Sex differences in sledging injuries: a retrospective 10-season study from a Swiss level 1 trauma centre.

Objectives: Sledging is a popular and traditional winter sport in Switzerland. This study examines injury patterns of patients who presented to a tertiary trauma centre in Switzerland following sledging trauma, focusing on sex differences. Methods: Retrospective single-centre study over 10 winters (2012-2022), including all patients experiencing sledging-related trauma. Injury history was collected and analysed from the patient data and demographic information. The Abbreviated Injury Scale and the Injury Severity Score (ISS) were used to classify injury types and severity. Results: 193 patients were identified with sledging injuries. The median age was 46 (IQR 28-65), and 56% were female. The most frequent mechanism of injury was a fall (70%), followed by collision (27%) and other fall on slopes (6%). Lower extremities (36%), trunk (20%) and head/neck (15%) were the most frequently injured body areas. Fourteen per cent of patients were admitted with head injuries, whereas females were significantly more likely to present with head injuries than males (p=0.047). Males were significantly more often admitted with fractures to the upper extremities than females (p=0.049). The median ISS was 4 (IQR 1-5), without significant differences between males and females (p=0.290). The hospital admission rate was 28.5% for sledging-related injuries. The median length of stay for patients admitted to the hospital was 5 (IQR 4-8) days. The total cost for all patients was CHF1 292 501, with a median of CHF1009 per patient (IQR CHF458-CHF5923). Conclusion: Sledging injuries are common and may result in serious injuries. The lower extremities, trunk and head/neck are frequently injured and could be specifically protected with safety devices. Multiple injuries were statistically more frequent in women compared with men. Males were significantly more often admitted with fractures to the upper extremities, and females were more likely to sustain head injuries. The findings can help to develop data-driven measures to prevent sledging accidents in Switzerland.

Within-network brain connectivity during a social optimism task is related to personal optimism and optimism for in-group members.

Optimism bias is the tendency to believe desirable events are more likely to happen than undesirable ones. People often display optimistic biases for themselves (personal optimism), but also for members of groups they like or identify with (social optimism). However, the neural bases of and connections between these two concepts are poorly understood. The present study hence used both questionnaires and a social optimism task performed during magnetic resonance imaging to investigate how network connectivity associates with personal and social optimism biases. Using sparse canonical correlation analysis, we found that a behavioral dimension that included both in-group optimism bias and personal optimism bias was positively associated with a dimension of network connectivity. This dimension comprised two networks with positive weights (dorsal precuneus-related default mode network and dorsal sensorimotor network), and three with negative weights (including parts of the salience and central executive networks). Our findings indicate that connectivity in networks adjacent to the temporoparietal junction favors propagation of both personal and social optimism biases. Meanwhile, low connectivity in more frontal networks associated with more complex cognition may also further such propagation.

Sex hormones influence survival of patients with metastatic urothelial carcinoma undergoing immune checkpoint therapy.

INTRODUCTION: Clinical trials investigating efficacy of immune checkpoint inhibitors (ICI) revealed sex-specific divergent outcomes in urothelial cancer (UC), suggesting that sex hormones might play an important role in gender-specific dimorphisms of response upon ICI. However, further clinical investigations are still needed to understand the influence of sex hormones in UC. The aim of this study was to get further insights on the prognostic and predictive value of sex hormone levels in patients with metastatic UC (mUC) who underwent ICI. MATERIAL AND METHODS: Sex hormone levels of patients with mUC including luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH ratio, prolactin, testosterone and 17ß-estradiol (E2) were evaluated at baseline and during ICI at 6/8 weeks and 12/14 weeks. RESULTS: Twenty-eight patients (10 women, 18 men) with a median age of 70 years were included. Metastatic disease was confirmed in 21 patients (75%) after radical cystectomy while seven patients showed mUC at first diagnosis. Twelve patients (42.8%) received first line and 16 patients second line pembrolizumab. The objective response rate (ORR) was 39% (CR in 7%). The median progression-free survival (PFS) and overall survival (OS) was 5.5 and 20 months. Focusing on changes of sex hormone levels during ICI, a significant increase in FSH levels and decrease of the LH/FSH ratio was noticed in responders (p = 0.035), yet without sex-specific significance. When adjusted for sex and treatment line, a significant increase of FSH levels was confirmed in men during second line pembrolizumab. Focusing on baseline levels, LH/FSH ratio was significantly higher in female responders (p = 0.043) compared to non-responders. In women, increased LH levels and LH/FSH ratio were associated with better PFS (p = 0.014 for LH, p = 0.016 for LH/FSH ratio) and OS (p = 0.026 and p = 0.018). In male patients, increased E2 levels were linked with improved PFS (p < 0.001) and OS (p = 0.039). CONCLUSION: Increased LH and LH/FSH values in women as well as high E2 levels in men were significant predictors of better survival. Elevated LH/FSH ratio was predictive of better response to ICI in women. These results show first clinical evidence of the potential role of sex hormones as prognostic and predictive biomarker in mUC. Further prospective analyses are needed to corroborate our findings.

