Predictive Factors of Pain and Functional Outcome 5 Years Following Total Hip Arthroplasty: A Prospective Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement Cohort Study.

BACKGROUND: Previous reports have identified a number of potential predictors of pain and function after total hip arthroplasty (THA). However, the results of these studies were conflicting, and most had a short follow-up after THA. The purpose of this study was to identify factors predictive of pain and function 5 years after THA. METHODS: A multicenter cohort of 7,934 primary unilateral THA patients was prospectively enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement consortium. Demographic data, comorbidities, and patient-reported outcome measures were collected preoperatively and postoperatively at 5 years, including the Hip Disability and OSteoarthritis Outcome Score (HOOS) pain and activities of daily living (ADL) scores. Multivariate logistic regression models with 95% confidence interval were used to identify independent predictors of pain and function at 5 years. RESULTS: The patient dissatisfaction percentage was 8.2% at 5 years after THA. The multivariate regression identified the following predictive factors for the HOOS pain score at 5 years: age, educational level, insurance, smoking, race, Charlson Comorbidity Index, back pain severity, number of other lower extremity painful joints, the Knee Injury and Osteoarthritis Outcome Score pain severity of the ipsilateral knee, preoperative Short-Form Health Survey 36-item (SF-36) mental component summary score, and HOOS pain scores. The multivariate regression identified the following predictor factors for HOOS ADL score at 5 years: body mass index, insurance, smoking, race, back pain severity, number of other lower extremity painful joints, Knee Injury and Osteoarthritis Outcome Score pain severity of ipsilateral knee, preop HOOS ADL, and preoperative SF-36 mental component summary score and SF-36 physical component summary score. CONCLUSIONS: Overall, 8.2% of patients were dissatisfied 5 years after primary THA. We have identified a number of factors that predict less improvement in pain and function 5 years after THA. These potentially modifiable factors can be targeted with preoperative patient optimization programs to improve patient outcomes and satisfaction after primary THA. Knowledge of these factors that predict less improvement in pain and function can assist the surgeon and patient during shared decision-making, and in setting appropriate patient expectations preoperatively.

Gender Differences in Pain, Function, and Quality of Life Five Years Following Primary Total Knee Arthroplasty.

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcomes after total knee arthroplasty (TKA). The impact of gender on outcomes after TKA remains controversial. Previous studies had less than 5 years of follow-up after TKA. The aim of this evaluation was to determine what differences in pain, function, and quality of life (QoL) exist between female and male patients 5 years after primary TKA. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients (7,284 females and 4,318 males) was prospectively evaluated. All patients were enrolled in the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement. Demographic data, musculoskeletal and medical comorbid conditions, and patient-reported outcome measures, including the Knee Injury and Osteoarthritis Outcome (KOOS) and Short-Form (36-item) Health Survey mental component score (MCS) and physical component score (PCS) were collected preoperatively and at 5 years after TKA. Descriptive statistics were generated, and stratified by gender, and differences in pain, function, and QoL between female and male patients were evaluated. Multivariate regression models with a 95% confidence interval (CI) were used to assess the role of patient gender as a predictive factor for KOOS pain and function in daily living (ADL) scores reported 5 years after primary TKA, while adjusting for other variables. RESULTS: Prior to surgery, female patients reported worse pain (KOOS pain 46 versus 52), function (KOOS ADL 53 versus 59), and QoL (KOOS QoL 26 versus 29) than male patients. The differences in preoperative scores ranged from 2.70 (KOOS QoL) to 6.12 (KOOS ADL). At 5 years after TKA, female patients reported slightly worse pain (87 versus 89), function (85 versus 87), and QoL (74 versus 75) when compared to male patients. The differences in the mean 5-year postoperative KOOS scores (range, 0.99 to 2.73), although statistically significant (P < .001), were clinically negligible. Female patients achieved greater improvement in pain (41 versus 37), function (32 versus 29), and QoL (48 versus 46) scores in comparison to male patients. Female patients also reported lower preoperative PCS global function (33 versus 35) scores, 5-year postoperative PCS scores (45 versus 46), and MCS global mental function scores (52 versus 54). Similarly, the differences in the 5-year postoperative Short-Form (36-item) Health Survey MCS and PCS scores were clinically negligible. Multivariate regression analysis showed that female gender was not independently predictive for either pain (ß = -1.08; 95% CI [-1.25 to 1.03] [P = .85]) or function (ß = 0.64; 95% CI [-0.51 to 1.79] [P = .28]) 5 years after surgery. CONCLUSIONS: There are no clinically significant gender differences in pain, function, or QoL 5 years after TKA. Female patients typically have worse symptoms prior to surgery, improve more than male patients, and end up with pain, function, and QoL scores clinically equal to male patients. These data can enhance the shared decision-making process between female patients and surgeons and assist in setting appropriate patient expectations prior to TKA.

