Nonparametric predictive model for sparse and irregular longitudinal data.

We propose a kernel-based estimator to predict the mean response trajectory for sparse and irregularly measured longitudinal data. The kernel estimator is constructed by imposing weights based on the subject-wise similarity on L2 metric space between predictor trajectories, where we assume that an analogous fashion in predictor trajectories over time would result in a similar trend in the response trajectory among subjects. In order to deal with the curse of dimensionality caused by the multiple predictors, we propose an appealing multiplicative model with multivariate Gaussian kernels. This model is capable of achieving dimension reduction as well as selecting functional covariates with predictive significance. The asymptotic properties of the proposed nonparametric estimator are investigated under mild regularity conditions. We illustrate the robustness and flexibility of our proposed method via extensive simulation studies and an application to the Framingham Heart Study.

Complications and Technical Consideration of Ultrasound-Guided Rectus Sheath Blocks: A Retrospective Analysis of 4033 Patients.

BACKGROUND: Although the ultrasound-guided rectus sheath block (RSB) is usually regarded as an easy and safe procedure in clinical settings, there is currently no report on complications incidence. Therefore, the present study investigated complications in a large cohort and described the technical considerations to minimize complications of real-time ultrasound-guided RSBs. METHODS: This was a retrospective cohort study of patients who underwent real-time ultrasound-guided RSBs for perioperative pain control in laparoscopic surgery with an umbilical port between February 1, 2017, and February 28, 2021, at the Asan Medical Center in South Korea. All RSBs were performed bilaterally using a 23-gauge Quincke needle, and a bilateral 2-block placement was regarded as 1 RSB. Patient data, including demographics, preoperative laboratory data, preoperative antiplatelet or anticoagulant medication with the duration of discontinuation, and type of surgery, were collected to show the study population characteristics and explore potential factors associated with adverse events such as hematoma. Ultrasound images of patients and adverse events of RSBs, including extrarectus sheath injections, vascular injuries, bowel injury, or local anesthetic systemic toxicity, were also analyzed accordingly. RESULTS: A total of 4033 procedures were analyzed. The mean body mass index of the patients was 24.1 (21.8-26.5) kg/m2. The preoperative laboratory data were within normal range in 4028 (99.9%) patients. Preoperative antiplatelets or anticoagulants were administered in 17.3% of the patients. Overall, 96 complications (2.4%) were observed. Among them, extrarectus sheath injection occurred in 88 cases (2.2%), which included preperitoneal injection (0.9%) and intraperitoneal injection (1.3%). Vascular injuries constituted 8 cases (0.2%) and all vascular injuries resulted in hematoma: 7 cases of inferior epigastric artery injury with rectus sheath hematoma and 1 of inferior mesenteric artery injury with retroperitoneal hematoma. Bowel injury or local anesthetic systemic toxicity was not reported. CONCLUSIONS: In this study of RSBs performed on 4033 patients using a 23-gauge Quincke needle in patients with low body mass index, there were 8 cases (0.2%) of vascular injury, all of which accompanied hematoma.

Predictive generalized varying-coefficient longitudinal model.

We propose a nonparametric bivariate varying coefficient generalized linear model to predict a mean response trajectory in the future given an individual's characteristics at present or an earlier time point in a longitudinal study. Given the measurement time of the predictors, the coefficients vary as functions of the future time over which the prediction of the mean response is concerned and illustrate the dynamic association between the future response and the earlier measured predictors. We use a nonparametric approach that takes advantage of features of both the kernel and the spline methods for estimation. The resulting coefficient estimator is asymptotically consistent under mild regularity conditions. We also develop a new bootstrap approach to construct simultaneous confidence bands for statistical inference about the coefficients and the predicted response trajectory based on the coverage rate of bootstrap estimates. We use the Framingham Heart Study to illustrate the methodology. The proposed procedure is applied to predict the probability trajectory of hypertension risk given individuals' health condition in early adulthood and to examine the impact of risk factors in early adulthood on a long-term risk of hypertension over several decades.

