The difficulty of computing stable and accurate neural networks: On the barriers of deep learning and Smale's 18th problem.

Deep learning (DL) has had unprecedented success and is now entering scientific computing with full force. However, current DL methods typically suffer from instability, even when universal approximation properties guarantee the existence of stable neural networks (NNs). We address this paradox by demonstrating basic well-conditioned problems in scientific computing where one can prove the existence of NNs with great approximation qualities; however, there does not exist any algorithm, even randomized, that can train (or compute) such a NN. For any positive integers K>2 and L, there are cases where simultaneously 1) no randomized training algorithm can compute a NN correct to K digits with probability greater than 1/2; 2) there exists a deterministic training algorithm that computes a NN with K ­1 correct digits, but any such (even randomized) algorithm needs arbitrarily many training data; and 3) there exists a deterministic training algorithm that computes a NN with K ­2 correct digits using no more than L training samples. These results imply a classification theory describing conditions under which (stable) NNs with a given accuracy can be computed by an algorithm. We begin this theory by establishing sufficient conditions for the existence of algorithms that compute stable NNs in inverse problems. We introduce fast iterative restarted networks (FIRENETs), which we both prove and numerically verify are stable. Moreover, we prove that only O(|log (ϵ)|) layers are needed for an ϵ-accurate solution to the inverse problem.

Complex and highly saturated soundscapes in restored oak woodlands reflect avian richness and abundance.

Temperate woodlands are biodiverse natural communities threatened by land use change and fire suppression. Excluding historic disturbance regimes of periodic groundfires from woodlands causes degradation, resulting from changes in the plant community and subsequent biodiversity loss. Restoration, through prescribed fire and tree thinning, can reverse biodiversity losses, however, because the diversity of woodland species spans many taxa, efficiently quantifying biodiversity can be challenging. We assessed whether soundscapes in an eastern North American woodland reflect biodiversity changes during restoration measured in a concurrent multitrophic field study. In five restored and five degraded woodland sites in Wisconsin, USA, we sampled vegetation, measured arthropod biomass, conducted bird surveys, and recorded soundscapes for five days of every 15-day period from May to August 2022. We calculated two complementary acoustic indices: Soundscape Saturation, which focuses on all acoustically active species, and Acoustic Complexity Index (ACI), which was developed to study vocalizing birds. We used generalized additive models to predict both indices based on Julian date, time of day, and level of habitat degradation. We found that restored woodlands had higher arthropod biomass, and higher richness and abundance of breeding birds. Additionally, soundscapes in restored sites had higher mean Soundscape Saturation and higher mean ACI. Restored woodland acoustic indices exhibited greater magnitudes of daily and seasonal peaks. We conclude that woodland restoration results in higher soundscape saturation and complexity, due to greater richness and abundance of vocalizing animals. This bioacoustic signature of restoration offers a promising monitoring tool for efficiently documenting differences in woodland biodiversity.

Medication burden in patients with dialysis-dependent CKD: a systematic review.

This systematic review aimed to statistically profile the medication burden and associated influencing factors, and outcomes in patients with dialysis-dependent chronic kidney disease (DD-CKD). Studies of medication burden in patients with DD-CKD in the last 10 years from 1 January 2013 to 31 March 2024 were searched from PubMed, Embase, and Cochrane databases. Newcastle-Ottawa Scale (NOS) or Agency for Healthcare Research and Quality (AHRQ) methodology checklist was used to evaluate quality and bias. Data extraction and combining from multiple groups of number (n), mean, and standard deviation (SD) were performed using R programming language (version4.3.1; R Core Team, Vienna, Austria). A total of 10 studies were included, and the results showed a higher drug burden in patients with DD-CKD. The combined pill burden was 14.57 ± 7.56 per day in hemodialysis (HD) patients and 14.63 ± 6.32 in peritoneal dialysis (PD) patients. The combined number of medications was 9.74 ± 3.37 in HD and 8 ± 3 in PD. Four studies described the various drug classes and their proportions, in general, antihypertensives and phosphate binders were the most commonly used drugs. Five studies mentioned factors associated with medication burden. A total of five studies mentioned medication burden-related outcomes, with one study finding that medication-related burden was associated with increased treatment burden, three studies finding that poor medication adherence was associated with medication burden, and another study finding that medication complexity was not associated with self-reported medication adherence. Limitations: meta-analysis was not possible due to the heterogeneity of studies.