Group sequential design with maximin efficiency robust test for immunotherapy with generalized delayed treatment effect.

The delayed treatment effect is a common feature of immunotherapy, characterized by a gradual onset of action ranging from no effect to full effect. In this study, we propose a generalized delayed treatment effect function to depict the delayed effective process precisely and flexibly. To reduce potential power loss caused by the delayed treatment effect in a group sequential trial, we employ the maximin efficiency robust test, which enhances power robustness across a range of possible delays. We present novel approaches based on the Markov chain method for determining group sequential boundaries, calculating the power function, and estimating the maximum sample size through iterative regressions between the square root of the maximum sample size and the normal quantile of power. Extensive simulation studies validate the effectiveness of our approaches, particularly in balanced trials, demonstrating the validity of group sequential boundaries and the accuracy of maximum sample size estimations. Additionally, we utilize a real trial as an example to compare our considered trial with group sequential trials using the log-rank and generalized piecewise weighted log-rank tests. The results show significantly reduced maximum sample sizes, highlighting the economic advantage of our approach.

Stabilizing Lattice Oxygen in a P2-Na0.67Mn0.5Fe0.5O2 Cathode via an Integrated Strategy for High-Performance Na-Ion Batteries.

P2-type Na0.67Mn0.5Fe0.5O2 (MF) has attracted great interest as a promising cathode material for sodium-ion batteries (SIBs) due to its high specific capacity and low cost. However, its poor cyclic stability and rate performance hinder its practical applications, which is largely related to lattice oxygen instability. Here, we propose to coat the cathode of SIBs with Li2ZrO3, which realizes the "three-in-one" modification of Li2ZrO3 coating and Li+, Zr4+ co-doping. The synergy of Li2ZrO3 coating and Li+/Zr4+ doping improves both the cycle stability and rate performance, and the underlying modification mechanism is revealed by a series of characterization methods. The doping of Zr4+ increases the interlayer spacing of MF, reduces the diffusion barrier of Na+, and reduces the ratio of Mn3+/Mn4+, thus inhibiting the Jahn-Teller effect. The Li2ZrO3 coating layer inhibits the side reaction between the cathode and the electrolyte. The synergy of Li2ZrO3 coating and Li+, Zr4+ co-doping enhances the stability of lattice oxygen and the reversibility of anionic redox, which improves the cycle stability and rate performance. This study provides some insights into stabilizing the lattice oxygen in layered oxide cathodes for high-performance SIBs.

Childhood trauma, peer victimization, and non-suicidal self-injury among Chinese adolescents: a latent variable mediation analysis.

BACKGROUND: Childhood and peer experiences can influence adolescents' perceptions of interpersonal relationships, which can, in turn, influence their emotional states and behavior patterns. Non-suicidal self-injury (NSSI) is now a common problem behavior among adolescents. The present study examined the role of childhood trauma and peer victimization in adolescents' NSSI. METHODS: A cross-sectional survey was conducted among 1783 adolescents (1464 girls and 318 boys) in the psychiatric outpatient clinics or wards of 14 psychiatric hospitals or general hospitals in nine provinces in China. Data were collected using the Multidimensional Peer Victimization Scale (MPVS), Short-form Childhood Trauma Questionnaire(CTQ-SF), and Functional Assessment of Self-Mutilation (FASM). Structural equation modeling (SEM) with latent variables was used to demonstrate the mediating role of peer victimization in the association between childhoodtrauma and NSSI. RESULTS: The SEM analysis demonstrated that peer victimization plays a partial mediating role in the relationship between childhood trauma and NSSI. In addition, several covariates (such as age, gender, education level, and place of residence) effectively regulated the relationship between peer victimization and NSSI. CONCLUSION: In future studies of NSSI among Chinese adolescents, attention should be paid to the roles of childhood trauma and peer bullying; there is a temporal sequence between these two variables and, to some extent, childhood trauma can have an impact on bullying during adolescence which, in turn, influences NSSI behavior.

