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Abstract Objective The aim of this study is to evaluate treatment patterns and long‐term oncological outcomes of patients with locally advanced prostate cancer (LAPCa). Patients and methods This is a population‐based study including LAPC (cT3‐4, M0) patients from the Stockholm region (Sweden). A sub‐analysis was performed in men treated with primary cystoprostatectomy or total pelvic exenteration (TPE) for cT4 prostate cancer (PCa). Cox regression was used to identify predictors of overall mortality (OM) and cancer‐specific mortality (CSM). Biochemical progression‐free survival (BPFS) and 90 days complications were reported for the radical surgery subgroup. Results We included 2921 patients with cT3(N = 2713) or cT4(N = 208), M0 PCa diagnosed between 2003 and 2019. Out of these, 249(9%), 1497(51%) and 1175(40%) underwent radical prostatectomy, RT + ADT and androgen deprivation therapy (ADT), respectively. Survival rates were 76% (IQR: 68, 83), 47% (IQR: 44, 50) and 23% (IQR: 20, 27), respectively at 10 years. Irrespective of treatment modalities, cT4 patients had worse survival compared to cT3 patients (OM: HR1.44, IQR:1.17,1.77; PCSM: HR1.39, IQR:1.06,1.82). Twenty‐seven patients with cT4, N0‐1, M0 were treated with cystoprostatectomy or TPE. Twenty‐two patients (81.5%) received neoadjuvant ADT. The 5‐year BPFS, CSS and OS rates were 39.6%, 68.8% and 63.8%, respectively. Nine patients (33.3%) had Clavien‐Dindo grade III and 1 (3.7%) grade IV complication within 90 days after surgery. Conclusions Pelvic surgery with radical intent as part of a multidisciplinary management may be an effective alternative for selected patients with locally advanced PCa leading to local tumour control and an acceptable morbidity.

Abstract Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP–SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP–SNP interactions. The results showed the cluster effect is a major cause of false-positive findings of SNP–SNP interactions. This cluster effect is due to high correlations between a causal pair and null pairs in a cluster. The clusters with a hub SNP with a significant main effect and a large minor allele frequency (MAF) tended to have a higher false-positive rate. In addition, peripheral null SNPs in a cluster with a small MAF tended to enhance false positivity. We also demonstrated that using the modified significance criterion based on the 3 p-value rules and the bootstrap approach (3pRule + bootstrap) can reduce false positivity and maintain high true positivity. In addition, our results also showed that a pair without a significant main effect tends to have weak or no interaction. This study identified the cluster effect and suggested using the 3pRule + bootstrap approach to enhance SNP–SNP interaction detection accuracy.

Abstract Background Autopsy work indicates that the widely-projecting noradrenergic pontine locus coeruleus (LC) is among the earliest regions to accumulate hyperphosphorylated tau, a neuropathological Alzheimer’s disease (AD) hallmark. This early tau deposition is accompanied by a reduced density of LC projections and a reduction of norepinephrine’s neuroprotective effects, potentially compromising the neuronal integrity of LC’s cortical targets. Previous studies suggest that lower magnetic resonance imaging (MRI)-derived LC integrity may signal cortical tissue degeneration in cognitively healthy, older individuals. However, whether these observations are driven by underlying AD pathology remains unknown. To that end, we examined potential effect modifications by cortical beta-amyloid and tau pathology on the association between in vivo LC integrity, as quantified by LC MRI signal intensity, and cortical neurodegeneration, as indexed by cortical thickness. Methods A total of 165 older individuals (74.24 ± 9.72 years, ~ 60% female, 10% cognitively impaired) underwent whole-brain and dedicated LC 3T-MRI, Pittsburgh Compound-B (PiB, beta-amyloid) and Flortaucipir (FTP, tau) positron emission tomography. Linear regression analyses with bootstrapped standard errors (n = 2000) assessed associations between bilateral cortical thickness and i) LC MRI signal intensity and, ii) LC MRI signal intensity interacted with cortical FTP or PiB (i.e., EC FTP, IT FTP, neocortical PiB) in the entire sample and a low beta-amyloid subsample. Results Across the entire sample, we found a direct effect, where lower LC MRI signal intensity was associated with lower mediolateral temporal cortical thickness. Evaluation of potential effect modifications by FTP or PiB revealed that lower LC MRI signal intensity was related to lower cortical thickness, particularly in individuals with elevated (EC, IT) FTP or (neocortical) PiB. The latter result was present starting from subthreshold PiB values. In low PiB individuals, lower LC MRI signal intensity was related to lower EC cortical thickness in the context of elevated EC FTP. Conclusions Our findings suggest that LC-related cortical neurodegeneration patterns in older individuals correspond to regions representing early Braak stages and may reflect a combination of LC projection density loss and emergence of cortical AD pathology. This provides a novel understanding that LC-related cortical neurodegeneration may signal downstream consequences of AD-related pathology, rather than being exclusively a result of aging.

