Assessing focal spot alignment in clinical linear accelerators: a comprehensive evaluation with triplet phantoms.

A fundamental parameter to evaluate the beam delivery precision and stability on a clinical linear accelerator (linac) is the focal spot position (FSP) measured relative to the collimator axis of the radiation head. The aims of this work were to evaluate comprehensive data on FSP acquired on linacs in clinical use and to establish the ability of alternative phantoms to detect effects on patient plan delivery related to FSP. FSP measurements were conducted using a rigid phantom holding two ball-bearings at two different distances from the radiation source. Images of these ball-bearings were acquired using the electronic portal imaging device (EPID) integrated with each linac. Machine QA was assessed using a radiation head-mounted PTW STARCHECK phantom. Patient plan QA was investigated using the SNC ArcCHECK phantom positioned on the treatment couch, irradiated with VMAT plans across a complete 360° gantry rotation and three X-ray energies. This study covered eight Elekta linacs, including those with 6 MV, 18 MV, and 6 MV flattening-filter-free (FFF) beams. The largest range in the FSP was found for 6 MV FFF. The FSP of one linac, retrofitted with 6 MV FFF, displayed substantial differences in FSP compared to 6 MV FFF beams on other linacs, which all had FSP ranges less than 0.50 mm and 0.25 mm in the lateral and longitudinal directions, respectively. The PTW STARCHECK phantom proved effective in characterising the FSP, while the SNC ArcCHECK measurements could not discern FSP-related features. Minor variations in FSP may be attributed to adjustments in linac parameters, component replacements necessary for beam delivery, and the wear and tear of various linac components, including the magnetron and gun filament. Consideration should be given to the ability of any particular phantom to detect a subsequent impact on the accuracy of patient plan delivery.

The Florida Geriatric Head Trauma CT Clinical Decision Rule.

BACKGROUND: Several clinical decision rules have been devised to guide head computed tomography (CT) use in patients with minor head injuries, but none have been validated in patients 65 years or older. We aimed to derive and validate a head injury clinical decision rule for older adults. METHODS: We conducted a secondary analysis of an existing dataset of consecutive emergency department (ED) patients >65 years old with blunt head trauma. The main predictive outcomes were significant intracranial injury and Need for Neurosurgical Intervention on CT. The secondary outcomes also considered in the model development and validation were All Injuries and All Intracranial Injuries. Predictor variables were identified using multiple variable logistic regression, and clinical decision rule models were developed in a split-sample derivation cohort and then tested in an independent validation cohort. RESULTS: Of 5776 patients, 233 (4.0%) had significant intracranial injury and an additional 104 (1.8%) met CT criteria for Need for Neurosurgical Intervention. The best performing model, the Florida Geriatric Head Trauma CT Clinical Decision Rule, assigns points based on several clinical variables. If the points totaled 25 or more, a CT scan is indicated. The included predictors were arrival via Emergency Medical Services (+30 points), Glasgow Coma Scale (GCS) <15 (+20 points), GCS <14 (+50 points), antiplatelet medications (+17 points), loss of consciousness (+16 points), signs of basilar skull fracture (+50 points), and headache (+20 points). Utilizing this clinical decision rule in the validation cohort, a point total ≥25 had a sensitivity and specificity of 100.0% (95% CI: 96.0-100) and 12.3% (95% CI: 10.9-13.8), respectively, for significant intracranial injury and Need for Neurosurgical Intervention. CONCLUSIONS: The Florida Geriatric Head Trauma CT Clinical Decision Rule has the potential to reduce unnecessary CT scans in older adults, without compromising safe emergency medicine practice.

Self-Report Tool for Identification of Individuals With Coronary Atherosclerosis: The Swedish CardioPulmonary BioImage Study.