How Back Pain Affects Patient Satisfaction After Primary Total Knee Arthroplasty.

BACKGROUND: Although back pain (BP) has been shown to be a predictor of dissatisfaction after total knee arthroplasty (TKA) in some reports, these studies did not use a scale to quantify the degree of pain. The purpose of this study was to quantify the effect of BP intensity on patient satisfaction reported at 1 year after TKA. METHODS: A multicenter prospective cohort was taken in which 9,057 patients undergoing primary unilateral TKA were enrolled in FORCE-TJR and demographic and clinical data were collected. Back pain (BP) intensity was assessed using the Oswestry back disability index (ODI) pain intensity questionnaire. Patients were classified into 4 categories based on the severity of BP. Patient-reported outcomes (PROs) were collected preoperatively and postoperatively after 1 year including the Knee injury and Osteoarthritis Outcome Score (KOOS) (total score, pain, Activities of Daily Living (ADL), and Quality of Life (QOL), Short-Form health survey 36-item (SF-36) Physical Component Score (PCS), and Mental Component Score (MCS)). We used a validated 5-point Likert satisfaction scale. Univariate analyses of the difference between the satisfied and dissatisfied patients' groups was performed. Multivariate logistic regression models with 95% confidence interval (CI) were used to quantify the effect of BP intensity on patient dissatisfaction at 1 year. Receiver operating characteristic (ROC) analyses were performed with measurement of area under curve (AUC). RESULTS: At 1 year, a total of 1,657 TKA patients (18.3%) were dissatisfied. A total of 4,765 patients (52.6%) reported back pain at the time of surgery, including mild BP in 2,264 patients (24.9%), moderate BP in 1,844 patients (20.3%), and severe BP in 657 patients (7.2%). Severe back pain was significantly associated with patient dissatisfaction at 1 year after TKA (P = .0006). The multivariate regressions showed that patients who had severe BP were 1.6 times more likely to be dissatisfied when compared to patients who had no BP [odds ratio (OR) 1.63; 95% confidence interval (CI) (1.23-2.16), P = .0006]. While patients who had mild BP [OR 0.98; 95% CI (0.82-1.17), P = .87] or moderate BP [OR 0.97; 95% CI (0.80-1.18), P = .78] were not associated with an increased likelihood of dissatisfaction. Other predictive variables for dissatisfaction, include age [OR for younger patients <65 years versus older patients ≥65 years, 0.74; 95% CI (0.59-0.92)], educational level [OR for post high school versus less, 0.83; 95% CI (0.71, 0.97)], smoking [OR for nonsmoker versus current smoker, 0.63; 95% CI (0.45, 0.87)], and Charlson comorbidity index [OR for CCI ≥2 versus 0, 1.25; 95% CI (1.05, 1.49)]. CONCLUSION: Increased BP intensity was associated with increased risk of dissatisfaction 1 year after TKA. Only patients who had severe BP were 1.6 times more likely to be dissatisfied. The data presented here can help to improve shared decision-making and patient counseling before surgery. Surgeons should consider a spine evaluation in patients who have severe BP prior to TKA.

Age-Related Differences in Pain, Function, and Quality of Life Following Primary Total Knee Arthroplasty: Results From a FORCE-TJR (Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement) Cohort.

