Effect of interface dead space on the time taken to achieve changes in set FiO2 during T-piece ventilation: is face mask the optimal interface for neonatal stabilisation?

BACKGROUND: T-piece is recommended for respiratory support during neonatal stabilisation. Bench studies have shown a delay >30 s in achieving changes in fraction of inspired oxygen (FiO2) at the airway when using the T-piece. Using a face mask adds dead space (DS) to the patient airway. We hypothesised that adding face mask to T-piece systems adversely affects the time required for a change in FiO2 to reach the patient. METHODS: Neopuff (Fisher and Paykel, Auckland, New Zealand) and rPAP (Inspiration Healthcare, Croydon, UK) were used to ventilate a test lung. DS equivalent to neonatal face masks was added between the T-piece and test lung. Additionally, rPAP was tested with nasal prongs. Time course for change in FiO2 to be achieved at the airway was measured for increase (0.3-0.6) and decrease (1.0-0.5) in FiO2. Primary outcome was time to reach FiO2+/-0.05 of the set target. One-way analysis of variance was used to compare mean time to reach the primary outcome between different DS volumes. RESULTS: In all experiments, the mean time to reach the primary outcome was significantly shorter for rPAP with prongs compared with Neopuff and rPAP with face mask DS (p<0.001). The largest observed difference occurred when testing a decrease in FiO2 with 10 mL tidal volume (TV) without leakage (18.3 s for rPAP with prongs vs 153.4 s for Neopuff with face mask DS). The shortest observed time was 13.3 s when increasing FiO2 with 10 mL TV with prongs with leakage and the longest time was 172.7 s when decreasing FiO2 with 4 mL TV and added face mask DS without leak. CONCLUSION: There was a delay in achieving changes in oxygen delivery at the airway during simulated ventilation attributable to the mask volume. This delay was greatly reduced when using nasal prongs as an interface. This should be examined in clinical trials.

Sport Participation Trajectories and Loneliness: Evidence From the Longitudinal Study of Australian Children.

BACKGROUND: This study aimed to identify patterns of overall, team, and individual sport participation and examine the prospective associations between these patterns and loneliness in young people. METHODS: We analyzed data from 4241 young people, from waves 3 (8-9 y) to 9 (20-21 y) of the Longitudinal Study of Australian Children. We conducted latent class analyses to identify overall and team versus individual sport participation trajectories and used adjusted log-Poisson regression models to examine the associations between these trajectories and loneliness at wave 9. RESULTS: Latent class analyses identified 4 distinct overall sport participation classes which were labeled: nonparticipants (24%), dropouts (42%), initiators (7%), and consistent participants (27%). Compared with nonparticipants, consistent participants had a lower risk of loneliness (risk ratios = 0.69; 95% CIs, 0.59-0.81). Latent class analyses also identified 4 distinct team versus individual sport participation classes: team and individual sport nonparticipants (38%), individual sport participants (14%), moderate team sport participants (14%), and high team sport participants (34%). Compared with the team and individual sport nonparticipants, the high team sports participants had a lower risk of loneliness (risk ratios = 0.70; 95% CIs, 0.53-0.92). CONCLUSIONS: Young people who continued participating in sport in general, and particularly in team sport, had a reduced risk of loneliness. Continued participation in sports should be promoted to improve a range of physical, mental, and social health benefits. Furthermore, team-based sport can provide additional health and well-being benefits, including reduced loneliness due to the group nature of participation.

Macroinvertebrate community and leaf litter breakdown measures lack concordance associated with singular or multiple stressors.

Freshwater ecosystems are being degraded by a wide range of stressors resulting from human activities. Various structural and functional metrics or indices are used to assess the 'health' or condition of riverine ecosystems. It is uncertain if structural or functional metrics or indices respond to different stressors and whether some are more responsive to stressors in general. Here we conducted a multi-study synthesis, similar to a meta-analysis, across four independent outdoor mesocosm experiments involving the manipulation of various chemical stressors - two types of salinity (synthetic marine salts (SMS) and sodium bicarbonate), two insecticides (malathion and sulfoxaflor), increased nutrients (N and P), increased sedimentation and two combinations of stressors (1: malathion, nutrients and sedimentation, 2: sulfoxaflor, nutrients and sedimentation). We compare the effects of these singular or multiple stressors on stream macroinvertebrate community structure, and Eucalyptus camaldulensis leaf litter breakdown rates by microbes and total (microbes and invertebrates). Macroinvertebrate communities were adversely affected by the two sets of multiple stressors, SMS, and both insecticides yet, and in contrast to several published studies, both microbial and total leaf litter was unaffected. Nutrients and sodium bicarbonate, increased breakdown rates or had a unimodal 'Ո' shaped response, with maxima at intermediate levels. Sedimentation by fine sand, however, decreased total leaf litter breakdown, while not affecting microbial leaf litter breakdown. Divergent responses between the effects of stressors on leaf litter breakdown rates that we observed and those in the literature may be caused by multiple mechanisms, including differences between communities, functional redundancy and differences in stressor magnitude and interactions with other (unknown) variables.