Impact of Macrocephaly, as an Isolated Trait, on EEG Signal as Measured by Spectral Power and Multiscale Entropy during the First Year of Life.

Macrocephaly has been associated with neurodevelopmental disorders; however, it has been mainly studied in the context of pathological or high-risk populations and little is known about its impact, as an isolated trait, on brain development in general population. Electroencephalographic (EEG) power spectral density (PSD) and signal complexity have shown to be sensitive to neurodevelopment and its alterations. We aimed to investigate the impact of macrocephaly, as an isolated trait, on EEG signal as measured by PSD and multiscale entropy during the first year of life. We recorded high-density EEG resting-state activity of 74 healthy full-term infants, 50 control (26 girls), and 24 macrocephalic (12 girls) aged between 3 and 11 months. We used linear regression models to assess group and age effects on EEG PSD and signal complexity. Sex and brain volume measures, obtained via a 3D transfontanellar ultrasound, were also included into the models to evaluate their contribution. Our results showed lower PSD of the low alpha (8-10 Hz) frequency band and lower complexity in the macrocephalic group compared to the control group. In addition, we found an increase in low alpha (8.5-10 Hz) PSD and in the complexity index with age. These findings suggest that macrocephaly as an isolated trait has a significant impact on brain activity during the first year of life.

Multiscale Entropy Algorithms to Analyze Complexity and Variability of Trunk Accelerations Time Series in Subjects with Parkinson's Disease.

The aim of this study was to assess the ability of multiscale sample entropy (MSE), refined composite multiscale entropy (RCMSE), and complexity index (CI) to characterize gait complexity through trunk acceleration patterns in subjects with Parkinson's disease (swPD) and healthy subjects, regardless of age or gait speed. The trunk acceleration patterns of 51 swPD and 50 healthy subjects (HS) were acquired using a lumbar-mounted magneto-inertial measurement unit during their walking. MSE, RCMSE, and CI were calculated on 2000 data points, using scale factors (τ) 1-6. Differences between swPD and HS were calculated at each τ, and the area under the receiver operating characteristics, optimal cutoff points, post-test probabilities, and diagnostic odds ratios were calculated. MSE, RCMSE, and CIs showed to differentiate swPD from HS. MSE in the anteroposterior direction at τ4 and τ5, and MSE in the ML direction at τ4 showed to characterize the gait disorders of swPD with the best trade-off between positive and negative posttest probabilities and correlated with the motor disability, pelvic kinematics, and stance phase. Using a time series of 2000 data points, a scale factor of 4 or 5 in the MSE procedure can yield the best trade-off in terms of post-test probabilities when compared to other scale factors for detecting gait variability and complexity in swPD.

Heart Rate Complexity and Autonomic Modulation Are Associated with Psychological Response Inhibition in Healthy Subjects.

BACKGROUND: the ability to suppress/regulate impulsive reactions has been identified as common factor underlying the performance in all executive function tasks. We analyzed the HRV signals (power of high (HF) and low (LF) frequency, Sample Entropy (SampEn), and Complexity Index (CI)) during the execution of cognitive tests to assess flexibility, inhibition abilities, and rule learning. METHODS: we enrolled thirty-six healthy subjects, recording five minutes of resting state and two tasks of increasing complexity based on 220 visual stimuli with 12 × 12 cm red and white squares on a black background. RESULTS: at baseline, CI was negatively correlated with age, and LF was negatively correlated with SampEn. In Task 1, the CI and LF/HF were negatively correlated with errors. In Task 2, the reaction time positively correlated with the CI and the LF/HF ratio errors. Using a binary logistic regression model, age, CI, and LF/HF ratio classified performance groups with a sensitivity and specificity of 73 and 71%, respectively. CONCLUSIONS: this study performed an important initial exploration in defining the complex relationship between CI, sympathovagal balance, and age in regulating impulsive reactions during cognitive tests. Our approach could be applied in assessing cognitive decline, providing additional information on the brain-heart interaction.

Regularity of kinematic data between single and dual-task treadmill walking in people with Parkinson's disease.