BACKGROUND: The impact of age on patient outcomes after total knee arthroplasty (TKA) remains controversial. Age has shown no effect on outcome in some studies, while others have reported better or worse outcome in younger patients. The aims of this study were to determine the differences in pain, function, and quality of life (QoL) reported 1 year after TKA across different age groups. METHODS: A prospective, multicenter cohort of 11,602 unilateral primary TKA patients was evaluated. Demographic data, comorbid conditions, and patient-reported outcome measures including the knee injury and osteoarthritis outcome score (KOOS), KOOS-12, KOOS Joint Replacement, and Short-Form health survey (12-item) were collected preoperatively and at 1-year postoperatively. Descriptive statistics were generated, stratified by age [<55 years (younger adult), 55 to 64 years (older adult), 65 to 74 years (early elder), and ≥ 75 years (late elder)], and differences in pain, function, and QoL among the 4 age groups were evaluated using Chi-square and Kruskal-Wallis tests. Multivariate regression models with 95% confidence interval were performed to determine if age was predictive for KOOS pain and function scores. RESULTS: Prior to surgery, younger patients (<55 years) reported worse KOOS pain (39), function (50), and QoL (18) scores with poor mental health score (47) than other older patient groups. The mean preoperative score differences across the age groups in the KOOS total score (9.37), KOOS pain (11.61), KOOS-12 pain (10.14), and KOOS/KOOS-12 QoL (12.60) reached the calculated minimal clinically important difference. At 1 year after TKA, younger patients (<55 years) reported lower KOOS pain, function, and QoL scores when compared to older patients (≥ 75 years). The differences in 1-year postop scores among the 4 age groups (ranging from 4.0 to 12.2) reached the minimal clinically important difference for pain (10.4) and QoL (12.2). Younger patients (<55 years) achieved higher baseline to 1-year pain (36.8 points), function (30.3 points), and QoL (40.7 points) score changes when compared to older patients aged ≥ 75 years. Although statistically significant, the differences in score changes among the age groups were clinically irrelevant. The multivariate regression analyses showed that age was a significant predictor for pain, but not for function at 1 year where KOOS pain score was predicted to be higher (less pain) (ß = 6.17; 95% confidence interval 4.12- 8.22) (P < .001) in older patients (≥ 75 years) when compared to younger patients (<55 years). CONCLUSION: A TKA provides a dramatic improvement in pain, function, and QoL in all age groups. However, there are age-related clinically significant differences in preoperative pain, QoL, and mental health and in final postoperative pain and QoL scores with younger patients (<55 years) reporting more pain, less QoL, and worse preoperative mental health. The patient-reported outcome measure data presented here can be used clinically to improve shared decision-making and patient expectations prior to TKA.

Observation of the Orbital Rashba-Edelstein Magnetoresistance.

We report the observation of magnetoresistance (MR) that could originate from the orbital angular momentum (OAM) transport in a permalloy (Py)/oxidized Cu (Cu^{*}) heterostructure: the orbital Rashba-Edelstein magnetoresistance. The angular dependence of the MR depends on the relative angle between the induced OAM and the magnetization in a similar fashion as the spin Hall magnetoresistance. Despite the absence of elements with large spin-orbit coupling, we find a sizable MR ratio, which is in contrast to the conventional spin Hall magnetoresistance which requires heavy elements. Through Py thickness-dependence studies, we conclude another mechanism beyond the conventional spin-based scenario is responsible for the MR observed in Py/Cu^{*} structures-originated in a sizable transport of OAM. Our findings not only suggest the current-induced torques without using any heavy elements via the OAM channel but also provide an important clue towards the microscopic understanding of the role that OAM transport can play for magnetization dynamics.

The Prevalence and Predictors of Patient Dissatisfaction 5-years Following Primary Total Knee Arthroplasty.