Abstract Background During the first year postpartum, about 25 per cent of Swedish women with severe perineal trauma (SPT), i.e., a third- or fourth-degree perineal laceration at childbirth, are unsatisfied with their healthcare contacts. Further, there is a lack of research on the more long-term experiences of healthcare encounters among women with persistent SPT-related health problems. This study explores how women with self-reported persistent SPT-related health problems experience their contact with healthcare services 18 months to five years after childbirth when the SPT occurred. Methods In this descriptive qualitative study, a purposive sample of twelve women with self-reported persistent health problems after SPT were individually interviewed from November 2020 – February 2022. The data was analysed using inductive qualitative content analysis. Results Our results showed a paradoxical situation for women with persistent health problems due to SPT. They struggled with their traumatised body, but healthcare professionals rejected their health problems as postpartum normalities. This paradox highlighted the women’s difficulties in accessing postpartum healthcare, rehabilitation, and sick leave, which left them with neglected healthcare needs, diminished emotional well-being, and loss of financial and social status. Our results indicated that these health problems did not diminish over time. Consequently, the women had to search relentlessly for a ‘key person’ in healthcare who acknowledged their persistent problems as legitimate to access needed care, rehabilitation, and sick leave, thus feeling empowered. Conclusions Our study revealed that women with persistent SPT-related health problems experienced complex health challenges. Additionally, their needs for medical care, rehabilitation, and sick leave were largely neglected. Thus, the study highlights an inequitable provision of SPT-related healthcare services in Sweden, including regional disparities in access to care. Hence, the authors suggest that Swedish national guidelines for SPT-related care need to be developed and implemented, applying a woman-centered approach, to ensure equitable, effective, and accessible healthcare.

The increased interest in printed electronics necessitates the development of suitable sustainable substrates for them. In this study, the suitability of acetylated cellulose nanofiber (ACNF) films as substrates for printed electronics were examined through (I) the ink-substrates interaction, (II) print quality, and (III) electrical and (IV) mechanical properties of the printed pattern on the ACNF substrates. The results have been compared with cellulose nanofiber (CNF) and commercial reference material (CRM) substrates. The wetting of the silver nanoparticle (AgNP) ink on the ACNF substrate was found out to be excellent. The thickness of the printed pattern increased and the hole area fraction decreased with each consecutive layer of ink. The comparative investigations demonstrated that the electrical properties of the printed patterns were almost as good for 4 layers of ink on the ACNF substrate (1.6 Ω resistance) as the ones on the CRM substrate (1.2 Ω resistance). Additionally, the printed pattern on the ACNF substrate endured the adhesion and bending tests significantly better compared to the CRM substrate. Therefore, this study demonstrates that ACNF substrates could be a suitable candidate for printed electronics, which are more sustainable yet with similar functionalities in comparison with the conventional fossil based substrates.

Abstract The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium‐induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries. Estradiol supplementation, however, aggravated the colitis in OVX mice, increasing the colitis score to a similar level than what was observed in the intact mice. Further, we observed that immune infiltration and gene expression of inflammatory interleukins Il1b, Il6, and Il17a were up to 200‐fold increased in estradiol supplemented OVX colitis mice, while a mild but consistent decrease was observed by SERM2 treatment in intact animals. Additionally, cyclo‐oxygenase 2 induction was increased in the colon of colitis mice, in correlation with increased serum estradiol levels. Measured antagonist properties of SERM2, together with the other results presented here, indicates an exaggerating role of ERα signaling in colitis. Our results contribute to the knowledge of ovarian hormone effects in colitis and encourage further research on the potential use of ER antagonists in the colon, in order to alleviate inflammation.

In Swedish school health services, local initiatives have been taken to use physical activity on prescription (PAP) to encourage physically inactive children to become more active. Previous research shows that interprofessional collaboration plays a crucial role in promoting physical activity in children, as well as in promoting health in schools. However, there is a lack of knowledge about PAP for children in the school setting, including how medical and educational staff can work together to encourage children who have been recommended PAP. Therefore, this study aims to explore the perceived facilitators and barriers concerning interprofessional collaboration regarding physical activity on prescription in the school setting, as viewed from the professionals’ perspectives. Semi-structured interviews were conducted with 21 professionals who work with the method in school settings. The data were analyzed using Reflexive Thematic Analysis. The results reveal both barriers and facilitators for interprofessional collaboration on PAP in the school setting, as perceived by professionals. Organizational and structural obstacles within school institutions hinder collaboration, while a shared commitment to PAP, characterized by consensus-building, acts as a facilitating factor. PAP for children in a school setting is still an unexplored area and further research is required.