BACKGROUND: Regularity, quantified by sample entropy (SampEn), has been extensively used as a gait stability measure. Yet, there is no consensus on the calculation process and variant approaches, e.g. single-scale SampEn with and without incorporating a time delay greater than one, multiscale SampEn, and complexity index, have been used to calculate the regularity of kinematic or kinetic signals. The aim of the present study was to test the discriminatory performance of the abovementioned approaches during single and dual-task walking in people with Parkinson's disease (PD). METHODS: Seventeen individuals with PD were included in this study. Participants completed two walking trials that included single and dual-task conditions. The secondary task was word searching with twelve words randomly appearing in the participants' visual field. Trunk linear acceleration at sternum level, linear acceleration of the center of gravity, and angular velocity of feet, shanks, and thighs, each in three planes of motion were collected. The regularity of signals was computed using approaches mentioned above for single and dual-task conditions. RESULTS: Incorporating a time delay greater than one and considering multiple scales helped better distinguish between single and dual-task walking. For all signals, the complexity index, defined as the summary of multiscale SampEn analysis, was the most efficient discriminatory index between single-task walking and dual-tasking in people with Parkinson's disease. Specifically, the complexity index of the trunk linear acceleration of the center of gravity distinguished between the two walking conditions in all three planes of motion. CONCLUSIONS: The significant results observed across the 24 signals studied in this study are illustrative examples of the complexity index's potential as a gait feature for classifying different walking conditions.

Childhood family structure and complexity in partnership life courses.

This study investigated the associations between childhood living arrangements and complex adult partnership trajectories. The authors defined first union dissolution as the event initiating a complex partnership life course, and measured the level of complexity using a weighted cumulative index of subsequent partnership episodes. The analyses were based on a representative sample of the German population born in 1971-73 from the German Family Panel and used multivariate hurdle models to estimate the probability of experiencing the initiation of a complex partnership trajectory, as well as the level of complexity. Results showed that respondents who did not grow up with both biological parents (i.e. those who experienced an alternative family structure) had both a greater likelihood of experiencing the dissolution of their own first union, and followed more complex subsequent partnership trajectories. These associations varied across types of (alternative) family structures experienced during childhood and according to the level of parental partnership (in)stability. This study contributes to our understanding of contemporary partnership complexity and its precursors using a long term life course theoretical and methodological frame. We acknowledge that continuities and disruptions in the development of adult (complex) partnership trajectories can be linked to a growing diversity of family structure in childhood. Thereby, we expand knowledge on intergenerational interdependencies of family instability and complexity beyond the reproduction of the event of union dissolution.

Consciousness Regained: Disentangling Mechanisms, Brain Systems, and Behavioral Responses.

How consciousness (experience) arises from and relates to material brain processes (the "mind-body problem") has been pondered by thinkers for centuries, and is regarded as among the deepest unsolved problems in science, with wide-ranging theoretical, clinical, and ethical implications. Until the last few decades, this was largely seen as a philosophical topic, but not widely accepted in mainstream neuroscience. Since the 1980s, however, novel methods and theoretical advances have yielded remarkable results, opening up the field for scientific and clinical progress. Since a seminal paper by Crick and Koch (1998) claimed that a science of consciousness should first search for its neural correlates (NCC), a variety of correlates have been suggested, including both content-specific NCCs, determining particular phenomenal components within an experience, and the full NCC, the neural substrates supporting entire conscious experiences. In this review, we present recent progress on theoretical, experimental, and clinical issues. Specifically, we (1) review methodological advances that are important for dissociating conscious experience from related enabling and executive functions, (2) suggest how critically reconsidering the role of the frontal cortex may further delineate NCCs, (3) advocate the need for general, objective, brain-based measures of the capacity for consciousness that are independent of sensory processing and executive functions, and (4) show how animal studies can reveal population and network phenomena of relevance for understanding mechanisms of consciousness.

Cerebral organoids: ethical issues and consciousness assessment.

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids (ie, human embryos) and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or (which is more likely) will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available (the Perturbational Complexity Index, a metric that is directly inspired by the main postulate of the Integrated Information Theory of consciousness), which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary.