BACKGROUND: Previous studies have evaluated patient dissatisfaction after total knee arthroplasty (TKA) at 1 year, but there is no data about the prevalence of dissatisfaction among TKA patients after prolonged follow-up. The purpose of this study is to determine patient dissatisfaction 5-years after TKA and to identify patient factors predictive of dissatisfaction. METHODS: Demographic and clinical data on 4402 patients undergoing primary unilateral TKA between 2012 and 2015 were collected prospectively through the Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) comparative effectiveness consortium including diverse community and academic practices distributed across 23 states in the United States. Data collected at 1 year preoperatively and 5 years postoperatively included patient satisfaction (using a 5-point Likert satisfaction scale) and patient-reported outcome measures (PROMs) including the Knee injury and Osteoarthritis Outcome Score (KOOS) and Short-Form health survey (36-item). A univariate analysis of the difference between the satisfied and dissatisfied patients' groups was performed. A multivariate logistic regression model with 95% confidence interval (CI) was used to identify independent predictors of dissatisfaction at 5 years. The regression model was performed after adjusting the following variables: age, gender, body mass index (BMI), Charlson Comorbidity Index (CCI), marital status, smoking, education, and insurance type. The Receiver Operating Characteristic (ROC) analysis was performed with the measurement of area under curve (AUC). Hosmer-Lemeshow goodness of fit test was performed to evaluate the validity of the model. RESULTS: A total of 12.7% patients (559/4402) reported dissatisfaction 5-years after TKA. Increased BMI, higher CCI, higher Oswestry disability index, and increased number of other painful lower extremities (LE) joints were significantly associated with dissatisfaction. Higher rates of dissatisfaction were present in young patients, patients with less education, and non-White patients. Patient dissatisfaction was significantly associated with poor preoperative and 5-year postoperative PROMs scores and less score improvement from baseline to 5 years (P < .001). The multivariate regression analysis showed that an increased number of other painful LE joints (OR = 1.81; 95% CI (1.14-2.88) (P = .01), increased Oswestry back disability index (OR = 1.40; 95% CI (1.07-1.82) (P = .01), non-White patients (OR = 1.74; 95% CI (1.26-2.40) (P = .001), and minimal preoperative functional disability with KOOS function in daily living (ADL) score ≥70 (OR = 0.64; 95% CI (0.43-0.95) (P = .02) were independent predictive factors for dissatisfaction at 5 years. CONCLUSION: A total of 12.7% patients reported dissatisfaction 5-years after TKA. Clinical profiles of the satisfied and dissatisfied patients were captured 5-years after TKA with differences in the preoperative demographic and clinical characteristic variables identified. Risk factors for long-term patient dissatisfaction after TKA have been identified and should be considered during shared decision making while planning for TKA. Surgeons should use these identified risk factors to set realistic expectations for patients at an increased risk for dissatisfaction aiming to optimize their outcomes and increase their long-term satisfaction after TKA.

Do Patient Outcomes Vary by Patient Age Following Primary Total Hip Arthroplasty?

BACKGROUND: Multiple authors have sought to determine what patient characteristics influence outcome after total hip arthroplasty (THA). Age has shown no effect on outcome in some evaluations, while others have reported higher functional improvement in younger patients. The aim of this study was to determine if outcome after THA varies based on patient age. METHODS: A prospective, multicenter cohort of 7,934 unilateral primary THA patients from the FORCE-TJR comparative effectiveness consortium was evaluated. Demographic data, comorbid conditions, and Patient-Reported Outcome Measures, including (HOOS), HOOS-12, HOOS JR, and SF-36 (PCS) and (MCS), were collected preop and at 1-year postop. Descriptive statistics were generated, stratified by age (<55 years [younger adult], 55-64 years [older adult], 65-74 years [early elder], and ≥75 years [late elder]), and differences in pain, function, and quality of life among the 4 age groups were evaluated. A multivariate regression model with 95% confidence interval (CI) was used to assess the role of patient age as a predictive factor for HOOS pain and function scores reported 1 year after primary THA. RESULTS: Prior to surgery, younger patients (<55 years) reported worse pain, function, and quality of life than the other 3 patient groups. At 1 year after THA, younger patients (<55 years) reported slightly worse pain and quality of life but better function scores than the 3 older patients' groups. Younger patients (<55 years) achieved higher baseline to 1-year pain, and function score changes when compared to the older patients' groups. The quality of life score changes was not different among the 4 age groups. The differences in 1-year postop scores (ranging from 2.74 to 8.46) and the magnitude of score changes from baseline to 1 year (ranging from 1.9 to 5.85), although statistically significant (P < .001), did not reach the minimal clinically important difference (MCID). The multivariate regression analysis shows that age is a significant predictor for pain at 1 year but not for function. Although HOOS pain score is predicted to be higher by 4.38 points (less pain) 1 year after THA in older patients (≥75), when compared to younger patients (<55 years), again the difference is well below the MCID and is clinically insignificant. CONCLUSION: Although there are statistically significant differences in pain relief, functional improvement, and quality of life between younger and older patients among different patients' age groups, there is no clinically significant difference. THA provides an improvement in quality of life by decreasing pain and increasing function in all 4 age groups, with large improvements in Patient-Reported Outcome Measures scores (>2 standard deviations) without clinically significant age-related differences in THA outcome at 1 year.