BACKGROUND: Coronary atherosclerosis detected by imaging is a marker of elevated cardiovascular risk. However, imaging involves large resources and exposure to radiation. The aim was, therefore, to test whether nonimaging data, specifically data that can be self-reported, could be used to identify individuals with moderate to severe coronary atherosclerosis. METHODS AND RESULTS: We used data from the population-based SCAPIS (Swedish CardioPulmonary BioImage Study) in individuals with coronary computed tomography angiography (n=25 182) and coronary artery calcification score (n=28 701), aged 50 to 64 years without previous ischemic heart disease. We developed a risk prediction tool using variables that could be assessed from home (self-report tool). For comparison, we also developed a tool using variables from laboratory tests, physical examinations, and self-report (clinical tool) and evaluated both models using receiver operating characteristic curve analysis, external validation, and benchmarked against factors in the pooled cohort equation. The self-report tool (n=14 variables) and the clinical tool (n=23 variables) showed high-to-excellent discriminative ability to identify a segment involvement score ≥4 (area under the curve 0.79 and 0.80, respectively) and significantly better than the pooled cohort equation (area under the curve 0.76, P<0.001). The tools showed a larger net benefit in clinical decision-making at relevant threshold probabilities. The self-report tool identified 65% of all individuals with a segment involvement score ≥4 in the top 30% of the highest-risk individuals. Tools developed for coronary artery calcification score ≥100 performed similarly. CONCLUSIONS: We have developed a self-report tool that effectively identifies individuals with moderate to severe coronary atherosclerosis. The self-report tool may serve as prescreening tool toward a cost-effective computed tomography-based screening program for high-risk individuals.

Sexualized drug use and chemsex: A bibliometric and content analysis of published literature.

Sexualized drug use (SDU) describes drug-facilitated sexual enhancement, and chemsex is an SDU subculture involving the use of specific drugs by men who have sex with men (MSM). This study aimed to identify research trends, foci, and themes within the SDU and chemsex-specific literature. The Web of Science Core Collection was searched with a list of SDU synonyms. All SDU-related articles were analyzed using the R package, bibliometrix. Full text review identified chemsex-specific records, and text was extracted verbatim for content analysis in Leximancer. The search returned 1,866 unique records. A total of 521 addressed SDU, and 301 papers specifically addressed chemsex. The small but growing SDU literature primarily addressed consensual encounters between MSM, and drug-facilitated assault experienced by women, in Western settings. Little attention was given to transgender communities or consensual SDU in cisgender heterosexual individuals. The literature primarily viewed SDU through a public health lens, specifically focusing on the risk conferred to sexual health.The SDU and chemsex-specific literature are potentially limited in scope and may inadequately capture the geographical, demographic, and cultural diversity of these phenomena. Future research should address the myriad social and health implications of SDU and chemsex participation across all relevant communities and settings.

Validation of Trøndelag Apnoea Score Proxy for Obstructive Sleep Apnoea in the General Population of Norway: The HUNT Study.

The aim was to validate a new seven-item "TASC" (Trøndelag Apnoea Score) proxy for obstructive sleep apnoea (OSA) against polysomnography in the general population. Objectives included validation against different polysomnographic criteria, stratification by age and gender, and estimation of OSA prevalence. From the fourth wave of the Trøndelag Health Study (HUNT4), 1,201 participants were randomly invited to a substudy focusing on sleep and headaches, of whom 232 accepted and 84 (64% women, mean age 55.0 years, and standard deviation 11.5 years) underwent polysomnography. The TASC proxy sums seven binary items for snoring, observed breathing pauses, restricted daytime activities, hypertension, body mass index (≥30 kg/m2), age (≥50 years), and gender (male). A single night of ambulatory (home) polysomnography was analysed using both the recommended and optional hypopnoea criteria of the American Academy of Sleep Medicine (AASM). We found 65% sensitivity and 87% specificity (Cohen's κ = 0.53, 95% confidence interval 0.34-0.72) for TASC ≥ 3 against AHI ≥ 15 (recommended AASM criteria). Validity was similar against AHI ≥ 30 but lower against AHI ≥ 5 and against the optional AASM criteria. Sensitivity and overall validity were higher among men and those above 50 years of age. The prevalence of an apnoea-hypopnoea index (AHI) of at least 5, 15, or 30 using the recommended (and optional) AASM criteria was 73% (46%), 37% (18%), or 15% (5%). A seven-item TASC proxy for OSA showed good validity and may be useful in screening and epidemiological settings. Sensitivity, specificity, and validity vary considerably by cut-off, by polysomnographic scoring criteria, and by gender and age strata.

Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.