Development of cortical shape in the human brain from 6 to 24months of age via a novel measure of shape complexity.

The quantification of local surface morphology in the human cortex is important for examining population differences as well as developmental changes in neurodegenerative or neurodevelopmental disorders. We propose a novel cortical shape measure, referred to as the 'shape complexity index' (SCI), that represents localized shape complexity as the difference between the observed distributions of local surface topology, as quantified by the shape index (SI) measure, to its best fitting simple topological model within a given neighborhood. We apply a relatively small, adaptive geodesic kernel to calculate the SCI. Due to the small size of the kernel, the proposed SCI measure captures fine differences of cortical shape. With this novel cortical feature, we aim to capture comparatively small local surface changes that capture a) the widening versus deepening of sulcal and gyral regions, as well as b) the emergence and development of secondary and tertiary sulci. Current cortical shape measures, such as the gyrification index (GI) or intrinsic curvature measures, investigate the cortical surface at a different scale and are less well suited to capture these particular cortical surface changes. In our experiments, the proposed SCI demonstrates higher complexity in the gyral/sulcal wall regions, lower complexity in wider gyral ridges and lowest complexity in wider sulcal fundus regions. In early postnatal brain development, our experiments show that SCI reveals a pattern of increased cortical shape complexity with age, as well as sexual dimorphisms in the insula, middle cingulate, parieto-occipital sulcal and Broca's regions. Overall, sex differences were greatest at 6months of age and were reduced at 24months, with the difference pattern switching from higher complexity in males at 6months to higher complexity in females at 24months. This is the first study of longitudinal, cortical complexity maturation and sex differences, in the early postnatal period from 6 to 24months of age with fine scale, cortical shape measures. These results provide information that complement previous studies of gyrification index in early brain development.

Phenotypic clustering: a novel method for microglial morphology analysis.

BACKGROUND: Microglial cells are tissue-resident macrophages of the central nervous system. They are extremely dynamic, sensitive to their microenvironment and present a characteristic complex and heterogeneous morphology and distribution within the brain tissue. Many experimental clues highlight a strong link between their morphology and their function in response to aggression. However, due to their complex "dendritic-like" aspect that constitutes the major pool of murine microglial cells and their dense network, precise and powerful morphological studies are not easy to realize and complicate correlation with molecular or clinical parameters. METHODS: Using the knock-in mouse model CX3CR1(GFP/+), we developed a 3D automated confocal tissue imaging system coupled with morphological modelling of many thousands of microglial cells revealing precise and quantitative assessment of major cell features: cell density, cell body area, cytoplasm area and number of primary, secondary and tertiary processes. We determined two morphological criteria that are the complexity index (CI) and the covered environment area (CEA) allowing an innovative approach lying in (i) an accurate and objective study of morphological changes in healthy or pathological condition, (ii) an in situ mapping of the microglial distribution in different neuroanatomical regions and (iii) a study of the clustering of numerous cells, allowing us to discriminate different sub-populations. RESULTS: Our results on more than 20,000 cells by condition confirm at baseline a regional heterogeneity of the microglial distribution and phenotype that persists after induction of neuroinflammation by systemic injection of lipopolysaccharide (LPS). Using clustering analysis, we highlight that, at resting state, microglial cells are distributed in four microglial sub-populations defined by their CI and CEA with a regional pattern and a specific behaviour after challenge. CONCLUSIONS: Our results counteract the classical view of a homogenous regional resting state of the microglial cells within the brain. Microglial cells are distributed in different defined sub-populations that present specific behaviour after pathological challenge, allowing postulating for a cellular and functional specialization. Moreover, this new experimental approach will provide a support not only to neuropathological diagnosis but also to study microglial function in various disease models while reducing the number of animals needed to approach the international ethical statements.

Relationship of multiscale entropy to task difficulty and sway velocity in healthy young adults.