Extreme Suppression of Antiferromagnetic Order and Critical Scaling in a Two-Dimensional Random Quantum Magnet.

Sr_{2}CuTeO_{6} is a square-lattice Néel antiferromagnet with superexchange between first-neighbor S=1/2 Cu spins mediated by plaquette centered Te ions. Substituting Te by W, the affected impurity plaquettes have predominantly second-neighbor interactions, thus causing local magnetic frustration. Here we report a study of Sr_{2}CuTe_{1-x}W_{x}O_{6} using neutron diffraction and µSR techniques, showing that the Néel order vanishes already at x=0.025±0.005. We explain this extreme order suppression using a two-dimensional Heisenberg spin model, demonstrating that a W-type impurity induces a deformation of the order parameter that decays with distance as 1/r^{2} at temperature T=0. The associated logarithmic singularity leads to loss of order for any x>0. Order for small x>0 and T>0 is induced by weak interplane couplings. In the nonmagnetic phase of Sr_{2}CuTe_{1-x}W_{x}O_{6}, the µSR relaxation rate exhibits quantum critical scaling with a large dynamic exponent, z≈3, consistent with a random-singlet state.

Tailoring Co3d and O2p Band Centers to Inhibit Oxygen Escape for Stable 4.6†V LiCoO2 Cathodes.

High-voltage LiCoO2 delivers a high capacity but sharp fading is a critical issue, and the capacity decay mechanism is also poorly understood. Herein, we clarify that the escape of surface oxygen and Li-insulator Co3 O4 formation are the main causes for the capacity fading of 4.6 V LiCoO2 . We propose the inhibition of the oxygen escape for achieving stable 4.6 V LiCoO2 by tailoring the Co3d and O2p band center and enlarging their band gap with MgF2 doping. This enhances the ionicity of the Co-O bond and the redox activity of Co and improves cation migration reversibility. The inhibition of oxygen escape suppresses the formation of Li-insulator Co3 O4 and maintains the surface structure integrity. Mg acts as a pillar, providing a stable and enlarged channel for fast Li+ intercalation/extraction. The modulated LiCoO2 shows almost zero strain and achieves a record capacity retention at 4.6 V: 92 % after 100 cycles at 1C and 86.4 % after 1000 cycles at 5C.

High operating temperature pBn barrier mid-wavelength infrared photodetectors and focal plane array based on InAs/InAsSb strained layer superlattices.

Improving the operation temperature of the focal plane array (FPA) imagers is critical in meeting the demands to reduce the size, weight, and power (SWaP) for mid-infrared detection systems. In this work, we report the demonstration of a 15 µm-pitch 640×512 middle-format pBn FPA device with a 50% cutoff wavelength of 4.8 µm based on short period of InAs/InAsSb-based "Ga-free" type-II strained-layer superlattices, which achieves a high operating temperature (HOT) reaching 185 K. The pBn FPA exhibits a mean noise equivalent differential temperature (NETD) of 39.5 mK and an operability of 99.6% by using f/2.0 optics for a 300 K background at 150 K. The mean quantum efficiency is 57.6% without antireflection coating and dark current density is 5.39×10-5 A/cm2 at an operation bias of -400 mV, by which the mean specific detectivity(D*) is calculated as high as 4.43×1011 cm.Hz½/W.

Upside-down InAs/InAs1-xSbx type-II superlattice-based nBn mid-infrared photodetectors with an AlGaAsSb quaternary alloy barrier.