School nurses are in a key position to promote children's physical activity. They engage all children in health dialogues and use different approaches to inform children about physical activity and motivate them to change their physical activity level. In a school context, it is important to explore and problematize school nurses’ views of children's physical activity and the influence of these views on their professional practice in the school health service. Identifying and problematizing school nurses' views of physical activity would enable them to create improved guidelines and equivalent ways of working in the future. Therefore, this study aims to discursively explore Swedish school nurses' views on school children's physical activity and its promotion and elucidate them through a discursive framework based on sensitizing concepts. This study uses a qualitative research design with a constructivist grounded theory approach. Semi-structured interviews were conducted with 24 school nurses. The analysis resulted in a core category describing how school nurses use intertwined views to lead children from sedentarity to physical activity. Furthermore, the school nurses' practices were identified in three categories: fostering everyday movement as a tool for health, battling children's sedentarity under difficult conditions, and promoting everyday movement and compensating for unequal access. The results indicate that school nurses lack common and clear guidelines for their mission to promote physical activity to children, which may lead to inequality in access to physical activity for children and young people.

Abstract Background Youth mental health is a major health concern in almost every country. Mental health accounts for about 13% of the global burden of disease in the 10-to-19-year age group. Still there are significant gaps between the mental health needs of young people and the quality and accessibility of available services. Collaboration between health and social service actors is a recognized way of reducing gaps in quality and access. Yet there is little scientific evidence on how these collaborations are applied, or on the challenges of cross-boundary collaboration in the youth mental health space. This study aims to explore how collaboration is understood and practiced by professionals working in the Swedish youth mental health system. Methods We conducted 42 interviews (November 2020 to March 2022) with health and social care professionals and managers in the youth mental health system in Sweden. Interviews explored participants’ experience and understanding of the purpose, realization, and challenges of collaboration. Data were analysed under an emergent study design using reflexive thematic analysis. Results The analysis produced three themes. The first shows that collaboration is considered as essential and important, and that it serves diverse purposes and holds multiple meanings in relation to professionals’ roles and responsibilities. The second addresses the different layers of collaboration, in relation to activities, relationships, and target levels, and the third captures the challenges and criticisms in collaborating across the youth mental health landscape, but also in growing possibilities for future development. Conclusion We conclude that collaboration serves multiple purposes and takes many shapes in the Swedish youth mental health system. Despite the many challenges, participants saw potential in further building collaboration. Interestingly our participants also raised concerns about too much collaboration. There was scepticism about collaboration directing attention away from young people to the professionals, thereby risking the trust and confidentiality of their young clients. Collaboration is not a panacea and will not compensate for an under-resourced youth mental health system.

The presence of Global Navigation Satellite System (GNSS) interference poses a significant risk to both GNSS and the infrastructures that depend on them. This article describes how an existing GNSS infrastructure, the Swedish Continuously Operating Reference Stations network SWEPOS with more than 500 stations, can be leveraged to control the quality of GNSS signals and to be able to detect interferences in GNSS and adjacent frequency bands. This study introduces a SWEPOS-based automatic system that effectively detects GNSS interference by examining the signal-to-noise ratio (SNR) of Global Positioning System, Globalnaya Navigatsionnaya Sputnikovaya Sistema, Galileo, and BeiDou frequency bands. By comparing the SNR of tracked satellites against historical data, the system detects radio frequency interference (RFI) by statistically characterizing the SNR of simultaneously tracked satellites. Furthermore, based on the SNR characteristics across satellites, the system distinguishes between RFI and non-RFI sources. The effectiveness of the detection system is demonstrated through both simulated signal interference waves and real-world interference events.

Purpose The suicidal process contains both observable and non-observable phases, and patients have described the process as characterized by loneliness and darkness. Ambulance clinicians encounter patients in all phases of the suicidal process but little is known on what meaning this encounter has to the patients. The aim of this study was to elucidate meanings of encountering ambulance clinicians while being in a suicidal process. Methods Data were collected through fifteen individual interviews with eight participants who had lived experiences of encountering ambulance clinicians. Inductive design using phenomenological hermeneutical approach was used. Findings Patients are impacted by the clinicians, both in how they find their value in the situation, but also in expected trajectory. Three themes; ‘Being impacted by representatives of society’, ‘Being unsure of one´s own value’ and ‘Regaining hope in moments of togetherness’ generated the main theme ´Navigating oneself through the eyes of the other´. Conclusion The way ambulance clinicians communicate impacts how patients navigate themselves in the ambivalence about living or dying, and the encounter either consolidate a feeling of being a burden, or instil hope of an endurable life. Through conversation, clinicians could support the patients in taking the first steps in the journey of recovery.