Initial severity-dependent longitudinal model with application to a randomized controlled trial of women with depression.

The assessment of initial severity of a disease is arguably one of the most important factors in identifying appropriate therapies. In this paper, we propose an initial severity-dependent longitudinal model to account for the influence of the initial severity of a disease on the posttreatment severity and the efficacy of medical treatments. The proposed model has the flexibility of nonparametric modeling, as it allows coefficients to vary with the initial severity of the disease. It also provides attractive and practical patient-specific interpretation of initial severity-dependent coefficients. As a result, the proposed model enables patient-specific modeling and treatment recommendations consistent with the assessment of the patient's initial severity, and thus, it can be used as a decision support tool for clinicians. A new empirical likelihood approach is employed for efficient estimation and statistical inference about the initial severity-dependent coefficients. In contrast to the literature on marginal regression models, the proposed estimation procedure allows nuisance parameters associated with the working correlation matrix and the error variances to vary smoothly with the initial severity. The effectiveness of the proposed procedure is demonstrated via simulation studies. We further apply the proposed method by analyzing a data set arising from a randomized controlled trial of women with depression and discover an interesting phenomenon; antidepressant medication intervention is effective for patients with moderate or severe depression, whereas psychotherapy intervention using manual-guided cognitive behavior therapy is effective for patients with a severe case of depression.

Haptic perception accuracy depending on self-produced movement.

This study measured whether self-produced movement influences haptic perception ability (experiment 1) as well as the factors associated with levels of influence (experiment 2) in racket sports. For experiment 1, the haptic perception accuracy levels of five male table tennis experts and five male novices were examined under two different conditions (no movement vs. movement). For experiment 2, the haptic afferent subsystems of five male table tennis experts and five male novices were investigated in only the self-produced movement-coupled condition. Inferential statistics (ANOVA, t-test) and custom-made devices (shock & vibration sensor, Qualisys Track Manager) of the data were used to determine the haptic perception accuracy (experiment 1, experiment 2) and its association with expertise. The results of this research show that expert-level players acquire higher accuracy with less variability (racket vibration and angle) than novice-level players, especially in their self-produced movement coupled performances. The important finding from this result is that, in terms of accuracy, the skill-associated differences were enlarged during self-produced movement. To explain the origin of this difference between experts and novices, the functional variability of haptic afferent subsystems can serve as a reference. These two factors (self-produced accuracy and the variability of haptic features) as investigated in this study would be useful criteria for educators in racket sports and suggest a broader hypothesis for further research into the effects of the haptic accuracy related to variability.

Coaxial bioprinting of a stentable and endothelialized human coronary artery-sized in vitro model.

Atherosclerosis accounts for two-thirds of deaths attributed to cardiovascular diseases, which continue to be the leading cause of mortality. Current clinical management strategies for atherosclerosis, such as angioplasty with stenting, face numerous challenges, including restenosis and late thrombosis. Smart stents, integrated with sensors that can monitor cardiovascular health in real-time, are being developed to overcome these limitations. This development necessitates rigorous preclinical trials on either animal models or in vitro models. Despite efforts being made, a suitable human-scale in vitro model compatible with a cardiovascular stent has remained elusive. To address this need, this study utilizes an in-bath bioprinting method to create a human-scale, freestanding in vitro model compatible with cardiovascular stents. Using a coaxial nozzle, a tubular structure of human coronary artery (HCA) size is bioprinted with a collagen-based bioink, ensuring good biocompatibility and suitable rheological properties for printing. We precisely replicated the dimensions of the HCA, including its internal diameter and wall thickness, and simulated the vascular barrier functionality. To simplify post-processing, a pumpless perfusion bioreactor is fabricated to culture a HCA-sized model, eliminating the need for a peristaltic pump and enabling scalability for high-throughput production. This model is expected to accelerate stent development in the future.

Bioprinting Methods for Fabricating In Vitro Tubular Blood Vessel Models.