Clinical Features, Adverse Events and Treatment Outcomes of Multidrug/Rifampicin-resistant Tuberculosis in Children and Adolescents: An Eight-year Retrospective Cohort Study in Bandung, Indonesia.

BACKGROUND: Data on childhood and adolescent multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) in Indonesia are lacking. We aimed to assess clinical features, adverse events (AEs) and treatment outcomes of childhood and adolescent MDR/RR-TB. METHODS: A retrospective cohort study was performed in children and adolescents aged <18 years treated for MDR/RR-TB at Hasan Sadikin General Hospital in Bandung, Indonesia, between June 2016 and March 2024. Multivariable logistic regression analyses were used to calculate adjusted odds ratios (aOR) for predictors of all-cause mortality. RESULTS: Among 84 included patients, 69 (82%) were adolescents aged 10-17 years, 54 (64%) were female, 54 (64%) were malnourished and 55 (65%) had culture-confirmed disease. Among 69 (82%) patients with known outcomes, 48 (70%) were successfully treated, 14 (20%) died (including 5 pretreatment deaths) and 7 (10%) were lost to follow-up (LTFU) (including 5 pretreatment LTFU). Predictors of all-cause mortality included shortness of breath on admission [aOR: 6.4, 95% confidence interval (CI): 1.3-49.1], high bacillary burden on Xpert MTB/RIF assay (aOR: 17.0, 95% CI: 1.6-260.5) and the presence of lung cavities on chest radiograph (aOR: 4.8, 95% CI: 1.1-23.3). Among 74 patients who initiated treatment, 39 (53%) had at least one grade 1-2 AE, and 4 (5%) had one grade 3-4 AE each, including hepatotoxicity, QT prolongation, hearing loss and rash/hyperpigmentation. CONCLUSION: Younger children were underrepresented among those treated for MDR/RR-TB, indicating reduced access to care. Severe AEs were uncommon during MDR/RR-TB treatment. Baseline indicators of extensive disease were associated with all-cause mortality. The high proportion of pre-treatment mortality and LTFU may reflect complex patient pathways limiting access to care.

Predicting antibiotic resistance in Enterobacterales to support optimal empiric treatment of urinary tract infections in outpatient veterans.

Objective: Bacterial resistance is known to diminish the effectiveness of antibiotics for treatment of urinary tract infections. Review of recent healthcare and antibiotic exposures, as well as prior culture results is recommended to aid in selection of empirical treatment. However, the optimal approach for assessing these data is unclear. We utilized data from the Veterans Health Administration to evaluate relationships between culture and treatment history and the subsequent probability of antibiotic-resistant bacteria identified in urine cultures to further guide clinicians in understanding these risk factors. Methods: Using the XGBoost algorithm, a retrospective cohort of outpatients with urine culture results and antibiotic prescriptions from 2017 to 2022 was used to develop models for predicting antibiotic resistance for three classes of antibiotics: cephalosporins, fluoroquinolones, and trimethoprim/sulfamethoxazole (TMP/SMX) obtained from urine cultures. Model performance was assessed using Area Under the Receiver Operating Characteristic curve (AUC) and Precision-Recall AUC (PRAUC). Results: There were 392,647 prior urine cultures identified in 214,656 patients. A history of bacterial resistance to the specific treatment was the most important predictor of subsequent resistance for positive cultures, followed by a history of specific antibiotic exposure. The models performed better than previously established risk factors alone, especially for fluoroquinolone resistance, with an AUC of .84 and PRAUC of .70. Notably, the models' performance improved markedly (AUC = .90, PRAUC = .87) when applied to cultures from patients with a known history of resistance to any of the antibiotic classes. Conclusion: These predictive models demonstrate potential in guiding antibiotic prescription and improving infection management.