PURPOSE/BACKGROUND: Multiscale entropy (MSE) is a nonlinear measure of postural control that quantifies how complex the postural sway is by assigning a complexity index to the center of pressure (COP) oscillations. While complexity has been shown to be task dependent, the relationship between sway complexity and level of task challenge is currently unclear. This study tested whether MSE can detect short-term changes in postural control in response to increased standing balance task difficulty in healthy young adults and compared this response to that of a traditional measure of postural steadiness, root mean square of velocity (VRMS). METHODS: COP data from 20 s of quiet stance were analyzed when 30 healthy young adults stood on the following surfaces: on floor and foam with eyes open and closed and on the compliant side of a Both Sides Up (BOSU) ball with eyes open. Complexity index (CompI) was derived from MSE curves. RESULTS: Repeated measures analysis of variance across standing conditions showed a statistically significant effect of condition (p < 0.001) in both the anterior-posterior and medio-lateral directions for both CompI and VRMS. In the medio-lateral direction there was a gradual increase in CompI and VRMS with increased standing challenge. In the anterior-posterior direction, VRMS showed a gradual increase whereas CompI showed significant differences between the BOSU and all other conditions. CompI was moderately and significantly correlated with VRMS. CONCLUSIONS: Both nonlinear and traditional measures of postural control were sensitive to the task and increased with increasing difficulty of standing balance tasks in healthy young adults.

Patient-Level Medication Regimen Complexity in Patients With HIV.

BACKGROUND: Patients with HIV often have multiple medications besides antiretrovirals (ARV). Medication regimen complexity-formulations, dosing frequencies, and additional directions-expands pill burden by considering self-care demands. Studies show an inverse association between ARV adherence and medication complexity for ARVs only. Patient-level medication regimen complexity beyond ARV complexity is unknown. OBJECTIVE: To measure and characterize Patient-level Medication Regimen Complexity Index (pMRCI) and Antiretroviral Medication Regimen Complexity Index (ARCI) for patients in 2 HIV clinics. We hypothesized that an all-medication complexity metric will exceed disease-state-defined complexity metrics; for ARVs only, the pMRCI score will be smaller than the ARCI score by capturing fewer features of regimens. Associations between complexity and adherence were not assessed. METHOD: Electronic records supplied a retrospective, random sample of adult patients with HIV; medication lists were used to code the pMRCI (n=200). A random subsample (n=66) was coded using ARCI for ARV regimens only. RESULT: Medication counts ranged from 1 to 27; pMRCI scores ranged from 2 to 67.5. ARVs contributed roughly 25% to the pMRCI; other prescriptions contributed about 66%. Dosing frequency made the largest contribution of all components (62%) to the pMRCI. For ARVs, pMRCI and ARCI scores did not differ statistically. CONCLUSION: Unique dosing frequencies raised complexity and may provide opportunities for intervention. Other prescriptions drove pMRCI scores, suggesting that HIV management programs should review all medications. A patient-level approach added value to understanding the role of medications in patient complexity; future work can assess association of pMRCI with adherence and patient outcomes.

Persistence in the Methadone Maintenance Program and Its Relationship with the Medication Regimen Complexity Index in Opioid-Dependent Patients.

It has been shown that the Medication Regimen Complexity Index (MRCI) is a useful and reliable tool for calculating the complexity of the pharmacotherapeutic regimen (CPR). Furthermore, a high MRCI is associated with lower adherence. However, the MRCI of opioid-dependent patients (ODP) has not been studied. The aim of this study is to calculate the Methadone Maintenance Program (MMP) persistence and the MRCI score in a ODP cohort. Second, to analyze its relationship and association with other variables. To accomplish this research, an observational study including adults with a confirmed diagnosis of opiate-dependency according to the DSM-5 in a MMP center was carried out. To define MMP-persistence, a group was created by the researchers who defined five weighted items according to their agreed importance. Our first contribution was to create a new definition of MMP-persistence. This study also identified age, comorbidities, and received methadone maintenance doses as successful predictors for MMP-persistence. We have also shown that the MRCI does not seem to be a useful tool to determine MMP-persistence, probably because there are multiple factors that influence it in addition to the CPR. It is necessary to continue searching for more precise selection and stratification tools for ODP to improve their persistence.

Exploring effects of anesthesia on complexity, differentiation, and integrated information in rat EEG.