Background: Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment. Methods: 161 older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's biomarkers, and brain MRI. Spontaneous CVR was quantified during 5 minutes of rest. Results: Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for Alzheimer's biomarkers and vascular risk factors. Conclusion: Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, indicating medial temporal microvascular dysfunction's role in cognitive decline.

Bacteroides expand the functional versatility of a universal transcription factor and transcribed DNA to program capsule diversity.

Human gut Bacteroides species encode numerous (eight or more) tightly regulated capsular polysaccharides (CPS). Specialized paralogs of the universal transcription elongation factor NusG, called UpxY (Y), and an anti-Y UpxZ (Z) are encoded by the first two genes of each CPS operon. The Y-Z regulators combine with promoter inversions to limit CPS transcription to a single operon in most cells. Y enhances transcript elongation whereas Z inhibits noncognate Ys. How Y distinguishes among cognate CPS operons and how Z inhibits only noncognate Ys are unknown. Using in-vivo nascent-RNA sequencing and promoter-less in vitro transcription (PIVoT), we establish that Y recognizes a paused RNA polymerase via sequences in both the exposed non-template DNA and the upstream duplex DNA. Y association is aided by novel 'pause-then-escape' nascent RNA hairpins. Z binds non-cognate Ys to directly inhibit Y association. This Y-Z hierarchical regulatory program allows Bacteroides to create CPS subpopulations for optimal fitness.

Ventriculo-arterial (VA) coupling and fQRS as new selection criteria for primary prevention ICD placement.

For decades, left ventricular ejection fraction (LVEF < 35%) has been a mainstay for identifying heart failure (HF) patients most likely to benefit from an implantable cardioverter defibrillator (ICD). However, LVEF is a poor predictor of sudden cardiac death (SCD) and ignores 50% of HF patients with mildly reduced and preserved LVEF. The current international guidelines for primary prophylaxis ICD therapy are inadequate. Instead of LVEF, which is not a good measure of LV contractility or hemodynamic characterization, we hypothesize ventriculo-arterial (VA) coupling combined with fragmented QRS (fQRS) will improve risk stratification and patient suitability for an ICD. Quantifying cardiac and aortic mechanics, and predicting active arrhythmogenic substrate, from varying fQRS morphologies, may help to stratify ischemic and non-ischemic patients with different functional capacities and predisposition for lethal arrhythmias. We propose HF patients with a low physiological reserve may not benefit from ICD therapy, whereas those patients with higher reserves and extensive arrhythmogenic substrate may benefit. Our hypothesis combining VA coupling with fQRS changes has the potential to widen HF patient participation (low and high LVEF) and advance personalized medicine for HF patients at high risk of SCD.

RETRACTED: PO-04-037 ARTIFICIAL INTELLIGENCE FOR ANALYSIS OF MOBILE CARDIAC TELEMETRY.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This abstract has been retracted at the request of the Authors; please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The abstract was withdrawn after being accepted for presentation at Heart Rhythm, the annual meeting of the Heart Rhythm Society, because there was substantial content development after it had been submitted, both in terms of more in-depth analyses and quantitative changes due to final adjudication of events. The Authors intended to withdraw the abstract from publication as well but omitted to do so. The Authors apologize for the inconvenience caused by this oversight.

Effects of individual traits vs. trait syndromes on assemblages of various herbivore guilds associated with central European Salix.

Plants employ diverse anti-herbivore defences that can covary to form syndromes consisting of multiple traits. Such syndromes are hypothesized to impact herbivores more than individual defences. We studied 16 species of lowland willows occurring in central Europe and explored if their chemical and physical traits form detectable syndromes. We tested for phylogenetic trends in the syndromes and explored whether three herbivore guilds (i.e., generalist leaf-chewers, specialist leaf-chewers, and gallers) are affected more by the detected syndromes or individual traits. The recovered syndromes showed low phylogenetic signal and were mainly defined by investment in concentration, richness, or uniqueness of structurally related phenolic metabolites. Resource acquisition traits or inducible volatile organic compounds exhibited a limited correlation with the syndromes. Individual traits composing the syndromes showed various correlations to the assemblages of herbivores from the three studied guilds. In turn, we found some support for the hypothesis that defence syndromes are composed of traits that provide defence against various herbivores. However, individual traits rather than trait syndromes explained more variation for all studied herbivore assemblages. The detected negative correlations between various phenolics suggest that investment trade-offs may occur primarily among plant metabolites with shared metabolic pathways that may compete for their precursors. Moreover, several traits characterizing the recovered syndromes play additional roles in willows other than defence from herbivory. Taken together, our findings suggest that the detected syndromes did not solely evolve as an anti-herbivore defence.