The effect of weapon handling during load carriage across a range of military-relevant walking speeds.

This study investigated the effects of weapon handling on the physiological responses and walking-gait kinematics during load carriage. Seventeen soldiers completed four twelve-minute bouts of treadmill walking at incremental speeds (3.5, 5.5, 6.5 km.h-1 and self-selected) carrying 23.2-kg of additional load, while either handling a weapon or not handling a weapon. Physiological, perceptual and biomechanical outcomes were measured throughout each trial. A weapon-by-speed interaction (p < .05) was observed for hip flexion-extension during loading response and mid-swing. Weapon handling elevated (p < .05) cardiorespiratory responses at 6.5 km.h-1. Main effects (p < .05) of weapon handling were observed for ventilation, oxygen pulse, effort perception, stride length and knee flexion-extension during toe-off. No main effects of weapon handling were observed for any other biomechanical measures. These findings demonstrate that physiological and biomechanical responses to weapon handling are likely walking-speed dependent.Practitioner summary: Weapon handling is an important part of many load-carriage tasks but is rarely investigated. Physiological and biomechanical responses were assessed at incremental speeds during load carriage. Despite similar biomechanics, there was greater physiological demands at faster walking speeds, suggesting an increased contribution from isometric muscle contractions for weapon stabilisation.

FreeClimb 88 catheter with Tenzing 8 delivery for contact aspiration mechanical thrombectomy of anterior circulation large vessel occlusions.

PURPOSE: Contact aspiration mechanical thrombectomy (CAMT) with 0.088-inch catheters may improve first-pass success rates, but delivery of such catheters can be challenging and limit effectiveness. This study examines the initial multicenter experience using the FreeClimb 88 catheter paired with the Tenzing 8 delivery catheter. MATERIALS AND METHODS: Retrospective analysis was performed of consecutive patients with large vessel occlusion (LVO) of the internal carotid artery (ICA) or M1 segment of the middle cerebral artery treated with off-label CAMT using the FreeClimb 88 and Tenzing 8 at eight sites participating in the early limited release for these devices. Demographic and procedural variables were collected and analyzed with descriptive statistics and multivariable analysis. RESULTS: Fifty-three consecutive patients were treated. Large vessel occlusion was located in the ICA in 19/53 (35.8%) patients; 34/53 (64.2%) were in the M1 segment. FreeClimb 88 was successfully delivered to the site of occlusion in 50/53 (94.3%) of patients. First-pass TICI 2c or 3 was achieved with FreeClimb 88 delivered by Tenzing 8 in 36 (67.9%) cases. Among cases with successful FreeClimb 88 delivery 9/50 (18.0%) required additional smaller devices to perform thrombectomy of distal occlusions after recanalization of the initial LVO. No complications or symptomatic hemorrhages occurred following thrombectomy. CONCLUSION: Contact aspiration mechanical thrombectomy performed for ICA or M1 LVOs using FreeClimb 88 delivered with Tenzing 8 was safe, effective, and efficient in this early experience, with first-pass TICI 2c or 3 was achieved in 68% of patients without procedural complications occurring in any cases.

Impact and limitations of 3D computational modelling in transcatheter mitral valve replacement-a two-centre Dutch experience.

BACKGROUND: Transcatheter mitral valve replacement (TMVR) has emerged as a minimally invasive alternative to mitral valve surgery for patients at high or prohibitive operative risk. Prospective studies reported favourable outcomes in patients with annulus calcification (valve-in-mitral annulus calcification; ViMAC), failed annuloplasty ring (mitral valve-in-ring; MViR), and bioprosthetic mitral valve dysfunction (mitral valve-in-valve; MViV). Multi-slice computed tomography (MSCT)-derived 3D-modelling and simulations may provide complementary anatomical perspectives for TMVR planning. AIMS: We aimed to illustrate the implementation of MSCT-derived modelling and simulations in the workup of TMVR for ViMAC, MViR, and MViV. METHODS: For this retrospective study, we included all consecutive patients screened for TMVR and compared MSCT data, echocardiographic outcomes and clinical outcomes. RESULTS: Sixteen out of 41 patients were treated with TMVR (ViMAC n = 9, MViR n = 3, MViV n = 4). Eleven patients were excluded for inappropriate sizing, 4 for anchoring issues and 10 for an unacceptable risk of left ventricular outflow tract obstruction (LVOTO) based on 3D modelling. There were 3 procedure-related deaths and 1 non-procedure-related cardiovascular death during 30 days of follow-up. LVOTO occurred in 3 ViMAC patients and 1 MViR patient, due to deeper valve implantation than planned in 3 patients, and anterior mitral leaflet displacement with recurrent basal septum thickening in 1 patient. TMVR significantly reduced mitral mean gradients as compared with baseline measurements (median mean gradient 9.5 (9.0-11.5) mm Hg before TMVR versus 5.0 (4.5-6.0) mm Hg after TMVR, p = 0.03). There was no residual mitral regurgitation at 30 days. CONCLUSION: MSCT-derived 3D modelling and simulation provide valuable anatomical insights for TMVR with transcatheter balloon expandable valves in ViMAC, MViR and MViV. Further planning iterations should target the persistent risk for neo-LVOTO.