Urothelial carcinoma (UC) presents as aggressive disease with a greater incidence in men, yet a more aggressive course of disease in women. Patients with metastatic UC receive a chemotherapy regimen as the gold standard, based on an included platin substance. In the case of having contraindications to chemotherapy, checkpoint immunotherapy, priming the immune system to the tumor, is the treatment of choice. Furthermore, immunotherapy is used as second line therapy in progressive disease after chemotherapy and as maintenance therapy in stable tumor conditions after completing the chemotherapy regimen.Evidence shows that sex hormones of the hypothalamus­hypophysis axis influence development and course of UC. The sex hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulate estrogen (E2) production with a negative feedback function on the LH and FSH secretion. High levels of E2 present with a protective effect against UC. Sex has furthermore shown to predict potential response to immunotherapy. This study therefore focused on monitoring and correlating changes of sex hormone levels in 28 patients during therapy with checkpoint inhibitors.This first study assessing changes in sex hormones and the influence of baseline sex hormone values on survival in UC shows that responders to immunotherapy had significantly increased FSH levels. FSH furthermore increased in male patients receiving second line immunotherapy. High values of LH and a high LH/FSH ratio at baseline correlated with better overall survival in female patients. High E2 levels were indicative of better survival in male patients. The study results represent first suggestive prognostic and predictive results to the response of immunotherapy in UC.

Trauma Characteristics Associated with E-Scooter Accidents in Switzerland-A Case Series Study.

E-scooters have gained popularity worldwide in the last few years. Due to the increase in users, more accidents related to e-scooters can be observed. The present study aimed to analyse epidemiological data, characteristics, and severity of injuries in patients admitted to a Level I trauma centre in Switzerland (Inselspital Bern, University Hospital Bern) after accidents associated with e-scooters. This retrospective case series evaluated 23 patients who presented to the University Hospital of Bern between 1 of May 2019 and 31 of October 2021 after an e-scooter accident. Data were collected on patient demographics, time and cause of the accident, speed, alcohol consumption, helmet use, type and localisation of injury, number of injuries per patient, and outcome. Men were most frequently affected (61.9%). The mean age was 35.8 (STD 14.8) years. Slightly more than half (52.2%) of all accidents were self-inflicted. Most accidents were reported during the night (7 p.m. to 7 a.m., 60.9%) and in summer (43.5%). Alcohol consumption was reported in 43.5% of cases, with a mean blood alcohol level of 1.4 g/l. Most injuries were observed in the face (25.3%) and head/neck area (20.25%). Skin abrasions (56.5%) and traumatic brain injury (43.5%) were the most common types of traumata in terms of total number of patients. Only in one case it was reported that a protective helmet had been worn. Five patients required hospitalisation and four patients underwent surgery. Three patients underwent emergency orthopaedic surgery, and one patient underwent emergency neurosurgery. E-scooter accidents result in a significant number of facial and head/neck injuries. E-scooter riders would potentially benefit from a helmet to protect them in the event of an accident. Additionally, the results of this study indicate that a significant number of e-scooter accidents in Switzerland occurred under the influence of alcohol. Prevention campaigns to raise awareness of the risks of driving e-scooters under the influence of alcohol could help prevent future accidents.

On the complex and dimensional relationship of maternal posttraumatic stress disorder during early childhood and child outcomes at school-age.