Ga-free InAs/InAsSb type-II superlattices (T2SLs) are emerging as candidate materials for high temperature operation of mid-infrared photodetectors, which are critical for infrared technology with an aim to provide low-cost and compact detection systems. In this work, by utilizing upside-down device structure, a closely lattice-matched Al0.83Ga0.17AsSb quaternary alloy as electron barrier was pre-grown before the growth of InAs/InAsSb T2SLs absorber in a nBn device. Based on this design, we have demonstrated 5-µm cut-off mid-wavelength infrared (MWIR) photodetectors that exhibited a dark current density of 1.55 × 10-4 A/cm2 at an operation bias 400mV at 150K. A saturated quantum efficiency at ∼4.0 µm reaches 37.5% with a 2 µm absorber and the peak responsivity reaches 1.2 A/W, which yields a peak specific detectivity as high as ∼1.82 × 1011 cm·H z1/2/W at a forward bias of 400mV.

Large Linear Negative Thermal Expansion in NiAs-type Magnetic Intermetallic Cr-Te-Se Compounds.

A large linear negative thermal expansion (NTE) and expanded NTE temperature range (ΔTNTE) were obtained in magnetoelastic CrTe1-xSex (0 ≤ x ≤ 0.15) compounds. For CrTe compound, its thermal expansion coefficient of volume (αV) was calculated to be -28.8 ppm K-1 with the temperature ranging from 280 to 340 K. Substituting Te with Se atoms, the NTE behavior and magnetic properties can be well manipulated. With increasing Se in CrTe1-xSex (0 ≤ x ≤ 0.15) compounds, the ΔTNTE increases from 60 K (280-340 K for x = 0), to 80 K (240-320 K for x = 0.05), to 95 K (200-295 K for x = 0.1), and finally to 100 K (170-270 K for x = 0.15). Furthermore, a linear NTE remains independent of temperature for samples with x ≤ 0.1. The relationship between tunable NTE and magnetic properties was analyzed in detail, indicating that the NTE in CrTe1-xSex compounds originates from the magnetovolume effect (MVE).

Identification of individuals by trait prediction using whole-genome sequencing data.

Prediction of human physical traits and demographic information from genomic data challenges privacy and data deidentification in personalized medicine. To explore the current capabilities of phenotype-based genomic identification, we applied whole-genome sequencing, detailed phenotyping, and statistical modeling to predict biometric traits in a cohort of 1,061 participants of diverse ancestry. Individually, for a large fraction of the traits, their predictive accuracy beyond ancestry and demographic information is limited. However, we have developed a maximum entropy algorithm that integrates multiple predictions to determine which genomic samples and phenotype measurements originate from the same person. Using this algorithm, we have reidentified an average of >8 of 10 held-out individuals in an ethnically mixed cohort and an average of 5 of either 10 African Americans or 10 Europeans. This work challenges current conceptions of personal privacy and may have far-reaching ethical and legal implications.

Using Cluster Analysis to Identify Patient Factors Linked to Differential Functional Gains After Total Knee Arthroplasty.

BACKGROUND: The basis of poor outcomes following total knee arthroplasty (TKA) is multifactorial. Previous research aimed at predicting outcome following TKA focuses largely on outcomes measured between two specific time points (pre-to post-TKA). Analysis of outcomes measured over multiple time points (trajectory) may expose relationships between patients' characteristics and longitudinal outcome patterns that may otherwise remain obscured. METHODS: The current study analyzed Short Form 36 Physical Component Score (PCS) trajectories of 656 patients composed of 3 time points over a 1-year period. Clusters were constructed utilizing MultiExperiment Viewer hierarchical clustering algorithm. Statistical significance of these clusters was assessed using MeV's built-in bootstrapping method. Patient characteristics of the resulting statistically conserved clusters were summarized and compared using Wilcoxon rank-sum test or chi-squared test as appropriate. RESULTS: Two distinct clusters of outcome trajectory were identified. Cluster 1 included 550 patients (84%) who demonstrated persistent PCS improvement at 6 and 12 months. Cluster 2 included 106 patients (16%) who demonstrated decline in PCS at 6 months followed by improvement at 12 months. Cluster 1 achieved earlier success, greater absolute mental and physical health scores as compared to Cluster 2 (P < .05), and demonstrated higher baseline mental health scores, lower baseline PCS, and a significantly higher proportion of non-Hispanic Whites (P ≤ .05). CONCLUSION: Cluster analysis identified distinct functional outcome trajectories following TKA. Specific differentiating patient factors were associated with differing trajectories. Future studies should focus on this method's ability to inform predictive models regarding patient outcomes.