Clearance and transport of amyloid ß by peripheral monocytes correlate with Alzheimer's disease progression.

Impaired clearance of amyloid ß (Aß) in late-onset Alzheimer's disease (AD) affects disease progression. The role of peripheral monocytes in Aß clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aß-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aß-binding monocytes with high phagocytic potential in both the periphery and CNS. We find lower surface Aß levels in mild cognitive impairment (MCI) and AD-dementia patients compared to cognitively unimpaired individuals. Monocyte infiltration from blood to CSF and migration from CNS to peripheral lymph nodes and blood are observed. Here we show that Aß-binding monocytes may play a role in CNS Aß clearance, suggesting their potential as a biomarker for AD diagnosis and monitoring.

Critical assessment of infants born to mothers with drug resistant tuberculosis.

Background: There have been no detailed descriptions of infants born to mothers treated for drug resistant TB in pregnancy. Critical case history assessment is important to identify risks and guide clinical practice. Methods: In a cohort of pregnant women with multidrug or rifampicin resistant (MDR/RR)-TB enrolled between 1 January 2013 and 31 December 2022, we followed mother-infant pairs until the infant was 12 months old. We performed critical case history assessments to explore potential mechanisms of Mycobacterium tuberculosis transmission to the infant, and to describe the clinical presentation and disease trajectories observed in infants diagnosed with TB. Findings: Among 101 mother-infant pairs, 23 (23%) included infants diagnosed with TB disease; 16 were clinically diagnosed and seven had microbiological confirmation (five MDR/RR-TB, two drug-susceptible TB). A positive maternal sputum culture at the time of delivery was significantly associated with infant TB risk (p = 0.023). Of the 12 infants diagnosed with TB in the first three months of life, seven (58%) of the mothers were culture positive at delivery; of whom four reported poor TB treatment adherence. However, health system failures, including failing to diagnose and treat maternal MDR/RR-TB, inadequate screening of newborns at birth, not providing appropriate TB preventive therapy (TPT), and M. tuberculosis transmission from non-maternal sources also contributed to TB development in infants. Interpretation: Infants born to mothers with MDR/RR-TB are at greatest risk if maternal adherence to MDR/RR-TB treatment or antiretroviral therapy (ART) is sub-optimal. In a high TB incidence setting, infants are also at risk of non-maternal household and community transmission. Ensuring maternal TB diagnosis and appropriate treatment, together with adequate TB screening and prevention in all babies born to mothers or households with TB will minimise the risk of infant TB disease development. Funding: South African Medical Research Council.

Experiences of social isolation and loneliness in chronic kidney disease: a secondary qualitative analysis.

BACKGROUND: Many patients with chronic kidney disease (CKD) experience loneliness and social isolation, which are associated with a higher risk of mortality, morbidity, and poor mental health. We aimed to describe the perspectives of patients with CKD and their caregivers on loneliness and social isolation, to inform strategies to increase social participation. METHODS: A secondary analysis of qualitative data from the Standardized Outcomes in Nephrology (SONG) initiative dataset (36 focus groups, three Delphi surveys and seven consensus workshops) was conducted. We extracted and thematically analyzed data from patients with CKD, including those receiving hemodialysis or peritoneal dialysis and those with a kidney transplant, as well as their caregivers, on the perspectives and experiences of loneliness and social isolation. RESULTS: Collectively the studies included 1261 patients and caregivers from 25 countries. Six themes were identified: restricted by the burdens of disease and treatment (withdrawing from social activities due to fatigue, consumed by the dialysis regimen, tethered to treatment, travel restrictions); external vulnerability (infection risk, anxiety of dining out); diminishing societal role (grieving loss of opportunities, social consequences of inability to work); fending for oneself in healthcare (no one to relate to, lost in uncertainty, unmet psychosocial needs); undermining self-esteem (unable to engage in activities which previously defined self, shame and self-consciousness about appearance, hindering confidence for intimate relationships); and feeling ostracized (disconnected by family and friends, fear of stigma and being misunderstood, guilt of burdening others). CONCLUSIONS: For patients with CKD and their caregivers, social participation is substantially impaired by the burden of CKD and its treatment, and fear of risks to health such as infection. This undermines patient and caregiver mental health, particularly self-esteem and sense of belonging. Additional interventions are needed to improve social connections among people with CKD and their caregivers.