BACKGROUND: Several studies have shown associations between maternal interpersonal violence-related posttraumatic stress disorder (PTSD), child mental health problems, and impaired socioemotional development. However, the existing literature lacks evidence linking constellations of risk factors such as maternal interpersonal-violence-related PTSD, psychopathology, and interactive behavior with toddlers and outcome measures at school-age. METHODS: This study involved a prospective, longitudinal investigation of 62 mothers and examined the relationship between maternal variables measured when children were in early childhood (mean age 27 months), and child outcomes when children were school-age (age mean = 83.2 months) while retaining a focus on the context of maternal PTSD. To identify and weigh associated dimensions comparatively, we employed sparse canonical correlation analysis (sCCA) aimed at associating dimensions of a dataset of 20 maternal variables in early childhood with that of more than 20 child outcome variables (i.e., child psychopathology, life-events, and socioemotional skills) at school-age. RESULTS: Phase 1 variables with the highest weights were those of maternal psychopathology: PTSD, depressive and dissociative symptoms, and self-report of parental stress. The highest weighted Phase 2 child outcome measures were those of child psychopathology: PTSD, anxiety, and depressive symptoms as well as peer bullying and victimization. CONCLUSIONS: sCCA revealed that trauma-related concepts in mothers were significantly and reliably associated with child psychopathology and other indicators of risk for intergenerational transmission of violence and victimization. The results highlight the dimensional and multifaceted nature-both for mothers as well as children-of the intergenerational transmission of violence and associated psychopathology.

Impact of allogeneic red blood cell transfusion on prognosis in soft tissue sarcoma patients. A single-centre study.

BACKGROUND: Perioperatively administered (leukocyte reduced) allogeneic red blood cell transfusions (lrRBCTs) may lead to transfusion-related immunomodulation and reduced overall survival (OS) in cancer patients. Herein, the effect of lrRBCT on local recurrence (LR), distant metastasis (DM), and OS in soft tissue sarcoma (STS) patients was analysed. METHODS: Retrospective study on 432 STS patients (mean age: 60.0 ± 17.8 years; 46.1% female), surgically treated at a tertiary tumour centre. Uni- and multivariate survival models were calculated to analyse impact of perioperative lrRBCTs on LR, DM, OS. RESULTS: Perioperatively, 75 patients (17.4%) had received lrRBCTs. Older patients, deep, large, lower limb STS rather required lrRBCTs (all p < 0.05). No significant association between lrRBCT administration and LR- (p = 0.582) or DM-risk (p = 0.084) was observed. LrRBCT was associated with worse OS in univariate analysis (HR: 2.222; p < 0.001), with statistical significance lost upon multivariate analysis (HR: 1.658; p = 0.059; including age, histology, size, grading, amputation, depth). Adding preoperative haemoglobin in subgroup of 220 patients with laboratory parameters revealed significant negative impact of low haemoglobin on OS (p = 0.014), whilst effect of lrRBCT was further diminished (p = 0.167). CONCLUSION: Unfavourable prognostic factors prevail in STS patients requiring lrRBCTs. Low haemoglobin levels rather than lrRBCT seem to reduce OS.

Pre-injury stimulant use in isolated severe traumatic brain injury: effect on outcomes.

PURPOSE: The aim of this study was to assess the impact of pre-injury stimulant use (amphetamine, cocaine, methamphetamine and/or ecstasy) on outcomes after isolated severe traumatic brain injury (TBI). METHODS: Retrospective 2017 TQIP study, including adult trauma patients (≥16 years old) who underwent drug and alcohol screening on admission and sustained an isolated severe TBI (head AIS ≥3). Patients with significant extracranial trauma (AIS ≥3) were excluded. Epidemiological and clinical characteristics, procedures and outcome variables were collected. Patients with isolated stimulant use were matched 1:1 for age, gender, mechanism of injury, head AIS and overall comorbidities, with patients with negative toxicology and alcohol screen. Outcomes in the two groups were compared with univariable and multivariable regression analysis. RESULTS: 681 patients with isolated TBI and stimulant use were matched with 681 patients with negative toxicology and alcohol screen. The incidence of hypotension and CGS <9 was similar in the two groups. In multivariable regression analysis, stimulant use was not independently associated with mortality (OR 0.95, 95% CI 0.61-1.49). However, stimulant use was associated with longer hospital length of stay (HLOS) (RC 1.13, 95%CI 1.03-1.24). CONCLUSION: Pre-injury stimulant use is common in patients admitted for severe TBI, but was not independently associated with mortality when compared to patients with negative toxicology. However, stimulant use was associated with a significant longer HLOS.