Accounting for Population Structure in Gene-by-Environment Interactions in Genome-Wide Association Studies Using Mixed Models.

Although genome-wide association studies (GWASs) have discovered numerous novel genetic variants associated with many complex traits and diseases, those genetic variants typically explain only a small fraction of phenotypic variance. Factors that account for phenotypic variance include environmental factors and gene-by-environment interactions (GEIs). Recently, several studies have conducted genome-wide gene-by-environment association analyses and demonstrated important roles of GEIs in complex traits. One of the main challenges in these association studies is to control effects of population structure that may cause spurious associations. Many studies have analyzed how population structure influences statistics of genetic variants and developed several statistical approaches to correct for population structure. However, the impact of population structure on GEI statistics in GWASs has not been extensively studied and nor have there been methods designed to correct for population structure on GEI statistics. In this paper, we show both analytically and empirically that population structure may cause spurious GEIs and use both simulation and two GWAS datasets to support our finding. We propose a statistical approach based on mixed models to account for population structure on GEI statistics. We find that our approach effectively controls population structure on statistics for GEIs as well as for genetic variants.

Integrating functional data to prioritize causal variants in statistical fine-mapping studies.

Standard statistical approaches for prioritization of variants for functional testing in fine-mapping studies either use marginal association statistics or estimate posterior probabilities for variants to be causal under simplifying assumptions. Here, we present a probabilistic framework that integrates association strength with functional genomic annotation data to improve accuracy in selecting plausible causal variants for functional validation. A key feature of our approach is that it empirically estimates the contribution of each functional annotation to the trait of interest directly from summary association statistics while allowing for multiple causal variants at any risk locus. We devise efficient algorithms that estimate the parameters of our model across all risk loci to further increase performance. Using simulations starting from the 1000 Genomes data, we find that our framework consistently outperforms the current state-of-the-art fine-mapping methods, reducing the number of variants that need to be selected to capture 90% of the causal variants from an average of 13.3 to 10.4 SNPs per locus (as compared to the next-best performing strategy). Furthermore, we introduce a cost-to-benefit optimization framework for determining the number of variants to be followed up in functional assays and assess its performance using real and simulation data. We validate our findings using a large scale meta-analysis of four blood lipids traits and find that the relative probability for causality is increased for variants in exons and transcription start sites and decreased in repressed genomic regions at the risk loci of these traits. Using these highly predictive, trait-specific functional annotations, we estimate causality probabilities across all traits and variants, reducing the size of the 90% confidence set from an average of 17.5 to 13.5 variants per locus in this data.

Identification of causal genes for complex traits.

MOTIVATION: Although genome-wide association studies (GWAS) have identified thousands of variants associated with common diseases and complex traits, only a handful of these variants are validated to be causal. We consider 'causal variants' as variants which are responsible for the association signal at a locus. As opposed to association studies that benefit from linkage disequilibrium (LD), the main challenge in identifying causal variants at associated loci lies in distinguishing among the many closely correlated variants due to LD. This is particularly important for model organisms such as inbred mice, where LD extends much further than in human populations, resulting in large stretches of the genome with significantly associated variants. Furthermore, these model organisms are highly structured and require correction for population structure to remove potential spurious associations. RESULTS: In this work, we propose CAVIAR-Gene (CAusal Variants Identification in Associated Regions), a novel method that is able to operate across large LD regions of the genome while also correcting for population structure. A key feature of our approach is that it provides as output a minimally sized set of genes that captures the genes which harbor causal variants with probability ρ. Through extensive simulations, we demonstrate that our method not only speeds up computation, but also have an average of 10% higher recall rate compared with the existing approaches. We validate our method using a real mouse high-density lipoprotein data (HDL) and show that CAVIAR-Gene is able to identify Apoa2 (a gene known to harbor causal variants for HDL), while reducing the number of genes that need to be tested for functionality by a factor of 2. AVAILABILITY AND IMPLEMENTATION: Software is freely available for download at genetics.cs.ucla.edu/caviar.