p 0.001). Conclusion The relation between adjustment responses Helpless-Hopeless and Anxious Preoccupation and anxiety, depression, HRQL and possibly poorer survival indicate that assessment of mental adjustment should be considered when planning treatment and rehabilitation in laryngeal cancer patients.

Abstract Objective Checkpoint inhibitors (CPIs) are in widespread clinical use. Little is known about which patients are at risk for developing toxicity. It is essential being able to identify patients with higher risk of experiencing immune‐related adverse events (IRAEs) before initiation of CPI treatment to optimize treatment decisions and follow‐up strategy. The aim of this study was to investigate whether a simplified frailty score based on performance status (PS), age, and comorbidity expressed as Charlson comorbidity index (CCI) could predict development of IRAEs. Methods We performed a retrospective cohort study at three Swedish centers. All patients (n = 596) treated with PD‐L1 or PD‐1 inhibitor for advanced cancer between January 2017 and December 2021 were included. Results In total, 361 patients (60.6%) were classified as nonfrail and 235 (39.4%) as frail. The most common cancer type was non‐small cell lung cancer (n = 203; 34.1%) followed by malignant melanoma (n = 195; 32.7%). Any grade of IRAE occurred in 138 (58.7%) frail and in 155 (42.9%) non‐frail patients (OR: 1.58; 95% CI: 1.09–2.28). Age, CCI, and PS did not independently predict the occurrence of IRAEs. Multiple IRAEs occurred in 53 (22.6%) frail and in 45 (12.5%) nonfrail patients (OR: 1.62; 95% CI: 1.00–2.64). Discussion In conclusion, the simplified frailty score predicted all grade IRAEs and multiple IRAEs in multivariate analyses whereas age, CCI, or PS did not separately predict development of IRAEs suggesting that this easy‐to‐use score may be of value in clinical decision making but a large prospective study is needed to assess its true value.

Abstract Background Early cancer detection is crucial for patients’ survival. The image quality in 111In-octreotide SPECT imaging could be improved by using Monte Carlo (MC)-based reconstruction. The aim of this observational study was to determine the detection rate of simulated liver lesions for MC-based ordered subset expectation maximization (OSEM) reconstruction compared to conventional attenuation-corrected OSEM reconstruction. Methods Thirty-seven SPECT/CT examinations with 111In-octreotide were randomly selected. The inclusion criterion was no liver lesions at the time of examination and for the following 3 years. SPECT images of spheres representing lesions were simulated using MC. The raw data of the spheres were added to the raw data of the established healthy patients in 26 of the examinations, and the remaining 11 examinations were not modified. The images were reconstructed using conventional OSEM reconstruction with attenuation correction and post filtering (fAC OSEM) and MC-based OSEM reconstruction without and with post filtering (MC OSEM and fMC OSEM, respectively). The images were visually and blindly evaluated by a nuclear medicine specialist. The criteria evaluated were liver lesion yes or no, including coordinates if yes, with confidence level 1–3. The percentage of detected lesions and accuracy (percentage of correctly classified cases), as well as tumor-to-normal tissue concentration (TNC) ratios and signal-to-noise ratios (SNRs), were evaluated. Results The detection rates were 30.8% for fAC OSEM, 42.3% for fMC OSEM, and 50.0% for MC OSEM. The accuracies were 45.9% for fAC OSEM, 45.9% for fMC OSEM, and 54.1% for MC OSEM. The number of false positives was higher for fMC and MC OSEM. The observer’s confidence level was higher in filtered images than in unfiltered images. TNC ratios were significantly higher, statistically, with MC OSEM and fMC OSEM than with AC OSEM, but SNRs were similar due to higher noise with MC OSEM. Conclusion One in two lesions were found using MC OSEM versus one in three using conventional reconstruction. TNC ratios were significantly improved, statistically, using MC-based reconstruction, but the noise levels increased and consequently the confidence level of the observer decreased. For further improvements, image noise needs to be suppressed.