To investigate mechanisms underlying loss of consciousness, it is important to extend methods established in humans to rodents as well. Perturbational complexity index (PCI) is a promising metric of "capacity for consciousness" and is based on a perturbational approach that allows inferring a system's capacity for causal integration and differentiation of information. These properties have been proposed as necessary for conscious systems. Measures based on spontaneous electroencephalography recordings, however, may be more practical for certain clinical purposes and may better reflect ongoing dynamics. Here, we compare PCI (using electrical stimulation for perturbing cortical activity) to several spontaneous electroencephalography-based measures of signal diversity and integrated information in rats undergoing propofol, sevoflurane, and ketamine anesthesia. We find that, along with PCI, the spontaneous electroencephalography-based measures, Lempel-Ziv complexity (LZ) and geometric integrated information (ΦG), were best able to distinguish between awake and propofol and sevoflurane anesthesia. However, PCI was anti-correlated with spontaneous measures of integrated information, which generally increased during propofol and sevoflurane anesthesia, contrary to expectations. Together with an observed divergence in network properties estimated from directed functional connectivity (current results) and effective connectivity (earlier results), the perturbation-based results seem to suggest that anesthesia disrupts global cortico-cortical information transfer, whereas spontaneous activity suggests the opposite. We speculate that these seemingly diverging results may be because of suppressed encoding specificity of information or driving subcortical projections from, e.g., the thalamus. We conclude that certain perturbation-based measures (PCI) and spontaneous measures (LZ and ΦG) may be complementary and mutually informative when studying altered states of consciousness.

Analyzing the Iatrogenic Triad: Discovering Strategies for Preventing Harm in the Elderly.

Objectives: The iatrogenic triad is a significant global health problem in the elderly population. This study aimed to evaluate the iatrogenic triad in the elderly and identify potential preventive measures to mitigate its occurrence. Materials and Methods: A preliminary observational study was conducted on 150 ambulatory elderly patients to assess potentially inappropriate medications (PIMs), polypharmacy, and drug interactions. The AGS Beers Criteria 2019, Polypharmacy, Medication Complexity Regimen Index (MRCI), and Micromedex (a drug information software) were used to assess the harmful triad. Before and after data collection, we observed, identified, and unfolded potential strategies to avoid the harmful triad in the elderly population. Results: MRCI is 30.49 ± 13.77, suggesting a moderate level of complexity in the drug regimens of elderly patients. Among the PIMs identified by the AGS Beer criteria for 2019, glimepiride (45) and diclofenac (23) were found to be the most frequently prescribed. Moderate-level drug-drug interactions were identified between aspirin and metoprolol (20), metoprolol and metformin (13), and aspirin and enalapril (11). All drug-ethanol and drug-food interactions were rapid and often unknown to patients. Furthermore, the study found that MRCI and polypharmacy were significantly associated with the number of PIMs and drug interactions (p < 0.01). Based on data collection, this study identified three possible ways to prevent the iatrogenic triad in elderly patients: interaction, collaboration, and continuing education. Conclusion: In conclusion, this study sheds light on medication regimen complexity, PIMs, and drug interactions in elderly patients. The study also highlights three possible ways to prevent the iatrogenic triad: interaction, collaboration, and continuing education. By implementing these strategies, healthcare providers can help prevent harm and improve the quality of care for elderly patients.

Cortical reactivity to transcranial magnetic stimulation predicts risk of post-stroke delirium.

OBJECTIVE: Post-stroke delirium (PSD) is a frequent and with regard to outcome unfavorable complication in acute stroke. The neurobiological mechanisms predisposing to PSD remain poorly understood, and biomarkers predicting its risk have not been established. We tested the hypothesis that hypoexcitable or disconnected brain networks predispose to PSD by measuring brain reactivity to transcranial magnetic stimulation with electroencephalography (TMS-EEG). METHODS: We conducted a cross-sectional study in 33 acute stroke patients within 48 hours of stroke onset. Brain reactivity to single-pulse TMS of dorsolateral prefrontal cortex, primary motor cortex and superior parietal lobule of the right hemisphere was quantified by response intensity, effective connectivity, perturbational complexity index (PCIST), and natural frequency of the TMS-EEG response. PSD development was clinically tracked every 8 hours before and for 7 days following TMS-EEG. RESULTS: Fourteen patients developed PSD while 19 patients did not. The PSD group showed lower excitability, effective connectivity, PCIST and natural frequency compared to the non-PSD group. The maximum PCIST over all three TMS sites demonstrated largest classification accuracy with a ROC-AUC of 0.943. This effect was independent of lesion size, affected hemisphere and stroke severity. Maximum PCIST and maximum natural frequency correlated inversely with delirium duration. CONCLUSIONS: Brain reactivity to TMS-EEG can unravel brain network states of reduced excitability, effective connectivity, perturbational complexity and natural frequency that identify acute stroke patients at high risk for development of delirium. SIGNIFICANCE: Findings provide novel insight into the pathophysiology of pre-delirium brain states and may promote effective delirium prevention strategies in those patients at high risk.