Dysfunctional blood vessels are implicated in various diseases, including cardiovascular diseases, neurodegenerative diseases, and cancer. Several studies have attempted to prevent and treat vascular diseases and understand interactions between these diseases and blood vessels across different organs and tissues. Initial studies were conducted using 2-dimensional (2D) in vitro and animal models. However, these models have difficulties in mimicking the 3D microenvironment in human, simulating kinetics related to cell activities, and replicating human pathophysiology; in addition, 3D models involve remarkably high costs. Thus, in vitro bioengineered models (BMs) have recently gained attention. BMs created through biofabrication based on tissue engineering and regenerative medicine are breakthrough models that can overcome limitations of 2D and animal models. They can also simulate the natural microenvironment in a patient- and target-specific manner. In this review, we will introduce 3D bioprinting methods for fabricating bioengineered blood vessel models, which can serve as the basis for treating and preventing various vascular diseases. Additionally, we will describe possible advancements from tubular to vascular models. Last, we will discuss specific applications, limitations, and future perspectives of fabricated BMs.

Sensitivity of spore germination and germ tube elongation of Saccharina japonica to metal exposure.

The sensitivity of early life stages of the brown seaweed Saccharina japonica to six metals (Cd, Cu, Hg, Ni, Pb, Zn) and two waste-water samples were investigated and a new toxicity bioassay developed. The two endpoints used were spore germination and germ tube elongation with an exposure time of 24 h. Optimal test conditions determined for photon irradiance, pH, salinity and temperature were darkness, pH 8, 35‰ and 15°C, respectively. The toxicity ranking of five metals was: Hg (EC(50) of 41 and 42 µg l(-1)) > Cu (120 and 81 µg l(-1)) > Ni (2,009 and 1,360 µg l(-1)) > Zn (3,024 and 3,897 µg l(-1)) > Pb (4,760 and 4,429 µg l(-1)) > Cd (15,052 and 7,541 µg l(-1)) for germination and germ tube elongation, respectively. The sensitivities to Cd, Cu and Ni were greater in germ tube elongation than in germination process. When tested against two different waste-water samples (processed animal and printed circuit board waste-water) values of EC(50) were between 21.29 and 32.02% for germination and between 5.33 and 8.98% for germ tube elongation. Despite differences in their chemical composition, the toxic effects of waste-water samples, as indicated by EC(50) values, did not differ significantly for the same endpoints. The CV range for both germination and germ tube elongation was between 4.61 and 37.69%, indicating high levels of precision of the tests. The results compare favourably with those from more established test procedures employing micro- and macroalgae. The advantages and potential limitations of the bioassay for the assessment of anthropogenic impacts on coastal ecosystems and commercial cultivation areas in near-shore environments are discussed.

Adjusting a subject-specific time of event in longitudinal studies.

Biomedical studies often involve an event that occurs to individuals at different times and has a significant influence on individual trajectories of response variables over time. We propose a statistical model to capture the mean trajectory alteration caused by not only the occurrence of the event but also the subject-specific time of the event. The proposed model provides a post-event mean trajectory smoothly connected with the pre-event mean trajectory by allowing the model parameters associated with the post-event mean trajectory to vary over time of the event. A goodness-of-fit test is considered to investigate how well the proposed model is fit to the data. Hypothesis tests are also developed to assess the influence of the subject-specific time of event on the mean trajectory. Theoretical and simulation studies confirm that the proposed tests choose the correctly specified model consistently and examine the effect of the subject-specific time of event successfully. The proposed model and tests are also illustrated by the analysis of two real-life data from a biomarker study for HIV patients along with their own time of treatment initiation and a body fatness study in girls with different age of menarche.

Educational differences in trajectories and determinants of healthy ageing in midlife and older Americans.

