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Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment.
Aims
To use a combination of transdiagnostic genetic and clinical factors to predict lithium response in patients with bipolar disorder.
Method
This study utilised genetic and clinical data (n = 1034) collected as part of the International Consortium on Lithium Genetics (ConLi+Gen) project. Polygenic risk scores (PRS) were computed for schizophrenia and major depressive disorder, and then combined with clinical variables using a cross-validated machine-learning regression approach. Unimodal, multimodal and genetically stratified models were trained and validated using ridge, elastic net and random forest regression on 692 patients with bipolar disorder from ten study sites using leave-site-out cross-validation. All models were then tested on an independent test set of 342 patients. The best performing models were then tested in a classification framework.
Results
The best performing linear model explained 5.1% (P = 0.0001) of variance in lithium response and was composed of clinical variables, PRS variables and interaction terms between them. The best performing non-linear model used only clinical variables and explained 8.1% (P = 0.0001) of variance in lithium response. A priori genomic stratification improved non-linear model performance to 13.7% (P = 0.0001) and improved the binary classification of lithium response. This model stratified patients based on their meta-polygenic loadings for major depressive disorder and schizophrenia and was then trained using clinical data.
Conclusions
Using PRS to first stratify patients genetically and then train machine-learning models with clinical predictors led to large improvements in lithium response prediction. When used with other PRS and biological markers in the future this approach may help inform which patients are most likely to respond to lithium treatment.
Schizophrenia is a severe and complex psychiatric disorder that needs treatment based on extensive experience. Antipsychotic drugs have already become the cornerstone of the treatment for schizophrenia; however, the therapeutic effect is of significant variability among patients, and only around a third of patients with schizophrenia show good efficacy. Meanwhile, drug-induced metabolic syndrome and other side-effects significantly affect treatment adherence and prognosis. Therefore, strategies for drug selection are desperately needed. In this study, we will perform pharmacogenomics research and set up an individualised preferred treatment prediction model.
Aims
We aim to create a standard clinical cohort, with multidimensional index assessment of antipsychotic treatment for patients with schizophrenia.
Method
This trial is designed as a randomised clinical trial comparing treatment with different kinds of antipsychotics. A total sample of 2000 patients with schizophrenia will be recruited from in-patient units from five clinical research centres. Using a computer-generated program, the participants will be randomly assigned to four treatment groups: aripiprazole, olanzapine, quetiapine and risperidone. The primary outcomes will be measured as changes in the Positive and Negative Syndrome Scale of schizophrenia, which reflects the efficacy. Secondary outcomes include the measure of side-effects, such as metabolic syndromes. The efficacy evaluation and side-effects assessment will be performed at baseline, 2 weeks, 6 weeks and 3 months.
Results
This trial will assess the efficacy and side effects of antipsychotics and create a standard clinical cohort with a multi-dimensional index assessment of antipsychotic treatment for schizophrenia patients.
Conclusion
This study aims to set up an individualized preferred treatment prediction model through the genetic analysis of patients using different kinds of antipsychotics.
The aim of this study was to analyze the profile of chest injuries, oxygen therapy for respiratory failure, and the outcomes of victims after the Jiangsu tornado, which occurred on June 23, 2016 in Yancheng City, Jiangsu Province, China.
Methods:
The clinical records of 144 patients referred to Yancheng City No.1 People’s Hospital from June 23 through June 25 were retrospectively investigated. Of those patients, 68 (47.2%) sustained major chest injuries. The demographic details, trauma history, details of injuries and Abbreviated Injury Scores (AIS), therapy for respiratory failure, surgical procedures, length of intensive care unit (ICU) and hospital stay, and mortality were analyzed.
Results:
Of the 68 patients, 41 (60.3%) were female and 27 (39.7%) were male. The average age of the injured patients was 57.1 years. Forty-six patients (67.6%) suffered from polytrauma. The mean thoracic AIS of the victims was calculated as 2.85 (SD = 0.76). Rib fracture was the most common chest injury, noted in 56 patients (82.4%). Pulmonary contusion was the next most frequent injury, occurring in 12 patients (17.7%). Ten patients with severe chest trauma were admitted to ICU. The median ICU stay was 11.7 (SD = 8.5) days. Five patients required intubation and ventilation, one patient was treated with noninvasive positive pressure ventilation (NPPV), and four patients were treated with high-flow nasal cannula (HFNC). Three patients died during hospitalization. The hospital mortality was 4.41%.