Self-rated professional competence and well-being at work after obtaining a Swedish nursing license: A longitudinal mixed-methods study of internationally and domestically educated nurses.

BACKGROUND: An inclusive workplace is where everyone is supported to thrive and succeed regardless of their background. Supportive working conditions and general self-efficacy have been found to be important for nurses' perceived competence and well-being at work, however, in the context of being a nurse in a new country, research is limited. Moreover, knowledge is lacking about whether different paths to a nursing license are related to nurses' perceived competence and well-being when working. OBJECTIVE: To examine determinants and experiences of nursing competence and well-being at work (thriving and stress) among internationally and domestically educated nurses. DESIGN: A longitudinal descriptive and correlational design with a mixed-methods convergent approach was used. METHODS: A longitudinal study was conducted between January 2019 and June 2022 with two groups of internationally educated nurses who had completed a bridging program or validation to obtain a Swedish nursing license and one group of domestically newly educated nurses. Data were collected on three occasions: Time1 at the end of the nursing licensure process (n = 402), Time2 after three months (n = 188), and Time3 after 12 months (n = 195). At Time3, 14 internationally educated nurses were also interviewed. Data were analyzed separately and then interpreted together. RESULTS: Multiple regression models showed that greater access to structural empowerment (B = 0.70, 95 % CI [0.31; 1.08]), better cooperation (B = 3.76, 95 % CI [1.44; 6.08]), and less criticism (B = 3.63, 95 % CI [1.29; 5.96]) were associated with higher self-rated competence at Time3, whereas the variable path to a nursing license was non-significant (R2 = 49.2 %). For well-being, greater access to structural empowerment (B = 0.07, 95 % CI [0.02; 0.12]), better cooperation (B = 0.36, 95 % CI [0.07; 0.66]) and being domestically educated (B = 0.53, 95 % CI [0.14; 0.92]) were associated with higher thriving at work (R2 = 25.8 %). For stress, greater access to structural empowerment (B = -0.06, 95 % CI [-0.09; -0.02]), better cooperation (B = -0.30, 95 % CI [-0.51; -0.10]), and less criticism (B = -0.28, 95 % CI [-0.46; -0.05]) were associated with having symptoms less frequently while being domestically educated was associated with having stress symptoms more often (B = 0.44, 95 % CI [0.07; 0.81]) (R2 = 43.3 %). Higher general self-efficacy at Time1 was associated with higher self-rated competence at Time2 (B = 4.76, 95 % CI [1.94; 7.59]). Quantitative findings concurred with findings from interviews with internationally educated nurses. However, qualitative findings also highlighted the importance of previous education, working experience, the new context, and communication abilities. CONCLUSIONS: Both quantitative and qualitative data showed that working conditions were important for nurses' self-rated competence and well-being at work. Although communication difficulties, previous education, and working experience were not statistically significant in the multiple regression models, in the interviews these factors emerged as important for internationally educated nurses' competence and well-being.

Gonococcal mastitis. / Gonokokkmastitt.

A young woman experienced pain and swelling in a non-lactating breast. The culture test result showed an unusual microbe, which is increasingly prevalent in Norway and internationally.

High inspired CO2 target accuracy in mechanical ventilation and spontaneous breathing using the Additional CO2 method.