Abstract Background A model for integrative medicine (IM) adapted to Swedish primary care was previously developed. The aim of this study was to explore the feasibility of a pragmatic randomised clinical trial to investigate the effectiveness of the IM model versus conventional primary care in the management of patients with non-specific back/neck pain. Specific objectives included the exploration of recruitment and retention rates, patient and care characteristics, clinical differences and effect sizes between groups, selected outcome measures and power calculations to inform the basis of a full-scale trial. Methods Eighty patients with back/neck pain of at least two weeks duration were randomised to the two types of care. Outcome measures were standardised health related quality of life (the eight domains of SF-36) complemented by a set of exploratory "IM tailored" outcomes targeting self-rated disability, stress and well-being (0-10 scales); days in pain (0-14); and the use of analgesics and health care over the last two weeks (yes/no). Data on clinical management were derived from medical records. Outcome changes from baseline to follow-up after 16 weeks were used to explore the differences between the groups. Results Seventy-five percent (80/107) of screened patients in general practice were eligible and feasible to enrol into the trial. Eighty-two percent (36/44) of the integrative and 75% (27/36) of the conventional care group completed follow-up after 16 weeks. Most patients had back/neck pain of at least three months duration. Conventional care typically comprised advice and prescription of analgesics, occasionally complemented with sick leave or a written referral to physiotherapy. IM care generally integrated seven treatment sessions from two different types of complementary therapies with conventional care over ten weeks. The study was underpowered to detect any statistically significant differences between the groups. One SF-36 domain showed a clinically relevant difference between groups that was also supported by a small distribution based effect size, i.e. vitality (-7.3 points, Cohen's d -0.34) which was in favour of IM. There was a clinical trend between groups showing that IM contributed to less use of prescription and non-prescription analgesics (-11.7 and - 9.7 percent units respectively) compared to conventional care. Exploring clinically relevant differences and the SF-36 as the basis for a main outcome measure showed that the sample sizes needed per arm to adequately power a full-scale trial depended on the target domain, i.e. ranging from 60 (vitality) to 339 (role emotion). Conclusion This pilot study investigated the implementation of IM in the primary care management of non-specific back and neck pain. Recruiting patients and implementing IM in routine clinical practice was feasible. The results warrant further exploration into different perspectives and relevant combinations of outcome measures including the use of health resources, drugs and cost-effectiveness to help understand the relevance of IM in primary care. Future research should prioritise larger scale studies considering variability, pain duration and small to moderate treatment effects. Trial registration Clinical trials NCT00565942

Abstract Background Aim of this longitudinal study was to investigate the sensitivity to change of the Swedish Self Evaluation of Communication Experiences after Laryngeal Cancer questionnaire (the S-SECEL), addressing communication dysfunction in patients treated for laryngeal cancer. Previous studies have highlighted the need for more specific questionnaires for this purpose. Methods 100 patients with Tis-T4 laryngeal cancer were included prior to treatment onset. Patients answered four questionnaires at six occasions during one year; the S-SECEL, the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Core Questionnaire (QLQ-C30) supplemented by the Head and Neck cancer module (QLQ-H&N35) and the Hospital Anxiety and Depression (HAD) scale. In addition, performance status was assessed. Differences within groups were tested with the Wilcoxon paired signed ranks test and between-group analyses were carried out using the Mann-Whitney U test. Magnitude of group differences was analyzed by means of effect sizes. Results The S-SECEL was well accepted with a response rate of 76%. Communication dysfunction increased at 1 month, followed by a continuous decrease throughout the year. Changes were statistically significant at most measurement, demonstrating the sensitivity of the S-SECEL to changes in communication over time. The S-SECEL and the EORTC QLQ-C30 with the QLQ-H&N35 demonstrated similar results; however the S-SECEL was more sensitive regarding communication dysfunction. The largest changes were found in the most diagnose specific items concerning voice and speech. Conclusion The S-SECEL was investigated in the largest Scandinavian longitudinal study concerning health-related quality of life (HRQL) in laryngeal cancer patients. The questionnaire was responsive to change and showed convergent results when compared to established HRQL questionnaires. Our findings also indicate that the S-SECEL could be a more suitable instrument than the EORTC QLQ-C30 with QLQ-H&N35 when measuring communication experiences in patients with laryngeal cancer; it is more sensitive, shorter and can be used on an individual basis. As a routine screening instrument the S-SECEL could be a valuable tool for identifying patients at risk for psychosocial problems and to help plan rehabilitation. It is therefore recommended for clinical use in evaluation of communication dysfunction for all patients with laryngeal cancer irrespective of treatment.