OBJECTIVES: To advance knowledge of the influence of educational level on trajectories and determinants of healthy ageing in midlife and older Americans. STUDY DESIGN: Data are from the Health and Retirement Study, a nationally representative, longitudinal survey of Americans age 51 and over. We used generalized estimating equations to examine trajectories and determinants of healthy ageing by level of education among 17,591 adults followed over a 14-year period. Educational level was categorized as less than a high school diploma, high school diploma, some college education, and a college or higher degree. Potential determinants included demographic factors, early-life characteristics (childhood health and childhood poverty), health-related factors (health behaviours, physical and mental health conditions), and psychosocial characteristics (perceived neighbourhood safety, volunteerism, and work status). MAIN OUTCOME MEASURES: Informed by earlier work, we defined healthy ageing as freedom from cognitive impairment, freedom from disability, and high physical functioning. RESULTS: The log odds of healthy ageing declined over time in all educational groups. Importantly, the decline was smaller in adults with a college or higher degree than in those without a high school diploma. Age, gender, wealth, health behaviours, productive engagement, depressive symptoms, and the presence of chronic conditions predicted healthy ageing across the educational spectrum; however, the impact of several factors (age, gender, race/ethnicity, childhood poverty, and volunteerism) varied by educational level. CONCLUSIONS: Education shapes trajectories of healthy ageing in the United States. Similarities and differences in determinants of healthy ageing are evident across levels of education. Findings highlight broad-based and education-specific targets for intervention.

A fiberoptic orotracheal intubation successfully performed using a modified Guedel airway in a sedated emergency patient - A case report.

BACKGROUND: Fiberoptic intubation is a powerful and safe technique to deal with airway difficulty, but it requires a lot of training to be able to perform correctly. There are various specialized oral airways for fiberoptic intubation, but none of them have perfect functionality. CASE: A 75-year-old male (body weight 71.6 kg, height 159.3 cm, body mass index 28.22 kg/m2) was diagnosed with acute appendicitis, and it was decided to do a laparoscopic appendectomy. After the induction of general anesthesia, it was impossible to insert the direct laryngoscope deep enough for vocal cord visualization without damaging the teeth because of limited mouth opening. We successfully performed fiberoptic intubation with a newly modified Guedel airway via a longitudinal channel on the convex side and a distal opened lingual end. CONCLUSIONS: Our modified Guedel airway can be useful in assisting fiberoptic intubation in unexpectedly difficult airway situations.

The Development of a Novel Device Based on Loss of Guidewire Resistance to Identify Epidural Space in a Porcine Model.

Background: The application of additive manufacturing (3D printing) has been recently expanded to various medical fields. The new technique named loss of guide wire resistance (LOGR) was developed via 3D printing for the detection of epidural space using a guide wire instead of air or saline used in the loss of resistance (LOR) technique. Methods: The prototype model of epidural space finder consists of a polyactic acid (PLA) or a resin. It was manufactured with 3D printing. Biocompatibility test (eluate and sterility tests) was performed in both products. The advantage of the newly developed device was compared with conventional loss of resistance (LOR) technique in a porcine model. Results: Eluate and sterility tests revealed that the PLA was more biocompatible than the resin. The LOGR technique facilitated rapid access to epidural space compared with the LOR technique (41.64 ± 32.18 vs. 92.28 ± 61.46 seconds, N = 14, p=0.0102, paired sample t-test), without any differences in success rate (87.5%). Conclusion: We conclude that LOGR technique is comparable to LOR technique to access the epidural space, although the advantage of either technique in terms of complications such as dural puncture or epidural hematoma is unknown. We demonstrated the potential benefit of 3D printer for the development of a new medical device for anesthesia.

Storage Stability of Vacuum-packaged Dry-aged Beef during Refrigeration at 4°C.

Although the production of dry-aged beef has been increasing, most purveyors are unaware of the changes in quality that ensue after completion of the aging period and do not adhere to specific guidelines for its packaging and storage. The objective of this study was to investigate the storage stability of vacuum-packaged dry-aged beef based on changes in microbial, physicochemical, and sensory properties during refrigeration at 4°C for 21 d. The total aerobic bacterial count exceeded 6 Log CFU/g at approximately day 11 and significantly increased after day 14. Freshness indicators such as pH and volatile basic nitrogen content were acceptable until day 14 and 21, respectively. Based on the evaluation of overall sensory acceptability, the dry-aged beef was acceptable until 14 d without any sensory deterioration. Therefore, vacuum-packaged dry-aged beef could be stored for 11 d at 4°C without any adverse effect on its microbial and sensory quality.