Introduction: Cerebrovascular reactivity imaging (CVR) is a diagnostic method for assessment of alterations in cerebral blood flow in response to a controlled vascular stimulus. The principal utility is the capacity to evaluate the cerebrovascular reserve, thereby elucidating autoregulatory functioning. In CVR, CO2 gas challenge is the most prevalent method, which elicits a vascular response by alterations in inspired CO2 concentrations. While several systems have been proposed in the literature, only a limited number have been devised to operate in tandem with mechanical ventilation, thus constraining the majority CVR investigations to spontaneously breathing individuals. Methods: We have developed a new method, denoted Additional CO2, designed to enable CO2 challenge in ventilators. The central idea is the introduction of an additional flow of highly concentrated CO2 into the respiratory circuit, as opposed to administration of the entire gas mixture from a reservoir. By monitoring the main respiratory gas flow emanating from the ventilator, the CO2 concentration in the inspired gas can be manipulated by adjusting the proportion of additional CO2. We evaluated the efficacy of this approach in (1) a ventilator coupled with a test lung and (2) in spontaneously breathing healthy subjects. The method was evaluated by assessment of the precision in attaining target inspired CO2 levels and examination of its performance within a magnetic resonance imaging environment. Results and discussion: Our investigations revealed that the Additional CO2 method consistently achieved a high degree of accuracy in reaching target inspired CO2 levels in both mechanical ventilation and spontaneous breathing. We anticipate that these findings will lay the groundwork for a broader implementation of CVR assessments in mechanically ventilated patients.

Recombination and polarity effects of Farmer chambers in a strong magnetic field.

PURPOSE: Ionisation chamber based reference dosimetry in magnetic resonance linear accelerators (MRL) aimed for radiotherapy requires correction for recombination losses. Published studies have found that such corrections can be carried out using the two-voltage method. These studies have, however, not included comparison with recombination corrections based on the Niatel method, which can be seen as a robust reference method due to its clear separation of initial and volume recombination and its explicit account of the pulsed nature of the dose delivery. The primary objective of this work therefore was to carry out such a comparison. MATERIALS AND METHODS: Four Farmer-type chambers (PTW-30006 and PTW-30013) were placed in a water phantom in 1.5 T Elekta Unity MRL. The chambers were oriented antiparallel or perpendicular to the static magnetic field B0 and irradiated at a source-to-surface distance of 133.5 cm with a 10 × 10 cm2 field size. RESULTS: The two-voltage method gave results in agreement (within 0.1%) with the recombination corrections derived from the Niatel method. The recombination corrections from three Niatel parameter sets (one based on a Varian Truebeam and two obtained directly in the MRL) deviated less than 0.1% from each other. A systematic shift in the recombination correction of less than 0.05% was observed if polarity corrections were not applied. CONCLUSIONS: The study supports the use of the two-voltage method in MRLs based on its excellent agreement with the Niatel method. This work, therefore, complements existing knowledge as previous studies have not included a comparison with the Niatel method.

A randomised trial of selective intracoronary hypothermia during primary PCI.

BACKGROUND: While experimental data suggest that selective intracoronary hypothermia decreases infarct size, studies in patients with ST-elevation myocardial infarction (STEMI) are lacking. AIMS: We investigated the efficacy of selective intracoronary hypothermia during primary percutaneous coronary intervention (PCI) to decrease infarct size in patients with STEMI. METHODS: In this multicentre randomised controlled trial, 200 patients with large anterior wall STEMI were randomised 1:1 to selective intracoronary hypothermia during primary PCI or primary PCI alone. Using an over-the-wire balloon catheter for infusion of cold saline and a pressure-temperature wire to monitor the intracoronary temperature, the anterior myocardium distal to the occlusion was selectively cooled to 30-33°C for 7-10 minutes before reperfusion (occlusion phase), immediately followed by 10 minutes of cooling after reperfusion (reperfusion phase). The primary endpoint was infarct size as a percentage of left ventricular mass on cardiovascular magnetic resonance imaging after 3 months. RESULTS: Selective intracoronary hypothermia was performed in 94/100 patients randomised to cooling. Distal coronary temperature decreased by 6°C within 43 seconds (interquartile range [IQR] 18-113). The median duration of the occlusion phase and reperfusion phase were 8.2 minutes (IQR 7.2-9.0) and 9.1 minutes (IQR 8.2-10.0), respectively. The infarct size at 3 months was 23.1±12.5% in the selective intracoronary hypothermia group and 21.6±12.2% in the primary PCI alone group (p=0.43). The left ventricular ejection fraction at 3 months in each group were 49.1±10.2% and 50.1±10.4%, respectively (p=0.53). CONCLUSIONS: Selective intracoronary hypothermia during primary PCI in patients with anterior wall STEMI was feasible and safe but did not decrease infarct size compared with standard primary PCI. (ClinicalTrials.gov: NCT03447834).