Conclusions:
Chest trauma was a common type of injury after tornado. The most frequent thoracic injuries were rib fractures and pulmonary contusion. Severe chest trauma is usually associated with a high incidence of respiratory support requirements and a long length of stay in the ICU. Early initiation of appropriate oxygen therapy was vital to restoring normal respiratory function and saving lives. Going forward, HFNC might be an effective and well-tolerated therapeutic addition to the management of acute respiratory failure in chest trauma.
Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD.
Method
Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model.
Results
Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64–0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40–0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models.
Conclusion
This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.
Synaptotagmin 1 (Syt1) is an abundant and important presynaptic vesicle protein that binds Ca2+ for the regulation of synaptic vesicle exocytosis. Our previous study reported its localization and function on spindle assembly in mouse oocyte meiotic maturation. The present study was designed to investigate the function of Syt1 during mouse oocyte activation and subsequent cortical granule exocytosis (CGE) using confocal microscopy, morpholinol-based knockdown and time-lapse live cell imaging. By employing live cell imaging, we first studied the dynamic process of CGE and calculated the time interval between [Ca2+]i rise and CGE after oocyte activation. We further showed that Syt1 was co-localized to cortical granules (CGs) at the oocyte cortex. After oocyte activation with SrCl2, the Syt1 distribution pattern was altered significantly, similar to the changes seen for the CGs. Knockdown of Syt1 inhibited [Ca2+]i oscillations, disrupted the F-actin distribution pattern and delayed the time of cortical reaction. In summary, as a synaptic vesicle protein and calcium sensor for exocytosis, Syt1 acts as an essential regulator in mouse oocyte activation events including the generation of Ca2+ signals and CGE.
The aim of this study is to characterize the injury profiles and outcomes of victims of a tornado in Jiangsu Province, China.
Methods:
This study retrospectively investigated the clinical records of 144 patients treated at a teaching hospital due to a tornado. Each patient’s demographic data, diagnosis, injury types, causes of injury, infection status, and outcomes were all reviewed.
Results:
Of the 144 patients, 64 (44.4%) were male, and 80 (55.6%) were female. The patients’ ages ranged from 2 months to 94 years; 91 (63.19%) were admitted within the first 12 h after the disaster. The most frequently injured sites were the body surfaces (24.48%), followed by the limbs and pelvis (21.79%) and chest (20.3%). Soft-tissue injuries and fractures were the most frequent injuries. Traumatic brain injuries were the main causes of death. Tornado-related injuries were primarily caused by flying/falling bricks, wood, and glass. Twenty-three (15.9%) patients suffered from infections, which consisted mainly of skin/soft tissue infections and pneumonia.
Conclusions:
Destructive tornadoes often cause heavy casualties with little warning. Medical aid agencies must be prepared to accommodate the massive numbers of injured patients after a catastrophe. Proper triage and prompt treatment of injured victims may decrease mortality. (Disaster Med Public Health Preparedness. 2019;xx:xxx-xxx).
We incorporate deep learning (DL) into tiled aperture coherent beam combining (CBC) systems for the first time, to the best of our knowledge. By using a well-trained convolutional neural network DL model, which has been constructed at a non-focal-plane to avoid the data collision problem, the relative phase of each beamlet could be accurately estimated, and then the phase error in the CBC system could be compensated directly by a servo phase control system. The feasibility and extensibility of the phase control method have been demonstrated by simulating the coherent combining of different hexagonal arrays. This DL-based phase control method offers a new way of eliminating dynamic phase noise in tiled aperture CBC systems, and it could provide a valuable reference on alleviating the long-standing problem that the phase control bandwidth decreases as the number of array elements increases.
This paper investigates a wideband and low axial ratio circularly polarized (CP) antenna, which is composed of a monopole on a novel polarization rotating reflective surface (PRRS) based on a corner-truncated artificial magnetic conductor (AMC) structure. By adjusting the dimensions of truncated corner properly, the PRRS has two polarization rotation (PR) frequency points. Then, a large PR band of 18% (5.55–6.65 GHz) can be achieved with two adjacent PR frequency points coming together. The profile of the newly PRRS is only0.04λ0. With corner-truncated AMC-based PRRS loading, a measured impedance bandwidth of 1.8 GHz (5.4–7.2 GHz) and the 3 dB axial ratio bandwidth of 1 GHz (5.55–6.65 GHz) could be obtained by the monopole antenna and validated by measurements. The values of AR were well below 1 dB at most of the CP region, which show a perfect CP performance. Moreover, the proposed antenna has exhibited a large axial ratio beamwidth in both the xoz- and yoz-planes and a peak gain of 6.1 dBic within the operational bandwidth.