MicroRNA mimics can distort physiological microRNA effects on immune checkpoints by triggering an antiviral interferon response.

The microRNA-200 family has wide-ranging regulatory functions in cancer development and progression. Above all, it is strongly associated with the epithelial-to-mesenchymal transition (EMT), a process during which cells change their epithelial to a mesenchymal phenotype and acquire invasive characteristics. More recently, miR-200 family members have also been reported to impact the immune evasion of cancer cells by regulating the expression of immunoinhibitory immune checkpoints (ICs) like PD-L1. Therefore, we aimed to comprehensively characterize this miR-200 family as a regulatory interface between EMT and immune evasion mechanisms in biliary tract cancer. Initial correlation analyses and transient overexpression experiments using miRNA mimics suggested miR-200c-3p as a putative regulator of ICs including PD-L1, LGALS9, and IDO1. However, these effects could not be confirmed in stable miR-200c-3p overexpression cell lines, nor in cells transiently transfected with miR-200c-3p mimic from an independent manufacturer. By shifting our efforts towards dissecting the mechanisms leading to these disparate effects, we observed that the initially used miR-200c-3p mimic triggered a double-stranded (ds)RNA-dependent antiviral response. Besides upregulating the ICs, this had substantial cellular consequences including an induction of interferon type I and type III expression, increased levels of intracellular dsRNA sensors, and a significantly altered cellular growth and apoptotic activity.Our study highlights the capability of miRNA mimics to non-specifically induce a dsRNA-mediated antiviral interferon response. Consequently, phenotypic alterations crucially distort physiological miRNA functions and might result in a major misinterpretation of previous and future miRNA studies, especially in the context of IC regulation.

Towards an automated approach for smart sterility test examination.

As new technologies emerge, deep learning applications are often integral parts of new products as features and often as differentiating benefits. This is especially notable in commercial consumer products in everyday applications, such as voice assistants or streaming content recommendation systems. Due to the power and applicability of these deep learning technologies significant efforts are being directed to the development and integration of appropriate models into science and engineering applications to supplant analogue systems that may be highly prone to human error. Here we present an innovative, low-cost approach to advance sterility assessment workflows that are required and regulated within drug release/manufacturing processes. The model system leverages off-the-shelf hardware as well as deep learning models to detect and classify different microbial contaminations in test containers. The paired hardware and software tools were evaluated in experiments using common model organisms (C. sporogenes, P. aeruginosa, S. aureus). With this approach we were able to detect all three test organisms across 40 experiments, furthermore we were capable of classifying the present organisms with an average classification accuracy of over 87%.

Comparability of Heart Rate Turbulence Methodology: 15 Intervals Suffice to Calculate Turbulence Slope - A Methodological Analysis Using PhysioNet Data of 1074 Patients.

Heart rate turbulence (HRT) is a characteristic heart rate pattern triggered by a ventricular premature contraction (VPC). It can be used to assess autonomic function and health risk for various conditions, e.g., coronary artery disease or cardiomyopathy. While comparability is essential for scientific analysis, especially for research focusing on clinical application, the methodology of HRT still varies widely in the literature. Particularly, the ECG measurement and parameter calculation of HRT differs, including the calculation of turbulence slope (TS). In this article, we focus on common variations in the number of intervals after the VPC that are used to calculate TS (#TSRR) posing two questions: 1) Does a change in #TSRR introduce noticeable changes in HRT parameter values and classification? and 2) Do larger values of turbulence timing (TT) enabled by a larger #TSRR still represent distinct HRT? We compiled a free-access data set of 1,080 annotated long-term ECGs provided by Physionet. HRT parameter values and risk classes were determined both with #TSRR 15 and 20. A standard local tachogram was created by averaging the tachograms of only the files with the best heart rate variability values. The shape of this standard VPC sequence was compared to all VPC sequences grouped by their TT value using dynamic time warping (DTW) in order to identify HRT shapes. When calculated with different #TSRR, our results show only a little difference between the number of files with enough valid VPC sequences to calculate HRT (<1%) and files with different risk classes (5 and 6% for HRT0-2 and HRTA-C, respectively). In the DTW analysis, the difference between averaged sequences with a specific TT and the standard sequence increased with increasing TT. Our analysis suggests that HRT occurs in the early intervals after the VPC and TS calculated from late intervals reflects common heart rate variability rather than a distinct response to the VPC. Even though the differences in classification are marginal, this can lead to problems in clinical application and scientific research. Therefore, we recommend uniformly using #TSRR 15 in HRT analysis.