The efficiency of detecting seabird behaviour from movement patterns: the effect of sampling frequency on inferring movement metrics in Procellariiformes.

BACKGROUND: Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths. METHODS: We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states. RESULTS: We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1-5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles. CONCLUSIONS: Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10-30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged.

Identification, mapping, and self-reported practice patterns of village doctors in Sitakunda subdistrict, Bangladesh.

Background: Informally trained health care providers, such as village doctors in Bangladesh, are crucial in providing health care services to the rural poor in low- and middle-income countries. Despite being one of the primary vendors of antibiotics in rural Bangladesh, village doctors often have limited knowledge about appropriate antibiotic use, leading to varied and potentially inappropriate dispensing and treatment practices. In this study, we aimed to identify, map, and survey village doctors in the Sitakunda subdistrict of Bangladesh to understand their distribution, practice characteristics, clinical behaviours, access to technologies, and use of these technologies for clinical decision-making. Methods: Using a 'snowball' sampling method, we identified and mapped 411 village doctors, with 371 agreeing to complete a structured survey. Results: The median distance between a residential household and the closest village doctor practice was 0.37 km, and over half of the practices (51.2%) were within 100 m of the major highway. Village doctors were predominately male (98.7%), with a median age of 39. After completing village doctor training, 39.4% had completed an internship, with a median of 15 years of practice experience. Village doctors reported seeing a median of 84 patients per week, including a median of five paediatric diarrhoea cases per week. They stocked a range of antibiotics, with ciprofloxacin and metronidazole being the most prescribed for diarrhoea. Most had access to phones with an internet connection and used online resources for clinical decision-making and guidance. Conclusions: The findings provide insights into the characteristics and practices of village doctors and point to the potential for internet and phone-based interventions to improve patient care and reduce inappropriate antibiotic use in this health care provider group.

Protocol for Designing a Model to Predict the Likelihood of Psychosis From Electronic Health Records Using Natural Language Processing and Machine Learning.

INTRODUCTION: Rapid identification of individuals developing a psychotic spectrum disorder (PSD) is crucial because untreated psychosis is associated with poor outcomes and decreased treatment response. Lack of recognition of early psychotic symptoms often delays diagnosis, further worsening these outcomes. METHODS: The proposed study is a cross-sectional, retrospective analysis of electronic health record data including clinician documentation and patient-clinician secure messages for patients aged 15-29 years with ≥ 1 primary care encounter between 2017 and 2019 within 2 Kaiser Permanente regions. Patients with new-onset PSD will be distinguished from those without a diagnosis if they have ≥ 1 PSD diagnosis within 12 months following the primary care encounter. The prediction model will be trained using a trisourced natural language processing feature extraction design and validated both within each region separately and in a modified combined sample. DISCUSSION: This proposed model leverages the strengths of the large volume of patient-specific data from an integrated electronic health record with natural language processing to identify patients at elevated chance of developing a PSD. This project carries the potential to reduce the duration of untreated psychosis and thereby improve long-term patient outcomes.

Periorbital Intravenous Lobular Pyogenic Granulomas: A Case Report and Literature Review of This Peculiar Pathology.