The SOS1 Inhibitor MRTX0902 Blocks KRAS Activation and Demonstrates Antitumor Activity in Cancers Dependent on KRAS Nucleotide Loading.

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the receptor tyrosine kinase (RTK)/mitogen-activated protein kinase (MAPK) pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway. MRTX0902 augmented the antitumor activity of the KRAS G12C inhibitor adagrasib when dosed in combination in eight out of 12 KRAS G12C-mutant human non-small cell lung cancer and colorectal cancer xenograft models. Pharmacogenomic profiling in preclinical models identified cell cycle genes and the SOS2 homolog as genetic co-dependencies and implicated tumor suppressor genes (NF1 and PTEN) in resistance following combination treatment. Lastly, combined vertical inhibition of RTK/MAPK pathway signaling by MRTX0902 with inhibitors of EGFR or RAF/MEK led to greater downregulation of pathway signaling and improved antitumor responses in KRAS-MAPK pathway-mutant models. These studies demonstrate the potential clinical application of dual inhibition of SOS1 and KRAS G12C and additional SOS1 combination strategies that will aide in the understanding of SOS1 and RTK/MAPK biology in targeted cancer therapy.

Feeling Safe in the Perioperative Period: Experiences from Patients Undergoing Orthopedic Day Surgery.

Introduction: Day surgery is often preferred by patients, but it can pose challenges in self-management after discharge. In addition, patients undergoing orthopedic surgery report poorer rates of postoperative recovery than patients undergoing general surgery. Understanding patients' perceptions of feeling safe while undergoing surgery facilitates individualized care and is important since it may affect their recovery. Objective: The aim of this study was to describe patients' perceptions of feeling safe in the perioperative period when undergoing orthopedic day surgery under regional anesthesia. Methods: The design was qualitative and descriptive. Data were collected through a cross-sectional questionnaire containing open-ended questions. Qualitative content analysis with an inductive approach was used for data analysis. Participants' characteristics were presented descriptively. The study population consisted of a consecutive sample of 97 patients who had undergone orthopedic day surgery under regional anesthesia between March and October 2022. Results: The categorization process resulted in the development of two categories describing participants' experience of perioperative feelings of safety when undergoing orthopedic day surgery: having someone near and having a sense of control. The results indicate that the relationship between patients and staff and the perceived feeling of control and participation are factors influencing patients' perception of feeling safe in the perioperative period. Conclusions: In perioperative care, nurses play a vital role in fostering patients' sense of safety by establishing relationships. This ensures that patients can be actively engaged in their own care. Patients also need access to professional and competent staff who strives to add a personal touch and considers their perspective. Since patients undergoing orthopedic day surgery might face a more demanding postoperative recovery than they had initially anticipated, further research is suggested to explore the association between a perceived feeling of safety and postoperative recovery.

Central autonomic network dysfunction and plasma Alzheimer's disease biomarkers in older adults.

BACKGROUND: Higher order regulation of autonomic function is maintained by the coordinated activity of specific cortical and subcortical brain regions, collectively referred to as the central autonomic network (CAN). Autonomic changes are frequently observed in Alzheimer's disease (AD) and dementia, but no studies to date have investigated whether plasma AD biomarkers are associated with CAN functional connectivity changes in at risk older adults. METHODS: Independently living older adults (N = 122) without major neurological or psychiatric disorder were recruited from the community. Participants underwent resting-state brain fMRI and a CAN network derived from a voxel-based meta-analysis was applied for overall, sympathetic, and parasympathetic CAN connectivity using the CONN Functional Toolbox. Sensorimotor network connectivity was studied as a negative control. Plasma levels of amyloid (Aß42, Aß40), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using digital immunoassay. The relationship between plasma AD biomarkers and within-network functional connectivity was studied using multiple linear regression adjusted for demographic covariates and Apolipoprotein E (APOE) genotype. Interactive effects with APOE4 carrier status were also assessed. RESULTS: All autonomic networks were positively associated with Aß42/40 ratio and remained so after adjustment for age, sex, and APOE4 carrier status. Overall and parasympathetic networks were negatively associated with GFAP. The relationship between the parasympathetic CAN and GFAP was moderated by APOE4 carrier status, wherein APOE4 carriers with low parasympathetic CAN connectivity displayed the highest plasma GFAP concentrations (B = 910.00, P = .004). Sensorimotor connectivity was not associated with any plasma AD biomarkers, as expected. CONCLUSION: The present study findings suggest that CAN function is associated with plasma AD biomarker levels. Specifically, lower CAN functional connectivity is associated with decreased plasma Aß42/40, indicative of cerebral amyloidosis, and increased plasma GFAP in APOE4 carriers at risk for AD. These findings could suggest higher order autonomic and parasympathetic dysfunction in very early-stage AD, which may have clinical implications.