Determination of Salable Shelf-life for Wrap-packaged Dry-aged Beef during Cold Storage.

We investigated microbial and quality changes in wrap-packaged dry-aged beef after completion of aging and subsequent storage in a refrigerator. After 28 days of dry aging (temperature, 4°C; RH, approximately 75%; air flow velocity, 2.5 m/s), sirloins were trimmed, wrap-packaged, and stored at 4°C for 7 days. Analyses of microbial growth, pH, volatile basic nitrogen (VBN), 2-thiobarbituric acid-reactive substance (TABRS), and instrumental color, myoglobin, and sensory evaluation were conducted on days 0, 3, 5, and 7. The results show that the number of total aerobic bacteria (TAB), yeast, and lactic acid bacteria increased with an increase in storage days, whereas no change in the growth of mold was observed during 7 days of storage. Based on the legal standard for TAB count, the estimated shelf-life of wrap-packaged dry-aged beef was predicted to be less than 12.2 days. However, the shelf-life should be less than 6.3 days, considering the result of sensory quality (odor, taste, and overall acceptance). No significant change in visible appearance was also observed during 7 days of storage. The results suggest that the present quality indicators for meat spoilage (pH, VBN, and TBARS) should be re-considered for dry-aged beef, as its characteristics are different from those of fresh and/or wet-aged beef.

eDNA-based bioassessment of coastal sediments impacted by an oil spill.

Oil spills offshore can cause long-term ecological effects on coastal marine ecosystems. Despite their important ecological roles in the cycling of energy and nutrients in food webs, effects on bacteria, protists or arthropods are often neglected. Environmental DNA (eDNA) metabarcoding was applied to characterize changes in the structure of micro- and macro-biota communities of surface sediments over a 7-year period since the occurrence of Hebei Spirit oil spill on December 7, 2007. Alterations in diversities and structures of micro- and macro-biota were observed in the contaminated area where concentrations of polycyclic aromatic hydrocarbons were greater. Successions of bacterial, protists and metazoan communities revealed long-term ecological effects of residual oil. Residual oil dominated the largest cluster of the community-environment association network. Presence of bacterial families (Aerococcaceae and Carnobacteriaceae) and the protozoan family (Platyophryidae) might have conferred sensitivity of communities to oil pollution. Hydrocarbon-degrading bacterial families (Anaerolinaceae, Desulfobacteraceae, Helicobacteraceae and Piscirickettsiaceae) and algal family (Araphid pennate) were resistant to adverse effects of spilt oil. The protistan family (Subulatomonas) and arthropod families (Folsomia, Sarcophagidae Opomyzoidea, and Anomura) appeared to be positively associated with residual oil pollution. eDNA metabarcoding can provide a powerful tool for assessing effects of anthropogenic pollution, such as oil spills on sediment communities and its long-term trends in coastal marine environments.

Ecogenomic responses of benthic communities under multiple stressors along the marine and adjacent riverine areas of northern Bohai Sea, China.

Benthic communities in the aquatic ecosystem are influenced by both natural and anthropogenic stressors. To understand the ecogenomic responses of sediment communities to the multiple stressors of polluted environments, the bacteria, protistan and metazoan communities in sediments from marine and adjacent riverine areas of North Bohai Sea were characterized by environmental DNA meta-systematics, and their associations with environmental variables were assessed by multiple statistical approaches. The bacterial communities were dominated by Firmicutes (mean 22.4%), Proteobacteria (mean 21.6%) and Actinobacteria (mean 21.5%). The protistan communities were dominated by Ochrophyta (33.7%), Cercozoa (18.9%) and Ciliophora (17.9%). Arthropoda (71.1%) dominated the metazoan communities in sediments. The structures of communities in sediments were shaped by both natural variables (spatial variability and/or salinity (presented as Na and Ca)) and anthropogenic contaminants, including DDTs, PAHs or metals (Cu, Al, Co, Cr, Cu, Fe, K, Mg, Mn, Ni and Zn). Particularly, the correlation network of multiple communities was modulated by the concentrations of Na and DDTs at the family level. Overall, environmental DNA meta-systematics can provide a powerful tool for biomonitoring, sediment quality assessment, and key stressors identification.