Intravenous lobular pyogenic granuloma (ILPG) is a seldom-documented pathology in oculoplastic and orbital literature. This study aims to elucidate the clinical presentation and histopathologic findings surrounding periorbital ILPG through a case presentation and literature review. We describe a 42-year-old male with a palpable periorbital subcutaneous nodule that was subsequently diagnosed as ILPG on immunohistochemistry. A literature review was performed by searching articles in the PubMed/MEDLINE database using the keywords "periorbital intravenous lobular pyogenic granuloma," "periorbital intravenous pyogenic granuloma," or "periorbital intravenous capillary hemangioma." The literature review identified 6 patients presenting with similar subcutaneous nodules that were diagnosed as periorbital ILPGs. All patients, including the one in this study, were treated with local excision. Only 1 patient (1/7; 14.3%) noted pain while 5 experienced swelling or fluctuance (5/7; 71.4%). In patients with documented pathology reports, all ILPGs involved the angular vein (6/6; 100%). Of the 3 patients who had follow-ups at 2 to 7 years postexcision, none had recurrence. Histopathologic findings demonstrate an intravascular lobular tumor composed of capillaries with endothelial cells and pericytes. Marked reactivity to anti-Wilms tumor type 1 (WT-1) and anti-Smooth muscle actin was noted in the capillary structure. ILPG can be included on the differential for well-circumscribed, subcutaneous periocular masses. While the etiology of periorbital ILPG is unknown, most cases are managed with surgical excision, and recurrence appears to be uncommon. In sharing these cases and histopathologic underpinnings of periorbital ILPG, we endeavor to describe this peculiar pathology for oculoplastic and reconstructive surgeons.

Sex differences in physiological correlates of affectively driven decision-making behavior in adult ADHD.

BACKGROUND: Sex differences in the symptomatology of adults with attention-deficit/hyperactivity disorder (ADHD) have often been overlooked when studying behavioral abnormalities. However, it is known that women exhibit considerably more stronger symptoms related to emotional competence than men. Since affective functions significantly influence the processing of risky decision-making and risk-engagement, we assume that risky behavior in ADHD is affected by sex differences. Therefore, we specifically investigated sex-specific effects on the interaction between emotionally induced changes in physiology and behavioral performance on a decision-making task. METHODS: Skin conductance responses of twenty-nine adults with ADHD (n = 16 male; n = 13 female) and thirty-three adults in the control group (n = 14 male; n = 19 female) were recorded during the performance in a modified version of the Balloon Analogue Risk Task (BART). Additional questionnaires were used to reveal insights in the self-assessment of emotional competence, risk perception, and feedback sensitivity. Emotional arousal and decision-making behavior were analyzed using linear mixed-effects models. RESULTS: Results showed different effects of sex on risk behaviors in controls and ADHD. In contrast to healthy controls, female adults with ADHD showed a significantly greater risk engagement in the BART compared to males with ADHD. This contrary sex relation was not observed in skin conductance responses and revealed a significantly different sex-dependent correlation of body response and behavioral task performance in ADHD. Comparisons with results from self-assessments furthermore indicate a reduced behavioral self-perception in women with ADHD, but not in men. CONCLUSION: In summary, we found an altered interaction between physiological activity and risky behavior in women with ADHD. Thus, the present study indicates a reduced sensitivity towards the own bodily responses in women with ADHD, which could consequently cause increased risky DM behavior in daily life. The current results suggest that more consideration needs to be given to sex-specific effects on physiological processes and behavior in adults with ADHD.

Preoperative Magnetic Resonance Guided Single-Dose Partial Breast Irradiation: 5-Year Results of the Prospective Single-Arm ABLATIVE Trial.

PURPOSE: Preoperative partial breast irradiation (PBI) can increase accuracy of target volume definition and decrease irradiated volumes compared with postoperative PBI. In the ABLATIVE trial (NCT02316561), 15 of 36 patients achieved pathologic complete response 6 to 8 months after preoperative PBI and breast-conserving surgery (BCS). We now present the 5-year results. METHODS AND MATERIALS: The ABLATIVE trial is a Dutch prospective cohort study conducted in 4 hospitals. Women aged ≥50 years with unifocal, nonlobular breast cancer, estrogen receptor-positive, HER2-negative, and a tumor negative sentinel node were treated between 2015 and 2018 with preoperative single-dose PBI followed by BCS after 6 or 8 months. The primary endpoint was pathologic complete response. Secondary endpoints were annually evaluated oncological outcomes, toxicity, cosmetic outcome (assessed by patients and physicians), and quality of life. RESULTS: Thirty-six patients were treated with BCS 6 (n = 15) and 8 (n = 21) months following PBI. Median tumor size was 13 mm (IQR 9-16 mm). After a median follow-up of 5.5 years (IQR, 5.1-6.0), 2 (6%) patients had ipsilateral breast events and 2 (6%) distant metastases. The 5-year overall survival was 94% (95% CI, 87-100). The 5-year cumulative incidence of clinician-reported grade 1/2 breast fibrosis and breast discomfort/pain were 94%/6% and 75%/6%, respectively. The proportion of patients (very) satisfied with the cosmetic results was 89% at baseline and 78% at 5 years. Cosmetic results evaluated using the BCCT.core software were excellent or good in all patients. The 4-year median global quality of life score was 83 (IQR, 67-92), similar to baseline (83; IQR, 75-83; P = .42). CONCLUSIONS: Preoperative single-dose PBI and BCS may be an oncologically safe treatment with mild late toxicity and no decline in cosmetic results and quality of life during 5 years of follow-up. This means that preoperative instead of standard postoperative irradiation has the potential to challenge the current clinical practice.