Assessment of Medication Regimen Complexity of COPD Regimens in Individuals Visiting Community Pharmacies.

Purpose: Non-adherence is common and linked to poor COPD outcomes. Medication Regimen Complexity Index (MRCI) scores affect other disease outcomes. Little is known about the implications of MRCI scores in COPD. Secondary analysis was done to calculate MRCI scores assessing relationship to symptoms, COPD severity and health literacy (HL) to identify potential interventions to optimize adherence. Patients and Methods: Secondary analysis was conducted of cross-sectional, non-randomized survey data. Participants with self-reported COPD completed a survey of demographics, exacerbations, symptoms (COPD Assessment Test (CAT)), and self-reported COPD regimens. COPD severity was classified into Global Initiative for Chronic Obstructive Lung Disease (GOLD) ABCD categories using exacerbation history and CAT. CAT scores were categorized as low (<10), high (>10) and very high (>20). A 1-year proportion of days covered (PDC) was calculated. A MRCI calculator scored regimens (primary endpoint). Published cut-off points were used to categorize MRCIs as low (≤4), medium (5-8) and high (>8) and inhaled device polypharmacy (IDP) as ≥3 devices. Risk for low HL was assessed using a Single Item Literacy Screener. Descriptive and Chi-squared statistics were used. Results: Participants' (N = 709) PDC for 1 maintenance medicine averaged 0.43 ± 0.37; 28.7% were adherent (PDC ≥ 80%). CAT scores were very high in 54.6% and high in 35.8%. Distribution of GOLD categories were A (6%), B (35%), C (4%) and D (55%). High, medium and low MRCI were 85%, 14% and 9%, respectively. Mean devices per regimen was 2.05 ± 0.8; IDP was 28%. MRCI and IDP increased with worsening CAT scores and COPD severity per GOLD category (p<0.05), but not low HL. Conclusion: MRCI scores for COPD regimens increased with COPD severity and symptoms. Overall adherence was low despite high symptom scores; high MRCI scores could contribute. All COPD medication classes are available in multiple devices, combinations, and daily formulations; there is potential to simplify regimens. Prospective studies are needed to evaluate if interventions minimizing MRCI scores improve adherence and COPD outcomes.

An integrated index developed for measuring precipitation complexity: a case study of Jinsha River basin, China.

Accurate quantification of precipitation complexity is vital for assessing the impact of changing environments on precipitation processes and guiding precipitation forecasting. However, previous research mostly quantified precipitation complexity from different perspectives, resulting in differences in complexity results. In this study, the multifractal detrended fluctuation analysis (MF-DFA; derived from fractal), Lyapunov exponent (derived from Chao), and sample entropy (derived from entropy) were used for investigating the complexity of regional precipitation. Then, the integrated complexity index was established by using the intercriteria correlation (CRITIC) method and the simple linear weighting (SWA) method. Finally, the proposed method is applied to China's Jinsha River basin (JRB). The research indicates that (1) the discriminability of the integrated complexity index is higher than that of MF-DFA, Lyapunov exponent, and sample entropy, which can better distinguish the precipitation complexity in the Jinsha River basin; (2) the higher complexity of monthly precipitation was mainly concentrated in the southeast, and the lower complexity was mainly located in the northwest; moreover, the monthly precipitation complexity for the selected study area is the highest at 0.854 at Weixi station and the lowest at 0.152 at Batang station; (3) the superimposed effects of the southwest monsoon, terrain, and reservoir construction have become the main factors that influence the spatial variation of complexity for precipitation. This study provides a new idea for developing an integrated complexity index, and the results are of great significance for regional precipitation disaster prevention and water resources management.