BackgroundMost patients diagnosed with breast cancer present with a node-negative disease. Sentinel lymph node biopsy (SLNB) is routinely used for axillary staging, leaving patients with healthy axillary lymph nodes without therapeutic effects but at risk of morbidities from the intervention. Numerous studies have developed nodal status prediction models for noninvasive axillary staging using postoperative data or imaging features that are not part of the diagnostic workup. Lymphovascular invasion (LVI) is a top-ranked predictor of nodal metastasis; however, its preoperative assessment is challenging. ObjectiveThis paper aimed to externally validate a multilayer perceptron (MLP) model for noninvasive lymph node staging (NILS) in a large population-based cohort (n=18,633) and develop a new MLP in the same cohort. Data were extracted from the Swedish National Quality Register for Breast Cancer (NKBC, 2014-2017), comprising only routinely and preoperatively available documented clinicopathological variables. A secondary aim was to develop and validate an LVI MLP for imputation of missing LVI status to increase the preoperative feasibility of the original NILS model. MethodsThree nonoverlapping cohorts were used for model development and validation. A total of 4 MLPs for nodal status and 1 LVI MLP were developed using 11 to 12 routinely available predictors. Three nodal status models were used to account for the different availabilities of LVI status in the cohorts and external validation in NKBC. The fourth nodal status model was developed for 80% (14,906/18,663) of NKBC cases and validated in the remaining 20% (3727/18,663). Three alternatives for imputation of LVI status were compared. The discriminatory capacity was evaluated using the validation area under the receiver operating characteristics curve (AUC) in 3 of the nodal status models. The clinical feasibility of the models was evaluated using calibration and decision curve analyses. ResultsExternal validation of the original NILS model was performed in NKBC (AUC 0.699, 95% CI 0.690-0.708) with good calibration and the potential of sparing 16% of patients with node-negative disease from SLNB. The LVI model was externally validated (AUC 0.747, 95% CI 0.694-0.799) with good calibration but did not improve the discriminatory performance of the nodal status models. A new nodal status model was developed in NKBC without information on LVI (AUC 0.709, 95% CI: 0.688-0.729), with excellent calibration in the holdout internal validation cohort, resulting in the potential omission of 24% of patients from unnecessary SLNBs. ConclusionsThe NILS model was externally validated in NKBC, where the imputation of LVI status did not improve the model’s discriminatory performance. A new nodal status model demonstrated the feasibility of using register data comprising only the variables available in the preoperative setting for NILS using machine learning. Future steps include ongoing preoperative validation of the NILS model and extending the model with, for example, mammography images.