Stimuli-responsive drug delivery systems for inflammatory skin conditions.

Inflammatory skin conditions highly influence the quality of life of the patients suffering from these disorders. Symptoms include red, itchy and painful skin lesions, which are visible to the rest of the world, causing stigmatization and a significantly lower mental health of the patients. Treatment options are often unsatisfactory, as they suffer from either low patient adherence or the risk of severe side effects. Considering this, there is a need for new treatments, and notably of new ways of delivering the drugs. Stimuli-responsive drug delivery systems are able to deliver their drug cargo in response to a given stimulus and are, thus, promising for the treatment of inflammatory skin conditions. For example, the use of external stimuli such as ultraviolet light, near infrared radiation, or alteration of magnetic field enables drug release to be precisely controlled in space and time. On the other hand, internal stimuli induced by the pathological condition, including pH alteration in the skin or upregulation of reactive oxygen species or enzymes, can be utilized to create drug delivery systems that specifically target the diseased skin to achieve a better efficacy and safety. In the latter context, however, it is of key importance to match the trigger mechanism of the drug delivery system to the actual pathological features of the specific skin condition. Hence, the focus of this article is placed not only on reviewing stimuli-responsive drug delivery systems developed to treat specific inflammatory skin conditions, but also on critically evaluating their efficacy in the context of specific skin diseases. STATEMENT OF SIGNIFICANCE: Skin diseases affect one-third of the world's population, significantly lowering the quality of life of the patients, who deal with symptoms such as painful and itchy skin lesions, as well as stigmatization due to the visibility of their symptoms. Current treatments for inflammatory skin conditions are often hampered by low patient adherence or serious drug side effects. Therefore, more emphasis should be placed on developing innovative formulations that provide better efficacy and safety for patients. Stimuli-responsive drug delivery systems hold considerable promise in this regard, as they can deliver their cargo precisely where and when it is needed, reducing adverse effects and potentially offering better treatment outcomes.

Einthoven's triangle adapted for horses: Proposal for the Delta configuration.

BACKGROUND: Reliable ECGs are crucial for diagnosing arrhythmias, yet a lack of standardization impedes arrhythmia diagnosis and treatment in horses. OBJECTIVES: To objectively determine an optimal position of Einthoven's triangle for ECG recordings in horses at rest, which can form the basis for standardized ECG recording and improve diagnosis and treatment of arrhythmias. ANIMALS: The study involved 72 healthy, warmblood horses aged between 3 and 20 years. METHODS: In view of future 12-lead studies and vectorcardiography, requiring an orthogonal system, Einthoven's triangle was positioned around the heart, in the transverse plane. Therefore, 11 electrodes were placed encircling the thorax behind the olecranon, to construct triangles with a horizontal base. Electrocardiogram recordings from different triangles were analyzed. Signal processing involved filtering, R peak detection, and median complex generation. Principal component analysis (PCA) and Euclidean distance measures were employed for data analysis. RESULTS: The left mid-thoracic and ventral regions had high PCA scores, indicating high information content. Base-down triangles exhibited higher summed Euclidean distances, contributing to enhanced diagnostic capabilities. A base-down triangle, called "Delta (Δ) configuration" emerged as most informative, while meeting all criteria. CONCLUSIONS AND CLINICAL IMPORTANCE: The base-down "Delta configuration" is the optimal Einthoven's triangle adapted for horses, providing large amplitudes and potential to provide basic insights into the mechanisms and origins of cardiac arrhythmias. Because the Delta configuration is positioned in the transverse plane, it forms the ideal basis for 12-lead ECG recordings that provide vectorcardiograms in an orthogonal coordinate system. Standardizing electrode positioning could improve ECG data comparability in equine cardiology.