Ten-Year Outcomes Following Roux-en-Y Gastric Bypass vs Duodenal Switch for High Body Mass Index: A Randomized Clinical Trial.

Importance: Results from long-term follow-up after biliopancreatic diversion with duodenal switch (DS) are scarce. Objective: To compare weight loss, health outcomes, and quality of life 10 years or more after Roux-en-Y-gastric bypass (RYGB) and DS surgery in patients with severe obesity-that is, a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 50 to 60. Design, Setting, and Participants: This open-label randomized clinical trial was conducted at 2 academic bariatric centers in Sweden and Norway. Sixty patients with a BMI of 50 to 60 were included from March 1, 2006, to August 31, 2007. Data were analyzed from August 12, 2022, to January 25, 2023. Interventions: Laparoscopic RYGB or laparoscopic DS. Main Outcomes and Measures: The main outcome was change in BMI after 10 or more years. Secondary outcomes included anthropometric measures, lipid and glycemic profiles, bone mass density, adverse events, gastrointestinal tract symptoms, and health-related quality of life. Results: Forty-eight of the original 60 patients (80%) were assessed after a median of 12 (range, 9-13) years (mean [SD] age, 48.0 [6.0] years; 35 women [73%]). At follow-up, the mean BMI reductions were 11.0 (95% CI, 8.3-13.7) for RYGB and 20.3 (95% CI, 17.6-23.0) for DS, with a mean between-group difference of 9.3 (95% CI, 5.4-13.1; P < .001). Total weight loss was 20.0% (95% CI, 15.3%-24.7%) for RYGB and 33.9% (95% CI, 27.8%-40.0%) for DS (P = .001). Mean serum lipid levels, except high-density lipoprotein cholesterol and hemoglobin A1c, improved more in the DS group during follow-up. Bone mass was reduced for both groups from 5 to 10 years, with lower bone mass after DS at 10 years. Quality-of-life scores (Obesity-Related Problem Scale and the 36-Item Short Form Health Survey) were comparable across groups at 10 years. The total number of adverse events was higher after DS (135 vs 97 for RYGB; P = .02). More patients in the DS group developed vitamin deficiencies (21 vs 11 for RYGB; P = .008) including 25-hydroxyvitamin D deficiency (19 for DS vs 9 for RYGB; P = .005). Four of 29 patients in the DS group (14%) developed severe protein-caloric malnutrition, of whom 3 (10%) underwent revisional surgery. Conclusions and Relevance: In this randomized clinical trial, BMI reduction was greater after DS, but RYGB had a better risk profile over 10 years. Biliopancreatic diversion with DS may not be a better surgical strategy than RYGB for patients with a BMI of 50 to 60. Trial Registration: ClinicalTrials.gov Identifier: NCT00327912.

Technical recommendations for implementation of Volumetric Modulated Arc Therapy and Helical Tomotherapy Total Body Irradiation.

As a component of myeloablative conditioning before allogeneic hematopoietic stem cell transplantation (HSCT), Total Body Irradiation (TBI) is employed in radiotherapy centers all over the world. In recent and coming years, many centers are changing their technical setup from a conventional TBI technique to multi-isocenter conformal arc therapy techniques such as Volumetric Modulated Arc Therapy (VMAT) or Helical Tomotherapy (HT). These techniques allow better homogeneity and control of the target prescription dose, and provide more freedom for individualized organ-at-risk sparing. The technical design of multi-isocenter/multi-plan conformal TBI is complex and should be developed carefully. A group of early adopters with conformal TBI experience using different treatment machines and treatment planning systems came together to develop technical recommendations and share experiences, in order to assist departments wishing to implement conformal TBI, and to provide ideas for standardization of practices.