Brain Structure and Optimism Bias: A Voxel-Based Morphometry Approach.

Individuals often anticipate an unrealistically favorable future for themselves (personal optimism bias) or others (social optimism bias). While such biases are well established, little is known about their neuroanatomy. In this study, participants engaged in a soccer task and estimated the likelihood of successful passes in personal and social scenarios. Voxel-based morphometry revealed that personal optimism bias varied as a positive function of gray matter volume (GMV) in the putamen, frontal pole, hippocampus, temporal pole, inferior temporal gyrus, visual association areas, and mid-superior temporal gyrus. Social optimism bias correlated positively with GMV in the temporoparietal junction and negatively with GMV in the inferior temporal gyrus and pre-supplementary motor areas. Together, these findings suggest that parts of our optimistic outlook are biologically rooted. Moreover, while the two biases looked similar at the behavioral level, they were related to distinct gray matter structures, proposing that their underlying mechanisms are not identical.

Whole-brain white matter correlates of personality profiles predictive of subjective well-being.

We investigated the white matter correlates of personality profiles predictive of subjective well-being. Using principal component analysis to first determine the possible personality profiles onto which core personality measures would load, we subsequently searched for whole-brain white matter correlations with these profiles. We found three personality profiles that correlated with the integrity of white matter tracts. The correlates of an "optimistic" personality profile suggest (a) an intricate network for self-referential processing that helps regulate negative affect and maintain a positive outlook on life, (b) a sustained capacity for visually tracking rewards in the environment and (c) a motor readiness to act upon the conviction that desired rewards are imminent. The correlates of a "short-term approach behavior" profile was indicative of minimal loss of integrity in white matter tracts supportive of lifting certain behavioral barriers, possibly allowing individuals to act more outgoing and carefree in approaching people and rewards. Lastly, a "long-term approach behavior" profile's association with white matter tracts suggests lowered sensitivity to transient updates of stimulus-based associations of rewards and setbacks, thus facilitating the successful long-term pursuit of goals. Together, our findings yield convincing evidence that subjective well-being has its manifestations in the brain.

Countering reproducibility issues in mathematical models with software engineering techniques: A case study using a one-dimensional mathematical model of the atrioventricular node.

One should assume that in silico experiments in systems biology are less susceptible to reproducibility issues than their wet-lab counterparts, because they are free from natural biological variations and their environment can be fully controlled. However, recent studies show that only half of the published mathematical models of biological systems can be reproduced without substantial effort. In this article we examine the potential causes for failed or cumbersome reproductions in a case study of a one-dimensional mathematical model of the atrioventricular node, which took us four months to reproduce. The model demonstrates that even otherwise rigorous studies can be hard to reproduce due to missing information, errors in equations and parameters, a lack in available data files, non-executable code, missing or incomplete experiment protocols, and missing rationales behind equations. Many of these issues seem similar to problems that have been solved in software engineering using techniques such as unit testing, regression tests, continuous integration, version control, archival services, and a thorough modular design with extensive documentation. Applying these techniques, we reimplement the examined model using the modeling language Modelica. The resulting workflow is independent of the model and can be translated to SBML, CellML, and other languages. It guarantees methods reproducibility by executing automated tests in a virtual machine on a server that is physically separated from the development environment. Additionally, it facilitates results reproducibility, because the model is more understandable and because the complete model code, experiment protocols, and simulation data are published and can be accessed in the exact version that was used in this article. We found the additional design and documentation effort well justified, even just considering the immediate benefits during development such as easier and faster debugging, increased understandability of equations, and a reduced requirement for looking up details from the literature.