Differential contribution of visual and auditory information to accurately predict the direction and rotational motion of a visual stimulus.

Vision and auditory information are critical for perception and to enhance the ability of an individual to respond accurately to a stimulus. However, it is unknown whether visual and auditory information contribute differentially to identify the direction and rotational motion of the stimulus. The purpose of this study was to determine the ability of an individual to accurately predict the direction and rotational motion of the stimulus based on visual and auditory information. In this study, we recruited 9 expert table-tennis players and used table-tennis service as our experimental model. Participants watched recorded services with different levels of visual and auditory information. The goal was to anticipate the direction of the service (left or right) and the rotational motion of service (topspin, sidespin, or cut). We recorded their responses and quantified the following outcomes: (i) directional accuracy and (ii) rotational motion accuracy. The response accuracy was the accurate predictions relative to the total number of trials. The ability of the participants to predict the direction of the service accurately increased with additional visual information but not with auditory information. In contrast, the ability of the participants to predict the rotational motion of the service accurately increased with the addition of auditory information to visual information but not with additional visual information alone. In conclusion, this finding demonstrates that visual information enhances the ability of an individual to accurately predict the direction of the stimulus, whereas additional auditory information enhances the ability of an individual to accurately predict the rotational motion of stimulus.

Nonparametric Functional Central Limit Theorem for Time Series Regression with Application to Self-normalized Confidence Interval.

This paper is concerned with the inference of nonparametric mean function in a time series context. The commonly used kernel smoothing estimate is asymptotically normal and the traditional inference procedure then consistently estimates the asymptotic variance function and relies upon normal approximation. Consistent estimation of the asymptotic variance function involves another level of nonparametric smoothing. In practice, the choice of the extra bandwidth parameter can be difficult, the inference results can be sensitive to bandwidth selection and the normal approximation can be quite unsatisfactory in small samples leading to poor coverage. To alleviate the problem, we propose to extend the recently developed self-normalized approach, which is a bandwidth free inference procedure developed for parametric inference, to construct point-wise confidence interval for nonparametric mean function. To justify asymptotic validity of the self-normalized approach, we establish a functional central limit theorem for recursive nonparametric mean regression function estimates under primitive conditions and show that the limiting process is a Gaussian process with non-stationary and dependent increments. The superior finite sample performance of the new approach is demonstrated through simulation studies.

Failure of Arm Movement Control in Stroke Patients, Characterized by Loss of Complexity.

We study the mechanism of human arm-posture control by means of nonlinear dynamics and quantitative time series analysis methods. Utilizing linear and nonlinear measures in combination, we find that pathological tremors emerge in patient dynamics and serve as a main feature discriminating between normal and patient groups. The deterministic structure accompanied with loss of complexity inherent in the tremor dynamics is also revealed. To probe the underlying mechanism of the arm-posture dynamics, we further analyze the coupling patterns between joints and components, and discuss their roles in breaking of the organization structure. As a result, we elucidate the mechanisms in the arm-posture dynamics of normal subjects responding to the gravitational force and for the reduction of the dynamic degrees of freedom in the patient dynamics. This study provides an integrated framework for the origin of the loss of complexity in the dynamics of patients as well as the coupling structure in the arm-posture dynamics.

Specification test for Markov models with measurement errors.

Most existing works on specification testing assume that we have direct observations from the model of interest. We study specification testing for Markov models based on contaminated observations. The evolving model dynamics of the unobservable Markov chain is implicitly coded into the conditional distribution of the observed process. To test whether the underlying Markov chain follows a parametric model, we propose measuring the deviation between nonparametric and parametric estimates of conditional regression functions of the observed process. Specifically, we construct a nonparametric simultaneous confidence band for conditional regression functions and check whether the parametric estimate is contained within the band.