Cell membrane fatty acids influence fundamental properties of the plasma membrane, including membrane fluidity, protein functionality, and lipid raft signalling. Evidence suggests that dietary n-3 PUFA may target the plasma membrane of immune cells by altering plasma membrane lipid dynamics, thereby regulating the attenuation of immune cell activation and suppression of inflammation. As lipid-based immunotherapy might be a promising new clinical strategy for the treatment of inflammatory disorders, we conducted in vitro and in vivo experiments to examine the effects of n-3 PUFA on CD4+ T cell membrane order, mitochondrial bioenergetics and lymphoproliferation. n-3 PUFA were incorporated into human primary CD4+ T cells phospholipids in vitro in a dose-dependent manner, resulting in a reduction in whole cell membrane order, oxidative phosphorylation and proliferation. At higher doses, n-3 PUFA induced unique phase separation in T cell-derived giant plasma membrane vesicles. Similarly, in a short-term human pilot study, supplementation of fish oil (4 g n-3 PUFA/d) for 6 weeks in healthy subjects significantly elevated EPA (20 : 5n-3) levels in CD4+ T cell membrane phospholipids, and reduced membrane lipid order. These results demonstrate that the dynamic reshaping of human CD4+ T cell plasma membrane organisation by n-3 PUFA may modulate down-stream clonal expansion.
The purpose of this study was to investigate the effects of 8-week green tea extract (GTE) supplementation on promoting postexercise muscle glycogen resynthesis and systemic energy substrate utilisation in young college students. A total of eight healthy male participants (age: 22·0 (se 1·0) years, BMI: 24·2 (se 0·7) kg/m2, VO2max: 43·2 (se 2·4) ml/kg per min) participated in this study. GTE (500 mg/d for 8 weeks) was compared with placebo in participants in a double-blind/placebo-controlled and crossover study design with an 8-week washout period. Thereafter, all participants performed a 60-min cycling exercise (75 % VO2max) and consumed a carbohydrate-enriched meal immediately after exercise. Vastus lateralis muscle samples were collected immediately (0 h) and 3 h after exercise, and blood and gaseous samples were collected during the 3-h postexercise recovery period. An 8-week oral GTE supplementation had no effects on further promoting muscle glycogen resynthesis in exercised human skeletal muscle, but the exercise-induced muscle GLUT type 4 (GLUT4) protein content was greater in the GTE supplementation trial (P<0·05). We observed that, during the postexercise recovery period, GTE supplementation elicited an increase in energy reliance on fat oxidation compared with the placebo trial (P<0·05), although there were no differences in blood glucose and insulin responses between the two trials. In summary, 8-week oral GTE supplementation increases postexercise systemic fat oxidation and exercise-induced muscle GLUT4 protein content in response to an acute bout of endurance exercise. However, GTE supplementation has no further benefit on promoting muscle glycogen resynthesis during the postexercise period.
Formation of the carbon nanotube (CNT) sock, which is an assemblage of nanotubes in a thin cylindrical shape, is a prerequisite for continuous production of thread and sheet using the floating catalyst growth method. Although several studies have considered sock formation mechanisms, the dynamics of the sock behavior during the synthesis process are not well understood. In this work, a computational technique is utilized to explore the multiphysics environment within the nanotube reactor affecting the sock formation and structure. Specifically the flow field, temperature profile, catalyst nucleation, and residence time are investigated and their influence on the sock formation and properties are studied. We demonstrate that it is critical to control the multiphysics synthesis environment in order to form a stable sock. Sock production rate was studied experimentally and found to be linearly dependent on the amount of effective catalyst (iron in the sock) inside the reactor. To achieve a high sock production rate, the proportion of effective iron has to be high when increasing the total amount of catalyst in the reactor. Based on the analysis, we suggest that using small size catalyst and growing longer CNTs by increasing temperature, increasing residence times etc. will increase the CNT production rate and improve the properties of CNT thread/sheet produced from the sock.
Beginning in 2007, all newly diagnosed cancer patients at the Koo Foundation Sun Yat-Sen Cancer Center (KF–SYSCC) were screened for psychosocial distress. Our social workers, as part of the psychosocial care team (PCT), have engaged in proactive outreach with patients identified as distressed. The goal of the present study was to assess the prevalence of psychosocial distress and the extent of contact between the PCT and distressed patients.