Purpose The aim of this study was to explore how health care providers at youth clinics (YCs) in Sweden engage with, focus on, and navigate across the mental health youth space, while upholding the core bedrock principle of “youth-centeredness”. Methods Qualitative interviews were conducted with 21 health care professionals working in three YCs located in three different regions of Sweden. Data were analysed using reflexive thematic analysis informed by the work of Braun and Clarke. Results The three themes were: 1) “youth mission—at the core of the YCs” work and challenged by a stronger involvement in mental ill health’; 2) “YCs” unique and complementary role in the youth mental health system: a holistic perspective, team work, and a focus on normalization’, and 3) “Caught between a rock and a hard place: to treat at a care level that is not optimal for the young users” needs or to refer within an unreliable system’. Conclusion This study reflects the individuality and key features of YCs, their widening roles within the mental health sphere, and the challenges faced in maintaining and expanding the characteristic “youth-centred” approach while expanding their work with mental health.

BackgroundProstate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.MethodsIn total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium. The PHS model was evaluated in four testing datasets: African ancestry, Asian ancestry, and two of European Ancestry-the Cohort of Swedish Men (COSM) and the ProtecT study. Hazard ratios (HRs) were estimated to compare men with high versus low PHS for association with clinically significant, with any, and with fatal prostate cancer. The impact of genetic risk stratification on the positive predictive value (PPV) of PSA testing for clinically significant prostate cancer was also measured.ResultsThe final model (PHS290) had 290 SNPs with non-zero coefficients. Comparing, for example, the highest and lowest quintiles of PHS290, the hazard ratios (HRs) for clinically significant prostate cancer were 13.73 [95% CI: 12.43-15.16] in ProtecT, 7.07 [6.58-7.60] in African ancestry, 10.31 [9.58-11.11] in Asian ancestry, and 11.18 [10.34-12.09] in COSM. Similar results were seen for association with any and fatal prostate cancer. Without PHS stratification, the PPV of PSA testing for clinically significant prostate cancer in ProtecT was 0.12 (0.11-0.14). For the top 20% and top 5% of PHS290, the PPV of PSA testing was 0.19 (0.15-0.22) and 0.26 (0.19-0.33), respectively.ConclusionsWe demonstrate better genetic risk stratification for clinically significant prostate cancer than prior versions of PHS in multi-ancestry datasets. This is promising for implementing precision-medicine approaches to prostate cancer screening decisions in diverse populations.

Abstract Objectives This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta‐blocker therapy (BB) and compare it to healthy controls. Methods Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age‐groups and four heart rate (HR) ranges. Results In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age‐groups compared to controls at HR 120–140 bpm (1–15 years: p

Objectives: Computed tomography pulmonary angiography (CTPA) is the gold standard diagnostic method for patients with suspected pulmonary embolism (PE), but it has its drawbacks, including exposure to ionizing radiation and iodinated contrast agent. The present study aims to evaluate the diagnostic performance of our in-house developed non-contrast MRI protocol for PE diagnosis in reference to CTPA. Methods: 107 patients were included, all of whom underwent MRI immediately before or within 36 hours after CTPA. Additional cases examined only with MRI and a negative result were added to reach a PE prevalence of approximately 20%. The protocol was a non-contrast 2D steady-state free precession (SSFP) sequence under free-breathing, without respiratory or cardiac gating, and repeated five times to capture the vessels at different breathing/cardiac phases. The MRIs were blinded and read by two radiologists and the results were compared to CTPA. Results: Of the 243 patients included, 47 were positive for PE. Readers 1 and 2 demonstrated 89% and 87% sensitivity, 100% specificity, 98% accuracy and Cohen’s kappa of 0.88 on patient level. In the per embolus comparison, readers 1 and 2 detected, 60 and 59/61 (98, 97%) proximal, 101 and 94/113 (89, 83%) segmental, and 5 and 2/32 (16, 6%) subsegmental emboli, resulting in 81 and 75% sensitivity respectively. Conclusion: The repeated 2D SSFP can reliably be used for the diagnosis of acute PE at the proximal and segmental artery levels.