Characteristics of mathematical modeling languages that facilitate model reuse in systems biology: a software engineering perspective.

Reuse of mathematical models becomes increasingly important in systems biology as research moves toward large, multi-scale models composed of heterogeneous subcomponents. Currently, many models are not easily reusable due to inflexible or confusing code, inappropriate languages, or insufficient documentation. Best practice suggestions rarely cover such low-level design aspects. This gap could be filled by software engineering, which addresses those same issues for software reuse. We show that languages can facilitate reusability by being modular, human-readable, hybrid (i.e., supporting multiple formalisms), open, declarative, and by supporting the graphical representation of models. Modelers should not only use such a language, but be aware of the features that make it desirable and know how to apply them effectively. For this reason, we compare existing suitable languages in detail and demonstrate their benefits for a modular model of the human cardiac conduction system written in Modelica.

Low Heart Rate Variability Predicts Stroke and Other Complications in the First Six Postoperative Months After a Hip Fracture Operation.

Background: One-year mortality after hip fractures is underestimated and is reported as 25%. An improved risk stratifying could contribute to a better follow up of these patients. Heart Rate Variability (HRV) is an easy point-of-care investigation and is been used in cardiology, endocrinology, and perioperative care. This observational study intended to explore relevant associations between HRV parameters and 6-months mortality and morbidity after a hip fracture. Methods: One hundred and sixty-five patients admitted to two hospitals were included, and short-time HRV measurements (5 min, and 10 min at the two hospitals, respectively) were obtained. Mortality data were gathered by means of the Norwegian central address register. Patients, close relatives of patients, and in some cases their general physicians or nursery home physicians were interviewed 6 months postoperatively regarding the incidence of pneumonia, cardiac events, or stroke. Results: One and hundred fifty-seven (95.2%) patients were followed up after 6 months post-surgery. Twenty-one (13%) died during this period. Twenty patients (13%) developed pneumonia, eight (5 %) stroke, and four (2%) myocardial infarction. No HRV parameter was associated with 6-month general mortality. However, patients who developed stroke had significantly lower High Frequency Power (HF, p < 0.001) and lower Very Low Frequency Power (VLF, p = 0.003) at inclusion compared to patients without complications. Patients who developed pneumonia had at the inclusion lower root mean square of successive differences (RMSSD, p = 0.044). Patients with a history of coronary heart disease (n = 41) showed a mortality of 7%. Mortality in this group was associated with standard deviation of beat-to-beat intervals (SDNN, p = 0.006), Total Power (TP, p = 0.009), HF (p = 0.026), and Low Frequency Power (LF, p = 0.012). Beta-blocker intake was associated with lower heart rate, but not with differences in HRV parameters. Conclusion: In this exploratory study, we present for the first-time significant associations between different preoperative HRV parameters and stroke, myocardial infarction, and pneumonia during a 6-month period after hip fracture. HRV might be a simple and effective tool to identify patients at risk that would warrant better follow-up.

Reduced network integration in default mode and executive networks is associated with social and personal optimism biases.

An optimism bias refers to the belief in good things happening to oneself in the future with a higher likelihood than is justified. Social optimism biases extend this concept to groups that one identifies with. Previous literature has found that both personal and social optimism biases are linked to brain structure and task-related brain function. Less is known about whether optimism biases are also expressed in resting-state functional connectivity (RSFC). Forty-two participants completed questionnaires on dispositional personal optimism (which is not necessarily unjustified) and comparative optimism (i.e., whether we see our own future as being rosier than a comparison person's future) and underwent a resting-state functional magnetic resonance imaging scan. They further undertook an imaginative soccer task in order to assess both their personal and social optimism bias. We tested associations of these data with RSFC within and between 13 networks, using sparse canonical correlation analyses (sCCAs). We found that the primary sCCA component was positively connected to personal and social optimism bias and negatively connected to dispositional personal pessimism. This component was associated with (a) reduced integration of the default mode network, (b) reduced integration of the central executive and salience networks, and (c) reduced segregation between the default mode network and the central executive network. Our finding that optimism biases are linked to RSFC indicates that they may be rooted in neurobiology that exists outside of concurrent tasks. This poses questions as to what the limits of the malleability of such biases may be.