Method:
Newly diagnosed patients who were treated at KF–SYSCC between 2007 and 2010 for cancer were eligible if there were at least 100 patients with the same type of cancer. Before treatment began, they were screened with the Pain Scale and the Distress Thermometer (DT) and had the option to specify a desire for help. The rates of distress were analyzed by cancer type and by probable related factors. Information regarding contact with the PCT was retrieved from computerized databases.
Results:
Overall, some 5,335 cancer patients representing 12 major cancer types were included in our study. Of these, 1,771 (33.20%) were significantly distressed. By multivariate logistic regression, younger age, female gender, higher pain score, and disease stage, but not cancer type, were found to be associated with higher rates of distress. Among these distressed patients, 628 (36%) had some contact with the PCT.
Significance of results:
This Taiwanese study with a large sample size revealed a prevalence rate of psychosocial distress similar to rates found in Western countries. Contact with the PCT was established in only 36% of significantly distressed patients, despite a proactive outreach program. It is very important to have screening results made available in a timely fashion to the psycho-oncology team so that appropriate care can be offered promptly.
There is an ongoing relationship between host plants and herbivores. The nutrient substances and secondary compounds found in the host plant can not only impact the growth and development process of herbivores, but, more importantly, may also affect their survival and reproductive fitness. Vitellogenesis is the core process of reproductive regulation and is generally considered as a reliable indicator for evaluating the degree of ovarian development in females. Vitellogenin (Vg) plays a critical role in the synthesis and secretion of yolk protein. In this study, the full-length cDNA of the Vg gene in an alien invasive species, the nipa palm hispid beetle Octodonta nipae Maulik (Coleoptera: Chrysomelidae) (OnVg) was cloned and, the effect of host plant on the OnVg expression level and ovarian development was investigated. The results revealed that the OnVg was highly and exclusively expressed in adult females, but barely detectable in larvae, pupae and adult males. The relative expression level of OnVg and egg hatchability were much higher in females fed on Phoenix canariensis (their preferred host) than those fed on Phoenix roebelenii. A positive correlation relationship between OnVg expression and egg hatchability was also detected. Additionally, the anatomy of the female reproductive system showed that the ovaries of individuals fed on P. canariensis were considerably more developed than in females fed on P. roebelenii. The results may be applicable to many pest management situations through reproductive disturbance by alternating host plant species or varieties or by reproductive regulation through vitellogenesis mediated by specific endocrine hormones.
In the previous chapter, we described LP and illustrated its application to solve some interesting problems in wireless networks. In this chapter, we describe convex programming [11], which is a popular tool to solve a wide range of problems in wireless networks. In terms of problem space, LP can be viewed as a special case of convex optimization. To facilitate our description, we define the following terms:
Convex set: A set is convex if for any two of its elements z1 and z2 and for any λ ∈ [0, 1], λz1 + (1 − λ)z2 is also an element of this set. For example, the set {(x, y): x2 + y2 ≤ 1} is a convex set but the set {(x, y) : 1 ≤ x2 + y2 ≤ 2} is not a convex set.
Convex and concave functions: A function f (x) is a convex function if for any x1 and x2 and any λ ∈ [0, 1], f (λx1 + (1 − λ)x2) ≤ λf (x1) + (1 − λ)f (x2), where x can be a single variable or a vector of variables.
When one door of happiness closes, another opens; but often we look so long at the closed door that we do not see the one which has opened for us.
Helen Keller
Problem complexity vs. solution complexity
The previous two chapters focus on developing optimal polynomial-time solutions following formal optimization methods from operations research (OR). For some problems, such an approach may not be always effective, and could lead to nonpolynomial-time solutions. For these problems, a customized approach following algorithm design from computer science (CS) could be more effective and lead to a polynomial-time solution.
It is important to distinguish a (solution) algorithm's complexity from the underlying problem's complexity. A problem's complexity determines the potential complexity of any algorithm that is designed to solve this problem. That is, for a problem not in P, unless P = NP, any algorithm that can find an optimal solution to this problem must have nonpolynomial-time complexity. In contrast, if an algorithm (design to solve the problem) has a nonpolynomial-time complexity, we cannot claim that this problem is not in P. Another algorithm designed by someone else may well solve the problem with a polynomial-time complexity.
In this chapter, we illustrate the above approaches and ideas with a case study. This case study is concerned with an optimal relay node assignment problem that arises in cooperative communications (CC) [139]. We first formulate the problem as a mixed-integer linear programming (MILP), following OR's optimization approach.