ABSTRACT Haemophilus influenzae is a major cause of community-acquired pneumonia. While studied extensively in various laboratory models, less is known about the cell function while inside the human lung. We present the first analysis of the global gene expression of H. influenzae while the bacteria are in the lung during pneumonia (in vivo conditions) and contrast it with bacterial isolates that have been cultured under standard laboratory conditions (in vitro conditions). Patients with pneumonia were recruited from emergency departments and intensive care units during 2018–2020 (n = 102). Lower respiratory samples were collected for bacterial culture and RNA extraction. Patient samples with H. influenzae (n = 8) and colonies from bacterial cultures (n = 6) underwent RNA sequencing. The reads were then pseudo-aligned to core and pan genomes created from 15 reference strains. While bacteria cultured in vitro clustered tightly by principal component analysis of core genome (n = 1067) gene expression, bacteria in the patient samples had more diverse transcriptomic signatures and did not group with their lab-cultured counterparts. In total, 328 core genes were significantly differentially expressed between in vitro and in vivo conditions. The most highly upregulated genes in vivo included tbpA and fbpA, which are involved in the acquisition of iron from transferrin, and the stress response gene msrAB. The biosynthesis of nucleotides/purines and molybdopterin-scavenging processes were also significantly enriched in vivo. In contrast, major metabolic pathways and iron-sequestering genes were downregulated under this condition. In conclusion, extensive transcriptomic differences were found between bacteria while in the human lung and bacteria that were cultured in vitro. IMPORTANCE The human-specific pathogen Haemophilus influenzae is generally not well suited for studying in animal models, and most laboratory models are unlikely to approximate the diverse environments encountered by bacteria in the human airways accurately. Thus, we have examined the global gene expression of H. influenzae during pneumonia. Extensive differences in the global gene expression profiles were found in H. influenzae while in the human lung compared to bacteria that were grown in the laboratory. In contrast, the gene expression profiles of isolates collected from different patients were found to cluster together when grown under the same laboratory conditions. Interesting observations were made of how H. influenzae acquires and uses iron and molybdate, endures oxidative stress, and regulates central metabolism while in the lung. Our results indicate important processes during infection and can guide future research on genes and pathways that are relevant in the pathogenesis of H. influenzae pneumonia.

Loss of animals is a considerable waste of resources in the meat supply chain, where quantitative data are scarce but critical for guiding improvements. In this study, we used material flow analysis to track the amount of beef diverted away from the food supply chain at the farm level. The beef losses (absolute and as the proportion of yearly initial production) were estimated from data on assisted and unassisted deaths of cattle on Swedish farms obtained from the central register of bovine animals for 2002–2021 combined with official statistics on slaughter weight. The fallen animals were grouped according to age, sex and breed, to enable estimations of the lost amount of carcass weight, both in total and per animal group. The yearly loss during primary production 2017–2021 was on average 13,000 ton carcass weight, or 8.5% of the initial production. No decreasing trend for the loss rate could be determined after 2015, when the Agenda 2030 target 12.3 (Halved food waste and reduced early losses) was introduced. Female dairy breeds showed greater beef losses than dairy males or beef breeds and crossbreeds of both sexes, and their beef losses mostly occurred at 4–5 years of age, thus constituting the hot spot group for lost beef. The results can serve as a base for directed reduction efforts.

ObjectiveHigh blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data.MethodsTo identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data.ResultsOver 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age.ConclusionOur findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals.Clinical trials registrationThe review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.

Single-cell studies of human white adipose tissue (WAT) provide insights into the specialized cell types in the tissue. Here the authors combine publicly available and newly generated high-resolution and bulk transcriptomic results from multiple human datasets to provide a comprehensive cellular map of white adipose tissue.

Abstract Background Metastatic breast cancer (MBC) is a challenging disease, and despite new therapies, prognosis is still poor for a majority of patients. There is a clinical need for improved prognostication where immuno-oncology markers can provide important information. The aim of this study was to evaluate serum immuno-oncology markers in MBC patients and their respective relevance for prediction of survival. Patients and methods We investigated a broad panel of 92 immuno-oncology proteins in serum from 136 MBC patients included in a prospective observational study (NCT01322893) with long-term follow-up. Serum samples were collected before start of systemic therapy and analyzed using multiplex proximity extension assay (Olink Target 96 Immuno-Oncology panel). Multiple machine learning techniques were used to identify serum markers with highest importance for prediction of overall and progression-free survival (OS and PFS), and associations to survival were further evaluated using Cox regression analyses. False discovery rate was then used to adjust for multiple comparisons. Results Using random forest and random survival forest analyses, we identified the top nine and ten variables of highest predictive importance for OS and PFS, respectively. Cox regression analyses revealed significant associations (P