An Understandable, Extensible, and Reusable Implementation of the Hodgkin-Huxley Equations Using Modelica.

The Hodgkin-Huxley model of the squid giant axon has been used for decades as the basis of many action potential models. These models are usually communicated using just a list of equations or a circuit diagram, which makes them unnecessarily complicated both for novices and for experts. We present a modular version of the Hodgkin-Huxley model that is more understandable than the usual monolithic implementations and that can be easily reused and extended. Our model is written in Modelica using software engineering concepts, such as object orientation and inheritance. It retains the electrical analogy, but names and explains individual components in biological terms. We use cognitive load theory to measure understandability as the amount of items that have to be kept in working memory simultaneously. The model is broken down into small self-contained components in human-readable code with extensive documentation. Additionally, it features a hybrid diagram that uses biological symbols in an electrical circuit and that is directly tied to the model code. The new model design avoids many redundancies and reduces the cognitive load associated with understanding the model by a factor of 6. Extensions can be easily applied due to an unifying interface and inheritance from shared base classes. The model can be used in an educational context as a more approachable introduction to mathematical modeling in electrophysiology. Additionally the modeling approach and the base components can be used to make complex Hodgkin-Huxley-type models more understandable and reusable.

Social optimism biases are associated with cortical thickness.

Optimism biases denote the tendency to see future desirable events as being more likely to happen to oneself than undesirable events. Such biases are important for mental health and may extend to other individuals or social groups (social optimism biases). However, little is known about whether social optimism biases relate to brain structure. Using sparse canonical correlation analysis, we associated cortical thickness (assessed by magnetic resonance imaging) with measures of social and personal optimism bias, trait optimism and related concepts. We identified a defensive self-enhancement dimension that associated significantly and reliably with the cortical thickness of the insula and inferior frontal cortex. This self-enhancement dimension included unfavorable biases toward unpopular out-groups and indicators of personal optimism and pessimism. A shared biological substrate underlying future expectancies that subserves the promotion of the self and the denigration of unpopular out-groups may render society-wide efforts to counteract stereotyping particularly difficult: such efforts may hinder the establishment of adaptive personal optimism biases.

External validation of the prognostic relevance of the advanced lung cancer inflammation index (ALI) in pancreatic cancer patients.

BACKGROUND: The advanced lung cancer inflammation index (ALI) was first introduced for prognosis prediction in lung cancer patients and since then evaluated in several other malignancies. However, in pancreatic cancer (PC) the ALI and its prognostic utility were only investigated in a comparably small and specific cohort of locally advanced PC patients treated with chemoradiotherapy. METHODS: In our single-center cohort study, we included 429 patients with histologically verified PC who were treated between 2003 and 2015 at our academic institution. The ALI was defined as body mass index (BMI; kg/m2 ) × serum albumin levels (g/dL)/neutrophil-lymphocyte ratio (NLR) and we defined the optimal cutoff for biomarker dichotomization by ROC-analysis. Kaplan-Meier method as well as uni- and multivariate Cox regression Hazard proportional models were implemented to assess the prognostic potential of ALI in PC patients. We considered cancer-specific survival (CSS) as the primary endpoint of the study. RESULTS: The ALI showed a significant negative correlation with CA19-9 levels and C-reactive protein levels whereas we found an association with localized tumor stage and better performance status (P < .05 for all mentioned variables). As opposed to patients with a high ALI, decreased ALI was significantly associated with shorter CSS (HR = 0.606, 95% CI: 0.471-0.779, P = .001). Multivariate analysis demonstrated tumor grade, tumor stage, chemotherapy, C-reactive protein levels, and CA19-9 levels to independently predict for CSS (all P < .05). In contrast the ALI failed to independently predict for CSS in the performed multivariate models (HR = 0.878, 95% CI: 0.643-1.198, P = .411). CONCLUSION: In this large cohort of PC patients, the ALI did not complement existing clinicopathological factors for outcome determination.